THE NORWEGIAN TENECTEPLASE STROKE TRIAL (NOR-TEST): RANDOMISED CONTROLLED TRIAL OF TENECTEPLASE VS. ALTEPLASE IN ACUTE ISCHAEMIC STROKE
N. Logallo1, V. Novotny1 and L. Thomassen1
1Haukeland University Hospital, Neurology, Bergen, Norway
Background and Aims: Alteplase is of proven benefit for treatment of acute ischaemic stroke. Tenecteplase is pharmacologically superior to alteplase and may overcome some of alteplase’s shortcomings. Phase II trials of tenecteplase vs. alteplase have shown promise. The Norwegian Tenecteplase Stroke Trial (NOR-TEST – NCT01949948) is the first phase III trial investigating efficacy and safety of tenecteplase vs. alteplase in acute ischaemic stroke.
Method: NOR-TEST is a multi-centre, randomised, open-label, blinded endpoint trial designed to establish superiority of tenecteplase 0.4 mg/kg compared to alteplase 0.9 mg/kg in acute ischaemic stroke. All patients with suspected acute cerebral ischaemia eligible for thrombolytic therapy are eligible for NOR-TEST. Randomisation tenecteplase:alteplase is 1:1. The two primary study endpoints are 1) clinical improvement at 24 hours measured by NIHSS and 2) favourable functional outcome defined by mRS at 90 days (sliding dichotomy based on baseline NIHSS). Secondary study endpoints are: 1) mRS at 90 days (ordinal shift analysis); 2) clinical improvement at 2 hours measured by NIHSS; 3) intracerebral bleeding at 24–36 hours; 4) death; 5) serious adverse events.
Results: Approximately 1100 patients have been recruited in 13 Norwegian stroke units from September 2012 to September 2016. The Data and Safety Committee found no reason to halt patient recruitment. Analysis of the data is in progress.
Conclusion: NOR-TEST will provide new evidence about new thrombolytics in stroke and may lead to a more effective, safer and easier treatment for all acute ischaemic stroke patients.
AS03-002
Official Welcome & Large Clinical Trials
EFFICACY OF EARLY COGNITIVE-LINGUISTIC TREATMENT FOR APHASIA DUE TO STROKE; A RANDOMISED CONTROLLED TRIAL (RATS-3)
F. Nouwens1, L. de Lau1,2, E. Visch-Brink1, M. van de Sandt-Koenderman3,4, H. Lingsma5, P. Koudstaal1 and D. Dippel1
1Erasmus MC – University Medical Center, Dept. of Neurology, Rotterdam, The Netherlands
2Slotervaart Medical Center, Dept. of Neurology, Amsterdam, The Netherlands
3Rijndam Rehabilitation, Dept. of Rehabilitation, Rotterdam, The Netherlands
4Erasmus MC – University Medical Center, Dept. of Rehabilitation Medicine, Rotterdam, The Netherlands
5Erasmus MC – University Medical Center, Dept. of Public Health, Rotterdam, The Netherlands
Background and Aims: Aphasia occurs in 30% of stroke-patients and is often severely disabling. Most patients receive speech and language therapy (SLT), but much is unknown about factors influencing its efficacy, such as timing of treatment.
We aimed to study whether early after stroke patients with aphasia benefit more from intensive cognitive-linguistic treatment (CLT, a form of impairment-based SLT) than from no SLT.
Method: This multicenter randomised controlled trial (PROBE-design) was carried out in over 85 institutions in the Netherlands. Stroke-patients with first-ever aphasia were randomised within two weeks after stroke to early intensive CLT (one hour/day) or no SLT, during the first four weeks after randomisation. Hereafter, both groups received regular SLT.
Patients were tested with a linguistic test-battery at four weeks, three and six months after randomisation. Primary outcome was the score on the Amsterdam-Nijmegen Everyday Language Test (ANELT; measuring everyday verbal communication), four weeks after randomisation. The study was powered to detect a clinically relevant 4-point difference on the ANELT.
Results: In total, 152 patients were included and 80 were allocated to intervention. Median treatment-intensity in the intervention-group was 24.5 hours. The adjusted difference between groups in mean ANELT-scores four weeks after randomisation was 0.39, 95%CI: [−2.70–3.47], p= 0.805. No statistically significant differences were found at three and six months after randomisation either.
Conclusion: Four weeks of intensive CLT initiated within two weeks of stroke is not more effective than no early language treatment for the recovery of post-stroke aphasia. Our results exclude a clinically relevant effect of very early CLT on verbal communication.
AS04-007
Official Welcome & Large Clinical Trials
CLOSURE OF PATENT FORAMEN OVALE, ORAL ANTICOAGULANTS OR ANTIPLATELET THERAPY TO PREVENT STROKE RECURRENCE (CLOSE): A RANDOMIZED CLINICAL TRIAL
J.L. Mas1, G. Derumeaux2, J.M. Juliard3, B. Guillon4, E. Massardier5, P. Guérin6, H. Hosseini7, E. Teiger2, L. Mechtouff8, C. Arquizan9, M. Giroud10, O. Detante11, C. Guidoux12, S. Canaple13, C. Vaduva14, C. Cordonnier15, I. Sibon16, P. Garnier17, J.R. Lusson18 and G. Chatellier19
1Hôpital Sainte-Anne, Neurology, Paris, France
2Hôpital Henri Mondor, Physiology, Créteil, France
3Hôpital Bichat-Claude-Bernard, Cardiology, Paris, France
4CHU Nantes, Neurology, Nantes, France
5CHU Rouen, Neurology, Rouen, France
6CHU Nantes, Cardiology, Nantes, France
7Hôpital Henri Mondor, Neurology, Créteil, France
8CHU Lyon, Neurology, Lyon, France
9Hôpital Gui de Chauliac, Neurology, Montpellier, France
10CHU Dijon, Neurology, Dijon, France
11CHU Grenoble, Neurology, Grenoble, France
12Hôpital Bichat-Claude-Bernard, Neurology, Paris, France
13CHU Amiens, Neurology, Amiens, France
14CH Saint-Brieuc, Neurology, Saint-Brieuc, France
15CHU Lille, Neurology, Lille, France
16CHU Bordeaux, Neurology, Bordeaux, France
17CHU Saint-Etienne, Neurology, Saint-Etienne, France
18CHU Clermont-Ferrand, Cardiology, Clermont-Ferrand, France
19Hôpital Européen Georges Pompidou, Biostatistiques, Paris, France
Background and Aims: Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale (PFO), oral anticoagulants and antiplatelet therapy in patients with PFO-associated cryptogenic stroke The aim of the CLOSE trial was to assess whether transcatheter PFO closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large PFO or a PFO associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke.
Method: CLOSE (NCT00562289) is an academic-driven, multicentre (32 sites in France and 2 sites in Germany), randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. A detailed etiological work-up was used to select patients with cryptogenic stroke. The echocardiographic examinations were centrally reviewed before randomization to confirm the diagnosis of PFO with large shunt and the diagnosis of ASA. Eligible patients were randomized within six months after the qualifying event in a 1:1:1 ratio to either PFO closure plus long-term antiplatelet therapy, long-term oral anticoagulants or long-term antiplatelet therapy. In case of contraindication to anticoagulant therapy or PFO closure, patients could be randomized between the non contraindicated experimental treatment and the reference treatment (antiplatelet therapy). The primary outcome was the occurrence of fatal or nonfatal stroke.
Results: Six hundred in sixty four patients were included between December 2007 and December 2014. Follow-up ended in December 2016 (mean follow-up: 5.5 years).
Conclusion: Results will be presented during the conference.
AS04-015
Official Welcome & Large Clinical Trials
PROBUCOL FOR PREVENTION OF CARDIOVASCULAR EVENTS IN ISCHEMIC STROKE PATIENTS WITH HIGH RISK OF CEREBRAL HEMORRHAGE (PICASSO) STUDY: A MULTICENTER, RANDOMIZED CONTROLLED TRIAL
E.J. Lee1, S. Kwon1, J.H. Park2, Y.J. Kim3, K.S. Hong4, J.S. Lee5, J. Lee6, J.M. Park7, J.H. Lee8, H.W. Nah9, S.H. Heo10, Y.D. Kim11, W.K. Seo12, E.G. Kim13, J.K. Cha9, J.H. Kwon14, S.I. Sohn15, J. Lee16, J.C. Navarro17 and K. Wong18
1Asan Medical Center, Neurology, Seoul, Republic of Korea
2Seonam University- Myongji Hospital, Neurology, Goyang, Republic of Korea
3Ewha Womans University, Neurology, Seoul, Republic of Korea
4Ilsan Paik Hospital, Neurology, Goyang, Republic of Korea
5Asan Medical Center, Clinical Research Center, Seoul, Republic of Korea
6Korea University, Biostatistics, Seoul, Republic of Korea
7Eulji General Hospital, Neurology, Seoul, Republic of Korea
8Sacred Heart Hospital, Neurology, Seoul, Republic of Korea
9Dong-A University, Neurology, Busan, Republic of Korea
10Kyung Hee University, Neurology, Seoul, Republic of Korea
11Severance Hospital, Neurology, Seoul, Republic of Korea
12Samsung Medical Center, Neurology, Seoul, Republic of Korea
13Busan Paik Hospital, Neurology, Busan, Republic of Korea
14Ulsan University Hospital, Neurology, Ulsan, Republic of Korea
15Dongsan Medical Center, Neurology, Daegu, Republic of Korea
16Yeungnam University Hospital, Neurology, Daegu, Republic of Korea
17University of Santo Tomas Hospital, Neurology, Manila, Philippines
18Prince of Wales Hospital, Medicine & Therapeutics, Hong Kong, China
Background and Aims: Lipid-lowering strategies in ischemic stroke patients with high risk of cerebral hemorrhage have not been established because statin use has been associated with increased risk of hemorrhagic strokes. Probucol, being both cholesterol-lowering and antioxidant agents, may be a good treatment option in such cases.
Method: This was a randomized, open-label trial performed at 67 centers in three countries (ClinicalTrials.gov, NCT01013532). Patients who had had non-cardioembolic ischemic stroke or transient ischemic attack within 180 days and had prior intracerebral hemorrhage or multiple cerebral microbleeds were randomly assigned to a probucol 500 mg/day or non-probucol. In both treatment arms, statin therapy of the guidelines was recommended. The co-primary endpoints were the safety endpoint of hemorrhagic stroke and the efficacy endpoint of a composite of stroke, myocardial infarction, or vascular death. Analysis was done by modified intention-to-treat, which includes all randomized patients but excludes 1) those who did not take study medication at all, 2) those with no record post-randomization.
Results: Between 2009 and 2015, 1512 patients were included in analysis (756 for each group). Median follow-up duration was 1.87 (interquartile range: 1.04–3.03) years. The primary efficacy outcome was reduced in the probucol group, as compared with the non-probucol group (Hazard ratio [HR] 0.69, 95% confidence interval [95%CI] 0.53–0.92, p = 0.016), while primary safety outcome was comparable (HR 0.65, 95%CI 0.30–1.41, p = 0.274)
Conclusion: In ischemic stroke patients with high risk of cerebral hemorrhage, 500 mg/day of probucol reduced the overall incidence of stroke, myocardial infarction, and vascular death.
AS01-010
Presidential Symposium – Awards & Trials
PROGNOSTIC AND TREATMENT IMPACT OF PENUMBRAL IMAGING IN POOLED ANALYSIS OF RANDOMIZED TRIALS OF ENDOVASCULAR STENT THROMBECTOMY
B. Campbell1, C. Majoie2, B. Menon3, S. Bracard4, M. Hill3, K.W. Muir5, A. Demchuk3, L. San Román6, A. van der Lugt7, D. Liebeskind8, S. Brown9, G. Sharma1, P. White10, F. Guillemin11, A. Dávalos12, T. Jovin13, J. Saver14, D.W.J. Dippel15, M. Goyal16 and P. Mitchell17
1Royal Melbourne Hospital and The University of Melbourne, Medicine and Neurology, Melbourne, Australia
2Academic Medical Center, Department of Radiology, Amsterdam, The Netherlands
3Hotchkiss Brain Institute- Cumming School of Medicine- University of Calgary- Foothills Hospital, Department of Clinical Neurosciences, Calgary, Canada
4University Hospital of Nancy- INSERM U 947, Department of Diagnostic and Interventional Neuroradiology, Nancy, France
5University of Glasgow- Queen Elizabeth University Hospital, Institute of Neuroscience & Psychology, Glasgow, United Kingdom
6Hospital Clínic, Department of Radiology, Barcelona, Spain
7Erasmus MC University Medical Center, Department of Radiology, Rotterdam, The Netherlands
8University of California Los Angeles, Neurovascular Imaging Research Core- Department of Neurology, Los Angeles, USA
9Altair Biostatistics,., St Louis Park, USA
10Newcastle University, Institute of Neuroscience, Newcastle upon Tyne, United Kingdom
11INSERM CIC-EC1433- University of Lorraine and University Hospital of Nancy, Department of Clinical Epidemiology, Nancy, France
12Hospital Germans Trias i Pujol, Department of Neurology, Barcelona, Spain
13Stroke Institute- University of Pittsburgh Medical Center, Department of Neurology, Pittsburgh, USA
14David Geffen School of Medicine- University of California Los Angeles, Department of Neurology and Comprehensive Stroke Center, Los Angeles, USA
15Erasmus MC University Medical Center, Department of Neurology, Rotterdam, The Netherlands
16University of Calgary- Foothills Hospital, Department of Radiology, Calgary, Canada
17Royal Melbourne Hospital and The University of Melbourne, Radiology, Melbourne, Australia
Background and Aims: The role of CT perfusion (CTP) and MR perfusion-diffusion imaging in patient selection for endovascular thrombectomy remains uncertain. We pooled data to investigate the association of perfusion imaging profiles with treatment effect and functional outcome in 7 randomized trials of endovascular stent-thrombectomy.
Method: Patient-level imaging data from the MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE and THRACE trials were pooled (HERMES Collaboration). CT and MR perfusion data were uniformly reprocessed using RAPID software (research version, IschemaView) as used in the EXTEND-IA and SWIFT PRIME trials. For CT perfusion, irreversibly injured ischemic core was estimated using a relative cerebral blood flow threshold < 30% of normal brain. MR diffusion lesions were manually outlined to their maximal visual extent. Tissue at risk of infarction (CTP and MR) was estimated using Tmax > 6s. The association between pre-treatment core and mismatch volumes and the 90-day modified Rankin scale (mRS) was examined by treatment status and reperfusion status. The number needed to treat (NNT) to achieve mRS 0–1, 0–2, 0–3 or at least 1 unit improvement in mRS with endovascular treatment versus control was calculated for a range of ischemic core volumes and mismatch volumes, based on model-derived adjusted treatment effects.
Results: The results will be presented at the conference and will include approximately 900 patients (600 with CT-perfusion and 300 with MRI).
Conclusion: This will comprise the largest patient series examined to date with penumbral imaging prior to endovascular therapy. Insights into whether penumbral imaging parameters are prognostic, treatment effect modifying or both will inform clinical practice.
AS01-053
Presidential Symposium – Awards & Trials
TESPI(THROMBOLYSIS IN ELDERLY STROKE PATIENTS IN ITALY): RANDOMIZED CONTROLLED TRIAL OF ALTEPLASE VERSUS STANDARD TREATMENT IN PATIENTS AGED >80 YEARS WITHIN 3HRS AFTER STROKE ONSET
S. Lorenzano1, A. Vestri2, D. Toni1, on behalf of and TESPI trial investigators3
1Sapienza University of Rome, Department of Neurology and Psychiatry- Unità di Trattamento Neurovascolare- Policlinico Umberto I Hospital, Rome, Italy
2Sapienza University of Rome, Department of Public Health, Rome, Italy
3Italy
Background and Aims: The Thrombolysis in Elderly Stroke Patients in Italy (TESPI) trial aimed to evaluate whether treatment with alteplase within three hours of symptom onset in patients aged >80 years resulted in improved outcome and favorable benefit/risk ratio compared with standard care.
Method: TESPI was a multicenter, open-label, controlled, randomized trial with blinded evaluation of outcome. Patients with acute ischemic stroke (AIS) aged >80 years were randomized to IV alteplase or standard treatment (1:1) within 3 hours of stroke onset. Main clinical endpoints were favorable functional outcome (modified Rankin Scale [mRS] score 0–2) and mortality at 90 days and symptomatic intracerebral hemorrhage (SICH). The trial was prematurely terminated for ethical reasons after publication of IST-3 trial results which provided evidence of treatment benefit in elderly.
Results: Of the planned 600 patients, a total of 191 (mean [SD] age 85.1 [3.7] years; 61.8% women; 88 assigned to receive alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls with an absolute difference of 5.7% in favor of alteplase which did not reach statistical significance. Rates of death and SICH were similar between the two groups (18.3% vs. 26.5%, P= 0.189 and 14.1% vs. 15.3%, P= 0.821, respectively).
Conclusion: TESPI data did not show statistically significant differences in the main outcomes between alteplase patients and controls, but results evidence a numerically higher proportion of alteplase patients achieving functional independence at 90 days and lower rate of deaths, with SICH rates being similar to controls.
AS06-002
Presidential Symposium – Awards & Trials
OFF LABEL USE OF ALTEPLASE FOR ACUTE ISCHEMIC STROKE (AIS) IN PATIENTS OVER 80 YEARS OF AGE: INDIVIDUAL-PATIENT-DATA META-ANALYSIS OF EIGHT TRIALS
W. Hacke1
1Heidelberg, Germany
Background and Aims: In Europe, alteplase for AIS may be used according to European Stroke Organisation (ESO) guidelines, or the European Medicines Agency (EMA label) that are more restrictive, especially by excluding treatment of patients aged > 80 years. We sought to estimate the potential effects on outcomes if the EMA age restriction were to be lifted.
Method: Using individual patient data from 8 large randomised trials testing iv alteplase (0.9 mg/kg) versus control for AIS, we analysed excellent outcome (modified Rankin score [mRS] 0–1), distribution of mRS, symptomatic intracerebral haemorrhage (ICH) and mortality, in 3 cohorts: patients satisfying current EMA label; patients who would meet an age-revised label; and patients not meeting the age-revised label.
Results: Among 6136 patients in 8 trials, 2421 (39%) satisfied the EMA label, 3461 (56%) an age-revised label, and 2675 (44%) were outwith the age-revised label. Alteplase increased the rate of excellent outcome in the current and age-revised cohorts (odds ratios 1.44, 95% CI 1.22−1.70 and 1.43, 1.24−1.66 respectively) but not in those outside the age-revised label (1.06, 0.89−1.25). The early risk of fatal ICH was similar in all 3 cohorts. By 90 days, the early hazard from fatal ICH was offset by benefit for the current and age-revised labels (HR 0.95, 0.74−1.22 and 1.01, 0.85–1.19 respectively) but not outside the age-revised label (1.18, 0.99 – 1.41).
Conclusion: An age-revised EMA label that more closely aligns with ESO guidelines increased eligibility for treatment and maintained significant benefit without altering haemorrhage rates or causing increased 90-day mortality.
AS01-003
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
LOW-DOSE VERSUS STANDARD-DOSE ALTEPLASE BY AGE, ETHNICITY, AND SEVERITY OF ACUTE ISCHAEMIC STROKE: THE ENCHANTED TRIAL
X. Wang1, T. Robinson2, T.H. Lee3, H. Arima4, P. Bath5, J. Broderick6, A. Demchuk7, G. Donnan8, J. Kim9, P. Lavados10, R. Lindley1, J. Pandian11, O. Pontes-Neto12, S. Ricci13, V. Sharma14, N. Thang15, J.G. Wang16, M. Woodward17, C. Anderson1 and J. Chalmers17
1The George Institute for Global Health, Neurological and Mental Health Department, Sydney, Australia
2University of Leicester-, Department of Cardiovascular Sciences and NIHR Biomedical Research Unit-, Leicester, United Kingdom
3Linkou Chang Gung Memorial Hospital and College of Medicine- Chang Gung University, Stroke Center and Department of Neurology, Taoyuan, Taiwan R.O.C.
4Fukeoka University, Department of Public Health, Fukeoka, Japan
5University of Nottingham-, Stroke Trials Unit- Division of Clinical Neuroscience, Nottingham, United Kingdom
6University of Cincinnati Neuroscience Institute- University of Cincinnati, Department of Neurology and Rehabilitation Medicine-, Cincinnati, USA
7Hotchkiss Brain Institute- University of Calgary, Departments of Clinical Neurosciences and Radiology, Calgary, Canada
8University of Melbourne, The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia
9University of Ulsan- Asan Medical Center, Department of Neurology, Seoul, Republic of Korea
10Facultad de Medicina- Clinica Alemana Universidad del Desarrollo-, Departamento de Neurología- Clinica Alemana de Santiago-, Santiago, Chile
11Christian Medical College, Department of Neurology, Ludhiana, India
12University of Sao Paulo- Ribeirao Preto School of Medicine-, Department of Neurosciences and Behavioural Sciences, Ribeirao Preto, Brazil
13Sedi di Citta di Castello, Uo Neurologia- USL Umbria 1, e Branca, Italy
14National University Hospital- Singapore, Yong Loo Lin School of Medicine- National University of Singapore and Division of Neurology-, Singapore, Singapore
15The People ‘115 Hospital-, Department of Cerebrovascular Disease-, HCM city, Vietnam
16Rui Jin Hospital and Shanghai Jiaotong University School of Medicine, The Shanghai Institute for Hypertension, Shanghai, China
17The George Institute for Global Health, Professional Unit, Sydney, Australia
Background and Aims: A lower dose of alteplase reduces the risk of symptomatic intracerebral haemorrhage (sICH) in patients with acute ischaemic stroke (AIS). Thus patients who are older, Asian, or severely affected – often considered at high risk – may benefit from this treatment.
Method: Data are from the ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED), an international, randomised, open-label, blinded-endpoint trial of low- (0·6 mg/kg) versus standard-dose (0·9 mg/kg) intravenous alteplase in AIS patients. Interaction of the treatment effects was investigated by pre-specified subgroups of age, ethnicity (Asian vs. non-Asian), and severity (defined by NIHSS) on death or disability and sICH (defined by various standard criteria).
Results: 3297 patients (1248 female), mean age 67 (SD 12.8) years, were included. After adjusting for baseline and management variables, increasing age and severity were associated with death or disability (P trend <0·001), but ethnicity was not (odds ratio 0·85, 95% confidence interval [0·66–1·09]; P = 0·200). There was an increased risk of sICH with increasing severity (P < 0·0001), according to NINDS and ECASS3 criteria, but not with increasing age, nor between Asians and non-Asians. In the comparison between low- and standard-dose alteplase across age groups, ethnicity, and severity, there were no significant treatment interactions with clinical outcomes, but consistent reductions in sICH with low-dose alteplase.
Conclusion: Increasing age and stroke severity predict poor outcomes in thrombolysis-treated AIS patients. There was no heterogeneity in the treatment effects on death or disability in these pre-specified subgroups, including ethnicity. Standard-dose alteplase should be preferred unless other characteristics suggest a particular risk of bleeding.
AS01-004
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
LOW-DOSE VERSUS STANDARD-DOSE ALTEPLASE BY TIME FROM ONSET TO TREATMENT FOLLOWING ACUTE ISCHEMIC STROKE: THE ENCHANTED TRIAL
X. Wang1, T. Robinson2, H. Arima3, R. Lindley4, M. Woodward5, C. Carcel4, C. Anderson4 and J. Chalmers5
1The George Institute for Global Health, Sydney, Australia
2University of Leicester, Department of Cardiovascular Sciences and NIHR Biomedical Research Unit, Leicester, United Kingdom
3Fukuoka University, Department of Public Health-, Japan, Japan
4The George Institute for Global Health, Neurological and Mental Health, Sydney, Australia
5The George Institute for Global Health, Professional Unit, Sydney, Australia
Background and Aims: It has been established that earlier alteplase administration is associated with bigger proportional benefits for patients with acute ischemic stroke (AIS). Time from onset to treatment (OTT) may alter the balance of risks and benefits in choosing low- and standard-dose alteplase.
Method: Data are from the ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial of low- (0·6 mg/kg) versus standard-dose (0·9 mg/kg) intravenous alteplase in AIS patients randomized within 4.5 hours of symptom onset. Interaction of the treatment effects was investigated by pre-specified subgroups of OTT (<3 versus 3–4.5 h) on death or disability (defined by the modified Rankin scale scores 2–6 at 90 days) and symptomatic intracerebral hemorrhage (sICH, defined by various standard criteria).
Results: 3297 patients (1248 female), mean age 67 years, were included. After adjusting for baseline characteristics, longer OTT, 3–4.5 h compared with <3 h, was not significantly associated with death or disability (odds ratio 1.02, 95% confidence interval [0·66–1·09]; P = 0·764) or sICH (0.86[0.49–1.51], P = 0.602). In the comparison between low- and standard-dose alteplase, there were no significant differences on clinical outcomes, nor was there significant heterogeneity with respect to sICH.
Conclusion: Increasing OTT within 4.5 h does not predict poor outcomes in thrombolysis-treated AIS patients and it does not alter the balance of risks and benefits in choosing low- and standard-dose alteplase for an individual patient.
AS01-023
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
LOW-DOSE VERSUS STANDARD-DOSE ALTEPLASE BY PRIOR STROKE AND DIABETES MELLITUS IN ACUTE ISCHEMIC STROKE: THE ENCHANTED TRIAL
G. Chen1, X. Wang2, T. Robinson3, R. Lindley2, S. Zhou4, L. Ping4, W. Liu4, L. Liu4, J. Chalmers2 and C. Anderson2
1Xuzhou Central Hospital, Neurology, Xuzhou, China
2The George Institute for Global Health- University of Sydney, Neurological & Mental Health Division, Sydney, Australia
3University of Leicester, Department of Cardiovascular Sciences and NIHR Biomedical Research Unit in Cardiovascular Diseases, Leicester, United Kingdom
4The Affiliated Xuzhou Center Hospital of Nanjing University of Chinese Medicine, Neurology Department, Xuzhou, China
Background and Aims: History of prior stroke (PS) and diabetes mellitus (DM) are considered relative contraindications for intravenous alteplase in acute ischemic stroke (AIS). We aimed to assess the relative benefits and risks of low– vs. standard–dose alteplase in AIS patients with a history of PS and DM.
Method: Data are from the ENhanced Control of Hypertension ANd Thrombolysis strokE study (ENCHANTED), an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial, that assessed the effects of low- (0.6 mg/kg body weight) vs. standard-dose (0.9 mg/kg) alteplase in AIS. Subgroup analyses was undertaken according to patient medical history of PS and DM on key efficacy and safety outcomes.
Results: 3288 patients (431 with PS, 489 with DM, and 157 with both) were included. After adjusting for baseline characteristics and management variables over the first seven days, history of PS and DM were not associated with poor outcome, whether defined by 90-day mRS score 2–6 (OR 0.85, 95% CI 0.55-1.32; P = 0.476) or mortality (1.25, 0.62-2.52; P = 0.533). In the comparison of low- and standard-dose alteplase, no significant differences were observed for 90-day dichotomized mRS (0–1 versus 2–6); ordinal shift of mRS, mortality, or symptomatic intracerebral hemorrhage by history of PS and DM.
Conclusion: History of PS and DM are not associated with poor outcome in a thrombolysis-eligible AIS patients and these variables did not influence the comparative treatment effects low- and standard-dose alteplase.
AS01-024
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
THROMBOLYSIS IMPLEMENTATION IN STROKE (TIPS) TRIAL: A CLUSTER RANDOMISED CONTROL TRIAL OF IMPLEMENTATION STRATEGIES FOR INTRAVENOUS THROMBOLYSIS
C. Levi1, R. Sanson-Fisher2, J. Attia2, A. Bivard2, M. Parsons1, N. Spratt1, S. Middleton3, C. Bladin4, R. Lindley5, E. Kerr1, A. Ryan2, G. Donnan4, C. Oldmeadow2, K. Morris1, M. Russell1, M. Evans1 and C. Paul2
1John Hunter Hospital, Neurology, Newcastle, Australia
2University of Newcastle, Medicine, Newcastle, Australia
3Australian Catholic University, Nursing Research Institute, Sydney, Australia
4University of Melburne, Medicine, Melbourne, Australia
5University of Sydney, The George Institute for Global Health, Sydney, Australia
Background and Aims: Intravenous thrombolytic therapy with tissue plasminogen activator (tPA) is relatively underutilized in many regions of the developed world. This relates, in part to barriers in implementation. However, strategies tested and proven as either effective or ineffective in randomized implementation trials are very limited.
Method: To test the effectiveness of a multi-component multidisciplinary tPA implementation “package” intervention compared to usual care as a strategy for increasing thrombolysis implementation for acute stroke patients, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes at three months.
Results: Significant differences in tPA implementation rates were seen between intervention and control hospitals after 9 months of “active” intervention (generalised linear mixed effects model with terms for treatment group, quarter and interaction). However, over the time span of 24 months covering 12 months “active” intervention and a 12 months sustainability period, thrombolysis rates in intervention hospitals showed regression to the mean and a non-significant trend only to increased rates in intervention hospitals (Primary outcome rate difference = 1.1%; 95%CI –1.5 to 3.7%; linear regression adjusted for baseline rate and strata).
Conclusion: The experimental intervention resulted in an initial but non-sustained increment in thrombolysis implementation rate suggesting potential benefit of the “package” intervention if active support for hospital acute stroke services is maintained. Further refinements in the intervention are warranted.
AS01-045
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
CHARACTERISTICS, MANAGEMENT AND RESPONSE TO TREATMENT IN CHINESE VS. NON-CHINESE PARTICIPANTS IN THE ENCHANTED TRIAL
L. Song1, X. Wang2, T. Robinson3, R. Lindley2, H. Arima4, P. Lavados5, X. Chen2, J. Chalmers6 and C. Anderson2
1The George Institute for Global Health at Peking University Health Science Cente, Cardiac and Stroke, Beijing, China
2The George Institute for Global Health, Neurology & Mental Health, Sydney, Australia
3University of Leicester, Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Sciences, Leicester, United Kingdom
4Fukuoka University, Department of Preventive Medicine and Public Health- Faculty of Medicine, Fukuoka, Japan
5Universidad de Chile, Departamento de Ciencias Neurológicas- Facultad de Medicina, Santiago, Chile
6The George Institute for Global Health, Cardiology, Sydney, Australia
Background and Aims: The characteristics and management of patients with acute ischemic stroke (AIS) varies across regions, with higher rates of small vessel disease (SVD) anduse of alternative therapies in Asia which may influence outcomes. We examined differential patterns of outcome between Chinese and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED) which tested different alteplase doses in AIS.
Method: ENCHANTED was an international, open, blinded-endpoint trial of the effects of low- (0.6 mg/kg) vs. standard-dose (0.9 mg/kg) alteplase on 90-day disability outcomes and symptomatic intracerebral hemorrhage (sICH) in 3310 AIS patients.
Results: Chinese participants (n = 1419, 48%) were younger, and more often male, hypertensive, and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared to other AIS patients. Although Chinese participants had more intracranial atheroma and SVD, were treated late and had differing ancillary management, they had similar disability outcomes (mRS 2–6, 55.6% vs 47.8%; odd ratio, adjusted for baseline and management factors 0.87, 95% CI 0.71–1.07; P = 0.20) and risk of sICH (SITS-MOST criteria 1.4% vs. 1.8%; P = 0.12) to non-Chinese participants. There was no heterogeneity in the treatment effects of low vs standard dose alteplase between Chinese and non-Chinese participants.
Conclusion: Chinese ENCHANTED AIS patients had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management to AIS patients in other regions.
AS01-048
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
THE NORWEGIAN SONOTHROMBOLYSIS IN ACUTE STROKE STUDY (NOR-SASS). A RANDOMIZED CONTROLLED STUDY OF CONTRAST-ENHANCED SONOTHROMBOLYSIS
A. Nacu1, C.E. Kvistad2, H. Naess2, U. Waje-Andreassen2, H. Øygarden1, N. Logallo2, K.D. Kurz3, J. Assmus4, G. Neckelmann5 and L. Thomassen2
1University of Bergen, Clinical Medicine, Bergen, Norway
2Haukeland University Hospital, Department of Neurology, Bergen, Norway
3Stavanger University Hospital, Department of Radiology, Stavanger, Norway
4University of Bergen, Department of Biostatistics, Bergen, Norway
5Haukeland University Hospital, Department of Radiology, Bergen, Norway
Background and Aims: The Norwegian Sonothrombolysis in Acute Stroke Study aimed to assess safety and effect of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population treated with thrombolysis.
Method: Prospective, randomised, open-label, blinded endpoint phase III study. IV thrombolysis with either tenecteplase or alteplase was allowed. A visible arterial occlusion on baseline computer tomography angiography (CTA) was not a prerequisite for inclusion. Randomisation was 1:1 to either contrast-enhanced sonothrombolysis (CEST) or Sham CEST within 4½ hours after symptom onset. Pulsed wave 2 MHz ultrasound was given for one hour and continuous contrast (SonoVue®) infusion for ∼30 minutes. Magnetic resonance imaging and angiography were performed after 22–36 hours. Primary study endpoints were neurological improvement at 24 hours and functional handicap at 90 days. Main secondary study endpoints were hemorrhagic transformation, symptomatic intracerebral hemorrhage and death.
Results: A total of 183 patients were randomly assigned to either CEST or Sham CEST. The rates of asymptomatic intracerebral haemorrhage, symptomatic intracerebral haemorrhage or death did not differ between the two groups. Neurological improvement at 24 hours and functional outcome at 90 days were also similar, both in the intention to treat analysis and the per protocol analysis.
Conclusion: Contrast-enhanced sonothrombolysis can be safely administered within 4½ hours after symptoms onset in an unselected acute ischaemic stroke population treated with iv thrombolysis, with or without a visible clot on CTA and with varying clinical severity.
AS08-012
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
INTRAVENOUS THROMBOLYSIS IN PATIENTS WITH STROKE UNDER RIVAROXABAN USING DRUG SPECIFIC PLASMA LEVELS – EXPERIENCE WITH A STANDARD OPERATION PROCEDURE IN CLINICAL PRACTICE
D. Seiffge1, C. Traenka1, A. Polymeris1, S. Thilemann1, B. Wagner1, H. Gensicke1, N. Peters1, C. Nickel2, C. Stippich3, S. Marsch4, R. Sutter4, R. Guzman5, U. Fisch5, P. Lyrer1, G.M. De Marchis1, L. Bonati1, D. Tsakiris6 and S. Engelter1
1University Hospital Basel, Stroke Center and Neurology, Basel, Switzerland
2University Hospital Basel, Emergency Department and Stroke Center, Basel, Switzerland
3University Hospital Basel, Neuroradiology and Stroke Center, Basel, Switzerland
4University Hospital Basel, Intensive Care Unit and Stroke Center, Basel, Switzerland
5University Hospital Basel, Neurosurgery and Stroke Center, Basel, Switzerland
Background and Aims: Standard operating procedures (SOP) based on plasma levels of Rivaroxaban (RivLev) might be helpful to select patients suitable for IV-thrombolysis (IVT) or endovascular treatment (EVT) for acute ischemic stroke under Rivaroxaban (AISuR)
Method: Single-center explorative analysis from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) about the use of IVT/EVT among consecutive AISuR-patients (09/2012-11/2016). The SOP distinguished three RivLev ranges with differential meanings: IVT-recommended (RivLevlow < 20 ng/ml), IVT-to-be-considered (RivLevintermediate20-100 ng/ml), and IVT-to-be-avoided (RivLevhigh > 100 ng/ml). Patients with intracranial occlusions should get IVT + EVT (RivLevlow/RivLevintermediate) or pure EVT (RivLevhigh). We evaluated (i) the frequency of IVT/EVT used, (ii) the door-to-needle-time (DNT), (iii) reasons for avoiding IVT/EVT, and (iv) rate of symptomatic intracranial or major extracranial hemorrhage.
Results: Among 114 AISuR-patients, 68 were suitable for IVT/EVT if not taking Rivaroxaban and 63 had RivLev measured. In the 63 patients (median: 81years, baseline NIHSS 6), median RivLev was 96 ng/ml (IQR18-259 ng/ml) and median time-since-last-intake was 11 hours (IQR 4,5-18,5 hours). Twenty-two of 63 patients (35%) received IVT/EVT. These included IVT in 15, IVT + EVT in 3, and pure EVT in 4 patients, respectively. Median DNT was 37 (IQR30-60) minutes. None of 31 patients with RivLevhigh > 100 ng/ml received IVT. Among patients with RivLevlow/RivLevintermediate, the main reason to restrain from IVT was minor stroke (8/11 patients). Neither symptomatic intracranial nor major extracranial bleedings occurred.
Conclusion: Adding RivLev in the decision process about the use of IVT/EVT in AISuR-patients enabled the use of recanalization therapies in 1/3 of patients which were not eligible based on current guidelines. The absence of safety concerns in our pilot population justifies future studies of this approach.
AS08-041
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
PROFESSIONAL GUIDELINE VERSUS PRODUCT LICENCE SELECTION FOR TREATMENT WITH IV THROMBOLYSIS: COMPLIANCE WITH PRODUCT LICENCES IS HIGHEST IN LOWER EFFICIENCY SITES AND RESTRICTS THROMBOLYSIS USAGE
A. Cameron1, J. Bogie2, A. Abdul-Rahim1, N. Ahmed3, M. Mazya3, R. Mikulik4, W. Hacke5 and K. Lees1
1University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
2NHS Greater Glasgow and Clyde, Department of Medicine, Glasgow, United Kingdom
3Karolinska Institute, Department of Clinical Neuroscience, Stockholm, Sweden
4St. Anne's University Hospital, Neurology Department, Brno, Czech Republic
5University of Heidelberg, Department of Neurology, Heidelberg, Germany
Background and Aims: Thrombolysis usage varies across sites. Differences between professional guidelines and product licences may contribute.
Method: We analysed SITS-registry patients enrolled January 2010 through June 2016. We grouped sites into tertiles by patient numbers arriving <2.5 h and treated <3 h, percentage arriving <2.5 h and treated <3 h, and number treated <3 h. We assigned scores of 1–3 (lower/middle/upper) for each variable and 2 for on-site thrombectomy treatment. We classified sites with scores 3–5 lower-efficiency, 6–8 medium-efficiency and 9–11 higher-efficiency.
Sites were grouped by compliance with European/American licences and guidelines (ESO 2008–9/AHA 2013): “close” (<5% off-label), “broad” (>5% off-label, <5% off-guideline) or “exceptional” (>5% off-guideline). We cross-tabulated site-efficiency and local compliance. We estimated the potential benefit of universally treating by ESO/AHA guidelines using OTT-specific NNTs for day 90 mRS 0–1.
Results 56,689 patients at 597 sites were included: 163 sites were higher-efficiency, 204 medium-efficiency and 230 lower-efficiency. 56 sites were “closely-compliant”, 204 “broadly-compliant” and 337 “exceptional” by locally applicable criteria.
There were strong associations between site-efficiency and compliance (P < 0.001). The majority of “closely-compliant” sites were lower-efficiency: 55 (98%) by European criteria.
If all patients were treated by European guidelines, an additional 17,031 would have received alteplase. This translates into 1,922 more patients with favourable 3-month outcomes. Considering if US criteria applied, the increase would be 13,070 patients treated, for 1,114 more favourable outcomes.
Conclusion: Compliance with product licences rather than professional guidelines is highest in lower efficiency sites. Closer alignment with guidelines than product licences would increase numbers of patients treated and favourable outcomes.
AS08-060
Scientific Communication (Oral Abstract Presentation) Thrombolysis – Understanding the trials
OUTCOME AFTER ISCHEMIC STROKE IN PATIENTS OVER 80 YEARS TREATED WITH IV THROMBOLYSIS IN THE 3–4.5H COMPARED TO 3H TIME WINDOW: RESULTS FROM SITS-ISTR
N. Ahmed1, K.R. Lees2, P.A. Ringleb3, C. Bladin4, D. Toni5 and G.A. Ford6
1Karolinska Institutet & Karolinska University Hospital, Department of Clinical Neuroscience and Department of Neurology, Stockholm, Sweden
2University of Glasgow, Institute of Cardiovascular & Medical Sciences, Glasgow, United Kingdom
3University hospital Heidelberg, Department of Neurology, Heidelberg, Germany
4Box Hill Hospital Monash University, Dept Neurosciences Eastern Health, Melbourne, Australia
5'Sapienza’ University Viale del Policlinico- Rome, Dept. of Neurology and Psychiatry, Rome, Italy
6Oxford University Hospitals NHS Foundation Trust and Radcliffe, Department of Medicine, Oxford, United Kingdom
Background and Aims: The risks and benefits of treatment with intravenous alteplase (IVT) for acute ischemic stroke (AIS) in >80-years in the 3–4.5 hr time window are disputed. Clinical guidelines recommend use but regulatory authorities do not presently approve use after 3 hr in >80-years. We determined outcomes and risks of IVT in >80-years for < = 3 hr and 3–4.5 hr in the SITS registry.
Method: 14,240 patients (Yr2003-2015) >80 years with AIS were treated with IVT ≤4.5 h of stroke onset (3,558 in 3–4.5 hr). Of these 8658 (2157 in 3–4.5 hr) were treated according to the European Summary of product criteria (EU-SmPC) for Actilyse. Outcomes were 3-month mortality, functional independence (modified Rankin scale 0–2), and symptomatic intracerebral haemorrhage SICH/SITS.
Results: Median age was 84 years, 61% female in both groups. Median NIHSS was 12 vs. 14 in the 3–4.5 hr and < = 3 hr respectively. In the entire cohort: Three month functional independence was 34% vs. 35%, adjusted odds ratio (aOR, 95% CI) 0.76 (0.67–0.86, p < 0.001). Mortality 31% vs. 32%, aOR 1.12 (1.00–1.26, p = 0.056), SICH/SITS 2.7% vs. 1.6%; aOR 1.83 (1.36–2.47), p < 0.001. In EU-SmPC compliant patients: Three month functional independence was 36% vs. 37%, aOR 0.76 (0.63–0.91), p = 0.002. Mortality 29% vs. 29.6%, aOR 1.1 (0.9–1.3, p = 0.45). SICH/SITS 2.7% vs. 1.6%, aOR 1.7 (1.1–2.8, p = 0.02).
Conclusion: In this observational study, unselected patients >80-years treated with IVT after 3 h had a slightly higher rate of SICH and similar unadjusted functional outcome but poorer adjusted outcome than < = 3 h. However, among EU-SmPC compliant patients, outcome differences between the 3–4.5 hr and < = 3 hr were less evident.
AS06-052
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
NON-VITAMIN-K-ANTAGONIST ORAL ANTICOAGULANTS VERSUS WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION AND PREVIOUS STROKE OR TIA: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
G. Ntaios1, V. Papavasileiou2, D. Sagris1, H.C. Diener3, K. Makaritsis1 and P. Michel4
1University Hospital of Larissa, Medicine, Larissa, Greece
2Leeds Teaching Hospitals NHS Trust and Medical School- University of Leeds, Stroke Service- Department of Neurosciences, Leeds, United Kingdom
3University Hospital Essen, Department of Neurology and Stroke Center, Essen, Germany
4Centre Hospitalier Universitaire Vaudois and University of Lausanne, Stroke Center, Lausanne, Switzerland
Background and Aims: In a previous systematic review and meta-analysis, we assessed the efficacy and safety of non-vitamin-K antagonist oral anticoagulants(non-VKAs) versus warfarin in patients with atrial fibrillation(AF) and stroke or transient ischaemic attack (TIA). Since then, new information became available. The aim of the present work was to update the results of the previous systematic review and meta-analysis
Method: We searched PubMed until 24/08/2016 for randomized clinical trials using the following search items:“atrial fibrillation” and “anticoagulation” and “warfarin” and “previous stroke or transient ischemic attack”. Eligible studies had to be phase-III trials in AF patients comparing warfarin with non-VKAs currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding and major gastrointestinal bleeding. We performed fixed-effects analyses on intention-to-treat basis.
Results: Among 183 potentially eligible articles, 4 were included in the meta-analysis. In 20500 patients, compared to warfarin, non-VKAs were associated with a significant reduction of stroke/systemic embolism [relative-risk-reduction (RRR):13.7%,absolute-risk-reduction (ARR): 0.78%, number-needed-to-treat to prevent one event (NNT):127], hemorrhagic stroke (RRR:50.0%, ARR:0.63%, NNT:157), any stroke (RRR:13.1%, ARR:0.7%, NNT:142) and intracranial haemorrhage (RRR:46.1%, ARR:0.88%, NNT:113) over 1.8–2.8years.
Conclusion: This updated meta-analysis in 20500 AF patients with previous stroke or TIA shows that compared to warfarin, non-VKAs are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke and intracranial bleeding.
AS18-010
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
EFFECTIVENESS OF DIRECT ORAL ANTICOAGULANTS IN A POPULATION STUDY OF INCIDENT ATRIAL FIBRILLATION
A.Y.X. Yu1, S. Malo2, L.P. Svenson2, S.B. Wilton3 and M.D. Hill1
1University of Calgary, Clinical Neurosciences, Calgary, Canada
2Alberta Health, Surveillance and Assessment Branch, Edmonton, Canada
3University of Calgary, Libin Cardiovascular Institute, Calgary, Canada
Background and Aims: Clinical trials show that direct oral anticoagulants (DOAC) are non-inferior to warfarin for stroke prevention in atrial fibrillation (AF). However, the effectiveness of DOAC in the general population is less well established. We aimed to determine the population risk of stroke and death in incident AF, stratified by anticoagulation status and type.
Method: We conducted a population-based cohort study with administrative health data linkage. Incident non-valvular AF cases, diagnosed after January 1st 2009, were followed through to December 31st 2015. We used Cox-proportional hazard modelling with anticoagulation status as a time-varying exposure and adjusted for sex, CHADS2 score, and renal disease. Primary outcomes were ischemic stroke and death.
Results: There were 34,965 incident AF cases identified. Among 24,983 ever-anticoagulated patients, 47.2% filled at least two prescriptions for a DOAC, 76.5% for warfarin, and 23.7% for both medications. Relative to never-anticoagulated patients, anticoagulation was associated with a reduced risk of ischemic stroke (HR CI95 0.76 [0.64–0.91] for DOAC and 0.75 [0.65–0.85] for warfarin) and death (HR CI95 0.31 [0.29–0.34] for DOAC and 0.41 [0.29–0.34] for warfarin). Relative to warfarin, DOAC use was associated with decreased risk of death (HR CI95 0.76 [0.70–0.83], but no difference in the risk of ischemic stroke (HR CI95 1.02 [0.85–1.23]).
Conclusion: In a real-world population-based study of patients with incident AF, mortality was lower in patients anticoagulated with DOAC compared to warfarin, but rates of ischemic stroke were similar. Anticoagulation was associated with a reduced risk of ischemic stroke and death.
AS18-020
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
PREDICTING RISK OF MAJOR BLEEDING IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH ORAL ANTICOAGULATION AFTER TIA OR STROKE: EXTERNAL VALIDATION OF RISK SCORES
N. Hilkens1, A. Algra2 and J. Greving1
1University Medical Center Utrecht- the Netherlands, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
2University Medical Center Utrecht- the Netherlands, Julius Center for Health Sciences and Primary Care- Department of Neurology and Neurosurgery- Brain Center Rudolf Magnus, Utrecht, The Netherlands
Background and Aims: Prediction models for major bleeding may help physicians to weigh benefits and risks of anticoagulation in patients with atrial fibrillation (AF) prior to start of treatment. Performance of these models in patients with a previous TIA or ischemic stroke, who are at higher risk of major bleeding including intracranial haemorrhage, is not well established. Our aim was to examine performance of existing prediction scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulation after TIA or ischaemic stroke.
Method: We performed a post-hoc subgroup analysis among patients with cerebral ischaemia in the RE-LY trial. The RE-LY trial randomised 18,113 patients with AF to dabigatran or warfarin, of whom 3,623 had a history of TIA or stroke. We identified six risk scores of which we could validate five: Shireman, HEMORRHAGES, HASBLED, ATRIA and ORBIT. Predictive performance of the models was assessed with the c-statistic and calibration plots.
Results: 266 patients experienced a major bleed during 6,922 person-years of follow-up (3.8 per 100 person years). Discriminatory performance of models ranged from 0.60; 95% CI 0.53–0.66 (Shireman), to 0.66; 95% CI 0.59–0.72 (ORBIT). Calibration was poor for ATRIA and moderate for other models
Conclusion: Performance of prediction models for major bleeding in patients with cardioembolic cerebral ischaemia is modest, but comparable to performance in patients with AF. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables, had a c-statistic of 0.66 and reasonable calibration.
AS18-021
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
EARLY RECURRENCE AND MAJOR BLEEDING IN PATIENTS WITH ACUTE ISCHAEMIC STROKE AND ATRIAL FIBRILLATION TREATED WITH DIRECT ORAL ANTICOAGULANTS. THE RAF-DOAC STUDY
M. Paciaroni1
1University of Perugia, Stroke Unit, Perugia, Italy
Background and Aims: The optimal timing to administer direct oral anticoagulants (DOACs) in patients with acute stroke and atrial fibrillation (AF) is unclear. This prospective multicenter international study evaluated the risk of early recurrence and major bleeding and their timing in patients with acute stroke and AF who received DOACs for secondary prevention.
Method: Early recurrence was defined as the composite of ischaemic stroke, transient ischaemic attack (TIA) and symptomatic systemic embolism within 90 days from acute stroke. Symptomatic cerebral and major extra-cranial bleedings were also assessed.
Results: Overall, 1,127 patients were eligible for the analysis: 381 (33.8%) treated with dabigatran, 366 (32.5%) rivaroxaban and 380 (33.7%) apixaban. Thirty-two patients (2.8%) had early recurrence and 27 (2.4%) symptomatic intracranial (1.6%) or major extra-cerebral bleeding. The rates of early recurrence and major bleeding were 1.8% and 0.5% in patients receiving dabigatran; 1.6% and 2.5% in those receiving rivaroxaban and 4.0% and 2.9% in those receiving apixaban. Patients who received dabigatran were significantly younger, had a significantly lower NIHSS score on admission, less commonly a CHA2DS2-VASc score higher than 4 and reduced renal function. Full dose low-molecular-weight heparin given before DOACs was associated with an increased risk of major bleeding (OR 4.80; 95% CI 1.98–11.61, p = 0.01). Considering the day of initiating DOACs, the composite risk of recurrence and major bleeding was lower in patients in whom DOACs were initiated 3–14 days after index stroke.
Conclusion: Early initiation of DOACs in patients with acute stroke and AF was associated with a low risk of recurrence and bleeding.
AS18-043
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
EVALUATING THE EFFECTIVENESS AND SAFETY OF NOVEL ORAL ANTICOAGULANTS COMPARED WITH VITAMIN-K ANTAGONISTS
S. Loo1,2, S. Dell'Aniello1, J. Brophy2,3 and C. Renoux1,2,4
1Lady Davis Institute for Medical Research- Jewish General Hospital, Centre for clinical epidemiology, Montreal, Canada
2McGill University, Epidemiology- Biostatistics- and Occupational Health, Montreal, Canada
3McGill University Health Centre, Cardiology, Montreal, Canada
4McGill University, Neurology and Neurosurgery, Montreal, Canada
Background and Aims: In routine clinical practice, the effectiveness and safety of novel oral anticoagulants (NOAC) in the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF) merit further evaluation.
Method: Using the UK’s Clinical Practice Research Datalink, we formed a cohort of all adult patients with an incident diagnosis of NVAF, newly-treated with an oral anticoagulant between 2011 and 2016. New NOAC and vitamin-K antagonist (VKA) users were matched 1:1 on high-dimensional propensity score. Cox regression was used to estimate separately the hazard ratios (HR) of ischemic stroke, major bleeding, and intracranial bleeding, comparing NOAC to VKA. Separate analyses were conducted with the exposure defined using either an as-treated or a time-dependent approach.
Results: Among 155,953 eligible NVAF patients, 10,787 were initiated on NOAC and 23,306 were initiated on VKA within the study period. Of these, up to 6,981 new NOAC users could be matched to new VKA users on high-dimensional propensity score. Using an as-treated approach, there was no difference in the rate of ischemic stroke (HR 0.98; 95% CI 0.64–1.51) or major bleeding (HR 0.97; 95% CI 0.62–1.50) between matched NOAC and VKA users. The rate of intracranial bleeding was 41% lower among NOAC users (HR 0.59; 95% CI 0.24–1.49). Results using a time-dependent exposure, and analyses stratified by age, sex, renal disease status, and history of stroke at baseline will be presented.
Conclusion: Our results suggest that NOAC are as effective as VKA in the prevention of ischemic stroke in NVAF, while reducing the rate of intracranial bleeding.
AS18-053
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
POPULATION-BASED STUDY OF PROGNOSIS OF BRIEF EPISODES OF ATRIAL FIBRILLATION ON 5-DAY HOME CARDAIC RHYTHM MONITORING AFTER TIA AND ISCHAEMIC STROKE
S. Lyons1, N. Lovett1, G.S. Yiin1 and P.M. Rothwell1
1Centre for the Prevention of Stroke and Dementia, Centre for the Prevention of Stroke and Dementia, Oxford, United Kingdom
Background and Aims: Atrial fibrillation is a major cause of stroke and is associated with worse outcomes. Recent evidence suggests that the stroke risk in paroxysmal atrial fibrillation (pAF) might be lower than previously thought, but the clinical relevance of brief episodes of pAF detected on ambulatory monitoring shortly after TIA or non-disabling ischaemic stroke is uncertain. We sought to determine the prognostic significance of the brief episodes (<2 min) of pAF in this group.
Method: Consecutive eligible consenting patients with TIA or non-disabling ischaemic stroke in sinus rhythm in a population based study (Oxford Vascular Study) underwent 5 days of cardiac rhythm monitoring (Novacor R-Test) within 1-month of the event and were followed-up. Those with AF<2-minutes were not anticoagulated unless there were other factors suggestive of cardio-embolic cause (multiple infarcts or echocardiographic abnormality).
Results: Of 814 patients (age mean/SD 68.17/14.03, range 21–98) pAF was detected in 154 (18.9%), with 101 (11.4%) having only episodes of <2-minutes. During 2368 patient-years of follow-up, 31 (3.9%) patients had a recurrent stroke or peripheral embolic vascular event, while 52 (6.5%) died. There was no increase in risk of stroke, systemic embolism, or death in patients with pAF < 2-minutes versus those with no pAF (HR = 0.72, 95%CI 0.21–2.51, p = 0.61; 0.62, 0.18–2.15, p = 0.45; 0.50, 0.19–1.28, p = 0.15, respectively). There was also no increase in risk of recurrent TIA or stroke combined (HR = 1.08, 0.55–2.10, p = 0.83).
Conclusion: A policy of not routinely anticoagulating patients with pAF < 2-minutes did not result in a clearly increased risk of stroke, TIA or systemic embolism.
AS18-055
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
PILOT STUDY OF CARDIAC MAGNETIC RESONANCE IMAGING IN EMBOLIC STROKE OF UNDETERMINED SOURCE (MR-ESUS)
L.M. Porto1, B.M.M. Gonçalves1, A.L. Andrade1, J.A. Torreão2, C.B. Pereira1, K.O. Garcia1, M.B. Catto1, P.J.R. Muinos1, R.M. Maia1, T.C. Silva1, P.A.P. Jesus3 and J. Oliveira-Filho3
1Universidade Federal da Bahia, Faculdade de Medicina da Bahia, Salvador, Brazil
2Hospital Santa Izabel- Santa Casa de Misericórdia da Bahia, Cardiologia, Salvador, Brazil
3Universidade Federal da Bahia, Biomorfologia, Salvador, Brazil
Background and Aims: Defining the underlying mechanism of ischemic stroke is one of the cornerstones of secondary prevention, but up to 30% are classified as embolic stroke of undetermined source (ESUS). We aimed to determine the added clinical value of cardiac magnetic resonance imaging (CMRI) in patients with ESUS.
Method: Consecutive patients admitted to an outpatient university-based stroke clinic were investigated for stroke etiologic subtyping using the Causative Classification of Stroke. Patients with ESUS were further investigated using CMRI. Variables associated with potential CMRI embolic sources were investigated using logistic regression (any embolic source, dichotomous dependent variable) and ordinal logistic regression (number of embolic sources, ordinal dependent variable).
Results: We studied 57 patients, mean age 52 +/− 13 years, 30 (53%) female. Main cerebrovascular risk factors were dyslipidemia (76%), followed by hypertension (74%), Chagas disease (23%), smoking (19%), diabetes (18%)and coronary artery disease (7%). A potential source for cardioembolism was found in 16 (28%) patients: 15 (26%) with wall fibrosis, four (7%) with wall edema and five (9%) with intracardiac thrombus. Chagas disease was independently associated with any embolic source (OR = 5.0; 95% CI = 1.1–23.0, p = 0.039) and number of embolic sources (OR = 11.7; 95% CI = 1.8–100.4, p = 0.014). Additionally, coronary artery disease was associated with number of embolic sources (OR 23.7; 95% CI = 1.4–821.0, p = 0.040).
Conclusion: Potential sources of cardioembolism are found on CMRI in over one of every four patients previously classified as ESUS, especially among patients with Chagas disease or coronary artery disease.
AS18-061
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
COMPARATIVE EFFECTIVENESS OF NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS AND WARFARIN IN THE SCOTTISH ATRIAL FIBRILLATION POPULATION: THE VALUE OF REAL WORLD EVIDENCE
G. Ciminata1, C. Geue1, O. Wu1 and P. Langhorne2
1Institute of Health and Wellbeing University of Glasgow, Heath Economics and Heath Technology Assessment HEHTA, Glasgow, United Kingdom
2Institute of Cardiovascular and Medical Sciences, Glasgow Royal Infirmary, Glasgow, United Kingdom
Background and Aims: Clinical data from randomised control trials (RCTs), providing evidence on efficacy, have been used to inform economic evaluations of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF). In contrast, real world data offer the advantage of providing evidence on the effectiveness of NOACs in clinical practice. However, the absence of randomisation in a real world scenario does not allow for an unbiased comparison between the treatment and the comparator. The aim of this study is to explore, within the comparative effectiveness framework, the safety and the effectiveness of NOACs in newly anti-coagulated patients in the Scottish clinical practice.
Method: Among newly anti-coagulated patients 50 years and older, hospitalised with a known diagnosis of AF or atrial flutter, 36,729 patients (79.1%) initiated warfarin and 9,722 (20.9%) initiated NOACs. With a propensity score by matching approach, a sub-sample of individuals on NOACs or Warfarin who share a similar propensity score value was created. Event rates, for ischaemic stroke, systemic embolism, clinical relevant bleeding, intracranial haemorrhage, myocardial infarction and death, for both cohorts, were compared.
Results: During the two-year follow up, patients on NOACs experienced lower annual rates for the combined endpoints of ischaemic stroke, systemic embolism or death (incidence rate: 1.28%) compared to warfarin (HR 0.91, 95% CI:0.75–1.11). Overall, however no significant difference between the two treatments was found.
Conclusion: NOACs seem to be effective in reducing death due to stroke. Additional analyses between NOACs, and exploring different propensity score methods will be needed to confirm the findings.
AS18-063
Scientific Communication (Oral Abstract Presentation) Atrial Fibrillation
PREDICTIVE FACTORS OF STROKE RECURRENCE IN PATIENTS WITH ISCHEMIC STROKE DUE TO ATRIAL FIBRILLATION
M. Silva1,2, L. Legrand3, R. Arjmand2, C. Oppenheim3, J.L. Mas2 and D. Calvet2
1, Nyon, Switzerland
2Centre Hospitalier Sainte-Anne, Service de Neurologie, Paris, France
3Centre Hospitalier Sainte-Anne, Service d’Imagerie Morphologique et Fonctionnelle, Paris, France
Background and Aims: The risk of ischemic stroke (IS) recurrence in patients with atrial fibrillation (AF) can be lowered with the use of oral anticoagulant but has to be balanced against an increased risk of intracranial hemorrhage (ICH). Our objective was to access the predictive factors of recurrent stroke in a cohort of IS patients with AF.
Method: From a cohort of 1490 consecutive IS patients admitted between Jan-2013 and Dec-2015 in our stroke unit, 385 had an AF. Most of them (91%) had an MRI. All patients had a detailed etiological work-up and were followed up to 2016. The predictive value of baseline clinical and imaging characteristics (infarct arterial territory, white matter changes, presence of cerebral microbleeds [CMBs]) with respect to occurrence of stroke during follow-up was assessed.
Results: Mean (±SD) age was 80 (11). 20% of patients had infarct in multiple territories, 39% had a Fazekas score ≥2, and 30% had CMBs. The proportion of patients with CMBs increased with CHA2DS2-VASc (p for trend = 0.006). Anticoagulation was initiated during hospitalization in 56% or delayed in 29% of patients.
The absolute risk of recurrent IS was 11.2% (6.9–15.5) at 2 years whereas only 4 patients had an ICH during follow-up. In a multivariable Cox analysis, only a previous cerebral ischemic event remained independently associated with a higher the risk of recurrent IS (OR: 2.31 95% CI [1.00–5.34]).
Conclusion: Despite a high proportion of patients under anticoagulation with markers of small vessel disease on MRI, the risk of recurrent stroke was mainly driven by IS recurrences.
AS04-004
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
OPTIMAL TIMING TO START RIVAROXABAN ADMINISTRATION TO PREVENT RECURRENT EMBOLISM IN ACUTE STROKE PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION (NVAF): THE RELAXED STUDY
M. Yasaka1, K. Minematsu2, K. Toyoda2, E. Mori3, T. Hirano4, T. Hamasaki5, H. Yamagami2, T. Nagao6, S. Yoshimura7 and S. Uchiyama8
1Kyushu Medical Center, Department of Cerebrovascular Medicine and Neurology, Fukuoka, Japan
2National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine, Suita, Japan
3Tohoku University Graduate School of Medicine, Department of Behavioral Neurology and Cognitive Neuroscience, Sendai, Japan
4Kyorin University, Department of Stroke and Cerebrovascular Medicine, Tokyo, Japan
5National Cerebral and Cardiovascular Center, Department of Advanced Medical Technology Development-, Suita, Japan
6Nippon Medical School Tama-Nagayama Hospital, Department of Neurology, Tokyo, Japan
7Hyogo College of Medicine, Department of Neurosurgery, Nishinomiya, Japan
8International University of Health and Welfare, Clinical Research Center for Medicine, Tokyo, Japan
Background and Aims: Evidence is lacking regarding the optimal timing to start rivaroxaban treatment in acute stroke patients with NVAF.
Method: In this multicenter observational study, patients with acute ischemic stroke and NVAF started to receive rivaroxaban at a daily dose of 15 mg (CLcr ≥ 50 mL/min) or 10 mg (CLcr = 15–49 mL/min) within 30 days after the onset of stroke. The primary efficacy (recurrent ischemic stroke) and safety (major bleeding) endpoints during a 3-month follow-up were investigated according to infarct volume measured by MRI-DWI.
Results: A total of 1,333 patients were enrolled at 157 sites in Japan. By tertile range of infarct size, patients with a small (<3.9 cm3) infarct, a medium (4.0 – 22.4 cm3) infarct, and a large (≥22.5 cm3) infarct started rivaroxaban treatment a median of 2.9 days, 2.9 days, and 5.8 days, respectively, after the index stroke. Ischemic stroke recurred and major bleeding occurred in 30 and 11, respectively, of 1,309 analysis set patients (mean, 77.1 ± 9.6 years old; 755 men), and in 28 (2.3%) and 11 (0.9%), respectively, of 1,205 patients with a known infarct size. Recurrent stroke and major bleeding were less frequent in patients with a known infarct size starting rivaroxaban <3 days after onset (1.7% and 0.76%) than in those starting rivaroxaban after ≥3 days (2.8% and 1.0%): p = 0.21 for stroke, p = 0.62 for bleeding (chi-square test).
Conclusion: Early started rivaroxaban may be effective and safe to prevent recurrent attack in acute stroke patients with NVAF and a small or medium-sized infarct.
AS04-008
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
NURSE-LED, TELEPHONE-BASED, SECONDARY PREVENTIVE FOLLOW-UP AFTER STROKE OR TIA IMPROVES BLOOD PRESSURE AND LDL CHOLESTEROL: THREE-YEAR RESULTS FROM THE RANDOMIZED CONTROLLED NAILED STROKE TRIAL
J. Ögren1, A.L. Irewall2, L. Söderström3 and T. Mooe4
1Department of internal medicine, Department of cerebrovascular diseases, Östersund, Sweden
2Umeå University, Public Health and Clinical Medicine, Östersund, Sweden
3Hospital of Östersund, Unit of Research- development and Education, Östersund, Sweden
4Umeå University, Public Health and Clinical Medicine, Umeå, Sweden
Background and Aims: Enhanced secondary preventive follow-up after stroke or transient ischemic attack (TIA) is necessary for improved adherence to recommendations regarding blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels. We investigated whether nurse-led, telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels three years after discharge.
Method: All eligible patients admitted for stroke or TIA at Östersund hospital were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C measurements were performed one month after discharge and thereafter yearly. Intervention group patients who did not meet target values received additional follow-up, including lifestyle counselling and titration of medication, to reach treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L).
Results: Out of 871 randomized patients 660 completed the three-year follow-up. The mean systolic and diastolic BP in the intervention group was 128.8 mmHg and 76.5 mmHg respectively. This was 6.0 mmHg (95% CI: 3.5 – 8.5) and 3.4 mmHg (95% CI: 1.8 – 5.0) lower compared to the controls. The mean LDL-C was 2.2 mmol/L, 0.3 mmol/L (95% CI: 0.2 – 0.4) lower compared to the controls. A larger proportion of the intervention group patients reached the treatment goal for BP (systolic: 80.6 vs 55.6%, p < 0.001, diastolic: 90.3 vs 77.6%, p < 0.001) as well as for LDL-C (69.7 vs 48.9%, p < 0.001).
Conclusion: Nurse-led, telephone-based secondary preventive follow-up, including medication adjustment, was significantly more efficient than usual care at improving BP and LDL-C levels three years after discharge.
AS04-016
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
TICAGRELOR VERSUS ASPIRIN IN ACUTE EMBOLIC STROKE OF UNDETERMINED SOURCE (ESUS)
P. Amarenco1, G.W. Albers2, H. Denison3, J.D. Easton4, S.R. Evans5, P. Held6, M.D. Hill7, J. Jonasson3, S.E. Kasner8, P. Ladenvall3, K. Minematsu9, C.A. Molina10, Y. Wang11, K.S.L. Wong12 and S.C. Johnston13
1Bichat University Hospital and Paris-Diderot- Sorbonne University, Department of Neurology and Stroke Center, Paris, France
2Stanford University Medical Center, Stanford Stroke Center, Palo Alto, USA
3AstraZeneca, Research and Development, Gothenburg, Sweden
4University of California San Francisco, Department of Neurology, San Francisco, USA
5Harvard T. H. Chan School of Public Health, Department of Biostatistics, Boston, USA
6AstraZeneca, Global Medicines Department, Gothenburg, Sweden
7Hotchkiss Brain Institute- University of Calgary, Department of Clinical Neurosciences, Calgary, Canada
8Perelman School of Medicine- University of Pennsylvania Health System, Department of Neurology, Philadelphia, USA
9National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine, Suita, Japan
10Hospital Vall d’Hebron, Stroke Unit, Barcelona, Spain
11Tiantan Hospital, Department of Neurology, Beijing, China
12Chinese University of Hong Kong, Department of Medicine & Therapeutics, Hong Kong, Hong Kong S.A.R.
13Dell Medical School- University of Texas, Dean’s Office, Austin, USA
Background and Aims: Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and therefore could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS) which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis.
Method: We randomized 13,199 patients with a non-cardioembolic, non-severe ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2–90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary endpoint was time to the occurrence of stroke, myocardial infarction, or death within 90 days.
Results: ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction (P = 0.83). Hazard ratio in ESUS patients was 0.87 (95% CI, 0.68 to 1.10; P = 0.24). However, HR was 0.51 (95%CI, 0.29 to 0.90, P = 0.02) in ESUS patients with ipsilateral stenosis < 50% or aortic arch atherosclerosis (n = 961) and 0.98 (95%CI, 0.76 to 1.27, P = 0.89) in the remaining ESUS patients (n = 3368) (P for heterogeneity = 0.04).
Conclusion: In this post-hoc, exploratory analysis we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720).
AS04-020
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
PRIMARY RESULTS OF EBBINGHAUS, A COGNITIVE STUDY OF PATIENTS ENROLLED IN THE FOURIER TRIAL
F. Mach1, R. Giugliano2, K. Zavitz3, A. Keech4, T. Pedersen5, M. Sabatine2, P. Sever6, C. Kurtz7, H. Honarpour7 and B.R. Ott8
1, Switzerland
2Brigham and Women Hospital, Cardiology, Boston, USA
3Cambridge cognition, CANTLAB, Cambridge, United Kingdom
4University of Sydney, Cardiology, Sydney, Australia
5Institut of Clinical Medicine, Department of Preventive Medicine, Oslo, Norway
6Imperial College, Clinical Pharmacology, London, United Kingdom
7Amgen- Inc, Cardiovascular, Thousand Oaks, USA
8Rhode Island Hospital, Neurology, Rhode Island, USA
Background and Aims: Statins and PCSK9 inhibitors lower LDL-C by upregulating LDL receptor expression. Non-randomized data have raised concern that statins may cause impaired neurocognitive function. To test whether the addition of a PCSK9 inhibitor to statin might also raise such concerns, we performed a dedicated neurocognitive study of pts enrolled in the FOURIER trial, a randomized, double-blind placebo-controlled cardiovascular outcome trial of the PCSK9 inhibitor evolocumab.
Method: FOURIER enrolled pts with prior MI, prior stroke or symptomatic PAD, treated with maximally tolerated statin. Pts in FOURIER could elect to participate in this prospective assessment of cognitive function (EBBINGHAUS). Key exclusions for EBBINGHAUS were diagnoses of dementia, cognitive impairment, or other significant mental/neurological disorders. Neurocognitive testing was performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The primary endpoint was the change in spatial working memory strategy index of executive function (SWMsi). Pts were tested at baseline, week 24, week 48, every 48 weeks thereafter and at the end of the study. An exploratory analysis will compare neurocognitive function in pts with, versus without, at least 1 post-baseline LDL-C value <25 mg/dL.
Results: A total of 1974 pts (mean age 63 yrs, 28% women, 71% high-intensity statin, 75% prior MI) participated in the study. The median follow-up was ∼2 years. Primary results will be ready for presentation at ACC March 2017.
Conclusion: EBBINGHAUS primary results will provide a first indication as to whether the addition of evolocumab to statin therapy affects cognitive function over time in pts with stable cardiovascular disease already receiving statin therapy.
AS04-022
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
A CULTURALLY-TAILORED, SKILLS-BASED INTERVENTION TO REDUCE BLOOD PRESSURE IN A MULTI-ETHNIC GROUP OF MILD/MODERATE STROKE SURVIVORS WITH HYPERTENSION: RESULTS FROM THE DESERVE TRIAL
B. Boden-Albala1, E. Goldmann1, A.S. Lord2, H.M. Kuczynski1, V. Torrico1, N. Appleton1, J. Birkemeier1 and S. Turhim3
1New York University College of Global Public Health, Epidemiology, New York, USA
2New York University Langone Medical Center, Neurology, New York, USA
3The Mount Sinai Hospital, Neurology, New York, USA
Background and Aims: Secondary stroke prevention strategies have proven suboptimal in underserved and minority populations. The Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial tested the efficacy of a culturally-tailored, innovative, skills-based intervention focused on risk perception, medication adherence, and patient-physician communication (vs. usual care enhanced with educational material [EUC]) on systolic blood pressure (SBP) reduction among mild/moderate stroke/TIA patients at 1 year post-discharge.
Method: We assessed the difference in mean SBP reduction between trial arms, overall and by race/ethnicity, among those with prehypertension/hypertension at baseline using linear regression, adjusting for any characteristics that differed between trial arms at baseline.
Results: A total of 321 of 552 stroke/TIA patients assessed at baseline were included in analyses (intervention, n = 163; EUC, n = 158; 29% white, 33% black, 33% Hispanic). Overall, there was a trend toward greater mean BP reduction in the intervention vs. EUC group (12.6 vs. 8.4 mmHg, p = 0.101). Mean SBP reduction was significantly greater in the intervention vs. EUC group among Hispanics (15.6 vs. 1.7 mmHg, p = 0.002). Among Hispanics, after adjusting for age, interview language, education, place of birth, and baseline SBP, mean SBP reduction was 8.2 mmHg greater in the intervention vs. EUC group (p = 0.041). Mean SBP reduction did not differ significantly between trial arms among non-Hispanics.
Conclusion: Few behavioral intervention studies in stroke survivors have reported significant long-term differences in vascular risk reduction, and fewer have focused on a skills-based approach. Culturally-tailored, skills-based interventions may be more useful than knowledge-focused interventions in achieving sustained vascular risk reduction and addressing race/ethnic stroke disparities.
AS04-024
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
SECULAR TRENDS IN PROCEDURAL STROKE OR DEATH RISKS OF STENTING VERSUS ENDARTERECTOMY FOR SYMPTOMATIC CAROTID STENOSIS – A POOLED ANALYSIS OF RANDOMISED TRIALS
M. Müller1, S. Von Felten2, A. Algra3, J.P. Becquemin4, M. Brown5, R. Bulbulia6, D. Calvet7, H.H. Eckstein8, G. Fraedrich9, A. Halliday10, J. Hendrikse11, G. Howard12, O. Jansen13, G. Roubin14, J.L. Mas7, T. Brott15, P. Ringleb16 and L. Bonati1,5
1University Hospital Basel, Neurology and Stroke Center, Basel, Switzerland
2University Hospital Basel, Clinical Trial Unit, Basel, Switzerland
3University Medical Center Utrecht, Neurology and Neurosurgery, Utrecht, The Netherlands
4University of Paris XII, Vascular Surgery, Paris, France
5University College London, Brain Repair and Rehabilitation, London, United Kingdom
6Oxford University, Clinical Trial Service Unit and Epidemiological Studies Unit, Oxford, United Kingdom
7Université Paris-Descartes, Neurology, Paris, France
8Klinikum rechts der Isar der Technischen Universität München, Vascular and Endovascular Surgery/Vascular Center, Munich, Germany
9Medical University of Innsbruck, Vascular Surgery, Innsbruck, Austria
10John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford, United Kingdom
11University Medical Center Utrecht, Radiology, Utrecht, The Netherlands
12UAB School of Public Health, Department of Biostatistics, Birmingham, USA
13UKSH Campus Kiel, Radiology and Neuroradiology, Kiel, Germany
14Cardiovascular Associates of the Southeast, Cardiology, Birmingham, USA
15Mayo Clinic, Neurology, Jacksonville, USA
16University of Heidelberg Medical School, Neurology, Heidelberg, Germany
Background and Aims: Stroke risk associated with carotid disease may have decreased over the past decades. It is less clear whether this is also true for the procedural risk of revascularisation.
Method: We analysed temporal changes in procedural risks among 4599 patients with symptomatic carotid stenosis treated with carotid artery stenting (CAS; n = 2327) or endarterectomy (CEA; n = 2272) in four randomised trials between 2000 and 2008, using generalised linear mixed models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, defined as occurring within 30 days after treatment.
Results: The procedural stroke or death risk in the CEA group decreased significantly over time (unadjusted OR per year 0.83, 95% CI 0.74-0.94, p = 0.007), while the change in CAS risk was not significant (unadjusted OR 0.96, 95% CI 0.88–1.04, p = 0.34). After adjustment for baseline characteristics, the results remained essentially the same (CEA: OR 0.81, 95% CI 0.72–0.92, p = 0.003; CAS: OR 0.96, 95% CI 0.88–1.05, p = 0.31). The treatment effect of CAS vs. CEA changed significantly over time (interaction p = 0.04).
Conclusion: The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over time, independent of clinical predictors of procedural risk. There was no significant change in procedural risk of carotid stenting.
AS04-025
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
RESTENOSIS AFTER STENTING VERSUS ENDARTERECTOMY FOR SYMPTOMATIC CAROTID STENOSIS AND ITS RELATIONSHIP WITH RECURRENT STROKE IN THE RANDOMISED INTERNATIONAL CAROTID STENTING STUDY (ICSS)
L. Bonati1, J. Gregson2, J. Dobson2, D. McCabe3, R. Featherstone4, P. Nederkoorn5, B. van der Worp6, G.J. de Borst7, J. Beard8, T. Cleveland8, S. Engelter1, P. Lyrer1, G. Ford9, P. Dorman10 and M. Brown4
1University Hospital Basel, Department of Neurology, Basel, Switzerland
2London School of Hygiene and Tropical Medicine, Department of Medical Statistics, London, United Kingdom
3The Adelaide and Meath Hospital, Department of Neurology, Dublin, Ireland
4UCL Institute of Neurology, Department of Brain Repair and Rehabilitation, London, United Kingdom
5Academic Medical Center Amsterdam, Department of Neurology, Amsterdam, The Netherlands
6Brain Center Rudolf Magnus- University Medical Center Utrecht, Department of Neurology and Neurosurgery, Utrecht, The Netherlands
7University Medical Center Utrecht, Department of Vascular Surgery, Utrecht, The Netherlands
8Sheffield Teachiing Hospitals, Sheffield Vascular Institute, Sheffield, United Kingdom
9Oxford University Hospitals NHS Trust, Division of Medical Sciences, Oxford, United Kingdom
10Royal Victoria Infirmary, Department of Neurology, Newcastle upon Tyne, United Kingdom
Background and Aims: The clinical relevance of carotid artery restenosis after stenting or endarterectomy is unclear. We investigated the relationship between restenosis and the risk of recurrent stroke in the International Carotid Stenting Study.
Method: Patients with symptomatic carotid stenosis were randomised to stenting or endarterectomy and examined clinically and with carotid ultrasound at baseline, 1 and 6 months, and annually up to 10 years. Degree of restenosis based on ultrasound velocities and clinical outcome events were adjudicated centrally, masked to treatment assignment. Restenosis was analysed using interval-censored models and its association with later ipsilateral stroke using Cox regression.
Results: 1713 patients were assigned to stenting (n = 855) or endarterectomy (n = 858), of whom 1530 (n = 737 and n = 793) with completed treatment were followed-up with ultrasound for a median of 4.0 years. Moderate or severe (≥50%) carotid restenosis or occlusion occurred more often in the stenting group (n = 274 patients) than in the endarterectomy group (n = 217 patients; cumulative 5-year risks 41% vs. 30%). Severe (≥70%) carotid restenosis did not differ significantly (11% vs. 9%). Patients with ≥50% restenosis had a significantly higher risk of ipsilateral stroke than patients without restenosis in the endarterectomy group (HR 5.75, 95% CI 1.80 to 18.33, p = 0.003), but not in the stenting group (HR 2.03, 95% CI 0.77 to 5.37, p = 0.15).
Conclusion: At least moderate carotid restenosis (≥50%) occurred more frequently after stenting than endarterectomy, but only restenosis after endarterectomy increased the risk of ipsilateral stroke. These findings might reflect differences in the pathogenesis of restenosis between the two procedures.
AS06-050
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
ENDOVASCULAR TREATMENT VERSUS ENDARTERECTOMY FOR CAROTID ARTERY STENOSIS: RESULTS FROM THE UPDATED SYSTEMATIC COCHRANE REVIEW
M. Müller1, P. Lyrer1, M. Brown2 and L. Bonati1,2
1University Hospital Basel, Neurology and Stroke Center, Basel, Switzerland
2University College London, Department of Brain Repair and Rehabilitation, London, United Kingdom
Background and Aims: Endovascular treatment by balloon angioplasty or primary stenting (EVT) is an alternative to carotid endarterectomy (CEA) for treatment of carotid artery stenosis.
Method: We selected all randomised controlled trials (RCTs) comparing EVT with CEA. Analysis was by intention-to-treat with Mantel-Haenszel (MH) random-effects models. The primary outcome was any stroke or death within 30 days of treatment or ipsilateral stroke thereafter.
Results: 20 trials including 9066 patients (5865 with symptomatic, 3201 with asymptomatic carotid stenosis) were included in this analysis. The primary outcome, as well as stroke, death or myocardial infarction within 30 days after treatment or ipsilateral stroke thereafter, occurred more often in EVT than CEA in patients with symptomatic carotid stenosis (OR 1.5, 95% CI 1.2–1.8, p < 0.0001 and OR 1.4, 95% CI 1.2–1.6, p = 0.0005 respectively), but did not differ significantly in patients with asymptomatic carotid stenosis (OR 1.3, 95% CI 0.9–2.0, p = 0.98 and OR 1.1, 95% CI 0.8–1.6, p = 0.62, respectively). The risk for ipsilateral stroke after the procedural period was similar in both treatments in symptomatic patients (OR 1.2, 95% CI 0.9–1.6, p = 0.35). There was no significant difference in the risk of severe restenosis between treatment groups (OR 1.3, 95% CI 0.8–2.1, p = 0.24).
Conclusion: The comparison of procedural safety and long-term efficacy in preventing recurrent stroke combined favours CEA in patients with symptomatic carotid stenosis. Outcomes in patients with asymptomatic stenosis did not differ, but confidence intervals of effect measures were wide, showing the need for further data from ongoing RCTs.
AS09-078
Scientific Communication (Oral Abstract Presentation) Prevention – Trials
THE EVOLUTION OF CAROTID INTERVENTION: SECULAR TRENDS IN STENT TYPE, CEREBRAL PROTECTION DEVICES AND MEDICATION IN ACST-2, A LARGE INTERNATIONAL RCT COMPARING SURGERY WITH STENTING
R. Bulbulia1, A. Halliday2, L. Bonati3, R. Peto1, D. Morris1, H. Pan1 and ACST-2 Collaborative Group1
1University of Oxford, Clinical Trial Service Unit & Epidemiological Studies Unit, Oxford, United Kingdom
2University of Oxford, Nuffield Department of Surgical Sciences, Oxford, United Kingdom
3University Hospital of Basel, Stroke Centre and Department of Neurology, Basel, Switzerland
Background and Aims: Patients with tight asymptomatic carotid artery stenosis can benefit from revascularisation to reduce long-term stroke risk. ACST-2 will provide reliable evidence of the short-term hazards and long-term benefits of both procedures, and allows description of contemporary carotid intervention practice.
Method: Patients enter ACST-2 when revascularization is felt to be clearly indicated, when both CEA and CAS are practicable, but where there is substantial uncertainty as to which is the most appropriate intervention. Collaborators are encouraged to use their normal techniques and CE-approved devices.
Results: Since 2008, over 2400 patients (70% male, median age 69) have been randomised. Most had a tight stenosis (median 80%), and 33% had a significant contralateral stenosis. At trial entry, most patients were taking triple medical therapy (antiplatelet: 90%; antihypertensive: 89%; lipid lowering therapy: 84%), of whom 43% were prescribed moderate and 30% intensive statin regimens, with good adherence several years post-procedure. Those allocated CAS had closed-cell (57%), open-cell (21%), hybrid (17%) or membrane (5%) stents and 85% had cerebral protection devices (67% filter and 18% reverse flow). Stenting has evolved, with an increased use of hybrid and subsequently membrane mesh covered stents observed in the last 2 years. In contrast surgery (72% GA; 44% patch closure and 22% shunted) has not changed during the last decade.
Conclusion: Modern stent designs and cerebral protection devices are being used increasingly widely to try to reduce procedural strokes. ACST-2 captures such changes in practice and will hence compare contemporary carotid stenting with conventional surgery.
AS14-012
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
AN EPIGENOME WIDE ASSOCIATION STUDY REVEALS AN ALTERED METHYLATION PATTERN ASSOCIATED WITH ACUTE NEUROLOGICAL OUTCOME AFTER ISCHEMIC STROKE
N. Cullell1, M. Mola-Caminal2, C. Soriano-Tárraga2, C. Gallego-Fabrega3, C. Carrera4, E. Muiño1, J. Krupinski5, N. Torres1, L. Heitsch6, L. Ibanez7, C. Cruchaga8, J. Montaner9, J.M. Lee10, A. Ois2, A. Rodriguez-Campello2, E. Cuadrado-Godia2, E. Giralt-Steinhauer2, J. Roquer2, J. Jimenez-Conde2 and I. Fernandez-Cadenas11
1Fundació docènca i recerca Mútua Terrassa, Stroke Pharmacogenomics and Genetics, Terrassa, Spain
2Hospital del Mar- IMIM, Department of Neurology- Neurovascular Research Group, Barcelona, Spain
3Massachusetts General Hospital- BroadInstitute, Center for Human Genetic Research- Program in Medical and Population Genetics, Boston- Cambridge, USA
4Vall d'Hebron Institute of Research- Universitat Autonoma de Barcelona, Neurovascular Research Laboratory, Barcelona, Spain
5Hospital Mútua de Terrassa, Neurology Service, Terrassa, Spain
6Washington University, The Department of Emergency Medicine, St. Louis, USA
7School of Medicine- Washington University, Department of Psychiatry, St. Louis, Spain
8School of Medicine- Washington University, Department of Psychiatry- Hope Center Program on Protein Aggregation and Neurodegeneration, St. Louis, USA
9Hospital Universitari Vall d'Hebron- Virgen del Rocio Hospital, Department of Neurology, Barcelona- Sevilla, Spain
10Washington University School of Medicine, Department of Neurology and the Hope Center for Neurological Disorders, St. Louis, USA
11Fundació docènca i recerca Mútua Terrassa- Vall d'Hebron Institute of Research- Universitat Autonoma de Barcelona, Stroke Pharmacogenomics and Genetics- Neurovascular Research Laboratory, Terrassa- Barcelona, Spain
Background and Aims: Neurological outcome within the early phase after stroke onset is highly variable. We aimed to study the role of epigenetics in the prognosis of stroke.
Method: We analyzed 450.000 CpG methylation sites using the Human-Methylation Beadchip (Illumina) in 780 ischemic stroke patients (662 from Mar Hospital, 118 from Vall d’Hebron Hospital). Both cohorts were analyzed as a single cohort.
Different strategies were used to analyze the role of epigenetics in neurological outcome: 1) ΔNIHSS-discharge (baseline NIHSS – NIHSS at discharge) for all patients.
2) ΔNIHSS-24 h (baseline NIHSS – NIHSS at 24 h) (n = 118).
3) ΔNIHSS-discharge for 200 patients with neurological improvement (ΔNIHSS-discharge ≥ 4).
Data processing, correction, normalization and analysis steps were implemented using R. Generalized linear model with sex, age, smoking status, batch and PCA as covariates was used.
Results: Depending on the analysis strategy we found: 1) Nine CpG sites suggestively associated (p-value < 1x10−5) with neurological outcome. One of them in a gene associated with neuronal development. 2) One CpG site was Epigenome-Wide significant (p-value = 1.8x10−7), it was located in 10q26.2, in a gene related with cell proliferation. 3) Three CpG sites were Epigenome-Wide significant and located in 1p35.1 (p-value = 5.39x10−8), 17q25.3 (p-value = 1.17x10−7) and 18q22.3 (p-value = 7.83x10−7). The gene in 1p35.1 was associated with cognitive function and genes in 17q25.3 and 18q22.3 were associated with neuronal activity and neuropathophysiological processes, respectively.
Conclusion: Our study found differential methylation status associated with neurological outcome after ischemic stroke. The study of patients with neurological improvement showed the most significant results. Replication analyses are necessary to confirm those associations.
AS14-019
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
RARE EXONIC VARIANTS IN EXTREMES OF MRI-MARKERS FOR CEREBRAL SMALL VESSEL DISEASE
A. Mishra1, G. Chauhan1,2, M.H. Violleau1, B. Mazoyer3, C. Tzourio1,4 and S. Debette1,5
1Université de Bordeaux, Centre de recherche INSERM U1219, BORDEAUX, France
2Indian Institute of Science, Centre for Brain Research, Bangalore, France
3Université de Bordeaux, CNRS-CEA UMR 5293, BORDEAUX, France
4CHU de Bordeaux, Service d’information médicale, Bordeaux, France
5CHU de Bordeaux, Department of Neurology, Bordeaux, France
Background and Aims: MRI-markers of cerebral small vessel disease (CSVD), comprising white matter hyperintensity volume (WMHV) and lacunar brain infarcts, are common in older community persons and strongly associated with stroke and dementia risk. While heritability of CSVD is high, only few common genetic risk variants are known. We performed association study between rare exonic variants and a composite, extreme MRI-defined CSVD phenotype (M-CSVD) in 500 participants from the 3C-Dijon population-based cohort (aged 73.30 ± 4.24 years, 59.24% women).
Method: The top M-CSVD group comprised 250 individuals in the upper extreme distribution of WMHV residuals, adjusted for age, gender, and intracranial volume, prioritizing individuals with lacunar brain infarcts. The bottom M-CSVD group comprised 250 participants without MRI-defined brain infarct who were in the lower extreme distribution of WMHV. These participants were whole-exome sequenced with average coverage of 100X. We performed gene-based burden tests, focusing on 8 candidate genes responsible for monogenic forms of CSVD considering only splice-site, stop-loss, stop-gain or frame-shift variants.
Results: Power calculations suggest a linear relationship between power of gene-based burden tests and proportion of detrimental rare variants within a gene. In our study design 80.18% power could be attained to identify association with a gene at p < 6.25 × 10−03 (correcting for 8 candidate genes) containing 100% of detrimental rare variants and 50% missing sites per gene. We identified nominal association of NOTCH3 gene (p = 0.019) with M-CSVD.
Conclusion: In a single-study population-based sample we show nominal association of rare variant burden in NOTCH3 with M-CSVD, suggesting some shared mechanisms between monogenic and multifactorial CSVD.
AS14-021
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
TARGETED LIPID PROFILING DISCOVERS NOVEL PLASMA BIOMARKERS OF LARGE VESSEL STROKE: RESULTS OF THE ASPIRE-STROKE STUDY
S.A. Sheth1, A.T. Iavarone2, G.J. Wong3, R. Liou4, K. Malhotra5, S. Starkman3, D.S. Liebeskind5, J.L. Saver5, S.I. Savitz1 and G. Nestor R6
1University of Texas Health Science Center at Houston, Neurology, Houston, USA
2University of California at Berkeley, QB3/Mass Spectrometry Facility, Berkeley, USA
3University of California- Los Angeles, Emergency Medicine, Los Angeles, USA
4University of California- Los Angeles, Neurosurgery, Los Angeles, USA
5University of California- Los Angeles, Neurology, Los Angeles, USA
6Cedars-Sinai Medical Center, Neurosurgery, Los Angeles, USA
Background and Aims: In the era of endovascular therapy, rapid identification and transport of patients with large vessel occlusions (LVO) to endovascular-capable hospitals has become increasingly important. We previously demonstrated that brain-specific sphingolipids (SLs) serve as useful plasma markers of brain injury. Here, we test and validate SL biomarkers for LVO in a large clinical cohort.
Method: We enrolled patients with symptoms concerning for acute ischemic stroke (AIS) and performed SL profiling using HPLC-MS/MS on blood samples obtained at hospital arrival. LASSO regression was used to create a classification method in a derivation arm, and then tested in an independent validation arm.
Results: Among 203 patients, 94 (46%) were female and median age was 74 (IQR 63–83). 84 (41%) were diagnosed with AIS, 35 (17%) with TIA, 8 (4%) with hemorrhage and 76 (37%) as stroke mimics. Time from last known well to blood collection was 124 minutes (IQR 65–285). Among patients with AIS, NIHSS was 6 (±6) and 25 (30%) had LVO on CTA/MRA (ICA, M1, M2). Among 49 SLs definitively identified, 17 were Ceramides and 30 were Sphingomyelins. 42 (86%) SLs were elevated in LVO compared to non-LVO AIS, fold change 1.1 (IQR 1.05–1.21). Using LASSO regression in the derivation cohort, a panel of 20 SLs differentiated LVO from non-LVO AIS with very good accuracy, Figure 1a (AUC 0.97). In the independent validation cohort, the panel again showed excellent accuracy, Figure 1b (AUC 0.81).
Conclusion: Plasma levels of brain-specific SLs may serve as sensitive biomarkers of LVO stroke at early time points.
AS14-026
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
DILATED PERIVASCULAR SPACES, A MARKER OF CEREBRAL SMALL VESSEL DISEASE, ARE HIGHLY HERITABLE
M.G. Duperron1, C. Tzourio1,2, M. Sargurupremraj1, B. Mazoyer3, S. Schilling1, P. Amouyel4,5,6, G. Chauhan1,7, Y.C. Zhu8 and S. Debette1,9
1INSERM U897, Univ. Bordeaux, BORDEAUX, France
2Pole de santé publique- Service d’information médicale, CHU de Bordeaux, Bordeaux, France
3Institut des Maladies Neurodégénératives- CNRS-CEA UMR 5293, Univ. Bordeaux, Bordeaux, France
4Inserm U1167, Inserm, Lille, France
5Lille University Hospital, Department of Public Health, Lille, France
6Pasteur Institute of Lille, Department of Epidemiology and Public Health, Lille, France
7Centre for Brain Research, Indian Institute of Science, Bangalore, India
8Pekin Union Medical College Hospital, Department of Neurology, Beijing, China
9CHU de Bordeaux, Department of Neurology, Bordeaux, France
Background and Aims: Dilated perivascular spaces (dPVS) is an emerging MRI-marker of cerebral small vessel disease. We examined the genetic contribution to dPVS burden by measuring its heritability and shared heritability with other MRI-markers of cerebral small vessel disease.
Method: Analyses were conducted on 1597 participants from the community-based 3C-Dijon study, who had a brain MRI with quantitative dPVS measurement and genome-wide genotyping. dPVS and lacunar brain infarcts (LI) were rated visually on a semi-quantitative scale, while an automated algorithm generated white matter hyperintensity volume (WMHV). We estimated dPVS heritability and shared heritability with WMHV and LI using GCTA, adjusting for age, sex, intracranial volume, and 20 principal components of population stratification.
Results: All participants had some degree of dPVS. WMHV and LI were correlated with dPVS burden, the strongest correlation being observed between WMHV and dPVS in basal ganglia. dPVS heritability was estimated at 0.53 ± 0.26 (p = 0.02), in the same range as WMHV heritability, estimated at 0.51 ± 0.26 (p = 0.02); LI heritability was lower (0.14 ± 0.24; p = 0.28). We found a trend towards a high shared heritability between dPVS and WMHV (0.56 ± 0.33; p = 0.06) with higher estimates for dPVS in basal ganglia (0.84 ± 0.53; p = 0.07) than in white matter (0.11 ± 0.50; p = 0.41). We also found that a genetic risk score for WMHV based on published loci was associated with dPVS in basal ganglia (p = 0.03).
Conclusion: We provide evidence for important genetic contribution to dPVS in older community-dwelling persons, some of which may be shared with WMHV. Differential heritability patterns for dPVS suggest at least partly distinct underlying processes according to dPVS location.
AS14-028
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
SERUM AMYLOID A AS AN EARLY PREDICTOR OF STROKE ASSOCIATED INFECTION
A. Bustamante1, V. Fétaud2, T. García-Berrocoso1, A. Penalba1, A. Simats1, M. Muchada3, M. Rubiera3, M. Katan4, J.C. Sanchez2 and J. Montaner1
1Institut de Recerca- Hospital Universitari Vall d'Hebron- Universitat Auntónoma, Neurovascular Research Laboratory, Barcelona, Spain
2University of Geneva, Department of Human Protein Sciences, Geneva, Switzerland
3Hospital Universitari Vall d'Hebron, Stroke Unit, Barcelona, Spain
4University Hospital Zürich, Department of Neurology, Zürich, Switzerland
Background and Aims: Infections represent one of the main causes of morbidity and mortality in stroke patients. Serum amyloid A (SAA) was identified by proteomics as a biomarker for infections in patients with subarachnoid hemorrhage and stroke. We aimed to further explore the role of SAA as an early biomarker of infection in acute ischemic stroke.
Method: Acute ischemic stroke patients admitted to Vall d’Hebron Emergency Department were enrolled. Blood samples were collected at admission. Infections were diagnosed according to Center of Disease Classification criteria, during hospital stay. Independent predictors of infections were determined by logistic regression, and the additional predictive value of SAA was assessed with integrated discrimination improvement (IDI) index.
Results: From August-2012 to August-2015, 367 patients (median age 79(67–84), median NIHSS 10(6–17)) were enrolled. Median time from stroke to blood collection was 2.5 hours. 111 patients developed infections, having higher baseline SAA (10.4(55.5–55.3)µg/mL vs. 7.2(3.7–18.7)µg/mL, p = 0.006). A cut-off point of SAA > 5.85 µg/mL had 73.9% sensitivity and 44.1% specificity to predict infection. In logistic regression, SAA > 5.85 was an independent predictor of infection (OR = 2.38(1.25–4.52), p = 0.008) after adjustment for significant baseline predictors of infection (NIHSS, atrial fibrillation, systolic blood pressure). The addition of SAA to clinical predictors slightly improved discrimination (IDI = 2.41%(0.48–4.34), p = 0.014). The additional predictive value of SAA was missed when adjusted by dysphagia.
Conclusion: SAA is an independent predictor of infections from hospital admission, before a dysphagia test may be performed. For its high sensitivity, SAA might be useful to identify patients at high risk for infection, to indicate closer monitoring and deeper diagnostic workup.
AS14-033
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
GENOME WIDE STUDY FOR RARE VARIANTS REVEALS LOCI ASSOCIATED WITH HEMORRHAGIC TRANSFORMATION AFTER RT-PA
C. Carrera Vásconez1, N. Cullell2, N. Torres2, E. Muiño Acuña2, J. Jimenez-Conde3, J. Roquer3, E. López-Cancio4, A. Dávalos4, J. Arenillas5, C. Vives-Bauza6, M. Ribó7, J. Krupinski8, D. Strbian9, T. Tatlisumak9, L. Heitsch10, L. Ibanez11, C. Cruchaga11, J. Montaner1,12, J.M. Lee13 and I. Fernández-Cadenas1,2
1Vall d'Hebron Institute of Research, Neurovascular Research Laboratory, Barcelona, Spain
2Fundació Docència i Recerca Mutua Terrassa, Stroke pharmacogenomics and genetics, Terrassa, Spain
3IMIM-Hospital del Mar, Neurovascular Research Group. Department of Neurology, Barcelona, Spain
4Hospital Germans Trias i Pujol, Department of Neuroscience, Badalona, Spain
5Hospital Clínico Universitario, Stroke Unit. Department of Neurology, Valladolid, Spain
6Fundaciò de Investigació Sanitaria de les Illes Baleares FISIB, Neurocience Laboratory, Palma de Mallorca, Spain
7Hospital Vall d'Hebron, Stroke Unit. Department of Neurology, Barcelona, Spain
8Hospital Universitari Mútua de Terrasa, Deparment of Neurology, Terrrassa, Spain
9Helsinki University Central Hospital, Department of Neurology, Helsinki, Finland
10Washington University School of Medicine, Division of Emergency Medicine, Saint Louis, USA
11Washington University School of Medicine, Department of Psychiatry, Saint Louis, USA
12Virgen del Rocío & Macarena Hospitals, Deparment of Neurology, Sevilla, Spain
13Washington University School of Medicine, Department of Neurology, Saint Louis, USA
Background and Aims: Hemorrhagic transformation (HT) is a potentially fatal complication after t-PA treatment of ischemic stroke patients and appears to be genetically modulated. Low-frequency genetic variants could contribute in the genetic risk to complex traits including pharmacogenetics. We aimed to identify low-frequency genetic variants associated with HT after t-PA administration.
Method: We analyzed 1195 t-PA treated ischemic strokes from Spain and Finland genotyped with Human Core Exome array (Illumina) using a gene-based approach. Minor allele frequency <5% and nonsynonymous variants were selected. Quality controls and meta-analysis were performed through SKAT and MetaSKAT libraries from R and PLINK software. Sex, age, cardioembolic etiology and principal components were used as covariates under null model for global hemorrhagic transformation analysis.
Results: 213 participants developed HT based on ECASS criteria, 878 genes and 3788 variants were analyzed. One gene was statistically associated with HT after Bonferroni correction (P = 5.4x10-5) and 14 genes presented a suggestive association (P < 0.001). The significant gene regulates action of RNA polymerase III and the synthesis of small RNAs. One of the suggestive genes was previously shown to be associated with inflammatory response and vascular homeostasis.
Conclusion: A gene-based approach of low frequency variants in t-PA treated patients has revealed a potential gene associated with HT following ischemic strokes. Replication and functional analysis will be needed to confirm these results.
AS14-034
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
PROTEOMIC SIGNATURE OF TIA/MILD STROKE FROM PERIPHERAL BLOOD SAMPLES DRAWN IN EMERGENCY DEPARTMENTS: THE SPECTRA STUDY
A.M. Penn1, V. Saly1, S.B. Coutts2, R.F. Balshaw3,4, K. Votova5,6, M.B. Bibok5, M.L. Lesperance7, M. Penn1, N.S. Croteau5,7, A. Trivedi8, A.M. Jackson9, D.S. Smith9, K.K. Lam10 and C.H. Borchers9
1Island Health Authority, Neurosciences, Victoria, Canada
2University of Calgary, Clinical Neurosciences- Radiology and Community Health Sciences, Calgary, Canada
3British Columbia Centre for Disease Control, Disease Research, Vancouver, Canada
4University of British Columbia, Statistics, Vancouver, Canada
5Island Health Authority, Research, Victoria, Canada
6University of Victoria, Division of Medical Sciences, Victoria, Canada
7University of Victoria, Mathematics and Statistics, Victoria, Canada
8University of Manitoba, Neurology, Winnipeg, Canada
9University of Victoria, Genome British Columbia Proteomics Centre, Victoria, Canada
10Proof Centre of Excellence, Laboratory Research, Vancouver, Canada
Background and Aims: Rapid intervention after Acute Cerebrovascular Syndrome (ACVS) can reduce subsequent stroke risk. However, less than 50% of patients presenting with acute neurological deficits are cerebrovascular. This leads to diagnostic uncertainty, particularly for patients without motor or speech deficits. SpecTRA is a large scale biomarker project to identify and validate a clinically useful blood test for mild-ACVS.
Method: In our first verification cohort, (first n = 545 participants out of 1750 recruited for SpecTRA) we measured 101 proteins previously implicated in stroke using LC/MRM mass spectrometry. Enrichment LC/MRM mass spectrometry was also employed on selected proteins. We compared plasma samples from mild-ACVS (n = 386) and Mimic participants using robust linear regression (FDR < 0.20). STRING analysis identified the biological pathways involved. Cross-validated penalized logistic regression analyses identified our biomarker panel with optimism-corrected classification performance estimates.
Results: 59 proteins met quantitation Quality Control (QC) criteria; 14 differed significantly between ACVS and Mimic. Our biomarker panel includes 16 proteins (8 with individual FDR < 0.20). Our classification model for ACVS yields overall AUC = 0.70; for non-motor and speech presentation, AUC = 0.76.
Conclusion: This is the first proteomic study to discriminate Mimic and ACVS to a clinically useful level, but awaits validation on our second cohort (n = 600). The proteomic signature is especially promising for non-motor or speech patients. We are also developing a refined panel for use on a clinically validated platform.
AS14-036
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
GENOME-WIDE INTERACTION ANALYSIS WITH HYPERTENSION IN ASSOCIATION WITH WHITE MATTER HYPERINTENSITY BURDEN: THE COHORTS FOR HEART AND AGING RESEARCH IN GENOMIC EPIDEMIOLOGY (CHARGE) CONSORTIUM
M. Sargurupremraj1, C. Sarnowski2, X. Jian3, H. Adams4, G. Chauhan5, E. Hofer6, J. Bis7, A. Teumer8, S. Hagenaars9, L. Yaneck10, N. Armstrong11, E. van Denakker12, A. Vernon Smith13, R. McWhirter14, S. Trompet15, K. Bharat Rajan16, S. Seshadri2, S. Debette1 and M. Fornage3
1INSERM U1219, Bordeaux Population Health, BORDEAUX, France
2Department of Biostatistics, Boston University School of Public Health, Boston, USA
3Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, USA
4Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands
5Centre for Brain Research, Indian Institute of Science, Bangalore, India
6Institute of Medical Informatics, Medical University Graz, Graz, Austria
7Department of Medicine, University of Washington, Seattle, USA
8Institute of Community Medicine, University Medicine Greifswald, Greifswald, Germany
9Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom
10GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, USA
11Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
12Molecular epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
13Faculty of Medicine, University of Iceland, Reykavik, Iceland
14Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia
15Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
16Rush Institute for Healthy Aging, Department of Internal Medicine, Chicago, USA
Background and Aims: MRI-defined white matter hyperintensity (WMH) burden is a powerful predictor of stroke and dementia with high heritability and recent identification of genetic risk loci through genome-wide association studies (GWAS). We sought to explore whether genetic variants interact with hypertension status (the strongest WMH risk factor) in modulating WMH burden.
Method: We used the “Joint Meta-analysis (JMA)” method to jointly analyze SNP main effects and SNP by hypertension effect at the genome-wide level in 24 large population-based cohorts from the CHARGE consortium comprising 21,000 stroke-free individuals of European descent. JMA was shown to have high power to detect novel associations in presence of effect modification by environment.
Results: Two loci identified in the European CHARGE WMH main effects GWAS also showed genome-wide significant association in JMA (17q25[TRIM65], P = 1.93 × 10−19, and 2p21[HAAO], P = 2.40x10−8). In addition, JMA identified one genome-wide significant locus (2q33.2[NBEAL1], P = 9.78x10−9), and additional suggestive associations with variants near FOXI1, CLSTN2, and TSNAX-DISC1 implicated in memory performance and psychiatric conditions, which were non-significant in the WMH main effects GWAS. Variants in the TRIM65 and NBEAL loci functioned as significant cis-eQTLs in brain, coronary and aortic arteries.
Conclusion: The JMA gene-environment interaction analysis enabled the identification of one novel genome-wide significant risk locus for WMH interacting with hypertension, whereas some associations were attenuated, suggesting a mediating effect of hypertension. Efforts to expand and replicate these findings are currently underway.
AS14-040
Scientific Communication (Oral Abstract Presentation) Genetics, genomics & proteomics
EXOME SEQUENCING AND CHIP ANALYSES OF SMALL SUBCORTICAL MRI-DEFINED BRAIN INFARCTS
D. Vojinovic1, G. Chauhan2, X. Jian3, S.H. Choi4, J. Bis5, A. Teumer6, N. Dueker7, M. Luciano8, E. Hofer9, Z. Wanting10, C.Y. Cheng11, H. Grabe12, R. Schmidt9, J. Wardlaw8, M. Fornage13, W. Longstreth14, S. Seshadri15, C. van Duijn16 and S. Debette17
1Erasmus MC, Departement of Epidemiology, Rottedam, The Netherlands
2Indian Institute of Science, Centre for Brain Research, Bangalore, India
3University of Texas Health Science Center at Houston, Imm – Human Genetics Department, Houston, USA
4Boston University School of Public Health, Department of Biostatistics, Boston, USA
5University of Washington, Cardiovascular Health Research Unit- Department of Medicine, Seattle, USA
6University Medicine Greifswald, Institute for Community Medicine, Greifswald, Germany
7University of Miami, John P. Hussman Institute for Human Genomics, Miami, USA
8University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology- Psychology, Edinburgh, United Kingdom
9Clinical Division of Neurogeriatrics- Medical University Graz, Department of Neurology, Graz, Austria
10Genome Institute, Duke-National University of Singapore- Graduate Medical School, Singapore, Singapore
11Duke-National University of Singapore- Graduate Medical School, Centre for Quantitative Medicine, Singapore, Singapore
12University Medicine Greifswald, Department of Psychiatry and Psychotherapy, Greifswald, Germany
13University of Texas Health Science Center at Houston, Institute of Molecular Medicine and Human Genetics Center-, Houston, USA
14University of Washington, Departments of Neurology and Epidemiology, Seattle, USA
15Boston University School of Medicine-, Department of Neurology, Boston, USA
16Erasmus University Medical Center, Department of Epidemiology, Rotterdam, The Netherlands
17Bordeaux University Hospital, Department of Neurology, Bordeaux, France
Background and Aims: Genetic architecture of small subcortical MRI-defined brain infarcts (SSBI) is virtually unexplored in the general population. To identify rare and common variants underlying SSBI, we performed a series of exome sequencing (ES) and exome chip (EC) based association studies.
Method: Our preliminary results comprised 8 cohorts, including 4,219 individuals with exome sequenced data, and 10,232 individuals with exome chip data, of whom 1,562 (10.8%) had at least one SSBI. Statistical analyses included single-variant association analyses adjusted for age, gender, and study-specific covariates, and gene-based tests limited on rare variants with predicted functional consequences (missense, splice, nonsense). The analyses were performed separately for ES and EC, and their summary statistics were further combined in a meta-analysis.
Results: One common intergenic variant on chromosome 9, surpassed exome-wide significance level in EC based association study (β = 0.38, p-value = 7.91 × 10−7). Functional annotation revealed that the variant lies in enhancer histone marks, DNase sites, and protein binding regions, and changes regulatory motifs based on the variant allele changes. The variant is mapped 2.6kb from ENG gene that encodes the major protein of vascular endothelium and it is involved in the regulation of angiogenesis. Gene-based meta-analysis of ES and EC revealed significant association of SSBI with SULF2 gene (p-value = 3.50 × 10−6) which is involved in cell signaling.
Conclusion: The present study using exome sequencing and exome chip data identifies novel loci associated with SSBI. We are in process of replicating findings.
AS10-015
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
IMPACT OF WHITE MATTER HYPERINTENSITIES, CEREBRAL MICROBLEEDS AND MEDIAL TEMPORAL LOBE ATROPHY ON SHORT AND LONG-TERM REHABILITATION OUTCOMES AFTER STROKE
J. Kwan1, V. Mak1, R. Hui1, B. Ng1, K. So1, G. Kai1 and H. Mak2
1The University of Hong Kong, Medicine, Hong Kong, Hong Kong S.A.R.
2The University of Hong Kong, Diagnostic Radiology, Hong Kong, Hong Kong S.A.R.
Background and Aims: The impact of MRI biomarkers of small vessel disease burden, i.e. white matter hyperintensities (WMH) and cerebral microbleeds (CMB), and medical temporal lobe atrophy (MTLA) on the short and long-term rehabilitation outcome after stroke remains unclear.
Method: We analysed the clinical data for 377 consecutive stroke patients between 2008–2014. 3-tesla MR images were obtained at 7–10 days post-stroke, and examined for the severity of WMH (Fazekas score), CMB (total count), and MTLA (Scheltens score). We assessed the short-term improvement in function outcomes between admission and discharge for Berg Balance Score, Rivermead Mobility Score, Barthel Index and Functional Independence Measure. Long-term primary outcome was death or vascular events at 2-years, and secondary outcomes included death from any cause, ischaemic stroke/TIA, bleeding events, post-stroke dementia, and admission for pneumonia or falls.
Results: Mean ± s.d. age was 70 ± 12 years; 94% were ischaemic strokes and the overall stroke severity was mild to moderate. Overall prevalence of periventricular WMH was 13%, subcortical WMH was 48%, CMB, was 11%, and MTLA was 36%. WMH, CMB and MTLA independently predicted short-term improvements in balance, mobility, functional and independence levels between admission and discharge. Periventricular WMH, CMB and MTLA also predicted long-term clinical outcomes at 2 years. However, after adjusting for case mix, only MTLA independently predicted pneumonia [OR 0.17 (0.05–0.56)], and periventricular WMH independently predicted falls [OR 5.0 (1.5–16.88)] at 2 years.
Conclusion: White matter hyperintensities, cerebral microbleeds and medical temporal lobe atrophy are prevalent amongst stroke rehabilitation patients, and independently predict short and long-term rehabilitation outcomes after stroke.
AS11-014
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
STEPWISE RELATIONSHIP BETWEEN SEVERITY OF ACUTE CEREBROVASCULAR EVENTS AND PRE/POST-EVENT DEMENTIA: POPULATION-BASED STUDY OF TIA AND STROKE
S. Pendlebury1, R. Wharton1, Z. Mehta1 and P. Rothwell1
1Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences- University of Oxford, Oxford, United Kingdom
Background and Aims: Available data suggest a shared susceptibility to stroke and dementia. If true, one would expect a stepwise relationship between severity of acute cerebrovascular event and risk of pre-event as well as post-event dementia. We therefore stratified pre- and post-event dementia rates by event severity in the first such population-based study to include the full range of event severity from TIA to fatal stroke.
Method: All patients with a first TIA or stroke from 2002–2012 in a defined population of 92 728 (Oxford Vascular Study) had baseline clinical/cognitive assessment and follow-up to 2017. Pre-and post-event dementia were ascertained through direct patient assessment supplemented by review of primary care records. Age/sex-standardised prevalence and morbidity ratios (SPR, SMR) were calculated versus UK-population dementia rates.
Results: In 2305 patients (mean age = 74.4, 1133/49% male, 689/30% TIA), pre-event dementia rates ranged (ptrend < 0.001) from 4.5% (95%CI = 3.1–6.4%) in TIA to 20.3% (15.5–26.1) in major stroke (NIHSS > 10). 5-year actuarial risk of new post-event dementia ranged (ptrend < 0.001) similarly from 5.6% (4.1–7.7) to 35.4%, (28.7–43.0), with highest rates in year-1. Both pre-event dementia SPR and post-event dementia SMR showed similar stepwise relationships with event severity; with new dementia in the first year event being 36.0 (29.5–43.3) times higher in major stroke than the age/sex-adjusted background population rate.
Conclusion: Whilst the stepwise relationship between event severity and post-event dementia might suggest lesional effects, the similar association with pre-event dementia suggests a shared susceptibility to stroke and dementia.
AS17-094
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
PREDICTORS OF DEMENTIA AFTER TIA/STROKE: 15-YEAR POPULATION-BASED FOLLOW-UP STUDY
S. Pendlebury1, R. Wharton2, L. Li2, Z. Mehta2 and P. Rothwell2
1, Oxford, United Kingdom
2Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences- University of Oxford, Oxford, United Kingdom
Background and Aims: Previous studies of risk factors for dementia after stroke have been conflicting owing to small sample sizes and methodological differences/sample selection. We examined predictors of dementia in a 15-year longitudinal population-based study, including the full range of event severity from TIA to major stroke, irrespective of age and co-morbidities.
Method: All patients with index TIA or stroke from 2002–2012 in a defined population of 92 728 (Oxford Vascular Study) had follow-up to 2017. New post-event dementia was ascertained through direct patient assessment, supplemented by review of primary care records. Baseline clinical and brain-imaging predictors were adjusted for age/sex/education.
Results: In 2108 patients (mean age = 73.6, 1057/50% male, 658/31% TIA), predictors of dementia on follow-up (all p < 0.001 unless stated) were age (OR = 1.07, 95%CI = 1.06-1.08/year), female sex (1.34,1.04–1.64, p = 0.019), <12 years education (1.74,1.35–2.23), prior stroke (1.80,1.32–2.46), premorbid Rankin > 3 (1.48,1.23–1.95, p = 0.005), diabetes (1.47,1.08–2.00, p = 0.014), event severity (1.04,1.02–1.06/NIHSS-point), moderate/severe leukoaraiosis (1.45,1.15–1.83, p = 0.002), low baseline cognitive score (4.89,3.65–6.54), dysphasia (1.95,1.49–2.54), acute (1.63,1.27–2.08) and old brain imaging lesions (2.17,1.39–3.39) and stroke recurrence (2.01,1.53–2.65). Independent predictors that remained on multivariate analysis included low baseline cognitive score, recurrent stroke and both factors related to pre-existing vulnerability/reserve (age, education, diabetes, leukoaraiosis) and to the stroke lesion (severity, dysphasia).
Conclusion: Post-event dementia risk is predicted both by markers of pre-morbid susceptibility/reserve and by cerebrovascular lesion severity/location. Post-stroke dementia risk is therefore likely to fall as measures to maintain pre-morbid brain health impact on susceptibility/reserve and as acute stroke care reduces lesional severity/complications.
AS26-008
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
TOTAL SMALL VESSEL DISEASE SCORE AND RISK OF RECURRENT STROKE – VALIDATION IN TWO LARGE COHORTS
G.K.K. Lau1,2, L. Li1, U. Schulz1, M. Simoni1, K.H. Chan2, S.L. Ho2, R.T.F. Cheung2, W. Kueker1, H.K.F. Mak3 and P. Rothwell1
1University of Oxford, Centre for Prevention of Stroke and Dementia, Oxford, United Kingdom
2University of Hong Kong, Division of Neurology- Department of Medicine, Hong Kong, Hong Kong S.A.R.
3University of Hong Kong, Department of Diagnostic Radiology, Hong Kong, Hong Kong S.A.R.
Background and Aims: In patients with transient ischaemic attack (TIA) and ischaemic stroke, we validated the “Total Small Vessel Disease (SVD) Score” by determining its prognostic value for recurrent stroke.
Method: Two independent prospective studies were conducted, one comprising predominantly Caucasians with TIA/ischaemic stroke (Oxford Vascular Study, OXVASC) and one predominantly Chinese with ischaemic stroke (University of Hong Kong, HKU). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH) and perivascular spaces (PVSs). Predictive value of Total SVD Score for risk of recurrent stroke was determined and potential refinements considered.
Results: In 2002 patients with TIA/ischaemic stroke (OXVASC n = 1028, HKU n = 974, 6924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischaemic stroke (adjusted HR per unit increase: 1.32, 1.16–1.51, p < 0.0001; c-statistic 0.61, 0.56–0.65, p < 0.0001) and intracerebral haemorrhage (ICH) (HR 1.54, 1.11–2.13, p = 0.009; c-statistic 0.65, 0.54–0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischaemic stroke subtypes (c-statistic 0.67, 0.59–0.74, p < 0.0001 and 0.60, 0.55–0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cut-off of basal ganglia PVSs potentially improved predictive power for ICH (c-statistic 0.71, 0.60–0.81, phet = 0.45), but not for recurrent ischaemic stroke (c-statistic 0.60, 0.56–0.65, phet = 0.76) on internal validation.
Conclusion: The Total SVD Score has predictive value for recurrent stroke after TIA/ischaemic stroke. Prediction of recurrence in patients with non-lacunar events highlights the potential role of SVD in wider stroke aetiology.
AS26-018
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
CEREBRAL MICROBLEEDS AND THE RISK OF INCIDENT ISCHEMIC STROKE IN CADASIL
L. Puy1, F. De Guio2, O. Godin1, M. Duering3, M. Dichgans3, H. Chabriat1 and E. Jouvent1
1AP-HP- Lariboisière Hospital- Department of Neurology- F-75475 Paris- France- and DHU NeuroVasc Sorbonne Paris Cité- Paris- France, Neurology, Paris, France
2INSERM, UMRS1161, Paris, France
3Institute for Stroke and Dementia Research- Klinikum der Universität München- Ludwig-Maximilians-University LMU- Feodor-Lynen-Str. 17- D 81377 Munich- Germany, Neurology, Munich, Germany
Background and Aims: Cerebral microbleeds (MB) are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that MB may also predict the risk of ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of MB and of ischemic stroke may differ. We aimed to test the relationships between the presence of MB an incident stroke in CADASIL, a severe monogenic small vessel disease responsible for both highly prevalent MB and a high incidence of ischemic stroke in young patients.
Method: MB were assessed on baseline MRI in 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during a follow-up period of up to 54 months (visit to the outpatient clinic every 18 months). Survival analyses were used to test the relationships between MB and incident ischemic stroke.
Results: 369 patients (mean age, 51.4 ± 11.4 years) were followed up over a median time of 39 months (25th to 75th percentile 35 to 54 months). The risk of ischemic stroke was higher in patients with MB than in patients without (35.8% vs 19.6%, HR 1.87 [95% CI 1.16 to 3.01], p = 0.009). These results persisted after adjustment for a previous history of ischemic stroke, age, gender, vascular risk factors and antiplatelet agents use (HR 1.89 [95% CI 1.10 to 3.26], p = 0.02).
Conclusion: The presence of MB is an independent risk marker of ischemic stroke in CADASIL, extending results obtained in other stroke populations. These results further question the pathophysiology and clinical significance of MB in stroke patients.
AS26-029
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
UP-REGULATION OF COL4A1 AND COL4A2 GENES THROUGH VARIOUS MECHANISMS LEADS TO SEVERE EARLY ONSET ISCHAEMIC SMALL VESSEL DISEASE, INCLUDING PADMAL
E. Tournier-Lasserve1, E. Verdura2, D. Hervé3, F. Bergametti2, C. Jacquet4, T. Morvan3, C. Prieto-Morin5, A. Mackowiak6, E. Manchon7, H. Hosseini8, C. Cordonnier4, I. Girard-Buttaz9, S. Rosenstingl10, C. Hagel11, G. Kuhlenbaumer12, L. Fleming13, T. Van Agtmael13, H. Chabriat3 and F. Chapon14
1France
2INSERM, U1161, Paris, France
3AP-HP, Neurology, Paris, France
4CHRU Lille, Neurology, Lille, France
5AP-HP, Genetics, Paris, France
6Hôpital St Philipert, Neurology, Lomme, France
7Hôpital de Gonesse, Neurology, Gonesse, France
8AP-HP CHU Creteil Henri Mondor, Neurology, Creteil, France
9Valenciennes Hospital, Neurology, Valenciennes, France
10Coulommiers Hospital, Neurology, Coulommiers, France
11Hamburg university hospital, Neuropathology, Hamburg, Germany
12Kiel University Hospital, Neurology, Kiel, Germany
13Glasgow university, Vascular Institute, Glasgow, United Kingdom
14CHRU Caen, Neuropathology, Caen, France
Background and Aims: Screening of known cSVD genes identifies the causative mutation in less than 15% of familial cSVD cases. We sought to identify novel causes of cSVD.
Method: We used linkage analysis, exome sequencing, and array comparative genomic hybridization to identify the causal mutation in 250 cSVD unrelated probands. Candidate variants were validated using Sanger sequencing, QMPSF and/or FISH analysis, depending of the nature of the candidate mutation. Segregation was analyzed in probands’ relatives. Mutations consequences were assessed with luciferase reporter assays and RT-qPCR.
Results: A candidate heterozygous variant located in a predicted miR-29 microRNA binding site, within the 3’UTR region of COL4A1, was identified in 6 unrelated families, including the original PADMAL family. Variants cosegregated with the affected phenotype (cumulative LOD score = 6.03). A highly significant difference was observed when comparing the number of variants within this binding site in cases and controls (p = 1.77 x 10E-12). RT-qPCR analyses of patients’ primary fibroblasts and luciferase reporter assays strongly favor an upregulation of COL4A1 mediated by disruption of miR-29 binding to its target site. In addition, 2 unrelated probands showed a duplication (patient 1) and a triplication (patient 2) of the entire COL4A1/COL4A2 loci. MRI features were characterized by the presence of multiple pontine infarcts in all patients carrying a PADMAL type mutation within the 3' UTR. A distinct phenotype was observed in the duplicated and triplicated patients.
Conclusion: Distinct mutations upregulating COL4A1/COL4A2 expression lead to severe early-onset ischaemic cSVD, including PADMAL, whose phenotypes strongly differ from those associated with COL4A1 missense glycine mutations.
AS26-032
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
SPATIAL RELATION BETWEEN LOBAR MICROBLEEDS AND JUXTACORTICAL PERIVASCULAR SPACES ON 7T MRI IN AMNESTIC MILD COGNITIVE IMPAIRMENT AND EARLY ALZHEIMER’S DISEASE
W. Bouvy1, S. van Veluw2, H. Kuijf3, J. Zwanenburg4, L.J. Kappelle1, P. Luijten4, D. Koek5, M. Geerlings6 and G.J. Biessels1
1University Medical Center Utrecht, Brain Center Rudolf Magnus- Department of Neurology, Utrecht, The Netherlands
2Massachusetts General Hospital and Harvard Medical School, J. Philip Kistler Stroke Research Center- Department of Neurology, Boston, USA
3University Medical Center Utrecht, Image Sciences Institute, Utrecht, The Netherlands
4University Medical Center Utrecht, Department of Radiology, Utrecht, The Netherlands
5University Medical Center Utrecht, Department of Geriatrics, Utrecht, The Netherlands
6University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
Background and Aims: It has been hypothesized that impaired drainage of interstitial fluid in cerebral amyloid angiopathy (CAA) causes dilation of juxtacortical perivascular spaces (jPVS). A direct spatial relation between CAA burden and dilated jPVS has not been shown in vivo. We examined on 7T MRI the topographical association between lobar cerebral microbleeds (CMBs), as a marker of CAA, and jPVS in patients with amnestic mild cognitive impairment (aMCI) or early Alzheimer’s Disease (eAD).
Method: Forty-six patients (74.7 ± 8.6 years) with aMCI or eAD underwent 7T MRI. Lobar CMBs were identified. We compared the degree [0–3] of jPVS dilation (using a reference template of operationally defined jPVS scores) within a diameter of 1 cm around lobar CMBs with reference sites (no CMB) in the contralateral hemisphere. Also, the mean jPVS degree assessed on six standardized locations was compared between patients with and without lobar CMBs.
Results: Eleven patients had lobar CMBs [total number = 35, median 1, range 1–14] of whom five had >1 CMB. The degree of jPVS was higher at the site of lobar CMBs [median 1.75, interquartile range (IQR) 1–2.5] than at reference sites [median 1.25, IQR 0.6–2.4], p = 0.03. In patients with >1 lobar CMB, the jPVS degree on the six standardized locations was higher [median 2.2, IQR 1.8–2.3] than in patients without lobar CMBs [median 1.4, IQR 1.0–1.8], p = 0.02.
Conclusion: We found a topographical association between a high degree of jPVS dilation and lobar CMBs, supporting a direct etiological link between CAA and PVS.
AS26-034
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
THE DIFFERENTIAL EVOLUTION OF ACUTE SMALL INFARCTS OVER TIME IN PATIENTS WITH SMALL VESSEL DISEASE
K. Wiegertjes1, A. Ter Telgte1, A. Tuladhar1, P. Barbosa Olievera1, M. Bergkamp1, H. van der Holst1, E. van Leijsen1, I. van Uden1, D. Norris2, M. Ghafoorian3, P. Bram3, E. van DIjk1, C. Klijn1 and F.E. de Leeuw1
1Radboud university medical centre- Donders Institute for Brain- Cognition and Behaviour, Centre for Cognitive Neuroscience- Department of Neurology, Nijmegen, The Netherlands
2Donders Institute for Brain- Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands
3Radboud university medical centre- Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Nijmegen, The Netherlands
Background and Aims: It has recently been suggested that acute ischemia, as detected by diffusion weighted imaging (DWI), is involved in the etiology of white matter hyperintensities (WMH) and possibly also in that of microbleeds based on pathology studies. We investigated the evolution of acute infarction seen on DWI over time.
Method: 503 patients with small vessel disease (SVD) from the RUNDMC study with three consecutive MRI scans in 2006, 2011 and 2015 (mean follow-up duration 8.7 years). Acute ischemia was defined as a DWI+ lesion. Imaging evolution of DWI+ lesions was examined on T2*, T1 and FLAIR on follow-up MRI. In addition, we assessed progression of WMH and lacunar infarcts between 2006 and 2015 in patients with and without DWI+ lesions.
Results: 380 patients (mean age 65.7 ± SD 8.8 years; 56.6% male) had at least one MRI scan during follow-up. We identified 19 incident DWI+ lesions in 13 patients (3.4%). 14 DWI+ lesions (73.7%) became WMH, 3 (15.8%) an infarction, 2 (10.5%) were no longer visible on follow-up imaging and none became microbleeds. Patients with a DWI+ lesion had a higher mean WMH progression rate (1.26 mL ± 1.23 per year) than those without DWI lesions (0.64 mL ± 0.94 per year; p < 0.011) and more often had an incident lacunar infarct (46.2% vs. 11.4%; p < 0.001).
Conclusion: DWI+ lesions occur in 3.4% of patients with SVD. Their evolution on follow-up imaging is heterogeneous with the majority becoming WMH or small infarcts. These findings call upon reappraisal of the origin of WMH.
AS26-037
Scientific Communication (Oral Abstract Presentation) Small Vessel Disease and Vascular Cognitive Impairment
PRECISE HISTOLOGICAL-RADIOLOGICAL CORRELATIONS OF BRAIN PATHOLOGY IN SMALL VESSEL DISEASE
C.A. Humphreys1, M. Jansen2, V. Gonzalez-Castro3, C. Pernet3, I.J. Deary4, R. Al-Shahi Salman5, J.M. Wardlaw3 and C. Smith1
1University of Edinburgh, Academic Neuropathology- Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
2University of Edinburgh, Centre for Cardiovascular Science, Edinburgh, United Kingdom
3University of Edinburgh, Neuroimaging Sciences- Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
4University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom
5University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
Background and Aims: Sporadic small vessel disease (SVD) is well characterised on neuroimaging (1) but the pathogenesis and heterogeneity at a cellular level is poorly understood(2). Using a prospective observational protocol we are making systematic imaging-histology correlations in and around SVD lesions, which, as far as we are aware, has not been done previously.
Method: Post-mortem tissue samples ranging from normal-severe SVD with detailed clinical information are taken from 16 standard areas (white and grey matter, brainstem, cerebellum) and formalin-fixed before undergoing 7-Tesla MRI, then processed for histology. Histology images are registered with MR to directly compare lesions (figure). Disease burden is independently assessed on MRI and histology.
Complimentary frozen tissue will assess biochemical and gene expression differences between SVD severities defined by the pathological-radiological-clinical analysis.
Results: We have developed and tested scanning, processing, registration and grading protocols in 41 cases to date; 21 intracerebral haemorrhage, 8 normal ageing, 12 controls. 24 with in vivo imaging (59%). We have obtained excellent quality images and addressed issues of variability, tissue quality and artefact, achieving a reliable standard approach. Lesion correlations will be presented.
Conclusion: Comprehensive, precise pathological-radiological-clinical correlations in SVD will provide greater insight into associations and pathophysiology underlying MRI findings in normal- and abnormal-appearing tissue, ex vivo and in vivo.
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
EFFECTS OF STATIN INTENSITY AND ADHERENCE ON THE LONG-TERM PROGNOSIS AFTER ACUTE ISCHEMIC STROKE: A NATIONWIDE POPULATION-BASED COHORT STUDY
J. Kim1, H.S. Lee2, C.M. Nam3 and J.H. Heo4
1CHA Bundang Medical Center- CHA University, Neurology, Bundang-gu- Seongnam-si, Republic of Korea
2Yonsei University College of Medicine, Biostatistics Collaboration Unit, Seoul, Republic of Korea
3Yonsei University College of Medicine, Department of Preventive Medicine, Seoul, Republic of Korea
4Yonsei University College of Medicine, Neurology, Seoul, Republic of Korea
Background and Aims: Statin is an established treatment for secondary prevention after ischemic stroke. However, the effects of statin intensity and adherence on the long-term prognosis after acute stroke are not well known.
Method: This study examined data on a nationwide population-based sample cohort that was collected by the National Health Insurance Service in South Korea. This study included patients who were hospitalized with acute ischemic stroke between 2002–2012 and followed for more than 1 year. Statin adherence and intensity were determined from the prescription data during 1 year after index stroke. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. Multivariate Cox regression analyses were performed. The censoring date was December 2013.
Results: Among 8,071 patients with acute ischemic stroke, patients with ‘no statin’, ‘poor adherence’, ‘intermediate adherence’, and ‘good adherence’ were 55.0 %, 15.3 %, 9.6 %, and 20.1 %, respectively. During the mean follow-up period of 4.95 ± 2.75 years, 2,302 patients developed a primary outcome. With reference of ‘no statin’, the adjusted hazard ratios [95% confidence interval] were 1.07 [0.95–1.20] for patients with poor adherence to statin, 0.94 [0.80–1.09] for patients with intermediate adherence, 0.83 [0.60–1.15] for patients with good adherence and low-intensity, 0.64 [0.55–0.75] for patients with good adherence and moderate-intensity, and 0.43 [0.23–0.81] for patients with good adherence and high-intensity. Neither statin adherence nor statin intensity was associated with the risk of hemorrhagic stroke.
Conclusion: After acute ischemic stroke, high-intensity statin therapy with good adherence was significantly associated with a lower risk of adverse events.
AS17-040
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
THE PREDICTIVE VALUE OF PULSE PRESSURE DURING ACUTE STAGE OF ISCHEMIC STROKE FOR FUTURE MAJOR VASCULAR EVENTS
1Seoul National University Bundang Hospital, Neurology, Bundang-Gu- Seongnam- Gyeonggi, Republic of Korea
2Chonnam National University Hospital, Neurology, Gwangju, Republic of Korea
3Chungbuk National University Hospital, Neurology, Cheongju, Republic of Korea
4Dong-A University Hospital, Neurology, Busan, Republic of Korea
5Dongguk University Ilsan Hospital, Neurology, Goyang, Republic of Korea
6Eulji General Hospital, Neurology, Seoul, Republic of Korea
7Eulji University Hospital, Neurology, Daejeon, Republic of Korea
8Hallym University Sacred Heart Hospital, Neurology, Anyang, Republic of Korea
9Inje University Ilsan Paik Hospital, Neurology, Goyang, Republic of Korea
10Jeju National University Hospital, Neurology, Jeju, Republic of Korea
11Keimyung University Dongsan Medical Center, Neurology, Daegu, Republic of Korea
12Seoul Medical Center, Neurology, Seoul, Republic of Korea
13Ulsan University Hospital, Neurology, Ulsan, Republic of Korea
14Yeungnam University Medical Center, Neurology, Daegu, Republic of Korea
15Asan Medical Center, Clinical Research Center, Seoul, Republic of Korea
16Korea University, Biostatistics, Seoul, Republic of Korea
Background and Aims: Pulse pressure (PP) is recognized as a marker of arterial stiffness, but has not been explored well in ischemic stroke. This study aimed to investigate whether PP captured during the acute stage of ischemic stroke is a powerful predictor for future vascular events.
Method: Patients with acute ischemic stroke who were hospitalized within 48 hours of onset and were enrolled consecutively in a multicenter prospective stroke registry in South Korea were subjected to this study. We analyzed blood pressure data measured within 3 days after symptom onset. Primary outcome was a composite of stroke recurrence, myocardial infarction and all cause death within one year, which was prospectively captured using a standardized protocol.
Results: A total of 9,840 patients were included in this study. The overall effect of PP was significantly associated with future composite events (P = 0.0008) and stroke recurrence (P = 0.0013). PP showed a non-linear distribution for composite events (quadratic term of PP, P = 0.0041) and stroke recurrence (quadratic term of PP, P = 0.0107). When predictive value of blood pressure parameters were compared using −2 log-likelihood differences, PP was a stronger predictor than SBP (8.49 vs. 5.91), DBP (11.42 vs. 11.05) and MAP (8.75 vs. 5.91) for composite events and also a stronger predictor than SBP (6.32 vs. 4.56), DBP (10.07 vs.4.56) and MAP (7.03 vs. 4.56) for stroke recurrence.
Conclusion: We have demonstrated that PP in acute period of ischemic stroke is a predictor of future major vascular events and has a stronger predictive power than SBP, DBP or MAP.
AS17-045
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
SOCIOECONOMIC STATUS AND THE RISK OF STROKE RECURRENCE. PERSISTING GAPS OBSERVED IN A NATIONWIDE SWEDISH STUDY 2001–2012
J. Pennlert1, K. Asplund1, E.L. Glader1, B. Norrving2 and M. Eriksson3
1Umeå University, Public Health and Clinical Medicine, Umeå, Sweden
2Lund University, Medical Sciences – Section of Neurology, Lund, Sweden
3Umeå University, Statistics, Umeå, Sweden
Background and Aims: This nationwide observational study aimed to investigate how socioeconomic status (SES) is associated with risk of stroke recurrence and how possible associations change over time.
Method: This study included 168 295 patients, previously independent in activities of daily living, with a first-ever stroke in the Swedish Stroke Register (Riksstroke) 2001–2012. Riksstroke was linked with Statistics Sweden as to add individual information on education and income. Subdistribution hazard regression was used to analyse time from 28 days after first stroke to stroke recurrence, accounting for the competing risk of other causes of death.
Results: Median time of follow-up was 3.0 years. During follow-up, 23 560 patients had a first recurrent stroke, and 53 867 died from other causes. The estimated cumulative incidence of stroke recurrence was 5.3% at 1 year, and 14.3% at 5 years. Corresponding incidence for other deaths were 10.3%, and 30.2%. Higher education and income were associated with a reduced risk of stroke recurrence. After adjusting for confounding variables, university vs. primary school education returned an HR of 0.902; 95% CI, 0.864–0.942, and the highest vs. the lowest income tertile an HR of 0.955; 95% CI, 0.922–0.989. The risk of stroke recurrence decreased during the study period, but the inverse effect of SES on risk of recurrence did not change significantly.
Conclusion: Despite a declining risk of stroke recurrence over time, the differences in recurrence risk between different socioeconomic groups remained at a similar level in Sweden during 2001–2012.
AS17-052
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
RISK OF DEATH, READMISSION, CARDIOVASCULAR AND BLEEDING EVENTS AMONG PATIENTS WITH AND WITHOUT ATRIAL FIBRILLATION AND MILD, MODERATE AND SEVERE ISCHEMIC STROKE
J. Prvu Bettger1, D.D. Bhandary2, D.L. Bhatt3, G.C. Fonarow4, P. Heidenreich5, S. Johansson6, L. Liang1, E.D. Peterson1, B. Reicher7 and E.E. Smith8
1Duke University School of Medicine, Duke Clinical Research Institute, Durham, USA
2AstraZeneca, Health Economics Outcomes Research, Wilmington, USA
3Brigham and Women's Hospital, Heart and Vascular Center, Boston, USA
4University of California- Los Angeles, Division of Cardiology, Los Angeles, USA
5VA, VA Palo Alto Health Care System, Palo Alto, USA
6AstraZeneca Global Medical Affairs, Medical Evidence and Observational Research Centre, Gothenburg, Sweden
7AstraZeneca, CVMD Global Medicines Development, Gaithersburg, USA
8University of Calgary, Cumming School of Medicine, Calgary, Canada
Background and Aims: To examine whether 1-year outcomes differ by history of atrial fibrillation (AF) for patients with mild, moderate or severe acute ischemic stroke (AIS).
Method: Data were examined from patients with an index AIS admission to a participating Get With The Guidelines-Stroke hospital in 2011–2014 who had Medicare fee-for-service healthcare insurance, an initial NIHSS score, and were discharged from the hospital alive. Patients were further defined by mild (NIHSS = 0–5), moderate (NIHSS = 6–10), and severe (NIHSS = 11+) stroke and history of AF. Proportional hazards models were used to examine 1-year death, all-cause rehospitalization and major clinical events adjusted for patient and hospital characteristics.
Results: Among 237,319 AIS patients, there were 23.7% with AF on admission. AF was more common among patients with more severe strokes (19.7% of mild, 25.9% of moderate, and 34.9% of severe strokes, p < 0.001). With the exception of intracranial bleeds, the unadjusted rate and adjusted risk of all 1-year outcomes was greater for patients with AF than those without in each category of stroke severity (Table 1). History of AF was associated with a higher risk of death, and all-cause rehospitalization/death among patients with mild stroke, and a higher risk of major vascular events among those with severe stroke.
Conclusion: AF was associated with worse outcomes after ischemic stroke in each category of stroke severity.
AS17-065
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
EMBOLIC STROKES OF UNDETERMINED SOURCE IN THE HELSINKI YOUNG STROKE REGISTRY: LONG-TERM OUTCOME
N. Martinez-Majander1, K. Aarnio1, J. Pirinen1,2,3, T. Lumikari1, T. Nieminen2, M. Lehto2, J. Sinisalo2, M. Kaste1, T. Tatlisumak1,4,5 and J. Putaala1
1Helsinki University Hospital, Department of Neurology, Helsinki, Finland
2Helsinki University Hospital, Department of Cardiology – Heart and Lung Center, Helsinki, Finland
3Helsinki University Hospital, Department of Clinical Physiology and Nuclear Medicine – HUS Medical Imaging Center, Helsinki, Finland
4Institute of Neuroscience and Physiology – The Sahlgrenska Academy at University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden
5Sahlgrenska University Hospital, Department of Neurology, Gothenburg, Sweden
Background and Aims: No prior reports exist on the prognosis of embolic stroke of undetermined source (ESUS) among younger patients (<50 years). We compared the risk of recurrent stroke, cardiovascular events, and all-cause mortality between young ESUS patients and those with defined causes.
Method: Of the eligible 773 patients from Helsinki Young Stroke Registry, 201 had ESUS and 572 defined causes (TOAST 1–4) underlying their strokes, of which 91 were cardioembolism (CE) from a high-risk source. Endpoints were stroke recurrence, cardiac events, and all-cause mortality. Kaplan-Meier analyses allowed univariate comparison of event rates. Cox regression analyses adjusted for demographics, dyslipidemia, current smoking, hypertension, migraine—and additionally NIH Stroke Scale score and lesion size in mortality analysis—were applied to assess the association of ESUS with outcome.
Results: Mean follow-up time was 10.2 ± 4.3 years. Among ESUS patients, there were 19 recurrent strokes (cumulative risk at 15 years, 11.8%), 13 cardiac events (11.1%), and 13 deaths (9.5%). Compared with all other defined causes, ESUS had a lower risk for cardiac events (hazard ratio 0.36; 95% confidence interval 0.21–0.65) and all-cause mortality (0.42; 0.24–0.76), but no difference in the risk of stroke recurrence (0.68; 0.41–1.13). Compared to CE, ESUS had also a lower risk for cardiac events (0.11; 0.06–0.21) and all-cause mortality (0.28; 0.14–0.56) but no significant difference emerged in stroke recurrence (0.58; 0.29–1.15).
Conclusion: Although young ESUS patients are more likely to survive their strokes than those with defined causes, their relatively high stroke recurrence risk suggests active underlying pathophysiological mechanisms and suboptimal preventive strategies.
AS17-066
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
EARLY TIME COURSE OF MAJOR AND INTRACRANIAL BLEEDING IN PATIENTS WITH CEREBRAL ISCHAEMIA ON ANTIPLATELET THERAPY
N. Hilkens1, A. Algra2, J. Kappelle3, J. Greving4 and X. CAT collaboration4
1UMC Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
2University Medical Center Utrecht- the Netherlands, Julius Center for Health Sciences and Primary Care- Department of Neurology and Neurosurgery- Brain Center Ruldof Magnus, Utrecht, The Netherlands
3University Medical Center Utrecht- the Netherlands, Department of Neurology and Neurosurgery- Brain Center Ruldof Magnus, Utrecht, The Netherlands
4University Medical Center Utrecht- the Netherlands, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
Background and Aims: Prior evidence suggests a higher risk of bleeding after TIA and minor stroke with dual antiplatelet treatment compared with monotherapy. Information about the time course of this increased risk is scarce. We aimed to study the early time course of major and intracranial bleeding in patients with cerebral ischaemia on dual and single antiplatelet therapy.
Method: We performed a post-hoc analysis on individual patient data from CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT and PRoFESS, including 46,194 patients with a TIA or non-cardioembolic ischaemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (<1, 1–3, 3–6, 6–12 and >12 months). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex.
Results: The incidence rate of major bleeding on aspirin-clopidogrel and aspirin-dipyridamole was highest in the first month: 5.8 and 4.9 per 100 person-years respectively, and was significantly higher compared with 1–3 months (rate ratio aspirin-clopidogrel 1.98; 95%CI 1.16–3.40 and aspirin-dipyridamole: 1.94; 1.24–3.03). Incidence rates on aspirin monotherapy and clopidogrel monotherapy were 2.7 and 2.5 per 100 person-years respectively in the first month, with no significant change over time. There was no early excess of intracranial haemorrhages in patients on either dual or single antiplatelet therapy.
Conclusion: Risk of major bleeding on dual antiplatelet therapy is approximately two times higher in the first month, compared with 1–3 months. No excess early risk is observed in patients on monotherapy.
AS17-072
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
POPULATION-BASED STUDY OF FREQUENCY, RISK FACTORS AND LONG-TERM PROGNOSIS OF TIA AND ISCHAEMIC STROKE IN PATIENTS WITH SYMPTOMATIC DISEASE IN OTHER VASCULAR BEDS
M.R. Heldner1, L. Li1, D.P. Howard1 and P.M. Rothwell1
1University of Oxford, Stroke Prevention Research Unit- Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom
Background and Aims: Cerebrovascular, coronary and peripheral vascular disease has common underlying arterial pathology and risk factors, but the clinical significance of multi-territory disease in patients with TIA/stroke is uncertain. We studied risk factors for multi-territory disease and determined whether number of affected territories still predicted long-term outcome in a cohort on intensive secondary prevention.
Method: In a population-based study of 92 728 individuals in Oxfordshire, UK (Oxford Vascular Study), we studied patients presenting with TIA/ischaemic stroke (April 2002-March 2014) irrespective of age, in relation to the number of other vascular beds (coronary, peripheral) affected by symptomatic (current or previous) disease.
Results: Among 2554 patients, 1842 (72.1%) had single (TIA/stroke only), 608 (23.8%) double- and 104 (4.1%) triple-territory symptomatic vascular disease. Patients with disease in other territories had more vascular risk factors than those with TIA/stroke only (p < 0.0001), with similar differences for double vs triple-territory patients (p < 0.0001). Compared to patients with TIA/stroke only, those with double- or triple-territory disease had more hypertension (adjusted odds ratio [OR] 3.43, 95% CI 2.76–4.27), diabetes (2.89, 2.27–3.66), hypercholesterolaemia (4.66, 3.85–5.66), and smoking (1.52, 1.26–1.84) (all comparisons p < 0.0001). Triple-territory disease was particularly strongly associated with hypercholesterolaemia (6.80, 4.39–10.53; p < 0.0001). Despite more intensive secondary prevention in patients with multi-territory disease, the 5-year risk of vascular death increased steeply with number of territories affected (13.1% vs 21.4% vs 33.7%; p < 0.0001 after adjustment for age/sex).
Conclusion: There is an unmet need for more effective secondary prevention in TIA/stroke patients with symptomatic disease in multiple vascular beds.
AS17-089
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
SELF-RATED HEALTH, ONE TO FIVE YEARS AFTER STROKE
K. Bjälkefur1, Å. Rejnö2, S. Nasic3, E. Bertholds2 and K. Jood4
1Municipality of Lidköping, Department of Health and Social Care, Lidköping, Sweden
2Skaraborg Hospital, Department of Medicine, Skövde, Sweden
3Skaraborg Hospital, Research and Development Centre, Skövde, Sweden
4the Sahlgrenska Academy at University of Gothenburg, Institute of Neuroscience and Physiology- Section of Clinical Neuroscience, Göteborg, Sweden
Background and Aims: Self-Rated Health (SRH) focuses on the patient’s own perception, and represents an important patient-reported long-term outcome. We investigated SRH one to five years after stroke and searched for factors associated to good SRH.
Method: Consecutive stroke patients admitted to Stroke Units at the Skaraborg Hospital, Sweden were included 2007–2009 (n = 2190). Patient-reported outcomes were collected annually over five years using a postal questionnaire. SRH was assessed by a question from SF-36; “In general, would you say your health is excellent, very good, good, fair, or poor? Good SRH was defined as “excellent”, “very good”, or “good”. Factors associated to SRH were investigated by multiple logistic regression analysis.
Results: Response-rate was >90% at all time-points. Overall 40.2%, 40.7% and 46.3% of the patients reported good SRH, one, three and five years after stroke. Ability to perform activities of daily living (ADL) was strongly associated to good SRH; 49.8% and 14.7% after one year in ADL independent and dependent survivors respectively (p < 0.001). In ADL independent stroke survivors one year after stroke, good SRH was associated with age (multivariable OR 0.97; 95% CI 0.96–0.99), female sex (1.60; 1.17–2.19), physical activity (1.83; 1.24–2.70), pain (0.46; 0.34–0.63), depression (0.27; 0.20–0.37), and having home care (0.58; 0.38–0.87). In ADL dependent survivors, depression (0.27; 0.13–0.56) was associated to good SRH one year after stroke. Similar patterns were observed throughout the follow-up.
Conclusion: After stroke, SRH is strongly associated to ADL function. Other important and possibly modifiable factors associated to SRH are depression, pain, having home care, and physical activity.
AS17-095
Scientific Communication (Oral Abstract Presentation) Prognosis – Recurrent events
PROGNOSTIC SIGNIFICANCE OF BLOOD PRESSURE VARIABILITY ON BEAT-TO-BEAT VERSUS AWAKE AMBULATORY AND DAY-TO-DAY MONITORING
A. Webb1, S. Mazzucco1, L. Li1 and P. Rothwell1
1University of Oxford, Stroke Prevention Research Unit- Department of Clinical Neuroscience, Oxford, United Kingdom
Background and Aims: Visit-to-visit and day-to-day BP-variability (BPV) predict increased risks of recurrent stroke and cardiovascular events, independent of mean BP, but only reflect one type of BPV and take time to assess. Beat-to-beat BPV can be assessed in minutes and might also be informative, particularly if raised mean BP and day-to-day BPV have been treated.
Method: In consecutive patients recruited within 6 weeks of TIA or non-disabling stroke (Oxford Vascular Study), BPV (CV, coefficient of variation) was measured over 1 week after 1-month home monitoring (HBPM, 3 readings, 3 times daily), on awake ABPM, and by 5 minute supine beat-to-beat monitoring (Finometer). Hypertension was treated intensively and residual BPV related (Cox proportional hazards) to recurrent stroke or death and cardiovascular events during 1–5 years of face-to-face follow-up.
Results: Of 500/520 patients with adequate monitoring, 22 were excluded due to current AF. Beat-to-beat and day-to-day BPV were weakly correlated (r2 = 0.014, p = 0.02) but beat-to-beat BPV was as predictive as day-to-day BPV of recurrent stroke, death and all cardiovascular events (HR per population SD, stroke: beat-to-beat 1.53,1.18–1.98, p = 0.002 vs day-to-day 1.33,1.02–1.75, p = 0.04; death/cardiovascular: 1.38,1.10–1.74, p = 0.005 vs day-to-day 1.37,1.11-1.69, p = 0.003), whereas awake ABPM-BPV was not (stroke 0.95,0.67–1.34, p = 0.76; death/cardiovascular 0.97,0.73–1.27, p = 0.80). When modelled with beat-to-beat BPV, the relationship between day-to-day BPV and stroke was attenuated (beat-to-beat 1.42,1.05–1.91, p = 0.02 vs day-to-day 1.27,0.95-1.71, p = 0.11) but the relationship with death and cardiovascular events was not (1.25,0.99-1.57, p = 0.06 vs 1.47,1.17–1.84, p < 0.001).
Conclusion: In patients with intensively treated hypertension, beat-to-beat BPV was as predictive of residual risk of cardiovascular events as remaining day-to-day BPV and may be a novel risk marker amenable to treatment.
AS03-019
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
INTRATHECAL BACLOFEN THERAPY COMPARED TO THE CONVENTIONAL TREATMENT: EFFICACY RESULTS IN THE MANAGEMENT OF POST-STROKE SPASTICITY OF THE SISTERS RANDOMIZED CONTROL TRIAL
M. Creamer1, G. Cloud2, P. Kossmehl3, M. Yochelson4, G. Francisco5, A. Ward6, J. Wissel7, M. Zampolini8, M. Loven9, N. Berthuy10, A. Abouihia10, A. Calabrese10 and L. Saltuari11,12
1Central Florida Pain Relief Centers,., Orlando, USA
2St George’s University Hospitals NHS Foundation Trust,., London, United Kingdom
11Landeskrankenhaus Hochzirl, Abteilung für Neurologie, Zirl, Austria
12Research Unit for Neurorehabilitation South Tyrol,., Bolzano, Italy
Background and Aims: Intrathecal Baclofen (ITB) is an effective treatment option for managing severe spasticity in post-stroke patients who have not reached their therapy goal with conventional treatments. SISTERS is a randomized, controlled, open-label multicenter study that compares the efficacy of the ITB therapy versus oral anti-spastic medications (Best Medical Treatment, BMT) in post-stroke patients with severe spasticity.
Method: Stroke patients who presented with spasticity in at least two extremities and an Ashworth Scale (AS) score ≥ 3 in a minimum of two affected muscle groups in the lower limbs were randomized to the ITB or BMT arm. Both groups received physiotherapy and were evaluated at baseline and 6 months of active treatment.
Results: Sixty subjects with severe post-stroke spasticity were randomized to the ITB (N = 31) and BMT (N = 29) groups across 18 centres (11 in Europe and 7 in the US). The mean (±SD) age and time since stroke were 55.9 ± 9.9 and 4.8 ± 3.6 years, respectively. Forty-eight subjects completed the 6 month follow-up visits and twelve patients prematurely terminated the study. Tone muscle assessed with AS in lower and upper extremities, function, pain, quality of life, patient satisfaction and safety were assessed and compared between the groups. The analysis of the outcomes is ongoing and the results will be presented.
Conclusion: The study will provide clinical evidence on the efficacy of ITB Therapy in treating severe spasticity in post-stroke patients.
AS03-020
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
MODAFINIL IN DEBILITATING FATIGUE AFTER STROKE (MIDAS): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSS-OVER TRIAL
A. Bivard1, T. Lillicrap1, V. krishnamurthy1, H. Elizabeth1, A. John1, H. Pagram1, M. Nilsson1, M. Parsons1 and C. Levi1
1University of Newcastle, Medicine, Newcastle, Australia
Background and Aims: This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent, in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesised that, 200 mg of modafinil daily for six weeks would result in reduced symptoms of fatigue compared to placebo.
Method: This single centre phase 2 trial used a, randomised, double blind, placebo controlled, crossover design. The key inclusion criteria was a multi-dimensional fatigue inventory (MFI) score of 60 or more. Patients were randomised to either modafinil or placebo for six weeks of therapy, then after a one week wash out period, swapped treatment arms for a second six weeks of therapy. The primary outcome was the MFI; secondary outcomes included the Montreal Cognitive Assessment (MoCA), the Depression, Anxiety and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The MFI is a self-administered questionnaire with a range of 0–100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527).
Results: 232 stroke survivors were screened and 36 were randomised. Participants receiving modafinil reported a significant decrease in fatigue (MFI −7.38, 95% CI, −21·76,- −2.99, p < 0·001) and improved quality of life (SSQoL11·81, 95% CI, 2·31, 21·31, p = 0·0148) compared to placebo. MoCA and DASS were not significantly improved with modafinil therapy during the study period (p > 0·05).
Conclusion: Stroke survivors with non-resolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil.
AS03-021
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
GENDER DIFFERENCE IN RESPONSE TO FAMILY-LED REHABILITATION AFTER STROKE
R. Lindley1, J. Pandian2, L. Harvey3, A. Forster4, M. Walker5, P. Langhorne6, G. Murthy7, M. Hackett1, P. Maulik8, C. Anderson1, S. Jan1, L. Billot1 and Q. Li1
1George Institute for Global Health- University of Sydney, Neurology and Mental Health, Sydney, Australia
2Christian Medical College, Neurology, Ludhiana, India
3University of Sydney, John Walsh Centre for Rehabilitation Research- Kolling Institute, Sydney, Australia
4University of Leeds, Bradford Institute for Health Research, Bradford, United Kingdom
5University of Nottingham, Faculty of Medicine & Health Sciences, Nottingham, United Kingdom
6University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
7Indian Institute of Public Health, Hyderabad, Hyderabad, India
8George Institute for Global Health India, Research and Development Division, Delhi, India
Background and Aims: Task shifting stroke rehabilitation to family members may provide a cost-effective model of stroke care, but little is known whether treatment response differs between men and women. We report new secondary results from the ATTEND Trial.
Method: ATTEND was a large multicentre randomized controlled trial of family-led rehabilitation after stroke in India. Patients and family carers were randomiSed to receive rehabilitation training or usual care during their initial hospital stay. The primary outcome was death or dependency measured on the Modified Rankin Score (mRS 3–6) by blinded assessors at 6 months. Secondary outcomes for patients included Barthel Index, quality of life (EuroQol health state) and anxiety and depression (HADS).
Results: 1,250 patients were recruited with 97% follow-up. At six months, there was no difference in mRS 3–6, 47.0% intervention; 47.4% control, Odds Ratio 0.98, 95% Confidence Interval 0.78 to 1.23, p = 0.87. There was a significant interaction by sex (men mRS 3–6: 41.6% intervention, 46.1% control, n = 837; women mRS 3–6: 58.1% intervention, 50.0% control, n = 413, p = 0.04 for interaction). Barthel Index: men 84.5 intervention, 83.1 control; women 77.2 intervention, 81.6 control. EuroQol: men 72.2 intervention, 72.9 control; women 65.7 intervention, 69.6 control. The intervention was associated with 5.3% less depression and 3.8% less anxiety in men but 10.8% more depression and 7% more anxiety in women, a significant interaction at p < 0.05.
Conclusion: Overall, the ATTEND rehabilitation intervention did not improve outcome after stroke. However, there was a significant interaction in the proportion dead or dependent by sex, with men appearing to benefit more than women.
AS03-043
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
EARLY USE OF ABOBOTULINUMTOXINA IN ADULTS WITH POST-STOKE SPASTICITY IMPROVES MUSCLE TONE AND INCREASES TIME TO REINJECTION: RESULTS FROM ONTIME AND ABCDE S STUDIES
R.L. Rosales1,2, K.H. Kong3, W. Kumthornthip4, M. Mazlan5, L. Abdul Latif5, M.M.D. De Los Santos1, C. Chotiyarnwong4, P. Tanvijit4, O. Nuez3, J. Balcaitiene6, P. Maisonobe6 and K.J. Goh7
1Metropolitan Medical Centre, Centre for Neurodiagnostic and Therapeutic Services, Manila, Philippines
2University of Santo Tomas, Department of Neurology & Psychiatry- Faculty of Medicine and Surgery, Manila, Philippines
3Tan Tock Seng Hospital, Department of Rehabilitation Medicine, Novena, Singapore
4Siriraj Hospital- Mahidol University, Department of Rehabilitation Medicine- Faculty of Medicine, Bangkok, Thailand
5University of Malaya Medical Centre, Department of Rehabilitation Medicine, Kuala Lumpur, Malaysia
6Ipsen Group, Medical Affairs, Boulogne-Billancourt, France
7University of Malaya Medical Centre, Division of Neurology- Department of Medicine, Kuala Lumpur, Malaysia
Background and Aims: Muscle tone changes may be apparent within 2 weeks post-stroke. Botulinum toxin A (BoNT-A) is effective in reducing upper limb spasticity (ULS), however in most studies has been injected >6 months post-stroke. The ONTIME and ABCDE S studies aimed to determine the efficacy and safety of early use of abobotulinumtoxinA (aboBoNT-A) in ULS patients.
Method: ABCDE S (NCT00234546; 2008) was a multicentre, randomised (1:1 aboBoNT-A [n = 80]:placebo [n = 83]), study assessing changes in muscle tone in patients within 2–12 weeks of first stroke, with a Modified Ashworth Scale (MAS) score of >1+. ONTIME (NCT02321436; 2016) was a 28-week, randomised (2:1, aboBoNT-A [n = 28]:placebo [n = 14]), double-blind study assessing time to appearance or reappearance of reinjection criteria (one criterion was based on MAS) in patients within 2–12 weeks post-stroke, with MAS score ≥2.
Results: MAS score improvements from baseline to Week 4 were greater in aboBoNT-A-treated patients than placebo in both studies (ABCDE S −1.5 vs. −0.5; ONTIME −1.25 vs. −0.25). At Week 12, 29.6% of ONTIME patients in the aboBoNT-A group met the reinjection criteria of ≥2 MAS score versus 69.2% placebo and in ABCDE S, at Week 12, 21.3% of treated patients had a score of ≥2 MAS versus 60.2% placebo (Table 1).
Conclusion: Both studies showed early use of aboBoNT-A post-stroke improves MAS scores within 4 weeks of aboBoNT-A treatment.
Study sponsored by Ipsen.
AS03-046
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
NOVEL NON-INVASIVE DYSPHAGIA DETECTION SYSTEM (DDS) FOR BEDSIDE ASSESSMENT OF SWALLOWING IN PATIENTS AT RISK OF OROPHARYNGEAL DYSPHAGIA: RESULTS FROM AN EXPLORATORY STUDY
C.M. Steele1, R. Mukherjee2, N. Muehlemann3, M. Jedwab3, P.M. Bath4, K.R. Lees5, A. Meretoja6, For the, SONAR Investigators
1Toronto Rehabilitation Institute – University Health Network, Swallowing Rehabilitation Research Laboratory, Toronto, Canada
2Cytel, Cytel, Cambridge MA, USA
3Nestlé Health Science, Medical Devices, Lausanne, Switzerland
4University of Nottingham, Division of Clinical Neuroscience, Nottingham, United Kingdom
5University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
6Helsinki University Hospital, Department of Neurology, Helsinki, Finland
Background and Aims: Oropharyngeal dysphagia is prevalent in stroke patients and other conditions. Early identification of dysphagia is critical for optimising outcomes, but available bedside screening tools perform inconsistently. A novel dysphagia detection system (DDS) to assess dysphagia at bedside was developed and compared to simultaneous Videofluoroscopic Swallowing Study (VFSS).
Method: Prospective collection and exploration of dual-axis accelerometry-based DDS signals during swallows of barium stimuli of wide-ranging rheology, among mixed populations in a prospective, multicentre study. Primary objective was to develop a swallowing impairment detection algorithm with Area Under the Curve (AUC) >0.8 on the Receiver Operating Characteristics (ROC) curve vs. VFSS.
Results: The study population numbered 332, with 107 (32%) post-stroke. 4229 boluses were analysed. Prevalence of VFSS-determined swallowing safety issues with thin boluses was 7.2% at bolus and 23% at patient level. Prevalence decreased substantially with increasing thickness of stimuli: 5.8%, 2.0%, 1.4% at bolus level, and 13.9%, 5.0%, 3.7% at participant level, respectively, for mild, moderate and extremely thick consistencies. Patients with swallowing impairment did not consistently exhibit issues with every bolus; four boluses were found to be a practical number of tries with thin consistency to detect a problem. For DDS, the ROC AUC was 0.82 (SD 0.06), with sensitivity and specificity of 86.7% (SD 8.8) and 60.4% (SD 4.9), respectively, for detecting swallow safety problems with thin stimuli.
Conclusion: This DDS reached targeted performance in detecting impaired swallowing safety with thin stimuli. Simultaneous measures by DDS and VFSS, as performed here, are critical for future validation research.
AS10-032
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
ANALYSIS OF MORTALITY AND MORBIDITY AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY(PEG) AND RADIOLOGICALLY-INSERTED GASTROSTOMY(RIG) – AN EIGHT –YEAR FOLLOW UP STUDY FROM THE UK
S. Munshi1, S. Raghunathan1, M. Barclay1, C. Chee1, T. Buchanan2, K. Teahon2, A. Shetty1, M. Maddula1, W. Sunman1, G. Subramanian1, L. Everton3, T. Reid1, N. Sprigg4, L. Taylor1, I. Brown5, S. Murphy1, L. Taylor1 and P. Bath4
1Nottingham Stroke Department, Stroke, Nottingham, United Kingdom
2Nottingham University Hospitals, Gastroenterology, Nottingham, United Kingdom
3Nottingham Stroke Department, Speech and language therapy, Nottingham, United Kingdom
4University of Nottingham, Neurosciences, Nottingham, United Kingdom
5Nottingham University Hospitals, Dept of Clinical Audit, Nottingham, United Kingdom
Background and Aims: The National Confidential Enquiry into Patient outcome and Death (NCEPOD 2004) in the UK showed substantially high mortality rates after Percutaneous Endoscopic Gastrostomy and Radiologically Inserted Gastrostomy (PEG/RIG) insertions for feeding in stroke patients. Inappropriate patient selection was cited as the main reason. We studied mortality and complication rates after PEG/RIG insertion.
Method: In a retrospective study all stroke patients undergoing PEG/RIG at our centre from June 2007 to May 2015 were included with follow up to 31 Dec 2015. Graph PRISM statistical software and Kaplan-Meier analyses were used for statistical analysis.
Results: The median survival rates after RIG and PEG insertions are 3.55 and 5.0 months respectively. High mortality rates reflect the very frail and vulnerable population. Mortality rates of stroke patients after PEG/RIG were – at 30 days: 14% after RIG, 15.4% after PEG; at 6 months- 65.1% with RIG, 54.1% with PEG; at 1 year: 79% with RIG, 71% with PEG. The average age of stroke patients here is 78.1 yrs. The average age of PEG patients is 80 yrs. Younger patients with PEG appear to have better outcomes.
Conclusion: In view of high mortality rates after PEG and RIG, careful selection of patients and shared, in-depth, decision-making with a Multi-disciplinary Team are indicated. Our immediate complication rates are low reflecting excellent selection by Specialist Nutrition nurse and great expertise of the endoscopist in performing the procedure. In future it would be useful to do a multivariate regression analysis of predictive factors for mortality rates post PEG and RIG.
AS10-059
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
OUTCOME MEASUREMENT IN STROKE UPPER LIMB REHABILITATION TRIALS: DO WE MEASURE WHAT MATTERS?
J. Duncan Millar1, M. Ali1, A. Pollock1 and F. van Wijck2
1Glasgow Caledonian University, NMAHP Research Unit, Glasgow, United Kingdom
2Glasgow Caledonian University, School of Health and Life Sciences, Glasgow, United Kingdom
Background and Aims: Improvement in upper limb (UL) rehabilitation is a stroke research priority. Numerous outcome measures (OM) are in current use across UL rehabilitation randomised controlled trials (RCTs). It is unclear whether these OM capture what matters to people affected by stroke. We identified and mapped the most commonly used UL OM to priority outcomes identified by stakeholders.
Method: We identified 243 RCTs from 43 systematic reviews of post-stroke interventions for UL rehabilitation and extracted data on OM use. We conducted 16 focus groups using Nominal Group Technique with stakeholders and content analysed data to identify and prioritise outcomes related to UL impairment following stroke. We mapped the top 3 OM identified from RCTs to stakeholders’ priority outcomes.
Results: The most commonly used OM were Fugl-Meyer (UL section; FMA-UL), Action Research Arm Test (ARAT), and Modified Ashworth Scale (mAS).
Focus group participants included 35 stroke survivors (SS), 8 carers (C) and 58 health professionals (HP).
Of 46 identified SS&C outcomes, the top 5 were ‘Loss of Independence and Freedom’, ‘Relying on Others’, ‘Difficulty with Routine Actions, ‘Everyday Tasks’, and ‘Ability to Work’.
Of the 33 HP outcomes, the top 5 included ‘Activities of Daily Living and Usual Activity’, ‘Pain’, ‘Coping and Self-management’, ‘Knowledge and Understanding’ and ‘Goal Attainment’.
‘Difficulty with Routine Actions’ was captured by ARAT and ‘Pain’ was captured by FMA-UL; no other priority outcomes were directly captured by current OM.
Conclusion: The top 3 OM currently used in stroke UL rehabilitation trials do not comprehensively capture the outcomes most important to stakeholders.
AS11-008
Scientific Communication (Oral Abstract Presentation) Rehabilitation and Recovery
WHEN NEGLECT IS BEING NEGLECTED: THE POOR SENSITIVITY OF SYMPTOM-BASED ASSESSMENT OF INATTENTION IN ACUTE STROKE
N. Demeyere1, N. Shalev1, M. Moore2, E. Slavkova1 and M.J. Riddoch1
1University of Oxford, Department of Experimental Psychology, Oxford, United Kingdom
2University of Indiana, Department of Psychological and Brain Sciences, Bloomington, USA
Background and Aims: Unilateral Neglect (UN) is a prevalent neuropsychological disorder affecting individuals after brain lesion. Up to two thirds of Stroke patients are thought to experience UN acutely post stroke (Stone et al 1991). UN is a predictor of poor recovery (Katz et al., 1999) and has been associated with poor functional outcomes. Although UN is considered to be a well-established phenomenon, there seems to be little agreement about the way it is diagnosed in clinical settings. While clinicians in acute stroke wards often turn to a symptom-based observational scale as the NIH Stroke Scale (NIHSS), Neuropsychologists rely mostly on variations of the Cancellation Task – a task aimed to identify spatial-attention biases.
Method: We present a direct comparison between the number of identified UN cases using the NIHSS and using a Cancellation Task in data from 410 stroke survivors, acquired in multiple sites.
Results: Nearly 50% of the individuals who were diagnosed as unimpaired in the inattention item of the NIHSS had a clear pattern of an attentional bias on a cancellation task. In addition, we describe the distribution of UN severity in the two assessment tools and their correlation, suggesting that severity is not the only factor determining a missed diagnosis of UN using the NIHSS. Finally, while the cancellation task enabled us to distinguish between subtypes of Neglect, which have been associated with differential recovery predictions, the NIHSS did not.
Conclusion: The NIHSS inattention item greatly underestimates the prevalence of UN
AS13-031
Scientific Communication (Oral Abstract Presentation) Epidemiology
POPULATION-BASED STUDY OF TEMPORAL TRENDS IN INCIDENCE, RISK FACTORS AND AETIOLOGY OF “YOUNG STROKE” IN OXFORDSHIRE, UK
L. Li1, C. Scott1, Z. Mehta1, L. Silver1, P.M. Rothwell1 and On behalf of the Oxford Vascular Study1
1Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom
Background and Aims: Several studies have reported that incidence of “young stroke” in high-income countries is increasing. However, reasons for this apparent increase are unclear.
Method: Among all incident strokes in two population-based cohorts in Oxfordshire, UK (OCSP 1981–1986 / 557 events; OXVASC 2002–2016 / 2065 events), we studied the temporal change in incidence at age < 55y vs. ≥55y, stratified by severity (mRS ≤ 2 vs. ≥3). We also compared the changes in incidence, control of pre-morbid risk factors, and diagnostic work-up during OXVASC (2002–2009/2009–2016).
Results: Stroke incidence fell at age ≥ 55y from 1981–1986 to 2002–2016 (standardized relative incidence = 0.71, 0.64–0.79), but not for age < 55y (1.20, 0.88–1.63; pdifference = 0.0003). However, the increase at age < 55y was only seen for non-disabling stroke (1.64, 1.13–2.37 vs. 0.75, 0.41–1.36 for mRS ≥ 3; pdifference = 0.02). Results were consistent by sex, and for ischaemic and haemorrhagic stroke. The increase of “young stroke” was mostly accounted for by an apparent jump after 2009 during OXVASC (> vs. <2009 – 1.47, 95%CI 1.13–1.93, p = 0.005; mRS ≤ 2 1.57, 1.15–2.14, mRS ≥ 3 1.20, 0.69–2.07), which coincided with an increase in use of MRI brain (78.2% vs. 55.6%, p = 0.0003). Nevertheless, of OXVASC patients aged < 55y, 36.4% (n = 76) had pre-morbid blood pressure ≥ 140/90, 51.8% (n = 86) had cholesterol ≥5.2 mmol/l, 61.2% (n = 134) were current/ex-smokers and 63.1% (n = 135) were overweight/obese.
Conclusion: Although the increase we observed in incidence of “young stroke” in recent years was mainly due to non-disabling events, which may partly reflect investigation bias, patients often had poorly controlled vascular risk factors, and future rates should be closely monitored.
AS13-034
Scientific Communication (Oral Abstract Presentation) Epidemiology
ISCHEMIC STROKE ETIOLOGIC SUBTYPES DISTRIBUTION: A POPULATION-BASED STUDY AND A META-ANALYSIS
S. Sacco1, R. Ornello1, C. Di Carmine1, D. Degan1, C. Tiseo1, L. Perciballi1, F. Pistoia1 and C. Antonio1
1University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'AQUILA, Italy
Background and Aims: We aimed to describe the current distribution of Ischemic stroke (IS) etiologic subtypes in an Italian population and to investigate their worldwide distribution and temporal changes.
Method: Cases of incident first-ever IS from multiple sources were prospectively collected over a two-year period (2011-2012) in the district of L’Aquila, central Italy. Cases were classified as due to cardioembolism (CE), large-artery atherosclerosis (LAA), small-artery occlusion (SAO), other determined causes (OC), and to undetermined (UND) cause. Additionally, we performed a meta-analysis of available studies reporting the distribution of IS etiologic subtypes.
Results: In a total of 605 patients, IS was due to CE in 215 (35.5%), to LAA in 70 (11.6%), to SAO in 86 (14.2%), to OC in 29 (4.8%), and to UND cause in 205 (33.9%). Sixty-one studies were included in the meta-analysis for a total of 108,386 IS cases. Distribution of IS etiologic subtypes is reported in Figure. In Whites, the leading IS etiologic subtype was CE whereas in Asians it was LAA. Changes over time in IS etiologic subtypes are reported in Table. Over time, IS due to CE increased in Whites, IS due to LAA increased in Asians, while IS due to SAO decreased globally.
Conclusion: Specific measures are needed to reduce the burden of IS due to CE and LAA, to evaluate factors related to the residual risk of IS due to SAO and to improve understanding, diagnosis and prevention of IS due to UND cause.
AS13-035
Scientific Communication (Oral Abstract Presentation) Epidemiology
TRENDS IN STROKE SEVERITY AND BASELINE RISK PROFILE IN PATIENTS TREATED ON A COMPREHENSIVE STROKE UNIT IN NORWAY IN 1994 VERSUS 2012
A.S. Labberton1,2, B. Thommessen3, O.M. Rønning2,3 and M. Barra1
1Akershus University Hospital, Health Services Research Unit, Lorenskog, Norway
2University of Oslo, Department of Medicine, Oslo, Norway
3Akershus University Hospital, Department of Neurology, Lorenskog, Norway
Background and Aims: Stroke mortality has decreased worldwide over the last four decades. Treatment on organized stroke units has been well-documented in decreasing mortality and improving function after stroke, and access to stroke units has generally improved. Furthermore, population-based studies indicate that the background characteristics of stroke patients have also changed, which may additionally influence outcome after stroke.
The aim of this study was to determine if the baseline characteristics and stroke severity of stroke unit patients have changed over the last two decades.
Method: We compared two cohorts of stroke patients admitted to the same comprehensive stroke unit in 1994–95 (n = 271) and 2012–13 (n = 546) to investigate how their baseline characteristics have changed in Greater Oslo and Akershus County, Norway.
Results: Compared to 1994, patients were slightly older (mean age 78.8 years vs 76.7 years, p = 0.001) and had less severe strokes at admission (proportion with mild stroke 66.1% vs 44.3%, p < 0.001 across all categories). They were more likely to have a diagnosis of atrial fibrillation (33.7% vs 21.4%, p < 0.001) and malignancy (19.2% vs 8.9%, p < 0.001), and more commonly prescribed anti-platelets (46.9% vs 26.2%, p < 0.001), warfarin (16.3% vs 5.5%, p < 0.001) and anti-hypertensive medications (69.6% vs 56.1%, p < 0.001) prior to admission. There were no significant differences in the proportion of patients with previous cerebrovascular disease, myocardial infarction, or those taking anti-diabetic medications.
Conclusion: The population of stroke patients treated on the stroke unit had a different stroke and risk factor profile in 2012 compared to 1994. These differences may influence outcome measures such as mortality and long-term function.
AS13-041
Scientific Communication (Oral Abstract Presentation) Epidemiology
DILATED PERIVASCULAR SPACES ARE ASSOCIATED WITH HIGH INCIDENT HEMORRHAGIC STROKE RISK
M.G. Duperron1, S. Sabrina1, Y.C. Zhu2, B. Mazoyer3, C. Tzourio1,4 and S. Debette1,5
1INSERM U897, Univ. Bordeaux, BORDEAUX, France
2Pekin Union Medical College Hospital, Department of Neurology, Beijing, China
3Institut des Maladies Neurodégénératives- CNRS-CEA UMR 5293, Univ. Bordeaux, Bordeaux, France
4CHU de Bordeaux, Pole de santé publique- Service d’information médicale, Bordeaux, France
5CHU de Bordeaux, Department of Neurology, Bordeaux, France
Background and Aims: Dilated perivascular spaces (dPVS) are commonly observed in older community persons. Long considered anatomical variations, dPVS recently emerged as an important MRI-marker of cerebral small vessel disease. We examined the longitudinal relationship of dPVS severity measured at baseline and 12-year incident stroke in older community-persons.
Method: The study sample at baseline comprised 1,571 participants from the 3C-Dijon population-based cohort study (aged 72.6 ± 4.0 years, 62.9% women), who were prospectively followed for up to 12 years. dPVS were studied as a global score and according to their location. We used Cox models with delayed entry, and age as time scale. Analyses were adjusted for sex, total intracranial volume, and for vascular risk factors, lacunes, and white matter hyperintensity volume in secondary analyses.
Results: During 9.05 ± 2.55 years of follow-up 58 participants suffered an incident stroke (48 ischemic strokes, 7 intracerebral hemorrhages). Increasing dPVS global score was associated with 12-year higher risk of all stroke (hazard ratio [HR], 1.18, 95% confidence interval [1.00–1.40], p = 0.47) and intracerebral hemorrhage (HR, 3.69[1.74–7.84], p = 0.0007), adjusting for sex and intracranial volume. The association with intracerebral hemorrhage was also independent of vascular risk factors and other MRI-markers of small vessel disease. When looking at dPVS subtypes, high degrees of dPVS in basal ganglia, but not subcortical regions, were significantly associated with higher risk of intracerebral hemorrhage.
Conclusion: In a large population-based study dPVS burden, especially in basal ganglia, was associated with increased risk of incident stroke, predominantly intracerebral hemorrhage, independently of vascular risk factors and other MRI-markers of cerebral small vessel disease.
AS13-070
Scientific Communication (Oral Abstract Presentation) Epidemiology
RAPID INCREASE OF THE INCIDENCE OF STROKE IN YOUNG ADULTS IN THE NETHERLANDS BETWEEN 1998 AND 2010
M. Ekker1, J. Verhoeven1, K. van Nieuwenhuizen2, E. van Dijk1, I. Vaartjes3, C. Klijn1 and F.E. de Leeuw1
1Radboud University Medical Centre- Donders Institute for Brain- Cognition and Behaviour, Neurology, Nijmegen, The Netherlands
2Brain Center Rudolf Magnus- University Medical Center Utrecht, Neurology and neurosurgery, Utrecht, The Netherlands
3Julius Center for Health Sciences and Primary Care- University Medical Center Utrecht, Neurology, Utrecht, The Netherlands
Background and Aims: Stroke in young adults (18-49 years) often strikes at life’s crossroads. Incidence has been suggested to increase, although mainly based on small studies. We therefore investigated time trends in the incidence of stroke in the young in the Netherlands.
Method: A nationwide cohort was established through linkage of national registries (hospital discharge-, cause of death-, and population register) using ICD-9 and -10 codes for stroke between 1998 and 2010. Patients, aged 18 to 49 years, with a first hemorrhagic or ischemic stroke or transient ischemic attack were included. Outcome was the yearly incidence and its change between 1998 and 2010, stratified by age-, sex- and stroke-subtype.
Results: We identified 23,923 patients (53% women; mean age: 42 years). Young stroke incidence increased from 19.2/100,000 in 1998 to 30.2/100,000 in 2010 (+57%), whereas overall stroke incidence in the Netherlands increased from 145.8/100,000 to 190.6/100,000 (+31%). Stroke was more frequently seen in women than men (18–44 years) (χ2 p < 0.01), except for those aged 45–49 (χ2 p = 0.38). Incidence increased exponentially with age (R2 = 0.99). Hemorrhagic stroke was more common in the youngest age groups (18–29) (20.9% of all stroke subtypes) compared to older age groups (30–49) (10.4%).
Conclusion: The incidence of young stroke has increased with 50% in about one decade, women being more affected then men. Our results warrant rapid identification of risk factors.
AS13-071
Scientific Communication (Oral Abstract Presentation) Epidemiology
THE MEDIATING ROLE OF THE MICROVASCULATURE ON THE EFFECT OF SMOKING ON ISCHEMIC STROKE: A CAUSAL MEDIATION ANALYSIS
M.K. Ikram1
1Erasmus MC, Departments of Neurology & Epidemiology, Rotterdam, The Netherlands
Background and Aims: Smoking is a well-established risk factor for ischemic stroke. A potential mechanism may go through microvascular pathology. However, in epidemiological studies, standard regression procedures have shortcomings when it comes to questions of interaction and mediation. In this study, we aimed to elucidate the mediating role of the microvasculature on the effect of smoking on ischemic stroke using the recently developed causal mediation analysis.
Method: This study is part of the prospective population-based Rotterdam Study including 9106 stroke-free persons (mean age: 63.7 years, 58% women). Smoking behavior was identified by interviewing the participants. Retinal arteriolar and venular calibers were measured semi-automatically on retinal fundus photographs. Participants were followed up for incident stroke until 2014. A regression-based approach was used to decompose the excess risk of smokers compared to nonsmokers into four components: mediation, interaction, both, or neither.
Results: During a mean follow-up of 11.7 years, 600 persons developed an ischemic stroke. After adjusting for other cardiovascular risk factors, current smokers had a higher risk of developing stroke compared to nonsmoker, odds ratio: 1.47, 95% confidence interval: 1.14; 1.75. When including wider retinal venules as a mediator, this excess relative risk could be decomposed into 13% due to both mediation and interaction, 5% mediation only, 4% interaction only, and 78% neither interaction with nor mediation through venular calibers (controlled direct effect).
Conclusion: This novel method reveals that in the pathophysiology of ischemic stroke the effect of smoking partly goes through the microvasculature, where there is both mediation and interaction between smoking status and the microvasculature.
AS13-072
Scientific Communication (Oral Abstract Presentation) Epidemiology
30-YEARS TREND IN BASELINE CARDIOVASCULAR RISK FACTORS AND OUTCOME FOLLOWING CAROTID ENDARTERECTOMY WITHIN THREE CONSECUTIVE RANDOMIZED TRIALS
L. Benjamin1
1Institute of Neurology, Brain repair and rehabilitaion, London, United Kingdom
Background and Aims: Long-term trends suggest that morbidity and mortality after stroke are falling, but trends in patients with symptomatic carotid stenosis are uncertain. We studied changes in baseline risk factors and cardiovascular-related outcome after carotid endarterectomy over a 30-year period.
Method: We investigated baseline vascular risk factors and vascular morbidity and mortality in three randomized controlled trials; European Carotid Surgery Trial [ECST 1981–1994) Carotid and Vertebral Artery Transluminal Angioplasty Study [CAVATAS 1992–1997] and International Carotid Stenting Study [ICSS 2001–2008]. We compared the 2-year rate of recurrent stroke, myocardial infarction[MI], and death using cox regression analyses to adjust for confounders.
Results: Across the three trials (n = 1657), there was a significant decline in baseline systolic and cholesterol levels, and an increase in age, diabetes and previous MI (Table 1). Non-procedural recurrent stroke (10%[ECST] vs 14[CAVATAS] vs 4; p
Conclusion: The decline in the 2-year rate of stroke and death in patients in the current century is consistent with better control of vascular risk factors and widespread use of statins since 2000 onwards. However, the doubling in the rate of baseline diabetes might have limited the benefits of improved health care.
AS16-060
Scientific Communication (Oral Abstract Presentation) Epidemiology
EARLY LIFE RISK FACTORS FOR STROKE IN THE UK BIOBANK
C. McHutchison1, F.M. Chappell1, D. Dickie1 and J.M. Wardlaw1
1University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
Background and Aims: Factors in adulthood including vascular factors and socioeconomic status (SES) are associated with stroke risk in later life. There is evidence to suggest that conditions in childhood including poorer SES and lower education are also related to stroke risk. We aimed to assess early life factors and risk of hospital-admitted stroke in volunteers in the UK Biobank.
Method: 502,641 participants undertook baseline assessment for the UK Biobank between April 2007 and July 2010 across England, Scotland and Wales. We identified participants with a hospital-admitted episode of stroke using the UK Biobank’s data linkage, and a random sample of non-stroke controls (n = 9860), and performed a logistic regression. We examined self-reported birthplace, number of siblings, years of education and whether they were breastfed as early life factors associated with risk of stroke. We included known risk factors in adulthood including vascular (diabetes and hypertension), SES (Townsend deprivation, income and employment status) and lifestyle factors (smoking and frequency of alcohol consumption).
Results: We identified 6548/502,641 (1.3%) people with a hospital episode of stroke aged 40–71 years (Mean = 61, SD = 7) and non-stroke controls (n = 9860, mean age = 57, SD = 8). When controlling for adult SES, vascular and lifestyle variables, stroke risk increased with being born in Scotland (OR = 1.38, 95% CI = 1.21–1.58) compared to England, having more siblings (OR = 1.02, 95% CI = 1.00–1.04) and not knowing whether they were breastfed (OR = 1.17, 95% CI = 1.06–1.28) compared to being breastfed.
Conclusion: Factors indicating lower SES in youth are associated with increased stroke risk in the UK, independent of adult factors.
AS28-009
Scientific Communication (Oral Abstract Presentation) Epidemiology
PATENT FORAMEN OVALE IS NOT ASSOCIATED WITH NEW DIFFUSION WEIGHTED IMAGING LESIONS ONE WEEK AFTER AN ISCHEMIC STROKE
T.B. Braemswig1,2,3, T. Usnich1, J.B. Fiebach3, H.J. Audebert1,2,3, M. Endres1,2,3 and C.H. Nolte1,2,3
1Charité – Universitätsmedizin Berlin, Klinik für Neurologie, Berlin, Germany
2Berlin Institute of Health, BIH, Berlin, Germany
3Charité – Universitätsmedizin Berlin, Center for Stroke Research Berlin CSB, Berlin, Germany
Background and Aims: Patent foramen ovale (PFO) is discussed as a potential cause of stroke in patients with stroke of (otherwise) undetermined etiology. In previous studies, stroke recurrence in patients with stroke of undetermined etiology and PFO was diagnosed by interview or brief neurologic examination. Cerebral imaging was not mandatory. For the first time, we investigated the risk of early recurrent diffusion-weighted imaging (DWI) lesions on magnetic resonance imaging in patients with and without PFO one week after the index event.
Method: Patients with an ischemic stroke of undetermined etiology underwent three MRI (3 Tesla) examinations: on admission, on the following day, and four to seven days after symptom onset. DWI lesions were delineated manually, coregistered and then analyzed visually for new DWI hyperintensities by raters blinded to clinical details. Presence of new DWI lesions were compared between patients with and without PFO. Additionally, patients with a stroke-related PFO were identified by using the Risk of Paradoxical Embolism (RoPE) score.
Results: Out of 98 patients with stroke of undetermined etiology, 32 had a PFO and 18 patients had a PFO with a high RoPE-score (>5 points). 38 patients had new DWI lesions. New DWI lesions were not more common in patients with PFO (OR 0.67 [95% CI 0.27–1.70], p = 0.403). New DWI lesions were even significantly less frequent in patients with PFO and a high RoPE-score (OR 0.26 [95% CI 0.07–0.96], p = 0.043).
Conclusion: PFO is not a risk factor for new DWI lesions within one week after an ischemic stroke.
AS09-005
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
CLINICAL ANALYSIS COMPARING EFFICACY BETWEEN A DISTAL FILTER PROTECTION DEVICE AND PROXIMAL BALLOON OCCLUSION DEVICE DURING CAROTID ARTERY STENTING
S.Y. Chung1 and M.S. Park1
1Eulji University Hospital, Neurosurgery, Daejeon, Republic of Korea
Background and Aims: The main concern during transfemoral carotid artery stenting (CAS) is preventing cerebral embolus dislodgement. We compared clinical outcomes and intraprocedural embolization rates of CAS using a distal filter protection device or proximal balloon occlusion device.
Method: From January 2011 to March 2015, a series of 58 patients with symptomatic or asymptomatic internal carotid artery stenosis ≥70% were treated with CAS with embolic protection device in single center. All patients underwent post-CAS diffusion-weighted magnetic resonance imaging (DW-MRI) to detect new ischemic lesions. We compared clinical outcomes and postprocedural embolization rates.
Results: CAS was performed in all 61 patients. Distal filter protection success rate was 96.6% (28/29), whose mean age was 70.9 years, and mean stenosis was 81%. Their preprocedural infarction rate was 39% (11/28). Subsequent DW-MRI revealed 96 new ischemic lesions in 71% (20/28) patients. In contrast, the proximal balloon occlusion device success rate was 93.8% (30/32), whose mean age was 68.8 years and mean stenosis was 86%. Preprocedure infarction rate was 47% (14/30). DW-MRI revealed 45 new ischemic lesions in 57% (17/30) patients. Compared with distal filter protection device, proximal balloon occlusion device resulted in fewer ischemic lesions per patient (p = 0.028). In each group, type of stent during CAS had no significant effect on number of periprocedural embolisms. Only 2 neurologic events occurred in the successfully treated patients (one from each group).
Conclusion: Transfemoral CAS with proximal balloon occlusion device achieves good results. Compared with distal filter protection, proximal balloon occlusion might be more effective in reducing cerebral embolism during CAS.
AS09-019
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
OUTCOMES FROM MECHANICAL THROMBECTOMY IN THE UNITED KINGDOM: COMPARISON OF SAFE IMPLEMENTATION OF THROMBOLYSIS IN STROKE-THROMBECTOMY REGISTRY (SITS-TBY) WITH HERMES META-ANALYSIS ENDOVASCULAR TRIALS DATA
J.S. Balami1, P. McMeekin2, P.M. White3, C. Roffe4, J. Chembala5, A. Clifton6, E. Littleton7, R. Veltkamp8, A. Dixit9, D. Flynn10, K. Halvorsrud10, C. Price11, K.R. Lees12 and G.A. Ford13
1University of Oxford and Norfolk and Norwich University Hospital NHS Trust, Centre for Evidence-Based Medicine, Oxford, United Kingdom
2Northumbria University, School of Health- Community and Education Studies, Northumbria, United Kingdom
3Newcastle University, Stroke Research Group- Institute of Neuroscience-, Newcastle, United Kingdom
4Keele University, Stroke Research in Stoke- Institute for Applied Clinical Studies-, Keele- Staffordshire, United Kingdom
5Keele University-, Stroke Research in Stoke- Institute for Applied Clinical Studies, Keele- Staffordshire, United Kingdom
6St George's University Hospitals NHS Foundation Trust, Clinical Radiology, London, United Kingdom
7Queen Elizabeth Hospital Birmingham, Neurology, Birmingham, United Kingdom
8Imperial College London, Faculty of Medicine- Department of Medicine, London, United Kingdom
9The Newcastle Upon Tyne NHS Foundation Trust, Older People's Medicine, Newcastle, United Kingdom
10Newcastle University, Institute of Health & Society, Newcastle, United Kingdom
11Newcastle University, Stroke Research Group- Institute of Neuroscience, Newcastle, United Kingdom
12University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
13Oxford University Hospitals NHS Foundation and University of Oxford, Radcliffe Department of Medicine, Oxford, United Kingdom
Background and Aims: Outcomes from new therapies in clinical practice may not match those seen in clinical trials.
To compare outcomes from mechanical thrombectomy (MT) in the United Kingdom (UK) seen in SITS-TBY registry to those in HERMES meta-analysis
Method: The SITS-TBY is a prospective observational registry of stroke patients treated with MT in routine clinical use. Outcome data contributed to the SITS-TBY registry from 19 UK centres between January 2012 and March 2016 were compared with those from HERMES.
Results: 393 patients were treated with combined IVT/MT or MT-alone in UK SITS-TBY and 634 in HERMES. The UK SITS-TBY patients were younger: median age 65 (IQR 52–75) vs 68 (57–77) years, with similar stroke severity: baseline NIHSS 16 (IQR 10–21) vs 17 (14–20). Onset-to-groin puncture time was 236-min (IQR 192–298) in UK SITS-TBY and onset-to-reperfusion was 285-min (IQR 210–362) in HERMES. Outcome data were available in 263 (67%) patients. The UK SITS-TBY cohort had similar recanalisation (TICI 2b/3) rates [65% vs 71%; p = 0.10, 90-day independent functional outcome (mRS ≤ 2) [49% vs 46%; p = 0.83] and 90-day mortality (19% vs 15%; p = 0.16). The reported rate of symptomatic intracerebral haemorrhage (sICH) was lower in UK SITS-TBY (1.3% vs 4.4% p < 0.01).
Conclusion: Outcomes reported after MT in UK routine practice were similar to randomised trials’ data but the much higher rate of missing data in this registry means interpretations drawn must be qualified. Under-reporting in practice compared with core lab reporting in RCTs probably explains the unusually low rate of sICH in UK SITS-TBY.
AS09-032
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
INTRACRANIAL ATHEROSCLEROTIC OCCLUSION ON ENDOVASCULAR REVASCULARIZATION THERAPY: ANALYSIS OF ACUTE STROKE DUE TO INTRACRANIAL ATHEROSCLEROTIC OCCLUSION AND NEUROINTERVENTION – KOREAN RETROSPECTIVE REGISTRY
Y.H. Hwang1, Y.W. Kim1, D.H. Kang2, Y.S. Kim2, J.H. Hong3, C.H. Kim4, H.W. Chang5, J.M. Hong6, S.J. Lee6, J.W. Choi7, A. Demchuk8, B. Ovbiagele9, S.I. Sohn3 and J.S. Lee6
1Kyungpook National University Hospital, Department of Neurology, Daegu, Republic of Korea
2Kyungpook National University Hospital, Department of Radiology, Daegu, Republic of Korea
3Keimyung University Dongsan Medical Center, Department of Neurology, Daegu, Republic of Korea
4Keimyung University Dongsan Medical Center, Department of Neurosurgery, Daegu, Republic of Korea
5Keimyung University Dongsan Medical Center, Department of Radiology, Daegu, Republic of Korea
6Ajou University Medical Center, Department of Neurology, Suwon, Republic of Korea
7Ajou University Medical Center, Department of Radiology, Suwon, Republic of Korea
8Hotchkiss Brain Institute, Department of Clinical Neurosciences and Radiology, Alberta, Canada
9Medical University of South Carolina, Department of Neurology, South Carolina, USA
Background and Aims: Little is known about outcome and its related features of endovascular therapy (EVT) for acute large vessel occlusion (ALVO) due to underlying intracranial atherosclerotic stenosis (ICAS). We aimed to analyze the characteristics of ICAS-related occlusions following EVT.
Method: Based on ASIAN-KR registry (n = 721), patients were included if their ALVO was in the anterior circulation and their onset-to-puncture time was less than 720 minutes. Two etiologic ELVO types (ICAS vs. embolic) were classified based on following definitions: ICAS as fixed significant (>50%) focal stenosis in the occlusion site with flow impairment or reocclusion, which could be seen during the procedure; and embolism as no significant stenosis after recanalization.
Results: The prevalence of ICAS-related occlusion was 14.1% (67 among 474 patients). Patients in the ICAS group showed some distinctive baseline characteristics compared to embolic group: younger age (63.7 vs. 68.2, years, p= 0.019), male predominance (74.6% vs. 50.9%, p< 0.001), lower NIHSS score (median 15 vs. 17, p= 0.020), more favorable ASPECTS (median 8 vs. 7, p= 0.025), and longer onset-to-puncture time (339.2 vs. 266.0, minutes, p< 0.001). The rate of successful reperfusion and major intracranial hemorrhages did not differ (mTICI 2b–3, 76.1% vs. 81.8%, p= 0.270; PH2 and/or SAH, 13.4% vs. 8.6%, 0.206). Underlying ICAS as an etiology of ALVO was associated with a lower probability of favorable outcome (3-month mRS 0–2, OR 0.438, 95% CI 0.255–0.915, p= 0.026) adjusted by well-known confounding factors.
Conclusion: Endovascular treatment for acute ICAS-related occlusions is still challenging compared to embolic occlusions. Further studies for overcoming this hurdle are warranted.
AS09-065
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
NATIONAL RESULTS OF ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE 2011–2015, DENMARK
T. Truelsen1, K. Hansen1, G. Andersen2, L. Sørensen3, C. Madsen4, A. Diaz5, T. Stavngaard6, H. Hundborg7, J. Højgaard1, N. Hjort2, H. Iversen1, S. Johnsen7 and C. Simonsen2
1Copenhagen University Hospital/Rigshospitalet, Neurology, Copenhagen, Denmark
2Aarhus University Hospital, Neurology, Aarhus, Denmark
3Aarhus University Hospital, Neuroradiology, Aarhus, Denmark
4Odense University Hospital, Neurology, Odense, Denmark
5Odense University Hospital, Neuroradiology, Odense, Denmark
6Copenhagen University Hospital/Rigshospitalet, Neuroradiology, Copenhagen, Denmark
7Aarhus University Hospital, Clinical Epidemiology, Aarhus, Denmark
Background and Aims: Endovascular treatment (EVT) of stroke patients with acute large vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of EVT in daily clinical routine is warranted.
Method: National data for Denmark (total population 5.6 million in 2013) from 2011 through 2015 on all EVT procedures in patients with acute ischemic stroke and CTA/MRA verified large vessel occlusion. Data were derived from the Danish Stroke Registry, a national clinical quality registry. Outcome (mRS) after 3 months was based on clinical examination, telephone interview, patient files, or the Danish National Registry of Deaths (DNRD). Data on time of death and cause of death were extracted from the DNRD with complete follow-up.
Results: A total of 1,016 patients were treated with an EVT procedure. The number of procedures increased from 128 in 2011 to 276 in 2015. The mean age was 67 years (range 18–96), median 69 years, and 58% males. Median NIHSS at baseline was 16 (range 0–38) and available from 73.3% (n = 745) patients. Mean and median time from symptoms onset to arrival at the angio-suite was 290 and 201 minutes, respectively. Reperfusion by mTICI score, was 0 = 14%, 1 = 2%, 2a = 4%, 2b = 29%, 3 = 44%, and unreported = 6%. The 3-months mRS (948 patients discharged before Sep30, 2015) was 0 = 9%, 1 = 18%, 2 = 16%, 3 = 10%, 4 = 14%, 5 = 5%, 6 = 13%, alive but unknown mRS = 14%; the 3-months intracranial hemorrhage proportion was 2% (n = 19).
Conclusion: Nationwide routine data on EVT in acute ischemic stroke in Denmark demonstrate that the procedure has been successfully implemented.
AS09-068
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
OUTCOME AND SAFETY OF ENDOVASCULAR TREATMENT IN DENMARK 2011–2015 APPLYING KEY INCLUSION CRITERIA FROM THE MR-CLEAN STUDY
T. Truelsen1, K. Hansen1, G. Andersen2, L. Sørensen3, C. Madsen4, A. Diaz5, T. Stavngaard6, H. Hundborg7, J. Højgaard1, N. Hjort2, H. Iversen1, S. Johnsen7 and C. Simonsen2
1Copenhagen University Hospital/Rigshospitalet, Neurology, Copenhagen, Denmark
2Aarhus University Hospital, Neurology, Aarhus, Denmark
3Aarhus University Hospital, Neuroradiology, Aarhus, Denmark
4Odense University Hospital, Neurology, Odense, Denmark
5Odense University Hospital, Neuroradiology, Odense, Denmark
6Copenhagen University Hospital/Rigshospitalet, Neuroradiology, Copenhagen, Denmark
7Aarhus University Hospital, Clinical Epidemiology, Aarhus, Denmark
Background and Aims: National data from Denmark on outcome and safety of acute endovascular treatment (EVT) of stroke patients with large vessel occlusions were collected from 2011 through 2015. Key entry criteria from the MR-CLEAN study were applied retrospectively.
Method: National data for Denmark (total population 5.6 million in 2013) from 2011 through 2015 on all EVT procedures in patients with acute ischemic stroke and CTA/MRA verified large vessel occlusion. Data were derived from the Danish Stroke Registry, a national clinical quality registry. Outcome (mRS) after 3 months was based on clinical examination, telephone interview, patient files, or the Danish National Registry of Deaths. Key inclusion criteria from the MR-CLEAN study were age ≥18 years, baseline NIHSS ≥ 2, time from symptom onset to groin puncture <6 hours, occlusion in distal intracranial carotid artery or middle/anterior (M1/M2/A1/A2) cerebral artery.
Results: During the 5 years a total of 1,016 patients were treated with an EVT procedure of which 50.5% (n = 513) met key MR-CLEAN inclusion criteria. There were 57% males (n = 293), median baseline NIHSS = 17 (range 3–29), and recanalization to TICI 2b/3 was achieved in 77% (n = 394). The 3 months mRS was (475 patients discharged before Sep30, 2015): 0 = 8%, 1 = 24%, 2 = 18%, 3 = 11%, 4 = 16%, 5 = 6%, 6 = 12%, missing data = 4%; mRS 0–2 50% vs. 32.6% in MR-CLEAN, RR = 1.54 (95%CI:1.25–1.88); the 3-months intracerebral hemorrhage proportion was 1.5% (n = 7). A total of 91% (n = 468) patients were treated with rtPA.
Conclusion: EVT of patients with acute ischemic stroke and large vessel occlusion is safe and effective and comparable to results from MR-CLEAN.
AS09-069
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
RISK FACTORS FOR SYMPTOMATIC INTRACRANIAL HEMORRHAGE AFTER ENDOVASCULAR THERAPY IN ACUTE STROKE WITH LARGE VESSEL OCCLUSION IN THE ANTERIOR CIRCULATION
J. Meyne1, L. Koch1, F. Wodarg2, J. Hensler2, A. Binder1 and O. Jansen2
1University Hospital Schleswig-Holstein, Department of Neurology, Kiel, Germany
2University Hospital Schleswig-Holstein, Department of Radiology and Neuroradiology, Kiel, Germany
Background and Aims: Symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) in acute stroke is associated with poor clinical outcome. We aimed to identify risk factors of sICH after EVT in patients with large vessel occlusion (LVO) in anterior circulation stroke.
Method: Between Jan 2010 and Sep 2016 478 patients were treated with EVT in this monocentric cohort. SICH was defined as neurological deterioration in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4.
Results: Of 476 patients 474 were analyzed in univariate analysis and 367 in multivariate regression. SICH was observed in 56 patients (11.8 %). NIHSS score on admission (16 vs. 14), ASPECT score (7 vs. 8), successful recanalization (71.4 vs. 86%), carotid artery stenting (32.1 vs. 19.8%), serum glucose (133 mg/dL vs. 116 mg/dL) and preexisting hypertension (92.6% vs. 76.7%) significantly differed between patients with and without sICH (sICH vs. No ICH each). In multivariate analysis NIHSS, TICI ≤ 2a, INR ≥ 1.7 and preexisting hypertension were predictors for sICH.
Conclusion: High NIHSS on admission, low ASPECT score, high INR and preexisting hypertension were associated with sICH after EVT in this monocentric cohort of patients with acute stroke from large vessel occlusion.
AS09-076
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
ACUTE ENDOVASCULAR TREATMENT OF CAROTID TANDEM LESIONS: STENTING OR NOT STENTING, THE NEVER ENDING STORY
C. FERNANDEZ1, E. GONZALEZ2, A. GIL2, J.J. FONDEVILA3, L. ION3, A. LUNA1, I. UGARRIZA1, T. PEREZ1, A. PINEDO4 and M. FREIJO5
Background and Aims: Several trials on endovascular treatment for ischemic stroke published in the last years have shown marked functional improvement in selected patients. Tandem lesions, occlusion or pseudo-occlusion of proximal internal carotid artery (ICA) associated with intracranial occlusion are at greater risk of developing extensive cerebral infarction and a worse clinical evolution. We analyzed the results of endovascular treatment of these lesions in our hospital.
Method: From our series of 485 patients with acute stroke treated with mechanical thrombectomy (MT), 59 (12’16%) had a tandem lesion. They were treated with a proximal carotid revascularization, performed by aspiration (5 cases), angioplasty (4) and stenting (50), depending on the nature of the proximal occlusion (thrombus/pseudo-occlusion/occlusion, respectively) followed by MT with stent retriever. The protocol for acute stenting included administration of an antiplatelet agent. Patients that showed formation of platelet aggregates half an hour after the stent placement received tirofiban.
Results: The clinical evolution was measured by the NIHSS scale in admission (15.52 ± 5.57), 24 hours after procedure (7.89 ± 6.99) and at discharge (4.18 ± 5.48). Regarding the recanalization rate, TICI3 was achieved in 37 patients (62.7%), TICI2b in 18 (30.5%) and TICI2a in 2 (3.38%). Symptomatic cerebral haemorrhage occurred in 5 (8.47%) cases. The mortality rate was 11.86%. 57.63% of the patients were independent 3 months after treatment (mRs 0–2). There were no recurrences of ipsilateral stroke.
Conclusion: The endovascular treatment of acute tandem lesions by placing stent in the proximal ICA and intracranial MT is safe and effective, with a good clinical evolution at three months of treatment.
AS09-079
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
OUT OF BOUNDS: ENDOVASCULAR TREATMENT OF STROKE BEYOND GUIDELINES IN A SINGLE CENTER EXPERIENCE
C. Perry1, I. Fragata1, C. Pinheiro1, J. Pamplona1, P. Ferreira2, J. Reis1 and A. Paiva Nunes2
1Centro Hospitalar Lisboa Central, Neuroradiology, Lisbon, Portugal
2Centro Hospitalar Lisboa Central, Unidade Cerebro-Vascular, Lisbon, Portugal
Background and Aims: Guidelines for treatment of acute large vessel occlusion (LVO) recommend mechanical thrombectomy (MT) in highly selected patients. It is unclear if patients outside reccomendations still benefit from LVO recanalization. We aimed to describe our experience with MT outside guideline reccommendations.
Method: Patients that underwent MT outside reccomendations were retrospectively selected from our prospective registry of acute stroke: admission NIHSS < 6, Alberta Stroke Program Early CT score (ASPECTS) < 6, onset to puncture time >360minutes, pre-morbid modified Rankin Scale (mRS) > 1, LVO other than distal internal carotid artery (ICA) or M1. Clinical variables and outcome were described.
Results: From 213 patients that underwent MT from January to Deceber 2016 in our center, 117 (55%) did not meet guidelines: admission NIHSS score <6 (11%), ASPECTS <6 (10%), premorbid mRS > 1 (23%), M2 occlusion (35%), posterior circulation (20%), cervical ICA occlusion (5%), symptom to groin puncture >360 min (22%). 39 (33%) subjects had more than one criterion for exclusion. Mean age was 71.6 ± 13.2, mean NIHSS was 15.9 ± 8.7, and median ASPECTS was 9 (4–10). 92.3% patients had successful recanalization (TICI 2b/3). Symptomatic intracranial hemorrhage occurred in 9.4% patients. 3-month follow-up was available in 72% patients, with 29.8% mortality and 39.3% mRS 0–2.
Conclusion: In a “real world” scenario, outcome results in patients not meeting guideline indications are comparable with the standards for outcome in MT. More than half of patients in our population would not have been treated if strict adherence to guidelines was followed. Additional studies are warranted to evaluate benefits of MT outside recommendations.
AS09-080
Scientific Communication (Oral Abstract Presentation) Neurointervention – after the trials
MECHANICAL THROMBECTOMY FOR STROKE IN THE ELDERLY
C.I. Gómez-Escalonilla1, L. Silva1, J. Carneado2, J. Díaz Guzman3, M. Moreu4, S. Rosati4, A. Vega Astudillo5, J. Campollo6, P. Simal1 and J. Egido1
1Hospital Clínico San Carlos, Neurology, Madrid, Spain
2Hospital Universitario Puerta de Hierro, Neurology, Madrid, Spain
3Hospital Universitario 12 de Octubre, Neurology, Madrid, Spain
4Hospital Clínico San Carlos, Radiology, Madrid, Spain
5Hospital Universitario Puerta de Hierro, Radiology, Madrid, Spain
6Hospital Universitario 12 de Octubre, Radiology, Madrid, Spain
Background and Aims: Endovascular revascularization has proven an effective treatment for large arteries occlusions in stroke patients, but in those older 80 year have less benefit and more mortality. We evaluate the safety and effectiveness of endovascular revascularization in stroke patients older 80 years and compare the results with younger patients.
Method: We prospectively collected since September 2013 to September 2016 to 376 consecutive patients subjected to mechanical thrombectomy. Older 80 years was 63 patients and 313 were younger.
We analyzed successful recanalization, symptomatic hemorrhagic transformation, favorable outcome and mortality in both groups.
Results: In the elderly group the median aged was 84 years (IQ 82–97) and 66 years (IQ 56–75) in the younger. There were not statistically significant differences in NIHSS median 18 (IQ 13–21) vs 18 (IQ 13–22), ASPECTS median 8 (IQ 7–10) vs 8 (IQ 7–9), successful recanalization rates 80,4% vs 73,1%, favorable outcome (modified Rankin Scale score ≤2 at 3 months) 41,3% vs 47,3%, symptomatic hemorrhagic transformation 12,7% vs 9,3% or mortality rates 22,2% vs 17,9%. There were statistically significant differences in arterial occlusion: distal M1 occlusion was more frequent in older patients (38,1% vs 19,5%, p = 0,002 Fisher exact test) and tandem occlusion in younger group (4,7% vs 18,5%, p = 0,003 Fisher exact test).
Conclusion: Our results show the safety and effectiveness of endovascular thrombectomy for large arterial occlusion in elderly patients, and supporting the use of this treatment without age restriction.
AS02-013
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
OUTCOME ANALYSIS FOR ANTIHYPERTENSIVE TREATMENT FOR ACUTE CEREBRAL HEMORRHAGE (ATACH) II TRIAL USING REPEATED SYSTOLIC BLOOD PRESSURE MEASURES
Y. Palesch1, V. Ramakrishnan2, L. Foster1, R. Martin1, W. Barsan3, C. Moy4 and A. Qureshi5
1Medical University of South Carolina, Public Health Sciences, Charleston, USA
2Medical University of South Carolina, Public Health Scineces, Charleston, USA
3University of Michigan, Neurology, Ann Arbor, USA
4National Institute of Neurological Disorders and Stroke, Office of Clinical Research, Bethesda, USA
5University of Minnesota, Neurology, Minneapolis, USA
Background and Aims: In the recently completed Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial, patients were randomly assigned to either intensive (<140 mmHg) or standard (140–180 mmHg) reduction and maintenance of systolic blood pressure (SBP). To monitor how well the targeted SBP was achieved in the two groups, maximum and minimum SBPs were measured at least once each hour from randomization through 24 hours. Considerable variability in the SBP profile was observed among the subjects. As secondary analyses, common approaches to summarize the 24-hour SBP profiles include mean SBP or area under the curve of the profile. However, these methods do not capture the within subject variability, and therefore, under-utilize information.
Method: In addition to using the mean SBP for each subject representing his/her treatment, we propose a method that incorporates the within subject variability in the treatment, i.e., we weight each subject’s contribution to the analysis model by normalized inverse of the variance of his/her SBP measurements.
Results: The table below shows the varying results of the ATACH II primary outcome analyses:
Conclusion: The weighted approach may provide additional efficiency. Variations on this approach, as well as application to other treatments (e.g., intensive glucose control, multiple infusion or dosing) also will be presented.
Treatment (adjusting for age, GCS, and IVH presence)
OR
95% CI
Intensive vs Standard (similar to the original analysis)
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
EFFICIENCY OF INTRAVENTRICULAR HEMORRHAGE REMOVAL IN THE CLOT LYSIS: EVALUATION OF ACCELERATED RESOLUTION OF INTRAVENTRICULAR HEMORRHAGE TRIAL (CLEAR III)
W. Ziai1, N. McBee1, R. Thompson2, G. Yenokyan2, J. Betz2, R. Dlugash1, K. Lane1, I. Awad3 and D. Hanley1
1Johns Hopkins Medical Institutions, Neurology, Baltimore, USA
2Johns Hopkins Medical Institutions, Biostatistics, Baltimore, USA
3University of Chicago, Neurosurgery, Chicago, USA
Background and Aims: CLEAR III was the first prospective large randomized trial testing the effectiveness of intraventricular hemorrhage (IVH) thrombolysis with alteplase (vs. saline). Although the trial was neutral on primary outcome of functional improvement, clinically important findings included low percentage of participants achieving the targeted 80% removal of IVH, and post hoc signal of benefit from greater clot removal. Factors affecting this finding require investigation.
Method: We recorded clinical and volumetric data including intracerebral hemorrhage and IVH volumes on diagnostic, stability, and end-of-treatment (EOT: 24 hours post administration of last dose of test article) CT scans. We tested for associations between IVH removal efficiency with baseline factors, and modified Rankin scale (mRS) scores at 180 days using multifactorial logistic regression models.
Results: Median [IQR] % IVH clot removal at EOT was 58% [34.7, 77.2] with a beneficial effect for alteplase vs. saline (P < 0.001). Targeted 80% IVH clot removal was achieved in 21%, with 85% and 90% removal occurring in 16% and 10.6% of subjects. IVH removal thresholds for reduction in mortality and improving day 180 mRS were 70% (hazard ratio: 0.48(0.32, 0.73) and 85% (adjusted odds ratio: 1.91(1.03, 3.55), respectively. Clinically meaningful 85% IVH volume reduction was independently associated with smaller IVH volume, younger age and placement of ventricular drainage catheters ipsilateral to dominant IVH volume, adjusting for alteplase treatment.
Conclusion: Full benefit from the CLEAR III intervention will likely require optimized positioning of ventricular drainage catheters and greater adherence to the removal of large amounts of IVH, not just relief of obstructive hydrocephalus.
AS03-025
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
INTRAVENTRICULAR HEMORRHAGE: WHO DIES AND WHY: MORTALITY REVIEW FOR THE CLOT LYSIS: EVALUATION OF ACCELERATED RESOLUTION OF INTRAVENTRICULAR HEMORRHAGE TRIAL (CLEAR III)
W. Ziai1, N. Mcbee1, J. Jallo2, C. Aldrich3, K. Lane1, R. Dlugash1, I. Awad4 and D. Hanley1
1Johns Hopkins Medical Institutions, Neurology, Baltimore, USA
2Jefferson University, Neurosurgery, Philadelphia, USA
3University of Maryland, Neurology, Baltimore, USA
4University of Chicago, Neurosurgery, Chicago, USA
Background and Aims: CLEAR III was a 500-subject, multicenter, randomized trial comparing extraventricular drainage (EVD) plus intraventricular alteplase vs. EVD plus placebo for treatment of severe intraventricular hemorrhage (IVH). Mortality for this disease ranges from 40–80%. We evaluated proximate causes of death in the acute and post-hospitalization phase and withdrawal of active treatment (WAT) decisions.
Method: We reviewed serious adverse event reports for 137 deaths within 1 year follow-up. We tested for associations between early death (<30 days) vs. later death (30-365d), and WAT with baseline factors, intracerebral hemorrhage (ICH) and IVH volumes in multifactorial logistic regression models.
Results: One year mortality was 137 (27.4%) at median [IQR] 41 [16, 97] days from symptom onset. The most common adjudicated primary causes of death were direct effects of primary hemorrhage(51%), cardiac(12%) and respiratory(12%) complications. Mechanism of death was brain death in 6%, WAT (42%), cardiac arrest (8%) and other medical complications (44%). Early death (<30d) vs. later death (30-365d) occurred in 58 (42.3%). Lower %IVH volume reduction (but not treatment assignment), and ICP >30 mmHg were independently associated with early death as were male sex, presentation GCS, and ICH volume after adjustment for WAT. Independent associations with WAT were poor neurologic grade (NIHSS, GCS), thalamic ICH, IVH volume (>20 mL), and anticoagulation at presentation, and North American site (vs. other).
Conclusion: The CLEAR III mortality rate remains below literature estimates for severe IVH. Approximately half of known causes of death are directly due to neurologic events. Reduction in IVH volume and ICP management may lower early mortality risk.
AS20-013
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
PREDICTORS OF NEUROLOGICAL DETERIORATION IN INTRACEREBRAL HAEMORRHAGE: RESULTS OF INTERIM DATA FROM THE TICH-2 TRIAL
Z. Kang Law1, K. Flaherty1, P. Scutt1, J.P. Appleton1, P.M. Bath1 and N. Sprigg1
1University of Nottingham, Stroke- division of clinical neuroscience, Nottingham, United Kingdom
Background and Aims: Neurological deterioration (ND) is a major predictor of poor outcome after intracerebral haemorrhage (ICH). Identifying predictors of ND is important in targeting treatments.
Method: Blinded data (to December 2016) from the ongoing Tranexamic acid in primary IntraCerebral Haemorrhage-2 (TICH-2) randomised controlled trial were analysed. ND was defined as an increase in National Institute of Health Stroke Scale (NIHSS) of ≥4 points or a fall in Glasgow Coma Scale (GCS) of ≥2 points from baseline or day 2 assessments. Logistic regression was used to identify predictors of ND and their effects on outcomes.
Results: From 1863 patients recruited, 556 (29.8%) had ND: 468 (84.2%) occurred within 48 hours and 88 (15.8%) between 48 hours and 7 days after randomisation. Predictors of ND included older age, male sex, higher NIHSS, lower GCS, intraventricular haemorrhage, lobar haemorrhage, higher diastolic blood pressure, antiplatelet therapy, and premorbid stroke, ischaemic heart disease and venous thromboembolism (table 1). ND was independently associated with higher 90-day mortality and worse functional outcome (table 2).
Conclusion: ND is an important outcome in acute ICH intervention trials as a surrogate marker of efficacy and safety.
AS20-030
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
TARGETING EXPANSION IN INTRACEREBRAL HEMORRHAGE: INTENSIVE BLOOD PRESSURE REDUCTION AND NON-CONTRAST CT MARKERS
A. Morotti1, G. Boulouis2, J. Romero3, B. Brouwers4, M. Jessel1, A. Vashkevich1, K. Schwab1, M.R. Afzal5, C. Cassarly6, S. Greenberg1, R. Hebert Martin6, A. Qureshi5, J. Rosand1 and J. Goldstein1
1Massachusetts General Hospital, J.P. Kistler Stroke Research Center, Boston, USA
2Université Paris Descartes- INSERM S894- DHU Neurovasc- Centre Hospitalier Sainte-Anne, Department of Neuroradiology-, Paris, France
3Massachusetts General Hospital, Neuroradiology Service- Department of Radiology-, boston, USA
4Brain Center Rudolf Magnus University Medical Center- Utrecht, Department of Neurosurgery-, Uthrectt, The Netherlands
5University of Minnesota, Zeenat Qureshi Stroke Research Center-, Minneapolis, USA
6Medical University of South Carolina, Department of Public Health Sciences-, Charleston, USA
Background and Aims: To validate various non-contrast CT (NCCT) predictors of intracerebral hemorrhage (ICH) expansion and investigate whether intensive blood pressure (BP) treatment reduces hematoma growth and improves outcome in subjects with these markers.
Method: We analyzed patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized trial. Patients were assigned to intensive (systolic BP < 140 mmHg) versus standard (systolic BP < 180 mmHg) treatment within 4.5 h from onset. The following NCCT markers were identified: intrahematoma hypodensities, black hole sign, swirl sign, blend sign, heterogeneous hematoma density and irregular shape (figure 1). ICH expansion was defined as hematoma growth > 33% and unfavorable outcome was defined as 90-days Rankin Scale > 3. Logistic regression was used to identify predictors of ICH expansion, and explore the association between NCCT signs and clinical benefit from intensive BP treatment.
Results: 989 patients were included (mean age 62, 61.9% males) of whom 186/869 experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable outcome. NCCT markers independently predicted ICH expansion (all p< 0.01) with overall accuracy ranging from 61% to 78% and good inter-rater reliability (k> 0.6 for all markers). There was no evidence of an interaction between NCCT markers and benefit from intensive BP reduction (all p> 0.10).
Conclusion: NCCT signs reliably identify subjects at high risk of ICH expansion. However, we found no evidence that patients with these markers specifically benefit from intensive BP reduction.
AS20-039
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
VERY EARLY HEMATOMA EXPANSION LIMITS EFFICACY OF HEMOSTATIC THERAPY IN THE SPOTLIGHT RANDOMIZED CONTROLLED TRIAL
F.S. Al-Ajlan1, D.J. Gladstone2, D. Song3, K.E. Thorpe4, R.H. Swartz2, K. Butcher5, M. del Campo2, D. Dowlatshahi1, H. Gensicke3, G.J. Lee3, M.L. Flaherty6, M.D. Hill3, R.I. Aviv7 and A.M. Demchuk3
1University of Ottawa, Neurology, Ottawa, Canada
2University of Toronto, Medicine Neurology, Toronto, Canada
3University of Calgary, Clinical Neurosciences, Calgary, Canada
4University of Toronto, Biostatistics, Toronto, Canada
5University of Alberta, Medicine Neurology, Edmonton, Canada
6University of Cincinnati, Neurology, Cincinnati, USA
7University of Toronto, Medical Imaging, Toronto, Canada
Background and Aims: SPOTLIGHT trial randomized CTA spot-sign positive acute ICH patients to Factor VIIa (rFVIIa) 80µg/kg or placebo within 6 h of onset aiming to limit hematoma expansion (HE). Practical delays (enrolment, consent, labs, drug preparation) to study drug administration after baseline imaging may limit efficacy of hemostatic therapy. We examined the impact of this delay on HE.
Method: We conducted blinded volumetric hematoma measurements at baseline CT; post-dose CT soon after study drug administration; 24 h CT. We compared total (ICH + IVH) volumes across the 3 CT timepoints to estimate HE occurring before vs. after study drug.
Results: 44/50 participants had all 3 CT scans. Median time (IQR) from baseline CT to study drug: 62.5 min (55,80); study drug to post-dose CT: 19 min (14.5,30). Median (IQR) total hematoma volume increased from baseline CT to post-dose CT by 10.0 ml (−0.7,18.5) (rFVIIa) vs. 5.4 ml (1.8,8.3) (placebo) (p = 0.96), and from post-dose CT to follow-up CT by 0.6 ml (−2.6, 8.3) (rFVIIa) vs. 0.7 ml (−1.6, 2.1) (placebo)(p = 0.98).
Conclusion: In SPOTLIGHT, almost all HE observed between the baseline CT and 24 h CT rapidly occurred between the baseline CT and early CT performed soon after study drug administration (and appeared completed within 3 h post-onset), limiting any possibility of a treatment effect from hemostatic therapy. Future hemostatic trials must treat ICH patients earlier from onset and eliminate delays between baseline CT and drug administration.
AS20-047
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
WHITE MATTER LESIONS INFLUENCE ON INTRACEREBRAL HEMORRHAGE EXPANSION AND FUNCTIONAL OUTCOME: A SECONDARY ANALYSIS OF MISTIE-II AND CLEAR-III
B.M. Hansen1, N. Ullman2, J. Muschelli3, B. Norrving1, R. Dlugash2, I. Awad4, M. Zuccarello5, W.C. Ziai2, D.F. Hanley2, R.E. Thompson3 and A. Lindgren1
1Lund University, Department of Clinical Sciences Lund- Neurology, Lund, Sweden
2Johns Hopkins Medical Institutions, Division of Brain Injury Outcomes, Baltimore- MD, USA
3Johns Hopkins Bloomberg School of Public Health, Department of Biostatistics, Baltimore- MD, USA
4University of Chicago, Department of Neurosurgery, Chicago- IL, USA
5University of Cincinnati, Department of Neurosurgery, Cincinnati- OH, USA
Background and Aims: Intracerebral hemorrhage (ICH) is commonly associated with white matter lesions (WML) which have been linked to poor stroke outcomes. We studied if WML affects hematoma expansion (HE) and post-stroke functional outcome.
Method: In ICH patients from the clinical trials MISTIE-II and CLEAR-III, WML-grade on the diagnostic CT scan (dCT, <24 hours after ictus) was assessed using the van Swieten scale (vSS, range 0–4). Hematoma expansion (HE) outcome was primarily defined as >33% or >6 mL ICH volume increase on the last pre-randomization CT scan (<72 hours of dCT) before active trial treatment. Secondary HE outcomes were: absolute ICH expansion, and >10.4 mL total clot volume increase. Poor 180-day functional outcome was defined as modified Rankin Scale (mRS) ≥4 with continuous mRS as a secondary end-point.
Results: Of 635 patients (median vSS 1; IQR 0–3), 55% had WML at dCT (median 2.2 hours from ictus), and 13% had subsequent HE. WML at dCT was not associated with primary or secondary HE definitions (P > 0.05) after adjustment for ICH volume, IVH volume, warfarin therapy/INR > 1.5, ictus-dCT time, age, diabetes mellitus, and thalamic ICH location. WML increased the odds for poor functional outcome (mRS ≥ 4) in univariate analyses (vSS 4; OR 4.16; 95% CI, 2.54-6.83; P < 0.001) which remained significant in multivariate analyses after adjustment for HE and other outcome risk factors, and when using mRS as a continuous ordinal scale.
Conclusion: Concomitant WML does not affect odds for hematoma expansion in ICH patients but increases the odds for poor functional outcome
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
INTENSIVE BLOOD PRESSURE LOWERING DOES NOT INCREASE RISK OF DIFFUSION WEIGHTED IMAGING HYPERINTENSE LESIONS IN INTRACEREBRAL HEMORRHAGE
A. Shoamanesh1, A. Morotti2, J.M. Romero3, J. Oliveira-Filho2, F. Schlunk2, M. Jessel2, A. Ayres2, A. Vashkevich2, K. Schwab2, K. Butcher4, L. Gioia5, M.R. Afzal6, C. Cassarly7, R.H. Martin7, A.I. Qureshi6, S.M. Greenberg2, J. Rosand8 and J.N. Goldstein9
1McMaster University / Population Health Research Institute, Medicine Neurology, Hamilton, Canada
2J. P. Kistler Stroke Research Center- Massachusetts General Hospital- Harvard Medical School, Neurology, Boston, USA
3J. P. Kistler Stroke Research Center- Massachusetts General Hospital- Harvard Medical School, Radiology, Boston, USA
4University of Alberta, Neurology, Edmonton, Canada
5Université de Montréal / CHUM, Neurology, Montréal, Canada
6Zeenat Qureshi Stroke Research Center- University of Minnesota, Neurology, Minneapolis, USA
7Medical University of South Carolina, Public Health Sciences, Charleston, USA
8J. P. Kistler Stroke Research Center- Massachusetts General Hospital- Harvard Medical School, Neurology Neurocritical Care and Emergency Neurology, Boston, USA
9J. P. Kistler Stroke Research Center- Massachusetts General Hospital- Harvard Medical School, Emergency Medicine and Neurology Neurocritical Care and Emergency Neurology, Boston, USA
Background and Aims: Associations between diffusion-weighted imaging hyperintense lesions (DWIHL) and greater degrees of blood-pressure lowering in acute intracerebral hemorrhage(aICH) have raised concerns regarding whether DWIHLs are iatrogenic. We analyzed imaging from a randomized trial of blood-pressure management to determine whether blood-pressure reduction was associated with DWIHL, and whether DWIHL are associated with worse clinical outcomes.
Method: ATACH-II was a randomized trial where 1000 aICH patients were assigned to intensive blood-pressure treatment (systolic of 110–139 mmHg) or standard treatment (140–179 mmHg). DWIHLs were rated in all participants who had MRI during hospitalization with interpretable DWI/ADC images.
Results: 187 patients had MRIs that could be evaluated for DWIHLs. DWIHLs were present in 23% of 187 patients (mean age 59 y). Black race (36% vs. 12%, p < 0.001), prior stroke/TIA(36% vs. 11%, p < 0.001), congestive heart failure(12% vs. 2%, p = 0.02), diabetes mellitus (34% vs. 18%, p = 0.03), lower glomerular filtration rate (<60; 36% vs. 20%, p = 0.03) and higher ICH volumes(>30cm3; 17% vs. 4%, p = 0.01) were overrepresented in patients with DWIHLs. There was no relationship between assignment to intensive treatment and DWIHLs(50% vs. 48%, p = 0.84). Patients with DWIHLs had a two-fold increased risk of any serious adverse event (SAE; RR 2.2, 1.2–4.1), after adjustment for age, baseline GCS, and presence of IVH. DWIHLs were not a risk factor for death/disability(1.5, 0.8–2.8), neurological deterioration within 24 h(1.3, 0.4–4.2) or hematoma expansion(1.1, 0.5–2.4). There were no interactions between DWHILs and treatment assignments for the primary outcome of death/disability.
Conclusion: DWIHLs are prevalent in aICH and predict SAEs within the first 3 months. Intensive blood-pressure lowering did not result in greater DWIHLs, suggesting alternate contributory mechanisms for DWIHL formation in aICH.
AS20-058
Scientific Communication (Oral Abstract Presentation) ICH – Acute Intervention
AGGRESSIVE BLOOD PRESSURE REDUCTION IN ACUTE INTRACEREBRAL HEMORRHAGE INCREASES ACUTE CEREBRAL ISCHEMIA WITH CLINICAL DETERIORATION
K. Uchino1, A.B. Buletko1, T. Thacker1, J. Mathew1 and J. Frontera1
1Cleveland Clinic, Cerebrovascular Center, Cleveland, USA
Background and Aims: Aggressive blood pressure reduction in acute intracerebral hemorrhage (ICH) has been associated with acute cerebral ischemia on MRI diffusion weighted sequence. We explored the consequences of institutional protocol change in systolic blood pressure (SBP) target from <160 mmHg to <140 mmHg in all acute ICH.
Method: We reviewed of primary ICH patients admitted to our institution from January 2013 through December 2014 who underwent MRI. In initial period target SBP was <160 and later period target was <140 (Group 2). Serial blood pressure measurements from admission to 72 hours were collected. Clinical deterioration was defined as any acute examination change not explained by seizure, hematoma expansion or other medical causes.
Results: Sixty-two in Group 1 and 52 in Group 2 met inclusion. Baseline clinical characteristics were similar between the 2 groups, including initial stroke severity, ICH volume, location, and admission SBP. Group 2 had lower mean SBP over the first 24 hours (Group 1: 143 mm Hg ± 11, Group 2: 134 mm Hg ± 10; p < 0.001). Group 2 had more frequent acute ischemia (Group 1: 10/62 (16%), Group 2: 18/57 (32%), p = 0.047) and more frequent clinical deterioration (Group 1: 1/62 (2%), Group 2: 11/57 (19%), p = 0.001). Among 28 with acute ischemia, 8 (29%) had clinical deterioration, whereas 4 of 91 (4%) without acute ischemia had deterioration. In multivariate analysis, acute ischemia was associated mean SBP over first 24 hours, but not ICH volume, location, leukoaraiosis, or microhemorrhage.
Conclusion: Symptomatic cerebral ischemia in acute ICH is frequent and is associated with aggressive blood pressure target.
AS08-059
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
NEUTROPHIL EXTRACELLULAR TRAPS IN THROMBI FROM PATIENTS WITH ACUTE ISCHEMIC STROKE
E. Laridan1, F. Denorme1, L. Desender1, O. François2, T. Andersson2,3, H. Deckmyn1, K. Vanhoorelbeke1 and S.F. De Meyer1
2AZ Groeninge, Department of Medical Imaging, Kortrijk, Belgium
3Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden
Background and Aims: Use of t-PA leads to dissolution of occluding ischemic stroke thrombi in some cases, but not in others. Surprisingly little is known about the exact composition of stroke thrombi. Fibrin and red blood cells are two main components. Recently, neutrophil extracellular traps (NETs) have been reported in various settings of thrombosis. This study aimed at assessing their presence in ischemic stroke thrombi.
Method: Sixty-eight thrombi from acute ischemic stroke patients were collected following thrombectomy. Besides standard H&E staining, NETs were visualized via immunohistochemistry using antibodies against citrullinated histone H3 (H3Cit), CD66b and neutrophil elastase. Extracellular DNA was visualized via DAPI. Per thrombus, H3Cit and neutrophil amount was quantified in regard to stroke etiology. Extracellular DNA was targeted by performing ex vivo lysis with DNase1 and t-PA on eight patient thrombi.
Results: Neutrophils were detected extensively throughout all thrombi with an average of 7110 ± 4067 per mm2. H3Cit, a hallmark of NETs, was observed in almost all thrombi and ranged from 0.21% to 13.45%. Fluorescent co-localization confirmed the presence of H3Cit on extracellular DNA released by neutrophils (CD66b). The majority of collected thrombi were of cardioembolic origin and showed a significantly higher amount of H3Cit compared to other etiologies (p < 0.05). The addition of DNase1 to t-PA treatment accelerated ex vivo lysis of patient stroke thrombi after two hours (p < 0.01).
Conclusion: We demonstrate the presence of neutrophils and NETs in human ischemic stroke thrombi and provide initial evidence to further investigate DNase1-based therapeutic strategies, which could improve thrombus dissolution in acute ischemic stroke.
AS12-001
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
IMAGING-GUIDED ADVANCES IN A MOUSE MODEL OF RADIOLOGICALLY SILENT TRANSIENT ISCHAEMIC ATTACK: ULTRA-SENSITIVE MOLECULAR MRI AND CONTRAST-ENHANCED MRI DISCLOSE ENDOTHELIAL DYSFUNCTIONS AND ALTERED FLUID DRAINAGE
C. Ali1, A. Quenault1, M. Gauberti1, S. Martinez de Lizarrondo1, O. Etard2, C. Orset1, H. Segal3, P. Rothwell3, E. Touzé1 and D. Vivien1
1INSERM U1237 PhIND, Université Caen Normandie – Cyceron, Caen, France
2CHU de Caen, Laboratoire des Explorations Fonctionnelles du Système Nerveux, Caen, France
3Stroke Prevention Research Unit- Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom
Background and Aims: Transient ischemic attack (TIA) is a warning sign of stroke, a major cause of death and dependency. A rapid identification of TIA is thus critical for the initiation of efficient secondary prevention of stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of specific test. Current conventional practice could thus benefit from new image-based evidence, in particular for radiologically silent cases (corresponding to the recommended tissue-based definition of TIA). The aim of this study was to investigate if new MRI modalities could improve the diagnosis and knowledge of TIA.
Method: In a mouse model of TIA, we developed ultra-sensitive MRI using antibody-based microparticles of iron oxide targeting P-selectin to detect cerebrovascular inflammation and contrast-enhanced MRI to investigate in vivo the drainage of extracellular fluids (also called perfusion of the glymphatic system) after minimally invasive injection of a gadolinium chelate in the cisterna magna.
Results: We show that while T2 and DWI sequences detect no brain infarction: i/ ultra-sensitive MRI of P-Selectin unmasks activated endothelial cells after experimental TIA and allows discriminating TIA from epilepsy and migraine, two important mimics and ii/ contrast-enhanced MRI reveals that TIA impairs the drainage of brain extracellular fluids.
Conclusion: These preclinical findings might improve the diagnosis of TIA and bring insights into our knowledge of post-TIA functional sequels.
AS12-028
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
NOVEL THERANOSTIC PROTOCELLS FOR INTRACEREBRAL HEMORRHAGE
H.G. Jeong1, B.G. Cha2, D.W. Kang1, M.J. Nam2, C.K. Kim3, D.Y. Kim1, S.K. Ki1, J. Kim2 and S.H. Lee1
1Seoul national university hospital, Neurology, Seoul, Republic of Korea
2Sungkyunkwan University, Chemical Engineering, Suwon, Republic of Korea
3Korea University Guro Hospital and Korea University College of Medicine, Neurology, Seoul, Republic of Korea
Background and Aims: Theranostics is an emerging concept of integrating therapy and imaging into a single platform. Specific treatment for intracerebral hemorrhage (ICH) has not been established, and secondary brain injury is a promising target of theranostics. We developed a novel theranostic protocells loaded with cerium oxide nanoparticles (CeNPs) for treatment and iron-oxide nanoparticles (FeNPs) for imaging.
Method: We synthesized 100-nm mesoporous silica nanoparticle (MSN) as a bio-compatiable nanocarrier, incorporated FeNPs in the core and CeNPs on the surface, and encapsulated MSN with lipid bilayer. Reactive oxygen species (ROS) scavenging and cytoprotective effects were assessed in vitro. Brain water content, macrophage infiltration, and behavior function were measured in vivo ICH model. Serial brain MR imaging was performed to confirm diagnostic ability of working site of protocells.
Results: Our synthesized protocells were monodisperse in water and highly loaded with CeNPs, which exhibited a strong ROS scavenging (−26%, P < 0.05) and cytoprotective effects (−51%, P < 0.01). Our protocells reduced macrophage infiltration (−58%, P < 0.01) and brain edema (−1% water content, P < 0.01) and improved neurologic outcome (+15% corner turn, P < 0.05). In serial T2-weighted MR imaging, our protocells that reached peri-hematomal area were clearly visualized.
Conclusion: As the first theranostic nanobiomaterial, our protocells could visualize its working site in peri-hematomal area by MR imaging, and improve inflammatory status and neurologic outcome after ICH. We are preparing for the next step of clinical application.
AS12-037
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
THROMBUS NEUTROPHIL EXTRACELLULAR TRAPS BURDEN IN THROMBI RETRIEVED DURING ENDOVASCULAR THERAPY ARE RESPONSIBLE FOR T-PA INDUCED THROMBOLYSIS RESISTANCE
C. Ducroux1, J.P. Desilles2, S. Loyau1, V. Ollivier1, W. Boisseau2, R. Blanc2, H. Redjem2, G. Ciccio2, S. Smajda2, R. Fahed2, J.B. Michel1, M. Piotin2, B. Ho-Tin-Noe1 and M. Mazighi2
1INSERM UMRS 1148, Team 1- Biology of atherothrombosis, Paris, France
2Rothschild Foundation hospital, Interventional Neuroradiology Department, Paris, France
Background and Aims: Neutrophil extracellular traps (NETs) have been recently identified as major triggers and structural factors of various forms of thrombosis. NETs are extracellular webs primarily composed of DNA from neutrophils. Recently, a study designated extracellular DNA threads from NETs as a potential therapeutic target for increasing the efficacy of t-PA-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the impact of NETs burden in thrombi retrieved during endovascular therapy in acute ischemic stroke (AIS) patients on t-PA induced thrombolysis, clinical outcome and AIS etiologies.
Method: We analyzed thrombi from 150 patients with AIS treated with endovascular therapy. Thrombi were characterized by HE staining, immunostaining and enzymatic assays.
Results: Histologic analysis revealed that NETs contributed to the scaffold of the majority of thrombi especially in their superficial layers. In vitro endonuclease treatment of thrombi revealed an important release in the supernatant of free DNA (p < 0.001) and neutrophil elastase (p < 0.001) reflecting a quantitative thrombus NETs burden. Thrombus NETs burden was not correlated with clinical outcome or AIS etiology. Recombinant deoxyribonuclease 1 (DNAse 1) accelerated the t-PA-induced thrombolysis in in vitro lysis assays (p = 0.02) whereas t-PA or DNAse 1 alone was both ineffective to induce a significant thrombolysis of these thrombi.
Conclusion: This study suggests that NETs in AIS thrombi could participate to the t-PA induced thrombolysis resistance independently of their etiology and localization. The efficacy of a strategy involving a co-administration of DNAse 1 in addition to t-PA to accelerate AIS thrombus fibrinolysis needs to be explored.
AS12-064
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
NEURONAL PROTHROMBIN MEDIATES ASTROCYTE ACTIVATED EARLY PROTECTIVE RESPONSE VIA PROTEASE-ACTIVATED RECEPTORS (PAR-1) IN ISCHEMIA
P.S. Rajput1, J. Lamb1, S. Kothari1 and P. Lyden1
1Cedars-Sinai Medical Center, Neurology, Los Angeles, USA
Background and Aims: Astrocytes protect neurons during cerebral injury through several postulated mechanisms. The signaling mechanism that activates astrocytes could be the injury if the insult is sub-lethal, or adjacent neurons could signal astrocytes to initiate protective functions. Our previous studies have shown that neurons contain prothrombin (FII) gene and transcribed protein. We hypothesized a signaling role of prothrombin from injured neurons in ischemia.
Method: We used invivo and invitro techniques to determine the role of neuronal prothrombin. Oxygen glucose deprivation experiments were performed in primary neuronal cultures isolated from rats and neuronal prothrombin knockout mice. The effect of released thrombin in media was studied on primary astrocytes cultures from rats, wild type mice and PAR-1 knockout mice. Conditional prothrombin knockout, PAR-1 knockout and wild type mice were subjected to middle cerebral occlusion to study the effect on astrocytes activation and infarct volume.
Results: Our studies demonstrated that stressed neurons secrete thrombin into the culture media; and causes astrocyte activation; such astrocyte activation can be reproduced with low doses of thrombin; and is blocked by either thrombin inhibitor or by knocking down or knocking out PAR-1 from the astrocytes. In animal studies neuronal prothrombin knockout, the region of MCAo induced infarction significantly enlarged and reduction of astrocyte activation in the ischemic bed and was partially restored by Lentivirus mediated prothrombin gene restoration.
Conclusion: Taken together, these results suggest thrombin constitutes a necessary and sufficient signal from neurons to activate adjacent astrocytes in a PAR-1 dependent manner.
AS12-068
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITORS ARE ALTERED IN CERVICOCEREBRAL ARTERY DISSECTION – RESULTS OF A PROSPECTIVE MULTICENTER STUDY ON INFLAMMATORY BIOMARKERS
B. Goeggel Simonetti1, D. Grandgirard2, S. Jung1, S. Franziska2, U. Fischer1, L. Bonati3, H. Sarikaya1, G.M. De Marchis3, P. Lyrer3, J. Gralla4, C. Traenka3, A. Pellaton5, R. Sztajzel6, S. Engelter3, S. Leib2 and M. Arnold1
1University Hospital of Berne, Neurology, Berne, Switzerland
2University of Bern, Institute for Infectious Diseases, Bern, Switzerland
Background and Aims: Spontaneous cervicocerebral artery dissection (CAD) is one of the most frequent causes of stroke in young adults. CAD is often preceded by an unspecific infection suggesting an inflammatory pathway in the pathogenesis of CAD, which remains widely unknown. This study aims to get further insight into the inflammatory process underlying CAD by analyzing inflammatory blood biomarkers.
Method: Prospective multicenter case-control-study including consecutive CAD-patients, control patients with an ischemic cerebrovascular event and healthy controls. Peripheral blood samples were drawn at diagnosis and 6 months after the event in order to assess inflammatory markers including the matrix-metalloproteinases (MMP) and their tissue inhibitors of matrix-metalloproteinases (TIMP).
Results: We included 267 patients with CAD, 210 with ischemic events and 184 healthy controls. During the acute phase, CAD-patients had lower MMP2-, and TIMP2-levels, and higher MMP9/TIMP2-ratios compared to both control groups. Compared with healthy controls, CAD-patients had higher concentrations of TIMP4 (p < 0.001) which may play a role in endothelial remodeling. The same was also observed for MMP-9. At 6 months, CAD-patients had lower levels of MMP-2 and TIMP2 (p < 0.001) than the healthy controls, whereas other biomarkers did not differ any more between CAD patients and controls.
Conclusion: Inflammation and particularly degradation of extracellular matrix by proteinases and their interplay with the inhibiting TIMPs seems to be involved in the pathogenesis of acute CAD. Moreover, the consistently low levels of TIMP2 in CAD-patients may point towards an underlying predisposition and vulnerability and provide the pathophysiologic basis for novel diagnostic and therapeutic approaches.
AS14-029
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
REDUCED PLASMA LEVELS OF NEURAL CELL ADHESION MOLECULE ARE ASSOCIATED WITH EARLY SEIZURES IN STROKE PATIENTS
A. Bustamante1, T. García-Berrocoso1, E. López-Cancio2, P. Cardona3, N. Giannini4, M. Millán2, M. Garces5, D. Cánovas6, L. Abraira7, E. Santamarina7, X. Ustrell8, E. Baldrich9, M. Rubiera7, J. Álvarez-Sabín7, J. Serena10, A. Dávalos2 and J. Montaner1
1Institut de Recerca- Hospital Universitari Vall d'Hebron- Universitat Auntónoma, Neurovascular Research Laboratory, Barcelona, Spain
2Hospital Universitario Germans Trias i Pujol, Department of Neurosciences- Stroke Unit, Badalona- Barcelona, Spain
3Hospital Universitari de Bellvitge, Stroke Unit, Barcelona, Spain
4Neurological Clinic- University of Pisa, Department of Experimental and Clinical Medicine, Pisa, Italy
5Hospital Universitari Verge de la Cinta, Stroke Unit, Tortosa, Spain
6Hospital Parc Taulí, Department of Neurology, Sabadell, Spain
7Hospital Universitari Vall d'Hebron, Department of Neurology, Barcelona, Spain
8Hospital Universitari Joan XXIII, Stroke Unit, Tarragona, Spain
9Institut de Recerca- Hospital Universitari Vall d'Hebron- Universitat Auntónoma, Molecular Biology and Biochemistry Research Center for Nanomedicine, Barcelona, Spain
10Hospital Universitari Josep Trueta, Stroke Unit, Girona, Spain
Background and Aims: No biomarker has been associated so far with the development of epilepsy or early seizures in stroke patients. Low levels of neural cell adhesion molecule (NCAM) have been found in cerebrospinal fluid of epileptic patients. We aimed to investigate whether plasma levels of NCAM could predict early seizures in stroke patients.
Method: From August-2012 to November-2013, patients with suspected stroke within the first 6 hours after symptom onset were enrolled at the emergency departments of six Hospitals in Catalonia. Blood samples were collected at admission, to measure a panel of 21 biomarkers related with stroke. Information about seizures was collected during hospital stay. Independent predictors of seizures were determined by logistic regression analysis.
Results: After exclusion of stroke-mimics, 590 stroke patients (494 ischemic and 96 hemorrhagic) were included. Of them, 17 patients presented early seizures during hospital admission (2.9%). Higher baseline NIHSS (16 (11–18) vs. 7 (3–16), p = 0.004), hemorrhagic etiology (7.3% vs. 2.0%, p = 0.012) and lower standardized levels of plasma baseline NCAM (0.027 (0.021–0.031) vs. 0.029 (0.025–0.038), p = 0.030) were related with early seizures. In logistic regression analysis, NCAM standardized levels < 0.0273 were independent predictors of the occurrence of early seizures (OR = 4.39 (1.45–13.25), p = 0.009) together with baseline NIHSS (OR = 1.09 (1.01–1.17), p = 0.024).
Conclusion: In the present study, low levels of plasma NCAM were related with the occurrence of early seizures. Measurement of NCAM might be useful to indicate closer monitoring in patients at risk. Future studies with larger follow-up periods will establish the role of NCAM in the prediction of post stroke-epilepsy.
AS15-003
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
LYMPHOCYTES PREVENT HEMORRHAGIC TRANSFORMATION IN SEVERE ISCHEMIC STROKE
A. Salas-Perdomo1, F. Miró-Mur2, X. Urra3, C. Justicia1, Y. Zhao3, V. Brait2, S. Rudilosso3, Á. Chamorro3 and A.M. Planas4
1Institut d’Investigacions Biomèdiques de Barcelona, Department of Brain Ischemia and Neurodegeneration, Barcelona, Spain
2Institut d’Investigacions Biomèdiques August Pi i Sunyer, Neurosciences, Barcelona, Spain
3Hospital Clínic- Barcelona, Functional Unit of Cerebrovascular Diseases, Barcelona, Spain
4Institut d'Investigacions Biomèdiques de Barcelona, Department of Brain Ischemia and Neurodegeneration, Barcelona, Spain
Background and Aims: Hemorrhagic transformation is frequent after severe ischemic stroke. Blood cells, in particular, high neutrophil to lymphocyte ratio, have been related to symptomatic intracerebral hemorrhage (sICH) following intravenous thrombolysis, probably due to damaging effects on the endothelium and blood-brain-barrier. We investigated the effects of lymphocytes in hemorrhagic transformation after cerebral ischemia/reperfusion using a translational approach.
Method: We evaluated 271 patients treated with mechanical thrombectomy and studied C57BL/6 J mice after intraluminal middle cerebral artery occlusion followed by reperfusion. In patients, lymphopenia was defined as <1000 cells/µL, thrombocytopenia as <100000 cells/µL, and sICH according to ECASS-II criteria. A group of mice was depleted of platelets and we used lymphocyte-deficient Rag2−/− mice in diverse studies aimed to investigate hemorrhagic transformation (n = 397).
Results: The proportion of patients with lymphopenia increased from 12.5% at baseline to 24% at 24 h. The rate of sICH increased in patients with lymphopenia and thrombocytopenia, and the relationship with lymphopenia remained significant in adjusted models (OR 6.28). In mice, hemorrhagic transformation occurred at reperfusion following severe, but not mild, ischemia. Platelet depletion increased the amount of blood in the brain parenchyma. Hemorrhagic transformation increased in Rag2−/− mice and was associated with impaired endothelial integrity, higher neutrophil infiltration, metalloproteinase activation, blood-brain-barrier breakdown and reduced accumulation of subendothelial platelet aggregates. Adoptive transfer of T cells to lymphocyte-deficient mice prevented these effects.
Conclusion: Lymphopenia predisposes to hemorrhagic transformation following ischemic stroke in mice and humans. As lymphopenia is frequent in patients with severe stroke, unraveling the mechanisms by which lymphocytes prevent hemorrhagic complications has important therapeutic implications.
AS18-044
Scientific Communication (Oral Abstract Presentation) Experimental & Translational
HEADS AND TAILS OF NATRIURETIC PEPTIDES: NEUROPROTECTIVE ROLE OF BRAIN NATRIURETIC
R. Iglesias-Rey1, I. López-Dequidt1, I. López-Loureiro1, A. Vieites Prado1, T. Sobrino1, M. Rodríguez-Yáñez1, F. Campos1 and J. Castillo1
1Hospital Clínico Universitario-Clinical Neurosciences Research Laboratory, Neurology, A Coruña-Santiago de Compostel, Spain
Background and Aims: Besides of the relevant role of B-type Natriuretic Peptide (BNP) as biomarker in stroke diagnosis, new experimental evidences suggest that this peptide may mediate neuroprotective effects in cerebral ischemia. However, clinical studies about the protective effect of BNP in stroke have not been performed so far. Our aim was to evaluate, for first time, the clinical association between BNP (by means of NT-proBNP analysis) and outcome variables in ischemic stroke patients.
Method: A study with 610 patients from a prospective stroke registry was performed. NT-proBNP concentration was analyzed within the first 12 hours from stroke onset. Primary predictor variable was functional outcome evaluated by modified Rankin Scale (mRS) at 3 months.
Results: Cardioembolic strokes presented a positive correlation between NT-proBNP concentration and mRS at 3 months (Spearman's coefficient = 0.577, p< 0.0001), however non-cardioembolic strokes presented a negative correlation (Spearman's coefficient = −0.486, p< 0.0001). ROC curves showed that concentration ≥340 pg/mL of NT-proBNP predict a cardioembolic stroke (area under the curve: 0.903; 95% CI: 0.815–0,971; p< 0.0001). In the logistic regression analysis, non-cardioembolic strokes with concentrations of NT-proBNP ≥ 340 pg/mL were independently associated with good outcome (OR: 3.45; 95% CI: 2.12 – 5.62; p< 0.0001).
Conclusion: The clinical evidences observed in this study regarding BNP support the potential role of NPs as a new source of neuroprotective treatments.
AS03-023
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
PARIETAL OPERCULUM AND MOTOR CORTEX ACTIVITIES PREDICT MOTOR RECOVERY IN MODERATE TO SEVERE STROKE (ON BEHALF OF ISIS-HERMES STUDY GROUP)
F.F. Hannanu1, O. Detante2, M. Hommel3, O. Heck4, A. Krainik4, A. Thuriot2, F. Renard1, L. Lamalle5, T. Zeffiro6 and A. Jaillard3
1University Grenoble Alpes, AGEIS, Grenoble, France
2CHU Grenoble Alpes, Stroke Unit, Grenoble, France
3CHU Grenoble Alpes, Research Pole, Grenoble, France
4CHU Grenoble Alpes, Neuroradiology, Grenoble, France
5INSERM, IRMaGe, Grenoble, France
6Neurometrika, Neuroimaging, Potomac, USA
Background and Aims: Objectives: We used functional MRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke and 2) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later.
Method: We used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction.
Results: During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional primary motor (MI), premotor and supplementary motor areas (SMA) and contralesional cerebellum and 2) higher activity in contralesional MI and parietal operculum OP1-OP4. Using multiple regression, we found that baseline motor-FMS, activity in ipsilesional-MI, putamen and ipsilesional-OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p < 0.001). When baseline motor-FMS was removed, ipsilesional-MI, ipsilesional-thalamus, contralesional-mid-cingulum, contralesional-OP4 and ipsilesional-OP1, predicted better motor outcome (djusted-R2 = 0.96; bootstrap p < 0.001).
Conclusion: Functional MRI predicted excellent clinical recovery prediction and id better than baseline motor-FMS. Furthermore, fMRI may provide reliable biomarkers for assessing new therapies in clinical trial contexts.
AS14-020
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
METABOLOMIC PROFILING IN CADASIL
F. Moreton1, N. Rankin2, G. Blackburn2, A. Welch3, K. Burgess2, K.W. Muir1 and C. Delles4
1University of Glasgow, Institute of Neuroscience & Psychology, Glasgow, United Kingdom
2University of Glasgow, Glasgow Polyomics Facility, Glasgow, United Kingdom
3NHS Greater Glasgow and Clyde, Stroke Research, Glasgow, United Kingdom
4University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
Background and Aims: Vascular dysfunction in CADASIL results from accumulation of abnormal extracellular NOTCH3 protein, but the pathophysiology is not fully elucidated. MR spectroscopy identified altered cerebral metabolism but obtaining brain tissue is difficult and mouse models may not recapitulate human disease. Metabolomics allows the analysis of samples from patients to explore the interactions occurring in biochemical networks, and provide insight into disease mechanisms.
Method: 22 patients with a genetic diagnosis of CADASIL (median age 53 years, range 26–67) were compared to 22 controls (52years, 29–63) without a history of stroke, dementia, vascular or renal disease. Medical history, demographics and cardiovascular risk factors were documented. Metabolomics was performed on extracted serum samples using HILIC chromatography on a ZIC-pHILIC column connected to an Exactive mass spectrometer.
Results: Quantitative information was obtained on 549 annotated metabolites. Using principal component analysis a clear separation was observed between CADASIL cases and controls (Figure 1). Differences between the groups were mainly due to changes in putatively identified metabolites in histidine, purine and glycerophospholipid pathways. For example the concentration of adenosine, which may be protective against ischaemia in white matter, was increased in patients with CADASIL.
Conclusion: To our knowledge, this is the first study to explore circulating metabolites in CADASIL versus healthy controls. Identified differences may offer pathophysiological insights, and the opportunity to identify markers of disease severity and progression.
AS14-023
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
NON-TARGETED SERUM METABOLOMICS AFTER HUMAN ISCHEMIC STROKE IDENTIFIES ACUTELY ELEVATED 2-AMINOBUTYRIC ACID AND PREGNENOLONE SULFATE
S. Tiedt1,2, S. Brandmaier3,4, I. Stoycheva1, V. Kautzky1, R. Wang-Sattler3,4, C. Gieger3,4 and M. Dichgans1,5
1Institute for Stroke and Dementia Research, Klinikum der Universität München- Ludwig-Maximilians-Universität LMU, München, Germany
2Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität LMU, Munich, Germany
3Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany
4Institute of Epidemiology II, Helmholtz Zentrum München, Munich, Germany
5Munich Cluster for Systems Neurology, SyNergy, Munich, Germany
Background and Aims: Currently, no blood biomarker supports the diagnosis of ischemic stroke (IS) in daily clinical practice. Being downstream of genetic, transcriptomic, proteomic and environmental variation, metabolites provide the most integrated and dynamic measure of phenotype and medical condition. We thus set out to identify metabolites associated with acute human IS.
Method: Serum samples of 75 IS patients were collected at hospital arrival (time from symptom onset to hospital arrival: 7.0 ± 6.6 hours), day 2 and day 90 (n = 33) as well as from 73 healthy controls. A ultra-high performance liquid chromatography/mass spectrometry platform (UPLC-MS/MS2) was used to perform non-targeted metabolomic profiling. Three different adjustment models (including age, sex, laboratory values and medication) were applied for multivariate analysis.
Results: Among 420 identified metabolites, 35 metabolites showed differential levels in all three models. Aside from known changes of metabolites after IS like the elevation of cortisol (p = 7.7x10−8) we identified acute upregulation of the excitatory neurosteroid pregnenolone sulfate (p = 4.8x10−5) and of 2-aminobutyric acid (p = 4.7x10−6), a metabolite involved in glutathione homeostasis. Plotting levels with the exact time since symptom onset revealed opposing trends: while pregnenolone sulfate showed an early peak with a subsequent decrease up to day 2 (r = −0.30, p = 0.0003), 2-aminobutyric acid increased up to day 2 (r = 0.56, p < 0.0001). Levels of both metabolites returned to control levels at day 90 after IS. 2-aminobutyric acid was also associated with infarct volume (r = 0.31, p = 0.04).
Conclusion: We identified a dynamic pattern of pregnenolone sulfate and 2-aminobutyric acid after human ischemic stroke. Replication in independent samples is underway.
AS15-012
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
INTERNAL CAROTID ARTERY DISSECTION IS ASSOCIATED WITH LONGER STYLOID PROCESS AND SHORTER STYLOID PROCESS – INTERNAL CAROTID ARTERY DISTANCE
J.M. Amorim1, D. Pereira2, M. Rodrigues3, J. Coelho4, M. Lopes5, A. Cunha3, S. Figueiredo6, M. Pinto2, C. Ferreira5, J. Sargento-Freitas4, S. Castro3 and J. Pinho5
1Hospital de Braga, Neuroradiology, Braga, Portugal
2Centro Hospitalar Universitário de Coimbra, Neuroradiology, Coimbra, Portugal
3Centro Hospitalar de Vila Nova de Gaia / Espinho, Neuroradiology, Vila Nova de Gaia, Portugal
4Centro Hospitalar Universitário de Coimbra, Neurology, Coimbra, Portugal
5Hospital de Braga, Neurology, Braga, Portugal
6Centro Hospitalar de Vila Nova de Gaia / Espinho, Neurology, Vila Nova de Gaia, Portugal
Background and Aims: Pathophysiology of internal carotid artery dissection (ICAD) is complex, despite the existence of several well known genetic and environmental factors which may predispose to or cause dissection. Our goal was to study the association of ICAD with morphological characteristics of the styloid process (SP).
Method: Multicentre retrospective case-control study of patients with ICAD and age- and sex-matched controls with ischemic stroke without dissection who performed cervical and cerebral angioCT. AngioCT images were reviewed by 2 independent observers and styloid process length and the shorter SP-ICA distance were measured.
Results: We included 62 patients with ICAD (65 arteries with dissection) and 70 controls. No difference in age, sex or admission NIHSS was found. Interobserver agreement was good for SP length and SP-ICA distance. SP ipsilateral to dissection were longer than left and right SP in controls (35.8 ± 14.4 mm Vs 30.4 ± 8.9 mm and 30.3 ± 8.2 mm, p = 0.011 and p = 0.008, respectively). SP-ICA distance ipsilateral to dissection was shorter than the left and right SP-ICA distance in controls (6.3 ± 1.9 mm Vs 7.2 ± 2.1 and 7.0 ± 2.3, p = 0.003 and p = 0.026, respectively). ROC curves analyses showed optimal trade-off for a SP length >30.1 mm and SP-ICA distance ≤6.7 mm, which were associated with increased odds of ICAD (OR = 2.7, 95%CI = 1.35–5.42 and OR = 3.63, 95%CI = 1.77–7.44, respectively).
Conclusion: The association of ICAD with longer SP and shorter SP-ICA distance suggests a possible contribution of the anatomical characteristics of SP to the pathophysiology of ICAD.
AS16-065
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
PLAQUE INFLAMMATION IMAGING IS USEFUL IN PREDICTING RECURRENT CEREBRAL ISCHEMIA IN CAROTID STENOSIS
V. Sharma1, P. Paliwal2, B.P. Chan2, H.L. Teoh2, E.Y. Ting3 and A. Sinha4
1National University of Singapore, Neurology, Singapore, Singapore
2National University Health System, Neurology, Singapore, Singapore
3National University Health System, Diagnostic Imaging, Singapore, Singapore
4National University of Singapore, Diagnostic Imaging, Singapore, Singapore
Background and Aims: Symptomatic carotid stenosis is associated with increased risk of stroke recurrence. Severity of ttenosis explains only the cerebral ischemic mechanism of regional hypoperfusion. Plaque inflammation, the initiating event for plaque rupture and thromboembolism (artery-to-artery embolism), is not evaluated routinely. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging in stroke recurrence patients with recently symptomatic carotid stenosis.
Method: This prospective study included patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as standardized uptake values (SUV, g/ml). Ratio of T1 hyperintensity of plaque to ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed images. Patients were followed for stroke recurrence within 90-days. Embolic potential of carotid plaque was estimated by presence of spontaneous microembolic signals (MES) on transcranial Doppler monitoring.
Results: of the Forty-six recruited patients, 9 (19.6%) developed recurrent ischemic event in same vascular territory within 90-days. Compared to patients without subsequent cerebral ischemia, patients with recurrent events showed higher mean T1 carotid-SCM ratio (2.78 versus 1.43; p < 0.0001) on HR-MRI and higher mean SUV value on FDG-PET (3.18 g/ml versus 1.44 g/ml; p < 0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.929, 95%CI 1.920–6.14; p < 0.0001), higher mean SUV on FDG-PET (OR 4.602, 95%CI 43.682–21.426; p = 0.005) and MES on TCD (OR 2.248, 95%CI 1.372–32.041; p = 0.014) were independent predictors of recurrent cerebral ischemia.
Conclusion: FDG-PET/CT and HR-MRI imaging of carotid stenosis help in identifying patients at higher risk of cerebral ischemia and may aid in better therapeutic decision-making.
AS23-014
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
INCREASED PLATELET ACTIVATION IN MICRO-EMBOLI NEGATIVE RECENTLY SYMPTOMATIC VERSUS ASYMPTOMATIC CAROTID STENOSIS: RESULTS FROM THE HAEMOSTASIS IN CAROTID STENOSIS (HEIST) STUDY
S. Murphy1, S.T. Lim1, J. Kinsella2, C. Coughlan1, S. Tierney3, B. Egan3, M. Feeley3, S. Murphy4, R. Walsh1, R. Collins5, T. Coughlan5, D. O'Neill5, J. Harbison6, P. Madhavan7, S. O'Neill7, M.P. Colgan7, D. Cox8, N. Moran8, G. Hamilton9 and D. McCabe1
1The Adelaide and Meath Hospital, Neurology, Dublin, Ireland
2St Vincent’s University Hospital, Neurology, Dublin, Ireland
3The Adelaide and Meath Hospital, Vascular Surgery, Dublin, Ireland
4The Adelaide and Meath Hospital, Academic Unit of Neurology, Dublin, Ireland
5The Adelaide and Meath Hospital, Age-Related Health Care, Dublin, Ireland
6St James Hospital, Medicine for the Elderly/Stroke Service, Dublin, Ireland
7St James Hospital, Vascular Surgery, Dublin, Ireland
8Royal College of Surgeons in Ireland, Molecular and Cellular Therapeutics, Dublin, Ireland
9Royal Free Hampstead NHS Trust, University Department of Surgery, London, United Kingdom
Background and Aims: Cerebral micro-embolic signals (MES) predict stroke risk in carotid stenosis patients. The mechanisms responsible for the higher stroke risk in symptomatic vs. asymptomatic MES + ve and MES-ve patients are not fully understood, but excessive platelet activation could play a role (J Thromb Haemost 2013;11:1407–16).
Method: A prospective, multi-centre, observational analytical study was performed to compare MES-status, platelet counts/parameters and platelet activation status in early-phase (≤4 weeks after TIA/stroke) and late-phase (≥3 months) symptomatic versus asymptomatic moderate-severe (≥50-99%) carotid stenosis patients. Platelet surface activation marker expression (CD62P and CD63) and leucocyte-platelet complexes were quantified with whole-blood flow cytometry. Bilateral, 1-hour simultaneous transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES +ve or -ve. Multiple linear regression analysis controlled for the potential influence of independent variables on observed differences between groups.
Results: Comprehensive TCD data were available in 35 early-phase symptomatic, 30 late-phase symptomatic and 28 asymptomatic patients. 28.6% of early symptomatic (P = 0.049) and 6.7%; (P = 0.996) of late symptomatic patients vs 7.1% of asymptomatic patients were MES + ve. There were no significant differences in platelet counts, mean platelet volume, %CD62P or %CD63 expression between early or late symptomatic vs. asymptomatic MES + ve or MES-ve patients (P > 0.05). However, the % lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic MES-ve patients (2.7% vs. 2.17%; P = 0.035).
Conclusion: Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-ve patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, combined with TCD, could aid risk-stratification in carotid stenosis.
AS23-022
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
JUXTALUMINAL ECHODENSITY AS AN INDEX OF CAROTID PLAQUE BEHAVIOUR
T. Tegos1, G. Stefanou1, C. Xerras1, K. Notas1, A. Papadimitriou1 and A. Orologas1
1AHEPA University Hospital, A Neurology Department, Thessaloniki, Greece
Background and Aims: Previous studies suggested that symptomatic carotid plaques are echolucent on ultrasound, whereas asymptomatic ones are echogenic. The aim of this study was to determine whether juxtaluminal plaque echodensity constitutes a better discriminator of the symptomatic and asymptomatic status, as compared to global plaque echodensity.
Method: Analysis included imaging by duplex of 150 carotid plaques of more than 50% stenosis (108 patients, 61 symptomatic and 89 asymptomatic plaques), capturing, digitisation and normalisation in a computer. The global(100%) plaque Grey Scale Median (GSM100) was evaluated semi-automatically to distinguish dark (low GSM) from bright (high GSM) plaques. Subsequently, in the same software the juxtaluminal 10%, 25%, 50% plaque area GSM (GSM10, GSM25, GSM50) were automatically calculated.
Results: Symptomatic plaques were associated with median GSM100 of 13 whereas the asymptomatic ones of 39 (p = 0.0001). The corresponding values for the median GSM10, GSM25, GSM50 were: (1,3,3) for symptomatic plaques and (32,35,40) for asymptomatic ones respectively (p = 0.0001). ROC curves failed to demonstrate a more adequate ability of GSM10, GSM25 and GSM50 over GSM100 in separating the symptomatic from the asymptomatic plaques, although a statistical trend was reached (difference between areas: 0.031, 0.022, 0.032, p > 0.05). Median stenosis for the symptomatic plaques was 80% and for the asymptomatic ones 65 %(p = 0.0001).
Conclusion: Our results suggested that juxtaluminal plaque echodensity failed to prove as a more adequate index, compared with global plaque echodensity, in the separation of symptomatic and asymptomatic carotid plaques. Larger studies are needed.
AS26-011
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
NEUROFILAMENT LIGHT CHAIN AS A SERUM MARKER FOR CEREBRAL SMALL VESSEL DISEASE
M. Konieczny1
1Institute for stroke and dementia ISD, Klinikum der Universität München, Munich, Germany
Background and Aims: Biomarkers for cerebral small vessel disease (SVD) depend mostly on MRI, but fluid biomarkers are lacking. Serum Neurofilament Light Chain (NfL) is recognized as a promising marker for neuroaxonal injury. The current study evaluated serum NfL in SVD together with established imaging markers.
Method: We studied two samples: genetically defined SVD (CADASIL, n = 51) for primary analysis and sporadic SVD (spSVD, n = 444) for subsequent independent validation. Serum NfL was measured by an electrochemiluminescence immunoassay. Imaging markers included white matter hyperintensity volume, lacune volume, brain volume and mean diffusivity from diffusion tensor imaging. Clinical evaluation comprised neuropsychological testing (processing speed), assessment of disability (modified Rankin scale, mRS) and dependence (Barthel index); the latter two only in CADASIL patients. Statistical associations between serum NfL, imaging and clinical measures were analyzed using (multiple) linear regression and (stepwise, ordinal) logistic regression.
Results: Serum NfL levels were significantly associated with all imaging markers, with mean diffusivity showing the strongest effect (R2 = 0.53, p = 1.01e-09 for CADASIL; R2 = 0.21, p = 2.20e-16 for spSVD). There was also a significant association between serum NfL and processing speed (R2 = 0.29, p = 2.62e-05 for CADASIL; R2 = 0.06, p = 4.80e-8 for spSVD). In spSVD, this association was independent from other markers in multiple linear regression analysis. In CADASIL patients, we found independent associations between serum NfL levels and disability (mRS: p = 2.17e-06) as well as dependence (Barthel index: p = 0.00148).
Conclusion: Serum NfL is a promising SVD biomarker showing strong associations with established imaging markers as well as clinical deficits across two independent SVD cohorts.
AS26-013
Scientific Communication (Oral Abstract Presentation) Pathophysiological Markers
IMPAIRMENT OF CEREBROVASCULAR REACTIVITY IS ASSOCIATED WITH INCREASED WHITE MATTER HYPERINTENSITY AND PERIVASCULAR SPACE BURDENS IN PATIENTS WITH ISCHAEMIC STROKE PRESENTATIONS OF SMALL VESSEL DISEASE
G. Blair1, Y. Shi1, M. Thrippleton1, I. Hamilton1, D. Dickie1, F. Doubal1, I. Marshall1 and J. Wardlaw1
1University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
Background and Aims: Impairment of cerebrovascular reactivity (CVR) may influence development of cerebral small vessel disease (SVD), but little data exist on tissue-specific or SVD lesion-specific CVR. We investigated the effects of SVD on CVR in patients with minor ischaemic stroke-related SVD presentation and a range of SVD features.
Method: 60 patients with minor (NIHSS < 7) ischaemic stroke underwent MRI at 1.5T with blood oxygen-level dependent (BOLD) sequence while breathing 6% CO2 in air for 2x3 minute blocks. We expressed CVR as %BOLD signal change/mmHg change in end-tidal CO2. We derived average grey and white matter CVR values by combining 14 manually drawn regions of interest and assessed SVD features by expert visual rating and measured white matter hyperintensity (WMH) volume semi-automatically.
Results: Usable data were obtained in 53 patients (age 68.0+/−8.8, 39 males). On univariate analysis, white matter CVR declined with higher systolic BP, pulse pressure (PP), WMH volume/score, perivascular space (PVS) score, lacunes and total SVD score (all p < 0.02), but not age or other demographics. On multivariate analysis controlling for age, systolic BP and PP, lower CVR remained associated with higher WMH volume and PVS score. Grey matter CVR decreased with increasing systolic BP, PP and PVS score on univariate analysis (all p < 0.05) but not on multivariate analysis.
Conclusion: CVR is reduced in white matter as WMH volume and PVS scores increases, independent of age and BP. These important associations support trialling of CVR as a surrogate endpoint in two ongoing clinical trials of potential SVD treatments (LACI-1 and SVDs@Target).
AS05-002
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
DIAGNOSTIC CRITERIA FOR TRANSIENT ISCHAEMIC ATTACKS (TIA) VERSUS LONG-TERM PROGNOSIS: A POPULATION-BASED STUDY
M.A. Tuna1, L. Li1, S. Gutnikov1, Z. Mehta1 and P. Rothwell1
1Oxford University, Centre for the Prevention of Stroke and Dementia- Nuffield Department of Clinical Neuroscience, Oxford, United Kingdom
Background and Aims: Diagnosis of TIA is based mainly on clinical phenomenology (National Institute of Neurological Disorders and Stroke – NINDS criteria). Although NINDS criteria have never been validated against long-term prognosis, NINDS-negative events, sometimes termed ‘transient neurological attacks’ (e.g. isolated brainstem symptoms), are often not investigated/treated. We did a population-based study of long-term stroke risk after NINDS-negative events, NINDS-TIAs and minor strokes.
Method: All patients who sought medical attention after transient neurological symptoms or minor ischaemic stroke (NIHSS-score < 5) were ascertained prospectively in 92,728 residents of Oxfordshire, UK (2002-14). Transient events were classified at baseline as NINDS-TIA, NINDS-negative possible-TIA, or definitely non-vascular. Predicted 90-day risk of stroke was assessed by ABCD2-score and actual 90-day and 10-year risks by face-to-face follow-up. Diffusion-weighted MRI-brain (DWI) was done from 2007–2014.
Results: Among 3116 patients, 1002 had minor stroke and 2114 had transient events, most commonly NINDS-negative possible TIA (n = 860 vs 674 definite-TIA vs 580 non-vascular). NINDS-negative possible-TIAs had lower ABCD-2 scores than definite-TIAs (p < 0.0001), were less likely to have acute ischaemic lesions on DWI (7.8% vs 16.9%; p = 0.001), and had a lower 90-day stroke risk (4.0% vs 8.5%; p < 0.001). However, NINDS-negative possible-TIAs had a high 10-year risk of stroke (20.9% vs 20.7% for definite-TIA, p = 0.99; and vs 4.7% for non-vascular events, p < 0.001).
Conclusion: Short-term stroke risk after NINDS-negative possible-TIA is lower than after definite-TIA, but long-term risks are similar, highlighting the need for full investigation and secondary prevention, and suggesting that diagnostic criteria may need to be broadened.
AS05-006
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
LOWER DEMENTIA RISK WITH DIFFERENT CLASSES OF ANTIHYPERTENSIVE MEDICATION IN OLDER PATIENTS
T. van Middelaar1,2, L. van Vught3, E. Moll van Charante3, L. Eurelings2, S. Ligthart3, J. van Dalen2, B.J. van den Born4, E. Richard1,2 and P. van Gool2
1Radboud University Medical Center, Neurology, Nijmegen, The Netherlands
2Academic Medical Center, Neurology, Amsterdam, The Netherlands
3Academic Medical Center, General Practice, Amsterdam, The Netherlands
4Academic Medical Center, Internal Medicine, Amsterdam, The Netherlands
Background and Aims: Use of antihypertensive medication (AHM) is potentially associated with a reduced risk of dementia. Both calcium channel blockers (CCBs) and angiotensin-2 receptor blockers (ARBs) are suggested to have a more pronounced protective effect. We aimed to study the association between different classes of AHM and dementia in older people.
Method: A subgroup of community-dwelling older people using AHM included in the 'Prevention of Dementia by Intensive Vascular Care' (preDIVA) randomised controlled trial was studied. Incident dementia rates in participants with different AHM classes (mono- and combination therapy) were compared to dementia rates in participants with any other AHM.
Results: At baseline, 1951 participants (55.3%) used AHM (mean age, 74.4 year [SD 2.5]; mean systolic blood pressure, 156.4 mmHg [SD 21.5]). 986 participants (50.5%) used beta-blockers, 798 diuretics (40.9%), 623 angiotensin converting enzyme inhibitors (31.9%), 522 CCBs (26.8%), and 402 ARBs (20.6%). After 6.7 years (interquartile range 6.0–7.3) of follow-up, 136 participants (7.0%) developed dementia. Both use of CCBs (hazard ratio [HR] 0.56, 95% confidence interval [95% CI] 0.36–0.87) and ARBs (HR 0.60, 95% CI 0.37–0.98) were independently associated with a decreased risk of dementia. The association of CCBs with dementia was most apparent in participants without a history of cardiovascular disease (HR 0.38, 95% CI 0.18–0.81) and with uncontrolled hypertension (HR 0.26, 95% CI 0.11–0.61). Systolic blood pressure was not significantly lower in participants using CCBs or ARBs.
Conclusion: Both use of CCBs and ARBs are independently associated with a decreased risk of dementia in older people.
AS05-011
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
AGE-SPECIFIC RISKS, SEVERITY, TIME-COURSE AND OUTCOME OF BLEEDING ON LONG-TERM ANTIPLATELET TREATMENT AFTER VASCULAR EVENTS: POPULATION-BASED STUDY
L. Li1, O.C. Geraghty2, Z. Mehta1, P.M. Rothwell1 and On behalf of the Oxford Vascular Study1
1Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom
2Department of Medicine, Imperial College London, London, United Kingdom
Background and Aims: Bleeding is a serious complication of antiplatelet treatment in secondary prevention, but is most commonly upper-gastrointestinal (GI), which had low case-fatality in previous trials and is not generally thought to cause long-term disability. Consequently, guidelines on routine use of proton pump inhibitors (PPI) are conflicting. Yet there are few published data on risk, time-course and functional outcome of upper-GI bleeding at older ages.
Method: In a population-based study (OXVASC/2002–2012) of patients with a first TIA/ischaemic stroke/myocardial infarction treated with antiplatelet drugs (mainly aspirin-based/without routine PPI use), bleeding events requiring medical attention were identified by multiple sources, including face-to-face follow-up. We determined the age-specific (</≥75 years) risk, severity (CURE criteria), outcome (disability/death), and time-course of bleeding.
Results: 3166 eligible patients (1582 aged ≥ 75y) had 405 first bleeding events during 13,509 patient-years of follow-up. Risk of non-major bleeding was unrelated to age, but risk of major bleeding increased steeply with age (HRage≥75y = 3.10, 2.27–4.24, p < 0.0001), and was sustained during long-term follow-up. The same was true of major upper-GI bleeds (4.13, 2.60–6.57, p < 0.0001), particularly if disabling or fatal (10.26, 4.37–24.13, p < 0.0001). At age ≥ 75y most major upper-GI bleeds were disabling or fatal (61.6% vs. 25.0% at < 75, p = 0.002), outnumbering disabling or fatal intracerabral haemorrhage (45 vs.18).
Conclusion: On aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is much higher and more sustained in older patients in routine practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper-GI bleeding.
AS05-024
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
POPULATION-BASED STUDY OF PROGNOSTIC VALUE AND CONTROL OF NOCTURNAL BP AFTER TIA AND STROKE
M.M. Kubiak1, N. Lovett1, A. Webb1, R.M. Wharton1 and P.M. Rothwell1
1Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, Oxford, United Kingdom
Background and Aims: In previous studies of treated hypertensive populations, nocturnal blood pressure (BP) was a stronger predictor than daytime BP of residual risk of stroke and cardiovascular events. However, it is unclear whether nocturnal hypertension explains residual risk of recurrent stroke after TIA/ischaemic stroke when antihypertensive medication is taken predominantly in the morning.
Method: In a population-based incidence study (Oxford Vascular Study), consecutive patients with TIA or non-disabling stroke had 24-hour ambulatory BP-monitoring (ABPM) at one-month follow-up. Antihypertensive medication was prescribed as per guidelines. Mean daytime and mean night-time BP were related to risk of recurrent stroke and of all cardiovascular events on follow-up after adjustment for age and sex. Nocturnal hypertension was also defined as asleep mean SBP ≥ 120 mmHg and daytime hypertension as awake mean SBP ≥ 140 mmHg.
Results: Among 1035 patients (mean/SD age 68.67/12.74) with ABPM, 372 (36.4%) had residual nocturnal hypertension and 190 (18.4%) had residual daytime hypertension (p < 0.0001). However, mean asleep and mean awake BP were only weak predictors of cardiovascular events (n = 92; HR per SD: 1.19, 95%CI 0.99–1.39; and 1.19, 0.97–1.39, respectively). There was also no greater risk of recurrent stroke (n = 76) in relation to nocturnal hypertension (HR = 1.37, 0.87–2.16,) than to daytime hypertension (HR = 1.67, 0.99–2.77). Indeed, residual daytime hypertension tended to be more predictive of all cardiovascular events (HR = 1.68, 1.06–2.66 vs 1.12, 0.73–1.71).
Conclusion: Residual nocturnal hypertension was more common than residual daytime hypertension, but it was not a major risk factor for stroke or cardiovascular events.
AS05-027
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
THE DIAGNOSIS OF UNCERTAIN ORIGIN BENIGN TRANSIENT EVENTS (DOUBT) STUDY
S. Coutts1, M. Hill1, F. Moreau2, M. goyal3, M.C. Camden4, N. Asdaghi5, T. Field6, A. Penn7, R. Swartz8, J.M. Boulanger9, B. Campbell10, M. Krause11, R. Mikulik12 and J. Mandzia13
1University of Calgary, Clinical Neurosciences, Calgary, Canada
2University of Sherbrooke, Medicine, Sherbrooke, Canada
3University of Calgary, Radiology, Calgary, Canada
4University of Laval, Medicine, Quebec City, Canada
5University of Miami, Medicine, Miami, USA
6University of British Columbia, Medicine, Vancouver, Canada
7Vancouver Island Health Authority, Medicine, Victoria, Canada
8University of Toronto, Medicine, Toronto, Canada
9University of Sherbrooke, Medicine, Greenfield Park, Canada
10University of Melbourne, Neurology, Melbourne, Australia
11Royal North Shore Hospital, Neurology, Sydney, Australia
13University of London Ontario, Neurology, London, Canada
Background and Aims: TIA and minor stroke offer a massive opportunity for stroke prevention. Patients with motor or speech symptoms have a higher risk of recurrent stroke. Many patients with transient or mild deficits do not have high-risk features (eg sensory symptoms). The aim of the DOUBT study was to assess what proportion of these lower risk patients have brain ischemia and to establish clinical predictors of brain schema in this population.
Method: DOUBT was a multicentre, international, prospective, observational, cohort study assessing the diagnosis and prognosis of patients with lower risk focal neurological symptoms. Patients aged ≥40, no previous stroke, with either very brief (<5 minutes) motor or speech symptoms, or non-motor or speech focal neurological symptoms (any duration) were included. Patients had a detailed neurological assessment and an MRI brain within 7 days of onset. Primary outcome was the proportion of patients with an acute DWI lesion.
Results: 1060 patients in Canada, Europe and Australia were prospectively enrolled in the study. All patients had a detailed neurological assessment prior to undergoing MRI brain. Preliminary analysis shows a 13.8% DWI positive rate in this population. Patients were more likely to have a DWI lesion if their symptoms were still persistent at the time of assessment (RR 1.75, 95%CI, 1.30–2.38. p = 0.004). Secondary analysis looking at detailed clinical predictors of DWI lesions status will be available at the meeting.
Conclusion: We found a small but significant proportion of true ischemic stroke among these lower clinical risk patients. Detailed neurological assessment may help us stratify these patients further.
AS06-015
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
THE ASSOCIATION OF ADULT VACCINATION AND THE RISK OF ISCHEMIC STROKE: A SYSTEMATIC REVIEW AND META-ANALYSIS
A. Katsanos1,2, R. Zand3,4, M. Fawad Ishfaq3, M. Taimur Malik4, A. Filippatou1, S. Tsiodras5, J. Parissis6 and G. Tsivgoulis1,3
1National and Kapodistrian University of Athens School of Medicine, Second Department of Neurology, Athens, Greece
2University of Ioannina School of Medicine, Department of Neurology, Athens, Greece
3University of Tennessee Health Science Center, Department of Neurology, Memphis- TN, USA
4Geisinger Health Sysytem, Department of Neurology, Danville- PA, USA
5National and Kapodistrian University of Athens School of Medicine, Fourth Department of Internal Medicine, Athens, Greece
6National and Kapodistrian University of Athens School of Medicine, Second Department of Cardiology, Athens, Greece
Background and Aims: There is mounting evidence indicating infection as an independent risk factor for ischemic stroke (IS). Literature data are conflicting on the effect of pneumococcal (PV) and influenza vaccination (IV) on the aforementioned risk.
Method: We performed a systematic literature search to identify available studies reporting associations of PV and/or IV with IS risk. We performed subgroup analyses, according to study type [randomized clinical trial (RCT) or observational cohort] and vaccination used (PV, IV or both).
Results: We identified a total of 15 studies (825,981 patients). In the overall analysis no association was detected between vaccination and IS risk (RR = 1.24, 95%CI: 0.97-1.59, p = 0.09) with significant heterogeneity being present among studies (I2 = 97%, p for Cochran Q < 0.001). In subgroup analysis according to study type no significant differences (p = 0.11) were detected among RCTs (RR = 0.66, 95%CI:0.30–1.47), prospective (RR = 2.07, 95%CI:0.88–4.84) and retrospective studies (RR = 1.17,95%CI:0.91–1.50). Significant differences were detected in subgroup analysis according to vaccination type (p < 0.001), with IV vaccination being related with a lower risk of IS (RR = 0.85, 95%CI: 0.73–0.99;Figure), while PV was not associated with IS risk (RR = 1.53, 95%CI: 0.73–3.18;Figure). In sensitivity analyses of RCTs, IV tended to be associated with a lower risk of IS (RR: 0.66; 95%CI:0.30–1.47; p = 0.31) without any heterogeneity (I2 = 0%).
Conclusion: IV appears to be related with a lower risk of IS. This preliminary finding requires independent validation in large RCTs.
AS06-038
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
ANTIPLATELET REGIMEN FOR PATIENTS WITH BREAKTHROUGH STROKES WHILE ON ASPIRIN: A SYSTEMATIC REVIEW AND META-ANALYSIS
M. Lee1, J. Saver2, K.S. Hong3, N. Rao2, Y.L. Wu4 and B. Ovbiagele5
1Chang Gung University and Memorial Hospital, Neurology, Puzi, Taiwan R.O.C.
2UCLA Stroke Center, Neurology, Los Angeles, USA
3Ilsan Paik Hospital- Inje University, Neurology, Goyang, Republic of Korea
4Chang Gung University, Research Services Center for Health Information, Taoyuan, Taiwan R.O.C.
5Medical University of South Carolina, Neurology, Charleston, USA
Background and Aims: There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following an ischemic stroke or transient ischemic attack (TIA) while on aspirin monotherapy. We therefore conducted a systematic review and meta-analysis to compare the effects of modifying the antiplatelet regimen vs. continuing aspirin among patients who experienced their stroke while on aspirin monotherapy.
Method: We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies. We included studies that collected data within cohort studies or clinical trials on patients who took aspirin before their index ischemic stroke or TIA; and reported quantitative estimates of relative risk (RR) and 95% confidence interval (CI) for major adverse cardiovascular events (MACE) or recurrent stroke associated with a switch to or addition of another antiplatelet agent vs. maintaining aspirin monotherapy. Estimates were combined using a random effects model.
Results: Five studies with 8723 ischemic stroke or TIA patients were identified. Clopidogrel was used in 4 cohorts and ticagrelor was used in 1. Pooling results showed that addition of or a switch to another antiplatelet agent, vs. aspirin monotherapy, was associated with reduced risks of MACE (RR 0.65, 95% CI 0.53 to 0.80) (Figure 1) and recurrent stroke (RR 0.65, 95% CI 0.51 to 0.84) (Figure 2).
Figure 1
Figure 2
Conclusion: Among patients who experience an ischemic stroke or TIA while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, vs. continuing aspirin monotherapy, is associated with a significant reduction in future vascular events including stroke.
AS15-018
Scientific Communication (Oral Abstract Presentation) Prevention – Targets
ARTERIAL STIFFNESS IS ASSOCIATED WITH BASAL GANGLIA ENLARGED PERIVASCULAR SPACES AND CEREBRAL SMALL VESSEL DISEASE LOAD
Y. Riba Llena1, J. Jiménez-Baladó2, X. Castañé2, A. Girona3, A. López-Rueda2, J. Álvarez-Sabin4, J. Montaner5 and P. Delgado2
1Vall Hebron Research Institute. Vall Hebron Hospital. Universitat Autònoma de Barcelona., Neurovascular Research Laboratory. Neurology service, Barcelona, Spain
2Vall Hebron Research Institute. Universitat Autònoma de Barcelona., Neurovascular Research Laboratory., Barcelona, Spain
4Vall Hebron Research Institute. Vall Hebron Hospital. Universitat Autònoma de Barcelona., Neurovascular Research Laboratory. Stroke Unit., Barcelona, Spain
5Vall Hebron Research Institute. Vall Hebron Hospital. Universitat Autònoma de Barcelona., Neurovascular Research Laboratory. Stroke Unit, Barcelona, Spain
Background and Aims: Lacunar infarcts (LI) and white matter hyperintensities (WMH) were previously associated with arterial stiffness (AS). However, the relation of other cerebral small vessel disease (cSVD) lesions like enlarged perivascular spaces (EPVS) or cSVD load with AS has been rarely investigated. We aimed to assess whether cSVD lesions and load are related to AS.
Method: Cohort of hypertensive Mediterranean individuals, aged 50–70 years, without previous stroke or dementia. Participants underwent brain MRI to assess LI, microbleeds (MB), WMH, basal ganglia (BG) and centrum semiovale (CSO) EPVS. cSVD load was calculated with an ordinal scale ranging 0–4 (one point per each: LI, extensive (Fazekas grade ≥ 2) WMH, deep MB and extensive (>10 lesions) BG EPVS) (Huijts et al.). AS was tested by carotid-femoral pulse wave velocity (cf-PWV) measurement with an oscillometric automatic device (VICORDER®).
Results: 782 participants, mean age was 62.7 ( ± 5.4), 49.6% female and mean blood pressure 98.67 (±10.47) mmHg. We found 7.2% LI, 6.4% MB, 10.2% extensive WMH, 24.5% extensive BG EPVS and 40.1% extensive CSO EPVS. Regarding cSVD load 72.4% scored 0, 19.7% scored 1, 6.5% scored 2, and 1.3% scored ≥3. Median cf-PWV was 10.54 (IQR: 9.23,11.92) m/s and was positively correlated to age, heart rate and mean blood pressure (all p-values<0.001). cf-PWV by SD increase was associated with LI (OR = 1.50; 95%CI = 1.09,2.08), extensive BG EPVS (1.51;1.24,1.84) and cSVD load (common OR = 1.57, 95%CI = 1.32,1.87) after adjusting for vascular risk factors, heart rate, anti-hypertensive drugs and previous cardiovascular disease.
Conclusion: AS is associated with the total load of cSVD, especially with LI and BG EPVS.
AS07-021
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
DRIP ‘N SHIP VERSUS DIRECT TO THROMBECTOMY CENTRE: CONDITIONAL PROBABILITY MODELLING IN IRELAND
J. Holodinsky1,2, A. Patel1,3, L. Jewett4, J. Thornton5,6, J. McCormack7, P. Marsden8, J. Harbison9, M. Hill1,2,10,11,12,13 and D. Williams14,15
1University of Calgary, Department of Community Health Sciences, Calgary, Canada
2University of Calgary, Hotchkiss Brain Institute, Calgary, Canada
3University of Calgary, O'Brien Institute For Public Health, Calgary, Canada
4University of Calgary, Department of Geography, Calgary, Canada
5Royal College of Surgeons in Ireland, Department of Neuroradiology, Dublin, Ireland
6Beaumont Hospital, Department of Neuroradiology, Dublin, Ireland
7Dublin City University, Faculty of Science and Health, Dublin, Ireland
8Health Services Executive, Department of Public Health, Tullamore, Ireland
9Trinity College Dublin, Department of Medical Gerontology, Dublin, Ireland
10University of Calgary, The Calgary Stroke Program, Calgary, Canada
11University of Calgary, Department of Medicine, Calgary, Canada
12University of Calgary, Department of Radiology, Calgary, Canada
13University of Calgary, Department of Clinical Neurosciences, Calgary, Canada
14Royal College of Surgeons in Ireland, Department of Geriatric and Stroke Medicine, Dublin, Ireland
15Beaumont Hospital, Department of Geriatric and Stroke Medicine, Dublin, Ireland
Background and Aims: In ischemic stroke, it is unknown if bypassing a thrombolysis centre in favour of endovascular therapy (EVT) at a thrombectomy centre (mothership) or transport to the nearest thrombolysis centre for alteplase and then transfer for EVT (drip and ship) provides the best outcomes.
Method: Probability of good outcome for patients with large vessel occlusions (LVO) was modelled for each transport strategy. Door to needle (DTN) times were obtained from the Irish National Stroke Register (N = 699), and door to groin puncture (DTP) times from an EVT registry at Beaumont Hospital, a referral centre for EVT (N = 312). Transport times were estimated using Google’s Distance Matrix API.
Results: Using current DTN, drip and ship rarely provides the best outcome (Figure 1); however, if DTN is reduced to 45 minutes (Figure 2) drip and ship is a superior option for patients in much of the country. Reducing DTP results in increased benefit of the mothership approach.
Conclusion: Modelling patient transport for system level planning is sensitive to treatment times at both thrombolysis and thrombectomy centres. These models apply to patients with LVOs, future studies should consider all suspected stroke patients presenting to EMS.
AS07-032
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
MORTALITY AND DISABILITY ACCORDING TO BASELINE BLOOD PRESSURE IN ACUTE ISCHEMIC STROKE PATIENTS ELIGIBLE FOR THROMBECTOMY: A COLLABORATIVE POOLED ANALYSIS
B. Maïer1, M. Mazighi1, R. Blanc1, M. Piotin1, J.P. Desilles1, S. Smajda1, H. Redjem1, G. Ciccio1, G. Taylor2, B. Lapergue3, J. Labreuche4, B. Gory5, A.C. Lukaszewicz6, J. Blacher7, F. Turjman5, R. Riva5, P.E. Labeyrie5 and A. Duhamel4
1Fondation Rothschild, Department of Interventional Neuroradiology, PARIS, France
2Fondation Rothschild, Department of Intensive Care Unit, PARIS, France
3Foch Hospital, Department of Neurology- Division of Neurology- Stroke Center, Paris, France
4CHU Lille, Department of Biostatistics, Lille, France
5Hôpital Pierre Wertheimer- Hospices Civils de Lyon, Department of Interventional Neuroradiology, Lyon, France
6Hospices Civils de Lyon- Hôpital Pierre Wertheimer, Department of Intensive Care Unit, Lyon, France
7Hôtel-Dieu, Hypertension Unit- cardiovascular prevention and therapeutic center, Paris, France
Background and Aims: High blood pressure (BP) is associated with worse clinical outcomes in the setting of acute ischemic stroke (AIS). The optimal blood pressure target is a matter of debate. We studied the association between baseline BP and mortality in AIS patients eligible for mechanical thrombectomy (MT).
Method: We analyzed the data from 1332 AIS patients eligible for MT enrolled from January 2012 to June 2016. Linear and polynomial logistic regression models were used to assess the effect of BP on mortality and functional outcome.
Results: Highest mortality was found at lower and higher baseline systolic BP (SBP) values following a J-shaped relationship, with a nadir at 157 mmHg. Odds for all-cause mortality for each 10 mmHg increments were 3.78 (95%CI,1.50–9.55) in SBP < 110 mmHg and 1.81(95%CI, 1.01–3.36) in SBP ≥ 180 mmHg. Baseline diastolic BP was also associated with mortality following a linear link (adjusted OR per 10 mmHg: 1.11(95%CI,1.01–1.22)). The rate of favorable outcome was the highest at low SBP values and the lowest at high SBP values (OR of decreased favorable outcome rate per 10 mmHg increase, 0.89(95%CI,0.84–0.94). The relationship's shape appeared non-linear, with a curve relatively flat for SBP values <180 mmHg, followed by a significant drop suggesting a threshold SBP effect.
Conclusion: In AIS patients eligible for MT, baseline BP is associated with all-cause mortality. In contrast to mortality, where lower and higher SBP impact negatively the prognosis, favorable outcome rate was the highest at low SBP values and lowest at high SBP values with a possible threshold SBP effect at 180 mmHg.
AS07-033
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
ESO ESMINT EAN SAFE SURVEY ON ACUTE ENDOVASCULAR STROKE CARE IN EUROPE
D. Aguiar de Sousa1, S. Abilleira2, T. Gattringer3, R. von Martial4, A. Kobayashi5, V. Caso6, M. Gallofré7, F. Fazekas3, I. Szikora8 and U. Fischer4
1Hospital de Santa Maria University of Lisbon, Department of Neurosciences and Mental Health, Lisbon, Portugal
2Agency for Health Quality and Assessment of Catalonia, Stroke Program, Barcelona, Spain
3Medical University of Graz, Department of Neurology, Graz, Austria
4University Hospital of Bern, Neurology, Bern, Switzerland
5Institute of Psychiatry and Neurology, Interventional Stroke Treatment Centre, Warsaw, Poland
6Santa Maria della Misericordia Hospital, Stroke Unit, Perugia, Italy
7Stroke Program, Catalan Health Department, Barcelona, Spain
8Interventional Neuroradiology, National Institute of Neurosurgery, Budapest, Hungary
Background and Aims: Randomized controlled trials have consistently shown that endovascular thrombectomy (EVT) in addition to best medical therapy significantly improves outcome compared with best medical therapy alone in patients with ischaemic stroke due to anterior circulation large vessel occlusion. However, detailed information regarding the current practice of EVT throughout Europe is lacking. The European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy(ESMINT), the European Academy of Neurology(EAN) and the Stroke Alliance for Europe(SAFE) set collaboration to perform a systematic survey on the current practice of endovascular stroke treatment throughout Europe.
We aim to assess current practices regarding management of acute stroke and EVT in Europe and to examine differences among European countries.
Method: Cross-sectional Pan-European survey divided in two levels, national and local. Leaders of national societies related to stroke, neurology and/or interventional radiology were identified by contacting ESO, EAN and ESMINT members from each European country and were asked to: (1)fill in a comprehensive form regarding national acute stroke care and (2)systematically identify all stroke centres involved in EVT in each country. In a second step, all centres providing EVT were asked to participate in a Web-based survey, whose responses were anonymously collected and stored electronically.
Results: By January 12th, 32 countries responded to the questionnaire. The final results will be presented in May/2017.
Conclusion: We report the results of a Pan-European survey of current treatment practices for acute stroke. This information is urgently needed to develop programs and generate support for a high quality stroke care in all European countries.
AS07-037
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
ONE STOP MANAGEMENT OF ACUTE STROKE PATIENTS: MINIMIZING DOOR TO REPERFUSION TIMES
M. Psychogios1, D. Behme1, K. Schregel1, I. Tsogkas1, I.L. Maier2, J.R. Leyhe1, M. Baehr2, M. Knauth1 and J. Liman2
Background and Aims: Intrahospital time delays significantly affect neurological outcome of stroke patients with large vessel occlusion. Multidetector CT prior to angiography is time-consuming. We report the 30 first consecutive patients triaged in our department with a flat detector CT (FDCT)-based one stop management
Method: In this observational study, we transported stroke patients with a NIHSS ≥ 10 directly to the angio suite, bypassing multidetector CT. Multimodal imaging consisted of noncontrast FDCT and biphasic FDCTA. Patients with large vessel occlusion remained on the angio table and were treated with mechanical thrombectomy; peripheral occlusions were treated with intravenous medication, intracranial hemorrhage and stroke mimics were treated as per guidelines. Intrahospital times were recorded and compared to our past benchmarks.
Results: Thirty patients were transferred directly to our angio suite from June to December 2016. Mean age was 76 (±14, 53% female). Symptom to onset to admission time was 105 min [(IQR) 69–173]. Ischemic stroke was diagnosed in 22/30 (73%), intracranial hemorrhage in 4 and Todd`s paresis in 4 patients. Admission to FDCT time was 9.5 min (IQR 6–12) and admission to groin puncture time was 20.5 min (IQR 17–27). Compared to patients triaged with multidetector CT in the first 6 months of 2016, we observed a highly significant reduction of door to groin times (P < 0.001).
Conclusion: One stop management is feasible for stroke triage and leads to a significant reduction of intrahospital times and suggests that one stop management with FDCT can securely identify hemorrhagic strokes.
AS07-038
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
TIME TO TREATMENT AND FUNCTIONAL OTUCOME AFTER INTRA-ARTERIAL TREATMENT IN CLINICAL PRACTICE – RESULTS FROM THE MR CLEAN REGISTRY
M. Mulder1, I. Jansen2, R.J. Goldhoorn3, V. Chalos4, E. Venema5, B. Emmer6, A. Van Es6, W. Van Zwam7, Y. Roos8, J. Boiten9, J.A. Vos10, R. Van Oostenbrrugge3, C. Majoie2, A. Lugt6, B. Roozenbeek4, H. Lingsma11 and D. DIppel4
1Erasmus MC, Neurology & radiology, Rotterdam, The Netherlands
2Academic Medical Center, Radiology, Amsterdam, The Netherlands
3Maastricht University Medical Center- Cardiovascular Research Institute Maastricht CARIM, Neurology, Maastricht, The Netherlands
4Erasmus University MC, Neurology, Rotterdam, The Netherlands
5Erasmus University MC, Public Health, Rotterdam, The Netherlands
6Erasmus University MC, Radiology, Rotterdam, The Netherlands
7Maastricht University Medical Center- Cardiovascular Research Institute Maastricht CARIM, Radiology, Maastricht, The Netherlands
8Academic Medical Center, Neurology, Amsterdam, The Netherlands
9MC Haaglanden, Neurology, The Hague, The Netherlands
10Sint Antonius Hospital, Radiology, Nieuwegein, The Netherlands
11Erasmus University MC, Publich Health, Rotterdam, The Netherlands
Background and Aims: Earlier intra-arterial treatment (IAT) for acute ischemic stroke results in better functional outcome. In the pooled trial data, every hour delay in reperfusion resulted in 4% lower probability of good outcome. We aim to assess the association of time with outcome from IAT in clinical practice.
Method: All IAT treated patients in the Netherlands have been registered since the final MR CLEAN trial inclusion. We analyzed patients included from March 2014 until June 2016, with anterior circulation occlusion that were treated within 6.5 hours. We investigated the association of time from onset to groin and time to reperfusion with functional outcome. Primary outcome was the 90-day modified Rankin Scale. We used multiple logistic and ordinal regression models.
Results: We analyzed 1221 patients. Median time from onset to groin was 206 minutes and to reperfusion 265 minutes. Both times were complete in >95% of the patients. Delays in reperfusion had a stronger association with outcome (aOR = 0.72(95% CI: 0.66–0.79)) than delays in groin puncture (aOR = 0.83(95% CI:0.76–0.91)). Every hour delay in reperfusion resulted in a 10% lower probability of good outcome (Figure 1). Effect of time on radiological parameters and complications will be presented at the conference.
Conclusion: In clinical practice effect of time delay on outcome is stronger than in the recent trials. Our results emphasize the importance of optimizing workflow for IAT.
AS07-042
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
TRANSFER-RELATED DELAY AND FUNCTIONAL OUTCOME AFTER INTRA-ARTERIAL TREATMENT; RESULTS FROM THE MR CLEAN REGISTRY
E. Venema1, V. Chalos2, M. Mulder2, B. Roozenbeek2, H. Lingsma1 and D. Dippel2
1Erasmus University Medical Center, Public Health, Rotterdam, The Netherlands
2Erasmus University Medical Center, Neurology, Rotterdam, The Netherlands
Background and Aims: Inter-hospital transfer delays intra-arterial treatment (IAT) for acute ischemic stroke. We investigated clinical characteristics and time parameters of transfer patients in clinical practice and assessed the potential effect of transfer-related delay on functional outcome.
Method: The MR CLEAN Registry consists of patients treated with IAT between March 2014 and June 2016 in 17 centers in the Netherlands (n = 1221). We compared patients directly admitted to an intervention center (direct patients) and patients transferred from a primary stroke center (transfer patients). With multivariable linear regression we assessed the effect of transfer on time to groin puncture, and with multivariable proportional odds regression we evaluated the association with functional outcome (90-days modified Rankin Scale (mRS)).
Results: In total 672 patients (55%) were transferred. Transfer patients had less pre-stroke disability (mRS ≥ 1; 120/647(19%) vs 134/538(25%), p < 0.01), arrived more often during off-hours (386/652(59%) vs 283/532(53%), p = 0.04), and received more frequently intravenous treatment (552/672(82%) vs 417/547(76%), p = 0.01). Total time from symptom onset to groin puncture was longer in transfer patients (median 225 vs 167 minutes, adjusted delay 43 minutes, 95%CI 35–51), despite a shorter time from admission at intervention center to groin puncture (median 43 vs 103 minutes, p < 0.01). Transfer was associated with poorer outcome, transfer patients achieved less frequently functional independency (mRS ≤ 2; 235/659(36%) vs 255/539(47%), aOR 0.66, 95%CI 0.53–0.81).
Conclusion: Inter-hospital transfer is an important cause of IAT delay and is associated with worse functional outcome in clinical practice. Adequate measures have to be taken to reduce transfers and to shorten transfer times.
AS07-044
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
SAFETY AND FUNCTIONAL OUTCOME AFTER INTRA-ARTERIAL TREATMENT FOR ACUTE ISCHEMIC STROKE WITHOUT PRIOR INTRAVENOUS THROMBOLYSIS IN CLINICAL PRACTICE: RESULTS FROM THE MR CLEAN REGISTRY
V. Chalos1, B. Roozenbeek1, M.J.H.L. Mulder1, E. Venema2, K.M. Treurniet3, J.M. Coutinho4, Y.B.W.E.M. Roos4, C.B.L.M. Majoie3, H.F. Lingsma2 and D.W.J. Dippel1
1Erasmus University Medical Center, Neurology, Rotterdam, The Netherlands
2Erasmus University Medical Center, Public health, Rotterdam, The Netherlands
3Amsterdam Medical Center, Radiology, Amsterdam, The Netherlands
4Amsterdam Medical Center, Neurology, Amsterdam, The Netherlands
Background and Aims: The need for intravenous thrombolysis with alteplase (IVT) prior to intra-arterial treatment (IAT) for acute ischemic stroke has been questioned. We aim to provide more insight in clinical characteristics, safety, and outcome of IAT patients treated with and without IVT in clinical practice.
Method: We used the MR CLEAN Registry, containing patients treated with IAT in the Netherlands from March 2014 until June 2016, with an anterior circulation occlusion and pre-stroke modified Rankin Scale (mRS) score ≤2, treated within 6.5 hours of symptom onset (n = 1221). We compared clinical characteristics, complications and outcomes of patients with and without prior IVT. With ordinal logistic regression we evaluated the association of prior IVT with functional outcome (90-day mRS).
Results: In total 969 (79%) patients were treated with IVT prior to IAT. These patients were younger (mean 67 vs 70 years, p = 0.010) and had lower cardiovascular comorbidity, such as atrial fibrillation (16% vs 43%, p < 0.001), a better pre-stroke mRS (mRS 0: 82% vs 65%, p < 0.001), and a slightly shorter onset-to-IAT time (median 205 vs 208 minutes, p = 0.149). Mortality was lower (22% vs 34%, p < 0.001) in the IVT-group, while there were no differences in symptomatic intracerebral hemorrhage (6% vs 7%, p = 0.554). Prior IVT was associated with better functional outcome (cOR 1.73; 95%CI: 1.34–2.23), also after adjustment (acOR 1.33; 95%CI: 1.01–1.74).
Conclusion: IAT patients with prior IVT have more favorable clinical characteristics. After adjustment prior IVT is associated with better functional outcome, but we cannot exclude the possibility this was partly caused by residual confounding.
AS07-061
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
THE IMPACT OF NATIONWIDE CENTRALLY ORGANIZED STROKE CARE SYSTEM ON RECANALIZATION RATES: CZECH REPUBLIC EXPERIENCE
A. Tomek1, M. Bar2, R. Herzig3, R. Mikulík4, J. Neumann5, D. Šaňák6, O. Škoda7, D. Školoudík8 and D. Václavík9
12nd Medical School of Charles University and Motol University Hospital, Department of Neurology, Prague, Czech Republic
2University Hospital Ostrava- Medical Faculty of Ostrava University, Department of Neurology, Ostrava, Czech Republic
3University Hospital Hradec Králové- Charles University Faculty of Medicine in Hradec Králové, Comprehensive Stroke Centre, Hradec Králové, Czech Republic
4St. Anne´s University Hospital and Faculty of Medicine- Masaryk University, Department of Neurology, Brno, Czech Republic
6Palacký Medical School and University Hospital, Comprehensive Stroke Center- Department of Neurology, Olomouc, Czech Republic
7Hospital Jihlava, Department of neurology, Jihlava, Czech Republic
8University Hospital Ostrava, Department of Neurology, Ostrava, Czech Republic
9Agel Research and Training Institute- Ostrava Vitkovice Hospital, Neurology, Ostrava, Czech Republic
Background and Aims: Organized stroke care was proven to be beneficial for all stroke patients regardless of time, severity or subtype. Centrally organized system of stroke care can increase the use of recanalization therapies and make them available to larger proportion of patients. System of stroke care in the Czech Republic (CR) was centrally accredited by the Ministry of Health (MH) in 2011. From 2013 a compulsory triage of acute stroke patients was established for emergency services and 12 quality of care indicators are evaluated annually. The aim was to assess the impact of the centrally organized system of stroke care on the availability of recanalization treatment in CR.
Method: Quality of care indicators collected by Ministry of Health from all 45 stroke centres servicing 10.5 million population of CR from 2013 to 2015 were analysed.
Results: In 2015 20% of patients received thrombolysis and 4% were treated with thrombectomy. When comparing years 2015 and 2013, the following significant differences were observed: thrombolysis administration (OR 1.72, 95% CI 1.63–1.82, P < 0.001), thrombectomy (OR 2.08, 95% CI 1.84–2.34, P < 0.001), door-to-needle time bellow 60 minutes (OR 2.25, 95% CI 2.01–2.53, P < 0.001).
Conclusion: Centrally organized stroke care system significantly improved rates of recanalization therapy in CR.
Indicator
2013
2014
2015
Hospitalizations - all strokes [n]
26383
25136
26781
Hospitalizations - ischemic strokes [n]
19732
18249
19467
Thrombolysis [n]
2435
2990
3800
Door-to-needle time <60 minutes [%]
63.33
72.36
79.55
Treated with thrombolysis [%]
12.34
16.38
19.52
Thrombectomy [n]
410
576
822
Treated with thrombectomy [%]
2.07
3.16
4.22
AS32-025
Scientific Communication (Oral Abstract Presentation) Thrombectomy in practice
VASCULAR AND CLINICAL OUTCOME IN ACUTE SYMPTOMATIC EXTRACRANIAL INTERNAL CAROTID ARTERY OCCLUSION
S. Hause1, A. Oldag1, A. Breja1, S. Schreiber1, H.J. Heinze1, Z. Halloul2 and M. Goertler1
1Otto-von-Guericke University Magdeburg, Department of Neurology, Magdeburg, Germany
2Otto-von-Guericke University Magdeburg, Department of General- Visceral and Vascular Surgery, Magdeburg, Germany
Background and Aims: To assess the vascular and clinical outcome of acute symptomatic extracranial internal carotid artery (ICA) occlusion.
Method: Between 09/2008 and 11/2016 vascular pathology of 4890 consecutive patients admitted to an university stroke center with an acute transient ischemic attack or ischemic stroke were examined on admission by CT angiography and duplex sonography. In patients with ICA occlusion routine duplex follow-up was scheduled after 2 days, 8 days, 6 weeks, 4.5 months and thereafter every 6 months. Clinical outcome was recorded at 4.5 months by modified Rankin scale.
Results: 126 patients (2.58%; 99 men, mean age 63.4 years, SD 11.6 years) demonstrated symptomatic occlusion of the extracranial ICA with open intracranial ICA and open middle cerebral artery (M1 segment and proximal M2 segments). Kaplan Meier analysis revealed a cumulative spontaneous recanalization rate of 13% at 2 days, 23% at 8 days, 30% at 6 weeks and 36% at 4.5 months. No additional recanalization was detected after 4.5 months. Modified Rankin scale in patients whose ICA has recanalized was significantly lower than in those with persisting occlusion (median 1 vs. 2; mean 1.6 vs. 2.5). 15 of these 21 patients underwent subsequent endarterectomy (14) or stenting (1). In patients without intervention ICA re-occluded (4) or follow up was terminated because patient died from cancer (2).
Conclusion: Spontaneous recanalization of acute symptomatic ICA occlusion may occur in up to 36% of patients predominantly within the first 2 weeks, offers the opportunity for secondary revascularization and may be associated with better functional outcome.
AS02-002
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
IMPACT OF CLINICAL TRIAL PARTICIPATION ON ‘DOOR-TO-NEEDLE’ TIME PERFORMANCE: THE ENCHANTED TRIAL
J. Yang1, X. Wang2, Y. Zhang1, J. Hang1, T. Robinson3, R. Lindley2, C. Anderson2 and J. Chalmers4
1Nanjing First Hospital- Nanjing Medical University, Department of Neurology, Nanjing, China
2The George Institute for Global Health, Neurological and Mental Health, Sydney, Australia
3University of Leicester, Department of Cardiovascular Sciences and NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester, United Kingdom
4The George Institute for Global Health, Professional Unit, Sydney, Australia
Background and Aims: Door-to-needle time (DNT) is a key performance indicator for efficient use of intravenous thrombolysis treatment in acute ischemic stroke. We aimed to determine (i) whether DNT improved over time among participants of the ENhanced Control of Hypertension ANd acute sTrokE stuDy (ENCHANTED), (ii) extent to which DNT in China differed from sites elsewhere, and (iii) the clinical predictors of DNT.
Method: Data were derived from the 3310 patients enrolled in ENCHANTED. Secular trends in DNT were assessed across fourths of time since the start of each site using analysis of variance. Predictors of longer DNT (>60 min) were determined in logistic regression models.
Results: The overall mean DNT (min) was 71.8 (95% confidence interval [CI] 70.4–73.2) and it decreased significantly over time (fourths): 77.9 (74.9–80.9), 69.3 (66.7–72.0), 69.1 (66.5–71.8) and 71.4 (68.7–74.2) (P for trend, 0.003). The reduction in DNT was particularly marked in China (P for trend, 0.001), but was not significant across the other participating countries (P for trend, 0.065). Independent predictors of longer DNT include recruitment from China, shorter onset-to-door time, fewer patients treated in the center, higher diastolic blood pressure, off-hour admission, and CT or MRI angiogram not showing proximal occlusion.
Conclusion: DNT in ENCHANTED declined progressively during the trial, especially in China. Participation in an acute stroke clinical trial can lead to improved DNT. However, the DNT in China is still longer than the guideline recommendations of ≤60 min. Effective national programs are needed to improve DNT in China.
AS02-012
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
12 month outcomes from A Very Early Rehabilitation Trial (AVERT)
P. Langhorne1, R. Lindley2, A. Thrift3, F. Ellery4, J. Collier4, L. Churilov5, M. Moodie6, H. Dewey7, G. Donnan8, J. Bernhardt4, &, the and AVERT Trial Collaboration Group4
1University of Glasgow, Cardiovascular and Medical Sciences, Glasgow, United Kingdom
2The University of Sydney, Sydney Medical School, Sydney, Australia
3Monash Health, Clinical Sciences, Clayton, Australia
4The Florey Institute of Neuroscience and Mental Health, Stroke, Heidelberg, Australia
5The Florey Institute of Neuroscience and Mental Health, Statistics and Decision Analysis, Heidelberg, Australia
6Deakin University, Centre for Population Health Research, Geelong, Australia
7Monash University, Eastern Health Clinical School, Box Hill, Australia
8The Florey Institute of Neuroscience and Mental Health, Stroke, Parkville, Australia
Background and Aims: A very early intensive out-of-bed mobilisation (VEM) protocol after stroke compared to usual care was associated with a reduction in odds of a favourable outcome at 3 months. We report pre-specified analyses to determine whether VEM post stroke results in better outcomes for patients at 12 months when compared to usual stroke unit care.
Method: We performed a prospective, parallel group, assessor-blinded, multi-centre, clinical trial with the following inclusion criteria: admission within 24 hours of stroke and physiological parameters within pre-set limits. Treatment with rt-PA was allowed. Patients with severe premorbid disability and/or severe comorbidities were excluded. Patients were randomised to VEM or usual care. The intervention, delivered by a physiotherapy/nurse team, started within 24 hours and continued for a maximum of 14 days. Analyses were intention-to-treat. Pre-specified adjusted analyses for 12 month outcomes included: (i) health related quality of life (HRQoL); (ii) favourable outcome mRS 0–2; (iii) deaths; and (iv) time to walking 50 metres unassisted.
Results: From July 2006 to October 2014, 2104 patients were recruited from five countries. Patient demographics: age median (IQR): 72.5 (62.9–80.3) years; NIHSS median (IQR): 7 (4–12); rt-PA treated 24.1%. Follow up was completed in 2052 patients (97.5%). No between group differences in: (i) HRQoL (adj median regression: −0.036 (95% CI −0.045–0.038, p = 0.865); (ii) mRS 0–2 (aOR 0.84, 95% CI 0.68–1.03, p = 0.089); (iii) deaths (aOR 1.29, 95% CI 0.96–1.72, p = 0.088); (iv) or time to walking (aHR 1.02, 95%CI 0.94–1.13, p = 0.553) were found.
Conclusion: Early intensive mobilisation after stroke did not improve 12 month outcomes after stroke.
AS02-023
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
INTENSIVE VERSUS GUIDELINE ANTIPLATELET THERAPY IN PATIENTS WITH MINOR ISCHAEMIC STROKE: DATA FROM THE TRIPLE ANTIPLATELETS FOR REDUCING DEPENDENCY IN ISCHAEMIC STROKE (TARDIS) TRIAL
L.J. Woodhouse1, K. Flaherty1, D. Havard1, T.J. England1, N. Sprigg1 and P.M. Bath1
1University of Nottingham, Stroke- Division of Clinical Neuroscience, Nottingham, United Kingdom
Background and Aims: The risk of recurrence following an ischaemic stroke (IS) or transient ischaemic attack (TIA) is high, especially immediately after the event. Since one antiplatelet agent is more effective than none, and two are superior to one, more intensive treatment might be even more effective in preventing recurrence providing bleeding does not become a limitation.
Method: TARDIS was an international multicentre prospective randomised open-label blinded-endpoint controlled trial. Patients with acute (<48 hours) non-cardioembolic IS or TIA were randomised to intensive antiplatelet therapy (combined aspirin, clopidogrel and dipyridamole) or guideline antiplatelets (clopidogrel alone, or combined aspirin and dipyridamole) given for one month. The primary outcome was recurrent cerebral events and their severity (based on modified Rankin Scale) at 3 months.
Results: Of 3,096 patients, 1259 (41%; Intensive 629, Guideline 630) were enrolled with minor stroke (NIHSS ≤ 3). At baseline: mean age 68 (SD 10); male 63%; prior stroke 10%; onset to randomisation <12 hours 7%, <24 hours 24%. By day 90, minor stroke patients randomised to receive intensive antiplatelets were less likely to suffer from mood disturbance when compared to guideline (Zung Depression Scale: mean difference −2.5, 95% confidence interval −4.5, −0.5). No differences in recurrence rates and their severity, death or other functional outcomes were present between the two treatment groups.
Conclusion: Minor stroke patients who received intensive antiplatelet treatment were less likely to suffer from mood disturbance at day 90. However, no differences were seen in any of the other outcome measures.
AS02-032
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
HYPOTHERMIA IN ADDITION TO DECOMPRESSIVE HEMICRANIECTOMY AFTER MALIGNANT INFARCTION
H. Neugebauer1, H. Schneider2, J. Bösel3, C. Hobohm4, S. Poli5, R. Kollmar6, J. Sobesky7, S. Wolf7, M. Bauer8, S. Tittel9, J. Beyersmann9, P. Heuschmann10 and E. Jüttler11
Background and Aims: Moderate therapeutic hypothermia in addition to early decompressive hemicraniectomy (DHC) within 48 hours from symptom onset may further reduce mortality and improve functional outcome in malignant middle cerebral artery infarction (MMI).
Method: We randomly assigned adults with MMI to early DHC plus standard care or early DHC plus hypothermia (33.0 ± 1.0°C) for at least 72 hours. The primary outcome was mortality at day 14. Mortality rates were compared with Fisher’s exact test and expressed as odds ratio (OR) with 95% confidence interval (CI) (OR <1.0 favoring TH). Rates of patient with serious adverse events (SAE) were estimated using identical methods for the period of the first 14 days and for the 12 month follow up, as the latter was essentially complete for all patients.
Results: We enrolled 50 patients at 6 centers in Germany from August 2011 through September 2015. Recruitment was suspended thereafter for safety concerns: 46% of patients in the hypothermia group and 29% of patients in the control group had at least one SAE within 14 days, OR 2.05 (CI 0.56–8.00; P = 0.25); after 12 month, rate of SAE was 77% in the hypothermia group and 42% in the control group, OR 4.52 (CI 1.19–19.19; P = 0.02). Mortality rate was 19% in the hypothermia group and 13% in the control group, odds ratio 1.65 (CI 0.28–12.01; P = 0.70).
Conclusion: In patients with MMI, moderate therapeutic hypothermia over at least 72 hours in addition to DHC did not improve early mortality. Instead, TH may cause serious physical harm in this specific setting.
AS02-035
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
SPECIFIC POINT-OF-CARE TESTING OF COAGULATION IN PATIENTS TREATED WITH NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS PART I (SPOCT-NOAC I)
F. Härtig1, I. Birschmann2, A. Peter3, C. Weyland4, M. Ebner5, J. Kuhn2, T. Peveto6, J. Spencer6, D. Pearman6, C.S. Zuern7, U. Ziemann4 and S. Poli4
1Tuebingen University Hospital – - 72076 Tübingen, Tuebingen, Germany
2Ruhr University, Institute for Laboratory and Transfusion Medicine- Heart and Diabetes Centre- Bad Oeynhausen, Bochum, Germany
3Department of Internal Medicine- Division of Endocrinology- Diabetology- Angiology- Nephrology and Clinical Chemistry, Tuebingen, Germany
4, Tuebingen, Germany
5Tuebingen University Hospital, Department of Neurology & Stroke- and Hertie Institute for Clinical Brain Research, Tuebingen, Germany
6Helena Laboratories, Helena Laboratories, Beaumont, USA
7, Department of Cardiology and Cardiovascular Medicine, Tuebingen, Germany
Background and Aims: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF). Stroke rate of NOAC-treated AF-patients is 1–2% per year. In future, stroke physicians will face a growing number of NOAC-treated acute stroke patients. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care tests (POCT) are suboptimal. For the first time we evaluate NOAC-specific POCT.
Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban.
Method: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N = 40 for each NOAC). Subjects receiving other anticoagulants are excluded. 6 blood samples are collected from each patient: before drug intake, 30 min, 1, 2, and 8 h after intake, and before next dose. Specific POCT is performed at each time-point using whole blood, citrated blood and citrated plasma. NOAC-concentrations are determined using mass spectrometry.
Results: 240 blood samples containing 0 to 275 ng/mL of dabigatran have been analyzed. Best ECT-POCT results were achieved using citrated plasma, where ECT ranged from 20 to 316 s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r = 0.96, p < 0.001). Concentrations >30 ng/mL (thrombolysis-threshold according to ESO guidelines) were detected by ECT-POCT >40 s with 99% sensitivity and 81% specificity. Heparin up to 4IE/mL did not influence ECT-POCT.
Conclusion: This is the first study evaluating NOAC-specific POCT. Results show excellent linear correlation of ECT-POCT and dabigatran-concentrations; relevant dabigatran-concentrations are reliably detected. First preliminary anti-Xa activity-POCT results will be presented.
AS06-009
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
ANTIBIOTIC PROPHYLAXIS IN ACUTE ISCHEMIC AND HEMORRHAGIC STROKE PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
2Division of Infectious Diseases, Medicine, Calgary, Canada
3O'Brien Insitute for Public Health, Community Health Sciences, Calgary, Canada
Background and Aims: Infections following stroke are associated with increased risk of complications and mortality. We sought to determine if prophylactic antibiotics following acute stroke patients help to prevent infections.
Method: We searched Embase (1974-), Medline (1946-), Cochrane Collaboration (1966-), and Pubmed (2015-). We also searched three major Infectious Diseases and Neurology journals to find unlisted publications, and explored trial registries for ongoing studies. We included randomized controlled trials that considered patients ≥18 years of age hospitalized following acute ischemic or hemorrhagic stroke. Screening and data extraction were done in duplicate. Meta-analyses were completed to evaluate the primary and secondary outcomes of relative risk (RR) of infection incidence and mortality between treatment and control groups, respectively. The impact of heterogeneity, study quality, and bias of included studies was considered in the meta-analyses.
Results: We included five studies for a total of 4030 patients. One study was of high, one of moderate and three of low quality. Pooling all five studies, there was no significant reduction in the incidence of infection (RR 0.69, 95% Confidence Interval [CI] 0.442–1.090; I-squared = 81.0%). Prophylactic antibiotics did not reduce mortality in studies with 90 day (RR 1.130, 95%CI 0.949–1.345, I-squared = 0.0%) or 180 day (RR 0.960, 95%CI 0.770–1.198, I-squared 0.0%) follow-up. No differences were noted regarding length of hospitalization or antibiotic-related adverse events but information were limited.
Conclusion: Based on the results of this systematic review, there is no compelling evidence to alter current guidelines to implement prophylactic antibiotics following acute stroke in adult patients.
AS32-005
Scientific Communication (Oral Abstract Presentation) Acute stroke – beyond reperfusion
DIAGNOSTIC VALUE OF NEW SEMIQUANTITATIVE IMAGING MARKERS OF CEREBRAL VENOUS THROMBOSIS: A MULTICENTER STUDY
V. Thijs1, S. Zuurbier2, C. Garcia-Esperon3, M. Barboza4, P. Costa5, I. Escudero Martinez6, D. Renard7, N. Hinteregger8, E. Giralt-Steinhauer9, S. Hiltunen10, A. Arauz4, J. Jiménez Conde11, F. Fazekas12, C. Weimar13, A. Pezzini5, J. Montaner6, J. Putaala10, T. Gattringer12, T. Tatlisumak14 and J. Coutinho2
1Florey Institute of Neuroscience and Mental Health, Stroke Division, Heidelberg, Australia
2AMC, Neurology, Amsterdam, The Netherlands
3HMRI, Neurology, Newcastle, Australia
4Instituto Nacional de Neurología y Neurocirugía in México City, Neurology, Mexico City, Mexico
5Clinica Neurologica- Università degli Studi di Brescia, Neurology, Brescia, Italy
6Hospital Universitario Virgen del Rocío, Neurology, Sevilla, Spain
7CHU Nîmes- Hôpital Caremeau, Neurology, Nîmes, France
8LKH-Univ. Klinikum Graz, Neuroradiology, Graz, Austria
9Parc de Salut Mar, Neurology, Barcelona, Spain
10Helsinki University Hospital, Neurology, Helsinki, Finland
11Institut Hospital del Mar d'Investigacions Mèdiques, Neurology, Barcelona, Spain
12LKH-Univ. Klinikum Graz, Neurology, Graz, Austria
14Sahlgrenska University Hospital, Neurology, Gothenburg, Sweden
Background and Aims: Semiquantitative imaging markers have recently been proposed which allow diagnosis of cerebral venous thrombosis on non-contrast computed tomography scans. The goal of this study was to assess the added diagnostic value of these imaging markers in the diagnosis of cerebral venous thrombosis (CVT).
Method: In a multicenter, case-control study of patients with confirmed recent onset CVT, two experts blindly assessed (1) the accuracy of the visual impression of CVT based on a combination of direct and indirect signs, (2) the accuracy of attenuation values of the venous sinuses in Hounsfield units (with adjustment for hematocrit levels) and (3) the accuracy of attenuation ratios of affected versus unaffected sinuses in comparison with gold standard MR or CT venography.
Results: We enrolled 285 patients with cerebral venous thrombosis and 303 controls from 10 international centers. Visual impression of thrombosis based on direct and indirect signs had a sensitivity of 56% (95% CI 0.54–0.57) and a specificity of 98% (95% CI 0.96–0.99). ROC analysis showed AUC values of 0.74 (95% CI 0.69–0.78) for measurement of sinus attenuation. The analysis of attenuation ratios of affected versus unaffected sinuses showed an AUC of 0.75 (95% 0.72–0.79). Adding this imaging marker to the visual impression of the rater, significantly improved the AUC to 0.81 (95% CI 0.76–0.84).
Conclusion: The added value of semiquantitative analysis of non-contrast CT for diagnosis of cerebral venous thrombosis is modest.
Imaging with MR Venography or CT Venography remains required, especially in patients without direct or indirect signs of cerebral venous thrombosis on non-contrast CT.
AS13-022
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
TEMPORAL TRENDS IN STROKE MORTALITY RATES FROM 1987 TO 2012 ACCORDING TO SEX. THE DIJON STROKE REGISTRY
M. Giroud1, B. Delpont1, C. Blanc1, C. Chazalon1, M. Hervieu-Bègue1, G.V. Osseby1, O. Rouaud1, D. Minier2, M. Giroud1 and Y. Béjot1
1Dijon Stroke Registry – EA4184 – University Hospital and Medical School of Dijon, Neurology, Dijon, France
2CH William Morey, Neurology, Chalon sur Saône, France
Background and Aims: The burden of stroke differs between men and women because of variations in the distribution of vascular risk factors. The aim of this study was to evaluate temporal trends in stroke mortality rates according to sex.
Method: All patients with acute stroke (ischemic stroke (IS), spontaneous intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and undetermined stroke) were identified through the population-based registry of Dijon, France, between 1987 and 2012. Stroke was considered to be fatal if death occurred within 30 days. Mortality rates were calculated using the population of Dijon as denominator, and were then standardized according to European population. Sex differences and temporal trends (according to 5-year time periods) were evaluated by calculating rate ratios (RRs) with Poisson regression.
Results: Over the study period, 5285 cases of stroke were recorded (52.7% women). Standardized mortality rates were 9.7/100,000/year in women and 15.3/100,000/year in men. Women:men sex RR was 0.70 (p < 0.01) with consistent results in IS (RR = 0.68, p < 0.01) and ICH (0.58, p < 0.01), but no sex difference for SAH and undetermined stroke. A decrease in mortality rates of overall stroke (mortality RR = 0.982, p < 0.01) and IS (RR = 0.978, p < 0.01) was observed with time in women but not in men (RR = 0.990, p = 0.148 and RR = 0.983, p = 0.064, respectively). Mortality rates of ICH and SAH remained stable in both sexes. Sex mortality RR did not change over time.
Conclusion: Mortality rates decreased in women over time, and sex differences remained stable, with an excess of stroke mortality in men
AS13-068
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
MARRIAGE, DIVORCE, SINGLE LIVING, WIDOWHOOD AND THE RISK FOR STROKE. A DANISH NATION-WIDE POPULATION-BASED STUDY
K.K. Andersen1 and T.S. Olsen2
1Danish Cancer Society Research Center, Section of Statistics, Copenhagen, Denmark
2Bispebjerg University Hospital – Copenhagen, Neurology, Copenhagen, Denmark
Background and Aims: Most studies indicate that marriage carries a lower risk of stroke than single living. Whether the marriage advantage is applicable with respect to all other marital status categories (divorced, single, widowed) remain far from resolved.
Method: We studied marital position (married, widowed, divorced, single) in all patients >40 years of age admitted for a first stroke to hospital in Denmark in 2003–2012 in comparison with the general Danish population (28.02 million person-years). Relative risks (RR) for stroke adjusting for age, sex, marital status, calendar year, household income, and length of education were estimated in log–linear Poisson regression models.
Results: We included 58847 patients with a first time stroke: Married 30525 (51.87%), singles 5039 (8.56%), divorced 7924 (13.46%), widowers 15359 (26.09%). Crude incidence of stroke was: 1.96 per 1000/yr (married), 1.52 per 1000/yr (singles), 2.36 per 1000/yr (divorced); 5.43/1000/yr (widowers). In comparison with married men risk for stroke was significantly increased for divorced (RR 1.23; CI 1.19–27) and single living men (RR1.07; CI 1.03–1.11) but not for widowed men (RR 1.00; CI 0.97–1.03). In comparison with married women risk was slightly increased for divorced women (RR 1.10; CI 1.06–1.15) while not for widowed (RR 1.00; CI 0.97–1.03) and single living women (RR 0.97; CI 0.92–1.03).
Conclusion: Divorce was associated with higher risk for stroke especially in men. Living in marriage or living alone as single or widowed did not affect risk for stroke into any clinical significant degree.
AS13-079
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
AGE- AND SEX-SPECIFIC ANALYSIS OF CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH EMBOLIC STROKE OF UNDETERMINED SOURCE
G. Ntaios1, G.Y.H. Lip2, K. Vemmos3, A. Rodríguez-Campello4, V. Arnao5, V. Caso5, M. Paciaroni5, E. Diez-Tejedor6, B. Fuentes6, A. Arauz7, S.F. Ameriso8, M.A. Hawkes9, F. Bandini10, A.G. Pastor11, J. Putaala12, T. Tatlisumak12, M.A. Barboza13, G. Athanasakis14, F. Gioulekas15 and V. Papavasileiou16
1University Hospital of Larissa, Medicine, Larissa, Greece
2University of Birmingham, Institute of Cardiovascular Sciences- City Hospital, Birmingham, United Kingdom
3Medical School of Athens- Alexandra Hospital, Department of Clinical Therapeutics, Athens, Greece
4Hospital del Mar. Neurovascular Research Group- IMIM-Hospital del Mar Institut Hospital del Mar d'Investigacions Mèdiques- Universitat Autònoma de Barcelona, Stroke Unit- Department of Neurology, Barcelona, Spain
5University of Perugia, Stroke Unit, Perugia, Italy
6La Paz University Hospital – Autónoma University of Madrid- IdiPAZ Health Research Institute, Department of Neurology and Stroke Center, Madrid, Spain
7Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez., Stroke Clinic, Mexico City, Mexico
8Institute for Neurological Research- FLENI, Department of Neurology-, Buenos Aires, Argentina
9Mayo Clinic, Department of Neurology- Division of Critical Care Neurology-, Minnesota, USA
10S. Paolo Hospital, Department of Neurology, Savona, Italy
11Hospital General Universitario Gregorio Marañón- IiSGM Health Research Institute- Universidad Complutense de Madrid, Vascular Neurology Section- Stroke Center-, Madrid, Spain
12Helsinki University Central Hospital and University of Helsinki, Department of Neurology, Helsinki, Finland
13Hospital Dr. Rafael A. Calderón Guardia- CCSS. University of Costa Rica, Neurosciences Department-, Costa Rica, Costa Rica
14Larissa University Hospital- School of Medicine- University of Thessaly, Department of Medicine, Larissa, Greece
15Sub-directorate of Informatics, Larissa General University Hospital, Larissa, Greece
16Leeds Teaching Hospitals NHS Trust and Medical School- University of Leeds, Stroke Service- Department of Neurosciences, Leeds, United Kingdom
Background and Aims: Age and sex modify the risk of recurrence and death in patients with previous ischemic stroke. We investigated whether this correlation is also evident in patients with embolic stroke of undetermined source (ESUS).
Method: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox-regression and Kaplan–Meier-product-limit analyses to investigate if age (<60, 60–80, >80years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death.
Results: Ischemic stroke/TIA recurrences and deaths per 100patient-years were 2.46 and 1.01 in patients <60years, 5.76 and 5.23 in 60–80years, 7.88 and 11.58 in >80years, 3.53 and 3.48 in women and 4.49 and 3.98 in men respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (HR:1.15, 95%CI:0.84–1.58) or death (HR:1.35, 95%CI:0.97–1.86). Compared with the <60years, the 60–80years and >80years groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9% and 37.0% respectively, p < 0.001) and death (6.4%, 40.6% and 100% respectively, p < 0.001), and higher risk for recurrent ischemic stroke/TIA (HR:1.90, 95%CI:1.21–2.98 and HR:2.71, 95%CI:1.57–4.70 respectively) and death (HR:4.43, 95%CI:2.32–8.44 and HR:8.01, 95%CI:3.98–16.10 respectively).
Conclusion: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is approximately 3- and 8-fold higher respectively above >80 years compared to <60 years. The age distribution in the ongoing secondary prevention ESUS trials may potentially have an impact on their power to detect a significant treatment effect.
AS17-018
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
TRAJECTORIES OF DEPRESSION SYMPTOMS LONG TERM AFTER STROKE IN MEN AND WOMEN: THE SOUTH LONDON STROKE REGISTER
S. Ayis1, A. Rudd2, L. Ayerbe3 and C. Wolfe4
1Kings College London, Primary Care and Public Health Sciences, LONDON, United Kingdom
2Kings College London, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
3Queen Mary University of London, Centre of Primary Care and Public Health, London, United Kingdom
4King's College London, Primary Care and Public Health Sciences, London, United Kingdom
Background and Aims: We extend our recent findings on trajectories of depression symptoms after stroke, and investigates these in men and women separately.
Method: Data from the South London Stroke Register (1998-2013), including 1098 patients (56% Males) who responded to the Hospital Anxiety and Depression scale (HADs), at least 3 times and survived at least 5 years, were used. Trajectories of depression were detected using group based trajectory modelling (GBTM).
Results: Three trajectories were identified for males: 47.3% have mild symptoms that may worsen over time, mean depression score, 1.8 (se = 0.24); 43.3% have mild/moderate symptoms that could increase over time, mean 5.9 (se = 0.33), and 9.4% had severe symptoms that persist over 5 years, mean 11.8 (se = 0.39), higher than 8 (recognised cut-off for depression casseness). For women, 4 groups were identified (I-IV) with stable but higher levels of symptoms. Predicted mean scores were, 2.4 (se = 0.23), 5.9 (se = 0.30), 9.7 (se = 0.39) and 14.4 (se = 0.47), and the groups comprised 4.6%, 18%, 46% and 31.4% respectively. Predicted means were consistent with observed means (Figure 1). Sensitivity analyse based on different inclusion criteria supported the 5 years’ results.
Conclusion: Women are at higher risk of depression, with 22.6% scoring above 8, compared to 9.4% of men. The study provides better insight into the natural history of depression that may help the provision of appropriate and timely health care.
Figure 1.
AS33-003
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
TRENDS IN ISCHEMIC STROKE RATES BY SEX FROM 2000 TO 2013: RESULTS FROM THE BRAIN ATTACK SURVEILLANCE IN CORPUS CHRISTI PROJECT
L. Lisabeth1, C. Li2, B. Sanchez3 and L. Morgenstern4
1University of Michigan, Ann Arbor, USA
2University of Michigan, Epidemiology, Ann Arbor, USA
3University of Michigan, Biostatistics, Ann Arbor, USA
4University of Michigan, Stroke Program, Ann Arbor, USA
Background and Aims: A recent study suggested that declining stroke rates were limited to men. Our objective was to compare trends in ischemic stroke rates by sex overall and within age groups.
Method: First-ever ischemic strokes from 2000–2013 were identified from the population-based Brain Attack Surveillance in Corpus Christi Project conducted in south Texas, USA. Annual population counts from the US Census for the same period were used to estimate the at-risk population. Poisson regression was used to model trends in ischemic stroke rates by sex and age group adjusting for ethnicity.
Results: There were 3,604 ischemic strokes (1,808 in women, 1,796 in men) during the study period. Women were older (median = 74 (IQR:62–83)) at stroke onset than men (median = 67 (IQR:57–77), p < 0.001). Significant decreases in stroke rates over time were observed in men and women in the two older age groups, while rates did not change significantly over time in the youngest age group (Figure). No differences in trends by sex were noted in any age group (p > 0.20 for all).
Conclusion: In our population-based study, similar rates of decline in ischemic stroke were observed for men and women ≥60 years for the fourteen year time period ending in 2013. Trends in those 45–59 years remained stable and did no differ by sex. Continued efforts to prevent stroke in the younger population are needed.
AS33-005
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
SEX DIFFERENCES IN RESPONSE TO THROMBOLYSIS IN ACUTE ISCHEMIC STROKE: ENCHANTED RESULTS
C. Carcel1,2, S. Else Charlotte3,4, X. Wang2,4, S. Sato4,5, C. Delcourt2,4, S. Yoshimura4,5, R. Lindley2,4, J. Chalmers2,6 and C.S. Anderson2,4,7
1The George Institute for Global Health, Neurological and Mental Health, Sydney, Australia
2The University of Sydney, Sydney Medical School, Sydney, Australia
3Oslo University Hospital, Department of Neurology, Oslo, Norway
4The George Institute for Global Health, Neurological and Mental Health Division, Sydney, Australia
5National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine, Osaka, Japan
6The George Institute for Global Health, Professorial Unit, Sydney, Australia
7The George Institute China at Peking University Health Science Center, Executive Unit, Beijing, China
Background and Aims: Women are more likely to present with severe deficits and have worse outcomes after acute ischemic stroke (AIS) than men. We investigated potential sex differences in characteristics and outcome among participants of the ENCHANTED trial.
Method: ENCHANTED was an international, randomized, open, blinded endpoint trial of low- (0.6 mg/kg) versus standard-dose intravenous alteplase in AIS patients who fulfilled the criteria for thrombolysis treatment. Effects of treatment and outcomes of symptomatic intracerebral hemorrhage (sICH) and death or disability at 90 days were assessed.
Results: Among 3297 participants, 1248 (38%) were women who tended to be older, have lower diastolic blood pressure, higher heart rate, higher National Institutes of Health Stroke Scale scores, more hypertension and atrial fibrillation, as compared to men. Women were also more likely to be admitted to a stroke unit and to receive rehabilitation, whereas men had higher sICH (odds ratio 0.52, 95% confidence interval 0.28–0.97) according to Safe Implementation of Thrombolysis in Stroke Monitoring Study criteria. In the comparison between low- and standard-dose alteplase, although consistent reductions in sICH was seen with low-dose, there were no significant treatment interactions with both sICH and death or disability.
Conclusion: Women with AIS tend to be older and have more severe neurological deficits at presentation than men. Although women were less likely to have sICH, there is no apparent gender differences with respect to the effects of lytic treatment and clinical outcome.
AS33-008
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
POORER QUALITY OF LIFE AT 3–6 MONTHS AFTER STROKE IN WOMEN COMPARED TO MEN IS DUE TO AGE AND SEVERITY BUT NOT CLINICAL CARE
S. Gall1, H. Phan1, L. Blizzard1, A. Thrift2, C. Anderson3, J. Kim2, N. Lannin4 and D. Cadilhac5
1University of Tasmania, Menzies Institute for Medical Research, Hobart, Australia
2Monash University, Department of Medicine, Melbourne, Australia
3University of Sydney, The George Institute for Global Health, Sydney, Australia
4La Trobe University, Faculty of Health Sciences, Melbourne, Australia
5Florey Institute of Neuroscience and Mental Health, Public Health- Stroke division, Melbourne, Australia
Background and Aims: Women have worse health-related quality of life (HRQoL) after stroke than men but the causes of this disparity are uncertain.
Method: First-ever strokes admitted to 44 hospitals participating in a clinical registry, from 2010–2014, had HRQoL assessed at 3–6 months after stroke using the EQ-5D-3L. Random-effects linear regression, accounting for hospital, estimated the mean differences (MD) in EQ5D utilities between women and men adjusting for sociodemographics, stroke type, walking on admission (proxy for severity) and evidence-based care (stroke unit care, thrombolysis, secondary prevention medications, mobilisation). For patients from one state, Queensland, further covariates included dysphagia screening and aspirin.
Results: Among 11,571 survivors, 6,415 EQ5D assessments. Women had lower HRQoL than men (MDcrude −0.048 95% CI −0.059, −0.037), and were also older (mean age 73.6 vs 69.7, p < 0.001), less able to walk on admission (35.6% vs 43.5%, p < 0.059), had longer length of stay (LOS, mean 8.0 vs 7.3 days, p = 0.0023) and less often discharged home (44.3% vs 51.5%, p < 0.001). In Queensland (n = 2,543), women also received less dysphagia screening (78% vs 81%, p = 0.009) and aspirin (77% vs 81%, p < 0.021) than men. Age, LOS and stroke severity but not clinical care attenuated the sex differences in HRQoL scores and the adjusted MD (MDadjusted −0.034 95% CI −0.046, −0.022) was small and unlikely to be clinically significant.
Conclusion: Poorer HRQoL in women after stroke was due to age and stroke severity but not clinical care received. Targeting stroke severity through acute therapies and improving care among for older patients may reduce sex differences in stroke outcomes.
AS33-011
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
SEX DIFFERENCES IN STROKE OUTCOMES: ANALYSIS FROM THE SOUTH LONDON STROKE REGISTER
A. Amarilla Vallejo1, T. Rudd1, C. Wolfe1 and A. Douiri1
1King's College London, Primary Care and Public Health Sciences, London, United Kingdom
Background and Aims: Sex-related differences in stroke burden are important, and limited data are available on these disparities in the long term outcomes. This study aims to evaluate a range of outcomes in men and women (death, recurrent stroke, disability, physical inactivity, cognitive impairment, depression and anxiety) in a large population-based cohort.
Method: We used data from patients included between 1-Jan-1995 and 31-Dec-2014 (n = 5,041) into the population-based South London Stroke Register of first-ever strokes in an inner London area. Patients were assessed at 7 days, 3 months, and yearly up to 20 years after stroke. The outcomes collected were death, recurrent stroke, disability, physical inactivity, cognitive impairment, depression and anxiety up to ten years post-stroke. Regression (Cox and Poisson) models were constructed to compare stroke outcomes between male and female.
Results: Of all participants 2466 (48.91%) were Female with a mean age of 67 (SD:14) years old while 2575(51%) were male, mean age of 73 (SD:15). After adjusting for age, pre-existing disability, stroke severity, subtypes and stroke risk factors, women had a 9% (HR: 0.9, 96% CI, 0.83 – 0.99) lower risk of death but a 24% (RR:1.24, (1.04 – 1.49)) greater risk of being cognitive impaired in the first year after stroke. Women have higher risk of being disabled 45% (RR: 1.45, (1.08 – 1.94)) and anxiety 32% (RR: 1.32, (1.03 – 1.68)) up to five years post-stroke.
Conclusion: After stroke, women have better survival than men but worse outcomes. Further studies are needed to confirm these findings.
AS33-016
Scientific Communication (Oral Abstract Presentation) WOMEN AND STROKE
PUERPERIUM BUT NOT PREGNANCY IS A RISK FACTOR FOR CEREBRAL VENOUS THROMBOSIS
S.M. Silvis1, S. Hiltunen2, E. Lindgren3, K. Jood3, L.J. Scheres4, S.M. Zuurbier1, F.L. Silver5, D.M. Mandell6, S. Middeldorp7, J. Putaala2, S.C. Cannegieter4, T. Tatlisumak3 and J.M. Coutinho1
1Academic Medical Center, Department of Neurology, Amsterdam, The Netherlands
2Helsinki University Central Hospital, Department of Neurology, Helsinki, Finland
3Sahlgrenska University Hospital, Department of Neurology, Gothenburg, Sweden
4Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands
5University of Toronto, Division of Neurology- Department of Medicine, Toronto, Canada
6University of Toronto, Division of Neuroradiology- Department of Medical Imaging, Toronto, Canada
7Academic Medical Center, Department of Vascular Medicine, Amsterdam, The Netherlands
Background and Aims: Pregnancy and puerperium are generally considered to be risk factors for cerebral venous thormbosis (CVT), but this has not been assessed in a controlled study.
Method: We performed an unmatched case-control study. Cases were consecutive adult patients with CVT admitted to four academic hospitals between 1987 and 2015. Controls were subjects from the control population of the Dutch MEGA study (Multiple Environtal and Genetic Assessment of risk factors for venous thrombosis). We excluded men, subjects older than 50, and women who used oral contraceptives. Puerperium was defined as the first 12 weeks after delivery. We adjusted for age and history of cancer. We stratified for pregnancy vs. puerperium, and 0–6 vs. 7–12 weeks postpartum.
Results: We included 146/714 cases and 1244/6296 controls in the analysis. Cases were younger (median 38 vs. 41 years) and more often had cancer (14% vs. 4%) than controls. A total of 39/146 (27%) cases and 82/1244 (7%) controls were pregnant or postpartum. Pregnancy or puerperium was associated with an increased risk of CVT (adjusted odds ratio 4.0; 95% confidence interval 2.5–6.3). This association was fully attributable to an increased risk during puerperium (11.4; 6.0–21.8). There was no association between pregnancy and CVT (1.2; 0.6–2.3). Women had the highest risk of CVT during the first 6 weeks after delivery (0 to 6 weeks: 21.1; 9.4–47.4 and 7 tot 12 weeks: 2.2; 0.6–8.6)).
Conclusion: Puerperium is a strong risk factor for CVT, in particular during the first 6 weeks. We did not find an association between pregnancy and CVT.
AS05-021
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
LOW FETAL HEMOGLOBIN PERCENTAGE IS ASSOCIATED WITH SILENT WHITE MATTER CHANGES IN ADULTS WITH HOMOZYGOUS SICKLE CELL DISEASE
D. Calvet1, T. Tuillier2, N. Mélé1, G. Turc1, A. Habibi3, L. Majhadi4, M. Edjalali5, F. Galactéros3 and P. Bartolucci3
1Sainte-Anne Hospital, Neurology, Paris, France
2Henri-Mondor Hospital, Neuroradiology, Paris, France
3Henri-Mondor Hospital, Sickle cell referral center, Paris, France
4Henri-Mondor Hospital, Neurology, Paris, France
5Sainte-Anne Hospital, Neuroradiology, Paris, France
Background and Aims: Silent White-matter changes (WMC) on brain imaging are common in sickle cell disease (SCD) individuals and associated with cognitive deficits in children. We assessed predictive factors of WMC in homozygous SCD adults without any neurological history.
Method: Patients were recruited among a cohort of homozygous SCD adults followed in a adult sickle cell referral center with available steady state biological parameters and who had a screening brain magnetic resonance imaging. WMC were rated by consensus using a validated age-related WMC scale.
Results: Among 83 included patients with no vasculopathy, the prevalence of WMC was 49% (95% confidence interval: 39–60). In univariable analysis, patients with WMC were more likely to be older (P = 0.003) to have an hypertension (P = 0.02), a lower red cell corpuscular volume (P = 0.005), a lower corpuscular hemologin concentration (P = 0.008), and a lower fetal hemoglobin percentage (%HbF) (P = 0.003). In the multivariable analysis, only a lower %HbF was associated with the presence of WMC (OR per 1% increase in %HbF = 0.84 [0.72–0.97, P = 0.021]). %HbF was also associated with WMC burden (P for trend = 0.007). The multivariable ordinal logistic regression analysis found an inverse association between higher WMC burden (age-related WMC score divided into 4 strata) and fetal hemoglobin level (OR for 1% increase in fetal hemoglobin: 0.89 [0.79–0.99], P = 0.039).
Conclusion: Our study suggests a protective effect of fetal hemoglobin level with regards to the presence and severity of silent WMC. Increasing fetal hemoglobin expression might be of interest in patients with WMC.
AS28-006
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
SCREENING FOR MONOGENIC CEREBRAL SMALL VESSEL DISEASE USING WHOLE GENOME SEQUENCING
R.Y.Y. Tan1, S. Gräf2 and H.S. Markus1
1University of Cambridge, Clinical Neurosciences, Cambridge, United Kingdom
2University of Cambridge, Medicine, Cambridge, United Kingdom
Background and Aims: Familial cerebral small vessel disease (F-SVD) presents with lacunar stroke, migraine and dementia. The most common cause is CADASIL caused by NOTCH3 mutations, although other genes have been identified including HTRA1 and COL4A1/2. Screening each gene individually is time consuming and expensive. New sequencing approaches allow simultaneous screening of multiple genes.
Method: As part of the NIHR BioResource-Rare Diseases (BRIDGE) Study, whole genome sequencing (WGS) was performed in 90 patients with suspected F-SVD and no NOTCH3 mutations, and 76 relatives.
Rare variants in 15 candidate genes were identified according to their minor allele frequency (<1x10−4) in 6476 unrelated non-SVD participants, and other control data sets (i.e. UK10K and ExAC databases). Only variants with a CADD score ≥15 were considered further.
Results: Known and novel cysteine-changing NOTCH3 mutations were identified in 3 patients. Previously reported HTRA1 mutations were identified in 2 patients, and 3 predicted pathogenic missense variants in regions of the HTRA1 gene affected by known mutations were identified in 1 patient and 2 families. Novel predicted deleterious missense variants were identified in COL4A2 (n = 1), COL3A1 (n = 1), CACNA1A (1 family) and ABCC6 (n = 1).
Conclusion: Beyond known disease-causing NOTCH3 and HTRA1 mutations, we also identified novel predicted deleterious missense HTRA1 variants; HTRA1 variants appear to be the second most common cause of F-SVD after CADASIL, occurring in 5.6% of our cases. We have diagnosed 13.3% of sequenced patients. Non-coding variation in known disease genes and potential novel disease genes remain to be identified. Our results also illustrate challenges in determining whether some variants are pathogenic.
AS28-007
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
ADDITIONAL CORTICOSTEROID TREATMENT IMPROVES OUTCOME IN CHILDHOOD STROKE DUE TO TRANSIENT FOCAL ARTERIOPATHY
M. Steinlin1, S. Bigi2, B. Stojanovski3, J. Gajera4, M. El Koussy5 and M. Mackay6
1, Bern, Switzerland
2Inselspital, Neuropaediatrics, Bern, Switzerland
3Royal Children's Hospital and Murdoch Research Institute, Neuropaediatrics, Parkville Melbourne, Australia
4Royal Children's Hospital, Neuropaediatrics, Parkville Melbourne, Australia
5Inselspital, Neuroimaging, Bern, Australia
6Royal Chidren's Hospital and Murdoch Research Institute, Neuropaedaitrics, Parkville Melbourne, Australia
Background and Aims: Focal cerebral arteriopathy (FCA) accounts for up to 35% of arterial ischemic stroke (AIS) in children, and is an important predictor of stroke recurrence. The study objective was to compare outcomes for children with FCA treated with combined corticosteroid antithrombotic treatment (CAT) to those receiving antithrombotic treatment (AT) alone.
Method: This multicenter retrospective Swiss/Australian cohort study analyzed consecutive children, aged 1 month-18 years, presenting with first AIS due to a FCA, from 1999–2014. Children with CAT were compared to those treated with AT. Primary outcome was the presence of neurological deficits at 6 months post AIS, as measured by the Pediatric Stroke Outcome Measure (PSOM). Secondary outcomes included resolution of stenosis and stroke recurrence.
Results: 73 children (51% males) were identified, 21 (29%) of whom received CAT. Mean (SD) age at stroke for the entire group was 7.9 years (4.7). Median (IQR) pedNIHSS was 3 (2.0–8.0) in the CAT-group and 5 (3.0–9.0) in the AT-group (p = 0.098). Median (IQR) PSOM 6 months post AIS was 0.5 (0-1.5) in the CAT-group, compared to 1.0 (0.5–2.0) in the AT-group (p = 0.035). Complete resolution of stenosis at last MRI was noted in 17 (81%) in the CAT-group compared to 24 (59%) in the AT-group (p = 0.197). Stroke recurrence occurred in one patient in each group.
Conclusion: Corticosteroid treatment provides additional benefit over antithrombotic treatment for improved neurological outcome in childhood AIS due to FCA. Larger prospective studies are warranted to further investigate these differences and understand mechanisms by which steroids modify outcome.
AS28-013
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
PREVALENCE AND TEMPORAL EVOLUTION OF COGNITIVE DYSFUNCTION IN YOUNG STROKE – FIRST DATA FROM A PROSPECTIVE SINGLE-CENTRE STUDY
D. Pinter1, M.S. Schweinzer2, T. Gattringer1, K. Niederkorn1, K. Krenn1, G. Bachmaier3, F. Fazekas1 and C. Enzinger4
1Medical University of Graz, Department of Neurology, Graz, Austria
2University of Graz, Department of Psychology, Graz, Austria
3Medical University of Graz, Institute for Medical Informatics- Statistics and Documentation, Graz, Austria
4Medical University of Graz, Department of Neurology and Department of Neuroradiology- Vascular and Interventional Neuroradiology, Graz, Austria
Background and Aims: The prevalence of young patients (55 years and younger) suffering from stroke globally increases. Studies assessing the prevalence of post-stroke cognitive deficits in young patients are rare. We therefore assessed the prevalence and course of cognitive dysfunction in a sample of young stroke patients at hospital admission (baseline, BL) and at three months follow-up (FU).
Method: Both at BL and FU, patients underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, executive function and word fluency.
Results: From February to November 2016, we consecutively examined 54 young patients (59% males; mean age: 44.7 +/−8.2 years) with an ischaemic (90.7%) or haemorrhagic stroke (9.3%). Within this period, 27 patients attended the FU assessment. At BL, deficits (defined by 1.5 standard deviations below standardised mean) were highly prevalent in general cognitive function (56.6%), processing speed (61.5%), attention (42.3%), executive function (44.2%) and word fluency (33.3%). In most domains, cognitive performance remained stable over FU, except for improvements in general cognitive function, processing speed and attention. In about one third of patients, considerable cognitive deficits were still present three months after stroke (general cognitive function: 29.6%; executive function: 33.3%; word fluency: 30.2%).
Conclusion: The high prevalence and generally missing improvement of cognitive deficits over short-term FU in young stroke patients highlight the importance of post-stroke cognitive assessment. Potential implications of these deficits (e.g. reduced quality of life, difficulties to return to work), emphasize the need for further investigations including development of targeted cognitive rehabilitation strategies.
AS28-020
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
FEASIBILITY AND SAFETY OF THROMBOLYSIS AND THROMBECTOMY IN CHILDREN WITH ACUTE ISCHAEMIC STROKE
S. Bigi1, A. Dulcey-Husi1, C. Bernasconi2, A. Melliger1, A. Datta3, M. Arnold2, J. Fluss4, J. Gralla5, A. Hackenberg6, O. Maier7, C. Poloni8, U. Fischer2 and M. Steinlin1
1University Children's Hospital, Department of Pediatrics- Division of Child Neurology, Bern, Switzerland
2University Hospital Bern, Department of Neurology, Bern, Switzerland
3University Children's Hospital, Department of Pediatrics- Division of Child Neurology, Basel, Switzerland
4University Hospital of Geneva, Department of Pediatrics- Division of Child Neurology, Geneva, Switzerland
5University Hospital Bern, Department of Diagnostic and Interventional Neuroradiology, Bern, Switzerland
6University Children's Hospital, Department of Pediatrics- Division of Child Neurology, Zürich, Switzerland
7Ostschweizer Kinderspital, Department of Pediatrics- Division of Child Neurology, St. Gallen, Switzerland
8University Children's Hospital, Department of Pediatrics- Division of Child Neurology, Lausanne, Switzerland
Background and Aims: Intravenous thrombolysis and/or endovascular therapy (IVT/ET) are evidence based treatment options in adults with an acute ischaemic stroke (AIS). However, randomised controlled trials in paediatric patients are lacking. This study aims to describe feasibility, safety and outcome of IVT/ET in children with AIS.
Method: Retrospective study (01/2000-12/2015) of a multicentre, prospective cohort with patients aged 1 month – 16 years diagnosed with AIS within 12 hours from symptom onset. Clinical and radiological data of patients receiving IVT/ET were compared with those receiving standard of care (SOC) using linear regression adjusting for potential confounders. Outcome was assessed 6 months after stroke using the paediatric stroke outcome measure (PSOM).
Results: Of 216 paediatric AIS patients, 81 (mean/SD age of 8.2/5.2 years; 32 females) were diagnosed within 12 hours after symptom onset. 4/5% patients received IVT and 11/14% ET. Patients receiving IVT/ET were older (mean age 11.4 vs 7.5 years, p = 0.01) and more severely affected (median pedNIHSS 13.0 vs 7.0, p < 0.001). Death and bleeding complications did not differ between the two groups, but patients receiving IVT/ET were more likely to experience stroke related complications (p = 0.017). Median (IQR) PSOM 6 months after AIS was 2.0 (1–3.4) and 1.0 (0–1.75) in the IVT/ET and SOC group respectively (p = 0.034). In a multiple regression analysis, higher baseline pedNIHSS remained associated with worse outcome (p = 0.029).
Conclusion: Only 38% of paediatric stroke patients were diagnosed within 12 hours after stroke onset. IVT and/or ET appears to be a feasible and safe treatment option in severely affected paediatric AIS patients.
AS28-034
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
SUBOPTIMAL USE OF SECONDARY PREVENTION AFTER STROKE IN YOUNG ADULTS: THE FUTURE STUDY
M. van Dongen1, M. Ekker1, R. Arntz1, N. Maaijwee2, H. Schoonderwaldt1, L. Rutten-Jacobs3 and F.E. de Leeuw1
1Radboud University Medical Center, Neurology, Nijmegen, The Netherlands
2Luzerner Kantonsspital, Neurology and Neurorehabilitation, Luzern, Switzerland
3University of Cambridge, Clinical Neurosciences, Cambridge, United Kingdom
Background and Aims: Almost every second patient experiences a recurrent vascular event after a stroke at young age (18–50 years). Although about one third of all young strokes have an unknown cause, in the remaining two thirds atherosclerosis often plays a role; providing an opportunity for secondary prevention. However, small studies suggest that prescription of secondary prevention is limited in these young patients. We therefore investigated (time trends in) the actual prescription of secondary prevention after a stroke in young adults in the FUTURE Study.
Method: 656 Patients with an ischemic stroke or TIA, aged 18–50 years were included between 1980 and 2010. We assessed (time trends in) the proportion of patients using secondary prevention after stroke (statins, antihypertensives, platelet inhibitors).
Results: Proportion of statin users increased up to 51.8% among patients included between 2000 and 2010. The proportion of those who used antihypertensives increased from 16.1% (1980–1989) to 29.2% (2000–2010). The use of platelet inhibitors increased from 63.6% to 80.1%. Conversely, one out of five young stroke patients does not receive any secondary prevention.
Conclusion: Although the use of secondary prevention after stroke at young age is increasing, many do not receive optimal secondary prevention yet. This provides a window of opportunity for further reduction of recurrent vascular events in these young patients with a long life expectancy.
AS28-035
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
RARE RNF213 VARIANTS LOCATED IN THE C-TERM REGION ENCOMPASSING THE RING DOMAIN ARE ASSOCIATED WITH MOYAMOYA IN CAUCASIANS
E. Tournier-Lasserve1, S. Guey2, M. Kraemer3, D. Hervé4, T. Ludwig5, M. Kossorotoff6, F. Bergametti2, J.C. Schwitalla3, S. Choi2, L. Broseus2 and E. Génin5
Background and Aims: Moyamoya angiopathy (MMA) is in East Asian countries strongly associated with the R4810K variant in RNF213 gene. This variant has never been detected in Caucasian patients. We aim to investigate if rare RNF213 variants are significantly associated with Moyamoya in Caucasian patients.
Method: 73 European Caucasian MMA patients and 577 controls from the French EXome project were included. Whole exome sequencing was performed in all subjects. A principal component analysis was performed with >16,000 SNP to ensure that patients and controls were ethnically matched. Association was tested using the fixed threshold collapsing method. Only functional variants with a minor allele frequency <0.01 were considered. The likelihood ratio (LR) statistics proposed by Ionita-laza et al. was used to test the presence of a region within RNF213 that would be significantly enriched in rare coding variants
Results: We showed a significant association between rare missense RNF213 variants and MMA in Caucasian patients (OR) = 2.23, 95% confidence interval (CI) = [1.18–4.08], p = 0.01). Probands variants had significantly higher pathogenicity scores and preferentially clustered in a c-terminal hotspot encompassing RNF213 RING domain (p < 10−3). This association was even stronger in childhood-onset and familial cases (OR = 3.76, 95% CI = [1.46–9.29], p = 0.003).
Conclusion: We provided significant evidence for the role of rare, non-R4810K, variants in the development of MMA in Caucasian patients, especially when located in the c-terminal part of the protein. Elucidation of the functional consequences of these rare missense variants upon the binding of RNF213 to its so far unknown substrates would be of major importance for the understanding of MMA mechanisms.
AS28-037
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
AFTER 30-YEARS INCREASING INCIDENCE OF HOSPITALIZATION FOR STROKE IN YOUNG ADULTS INCIDENCE IS NOW DECREASING. A NATION-WIDE POPULATION-BASED STUDY OF STROKE IN DANISH HOSPITALS 1980–2014
K.K. Andersen1 and T.S. Olsen2
1Danish Cancer Society Research Center, Section of Statistics, Copenhagen, Denmark
2Bispebjerg University Hospital – Copenhagen, Neurology, Copenhagen, Denmark
Background and Aims: Studies have reported increasing incidence of stroke in young adults. The aim of this study was to investigate incidence of hospitalization for stroke among young adults in Denmark.
Method: The Danish National Patient Register registers all Danes admitted with stroke. By linkage to population registries, we identified all persons in Denmark 20–100 years of age registered with incident stroke during years 1980–2014. We calculated yearly-standardized incidence rates of hospitalization for male and female stroke patients 20–40 years and 20–100 years of age, respectively.
Results: During the 34-year period, there was 139.5 million person-years at risk (for the 20–40 years olds 55.1 million person-years at risk). For age group 20–100 year incidence in 1980 was 219 (214–225) per 100,000 person-years for men and 242.8 (236.5–249.3) for women. Over the 34-year period, the incidence steadily increased to 345.0 (334.9–350.7) for men and 305.2 (297.9–312.6) for women, respectively. For the 20–40 years old men incidence was 19.4 (16.4–23.0) in 1980 increasing steadily to 50.5 (45.4–56.0) in 2010 and since then decreasing to 37.9 (33.6–42.6) in 2014. For the 20–40 years old women incidence was 19.8 (16.7–23.5) in 1980 increasing steadily to 60.7 (55.0–66.8) in 2009 and since then decreasing to 46.0 (41.2–51.2) in 2014.
Conclusion: A 30-year on-going increase in incidence of hospital admission for stroke among young adults has, since 2009, reverted and is now decreasing. Incidence has been higher in young women compared to men, but the changes in incidence has been similar in both sexes.
AS28-048
Scientific Communication (Oral Abstract Presentation) Young Stroke and Rare Causes
UTILITY OF CURRENT THROMBOPHILIA SCREENING IN YOUNG STROKE AND TIA PATIENTS
V. Alakbarzade1, A. Taylor2, M. Scully3, R. Simister4 and A. Chandratheva5
1University College Hospital- St Georges Hospital, Hyper-acute Stroke Unit, London, United Kingdom
2University College Hospital, Haematology department, London, United Kingdom
3University College London, Haematology department, London, United Kingdom
4University College Hospital, Hyper-acute Stroke Unit, London, United Kingdom
5University College London, Hyper-acute Stroke Unit, London, United Kingdom
Background: We aimed to determine the yield of current thrombophilia testing for young transient ischaemic attack (TIA) and stroke patients.
Methods: Setting: University College London Hospital stroke unit and daily TIA clinic, main referral centre for North-Central London region. Consecutive records and thrombophilia tests for ≤60yrs stroke/TIA patients were reviewed from 1st January 2015–1st August 2016. Standard thrombophilia testing included: Factor V Leiden(FVL) or prothrombin gene mutations(PGM), antiphospholipid antibody(APA), protein S, C and antithrombin testing.
Results: 628 stroke and TIA patients were ≤60yrs, mean age was 49.1yrs(SD+/−9.2). Of 360(57%) thrombophilia screened, 50(14%) were positive, 24(48%) <50yrs and 26(52%) 51–60yrs; 39(11%) stroke and 11(3%) TIA. Median vascular risk factors were 1(0–5 IQR). Of 50, 2(4%) had carotid artery stenosis >70%, 4(8%) carotid dissection, 11(22%) lacunar syndrome, 14(28%) cardioembolic aetiology and 19(38%) unknown aetiology.
Thirteen(4%) were homo/heterozygous FVL or PGM. Of 28(8%) positive for an APA (anticardiolipin antibody, beta-2-glycoprotein antibody or lupus anticoagulant), 21(6%) were single antibody positive, 5(1%) double antibody positive and 2(0.6%) triple antibody positive. 26(7%) had protein C, S or antithrombin deficiency but 17 acquired causes were excluded. In total 10(2.8%) were presumed hereditary deficiency.
Conclusion: Thrombophilia testing was positive in 11% stroke and 3% TIA patients with half 51–60yrs. 6% had a positive APA on one occasion and only 0.6% were triple APA positive. Thrombophilia mutations and protein C, S or antithrombin deficiency were rarely true positives. Further studies are required to identify clinical characteristics to help stratify cost and clinical utility of thrombophilia screening.
AS08-005
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
SEROTONIN REUPTAKE INHIBITORS AND RISK OF SYMPTOMATIC INTRACEREBRAL HEMORRHAGE FOLLOWING THROMBOLYSIS – FINDINGS FROM THE TRISP COLLABORATION
J.F. Scheitz1, G. Turc2, D. Strbian3, M.R. Heldner4, H. Erdur1, M. Endres1, P.J. Nederkoorn5, S.T. Engelter6 and C.H. Nolte1
1Charité – Campus Benjamin Franklin, Neurology, Berlin, Germany
2Centre Hospitalier Sainte Anne, Neurology, Paris, France
3Helsinki University Central Hospital, Neurology, Helsinki, Finland
Background and Aims: Selective serotonin reuptake inhibitors (SSRI) impair platelet function and have been linked to a higher risk of intracerebral hemorrhage. Therefore, we aimed to assess the impact of preadmission treatment with SSRIs on the risk of symptomatic intracerebral hemorrhage (sICH) after thrombolysis for ischemic stroke.
Method: As part of the TRISP collaboration, we pooled data from six European centers operating prospective registries of thrombolyzed stroke patients. Information of preadmission use of SSRIs was retrospectively collected. Logistic regression was used to analyze the association between SSRI and sICH (ECASS-II definition). Variables with potential association in univariable comparisons (p < 0.1) were considered for the multivariable regression analysis.
Results: 5672 patients were included (mean age 70 ± 14years, 44% female, median NIHSS 9 [IQR 5,16]). Preadmission treatment with SSRIs was present in 4.6% (n = 263) and sICH occurred in 4.2% (n = 236) of patients. Preadmission use of SSRIs was not associated with sICH in unadjusted (OR 1.0, 95%CI 0.5–1.9) or adjusted (OR 0.9, 95%CI 0.4–1.8) logistic regression. There was a significant interaction of concurrent use of oral anticoagulants (OAC) and SSRI for occurrence of sICH (p = 0.004), but no interaction of concurrent use of antiplatelets and SSRI (p = 0.89). Patients taking both OAC and SSRI had a significantly increased risk of sICH (adjusted OR 7.7, 95%CI 1.8–32.9,reference patients with no OAC and SSRI).
Conclusion: Exposure to SSRIs prior to thrombolysis did not affect the risk of sICH in this European collaborative cohort study. However, there was a strong signal of an increased risk of sICH in SSRI-treated patients with concurrent use of OAC.
AS08-015
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
INTRAVENOUS THROMBOLYSIS FOR PATIENTS WITH IN-HOSPITAL STROKE ONSET: PROPENSITY-MATCHED ANALYSIS FROM THE SITS-EAST REGISTRY
G. Tsivgoulis1,2, A. Katsanos1,3, P. Kadlecová2, A. Czlonkowska4,5, A. Kobayashi4,6, M. Brozman7, V. Švigelj8, L. Csiba9, K. Fekete9, J. Kõrv10, V. Demarin11, A. Vilionskis12, D. Jatuzis13, Y. Krespi14, C. Liantinioti1, S. Giannopoulos3 and R. Mikulik2,15
1University of Athens School of Medicine, Second Department of Neurology, Athens, Greece
2St. Anne’s Hospital, International Clinical Research Center and Neurology Department, Brno, Czech Republic
3University of Ioannina School of Medicine, Department of Neurology, Ioannina, Greece
4Institute of Psychiatry and Neurology, Second Department of Neurology, Warsaw, Poland
5Medical University of Warsaw, Department of Experimental and Clinical Pharmacology, Warsaw, Poland
6Institute of Psychiatry and Neurology, Interventional Stroke and Cerebrovascular Disease Treatment Centre, Warsaw, Poland
7Faculty Hospital Nitra- Constantine University Nitra, Department of Neurology, Nitra, Slovak Republic
8University Medical Centre Ljubljana, Department of Vascular Neurology and Neurological Intensive Care, Ljubljana, Slovenia
9Medical and Health Science Center- University of Debrecen, Department of Neurology, Debrecen, Hungary
10University of Tartu, Department of Neurology and Neurosurgery, Tartu, Estonia
11Sestre Milosrdnice University Hospital Centre, Department of Neurology, Zagreb, Croatia
12Vilnius University and Republican Vilnius University Hospital, Department of Neurology and Neurosurgery, Vilnius, Lithuania
13Vilnius University- Center for Neurology, Department of Neurology and Neurosurgery, Vilnius, Lithuania
14Memorial Şişli Hospital Istanbul, Neurology Department and Stroke Center, Istanbul, Turkey
15Medical faculty of Masaryk University, Department of Neurology, Brno, Czech Republic
Background and Aims: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital (IHS) acute ischemic stroke (AIS) onset is associated with unfavourable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke onset (OHS) treated with IVT. We sought to compare outcomes between IVT treated IHS and OHS patients by analysing propensity score matched (PSM) data from the SITS-EAST registry.
Method: We compared the following outcomes for all PSM patients: 1.symptomatic intracranial hemorrhage (sICH) defined with the SITS-MOST criteria, 2.favourable functional outcome (FFO) defined as a modified Rankin Scale (mRS) score of 0–1 at three months, 3. Functional independence (FI) defined as a mRS score of 0–2 at three months, 4.3-month mortality.
Results: Out of total 19,077 AIS patients treated with IVT, 196 IHS patients were matched to 5124 OHS patients, with no differences in all baseline characteristics (p > 0.08). IHS patients had lower median onset-to-treatment time [126 (80–150) vs. 155 (120–187), p < 0.001], but higher door-to-needle time [126 (80–150) vs. 65 (47–95), p < 0.001] compared to OHS patients. No significant differences were found between the two groups on the rates of sICH (1.6% vs 1.9%, p = 0.756), three-month median mRS scores [2 (0–4) vs 2 (1–4), p = 0.273], FFO (46.4% vs 42.3%, p = 0.257), FI (60.7% vs. 60.0%, p = 0.447) and mortality (14.3% vs 15.1%, p = 0.764) rates at three months.
Conclusion: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tPA delivery in patients with IHS.
AS08-020
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
REDUCING DOOR-TO-NEEDLE TIMES AT 17 HOSPITALS TO 36 MINUTES
N. Kamal1, T. Jeerakathil2, E.E. Smith1, B. Mann3, M.D. Hill1 and on behalf of the QuICR Alberta Stroke Program1
1University of Calgary, Clinical Neuroscience, Calgary, Canada
2University of Alberta, Neurology, Edmonton, Canada
3Alberta Health Services, Cardiovascular Health & Stroke- Strategic Clinical Network, Edmonton, Canada
Background and Aims: The effectiveness of intravenous alteplase is highly time dependent, and very short door-to-needle times (DNT) of 30 minutes or less have been reported in single centre hospitals, but never in an entire population. QuICR (Quality Improvement and Clinical Research) Alberta Stroke Program aimed to reduce DNT to a median of 30 minutes across the Canadian province of Alberta, which has a population of 4.1 million.
Method: We used the Improvement Collaborative Methodology from early 2015 to September 2016 with participation from all 17 Stroke Centres in Alberta. This methodology included 4 face-to-face workshops, site visits, webinars, data collection, data feedback, intensive process mapping, and process improvements. We compared data from 2009–2014 (collected during the Alberta Provincial Stroke Strategy) to data from March 2016-December 2016 (collected during the QuICR DTN Collaborative). Data from January 2015-February 2016 were excluded, as improvements were being implemented during this time.
Results: There were a total of 2,241 treated cases in the pre and post periods. The results are shown for all cases by hospital type in the table.
Conclusion: There were 19–42 minute reductions in median DTN across all hospital types including smaller rural and community hospitals without a dedicated stroke service or 24–hour neurology coverage. A targeted multi-site improvement collaborative can be an effective intervention to reduce DNT across an entire population.
AS08-025
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
EXPLANATIONS OF LATE ADMISSION OUTSIDE THE THERAPEUTIC TIME WINDOW IN ACUTE ISCHEMIC STROKE: INTERVIEW OF 1114 STROKE PATIENTS
T. Kharitonova1, E. Kashaeva2 and I. Voznjouk3
1Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Department of organisation of emergency medical care, Saint-Petersburg, Russia
2Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Department of Neurology, Saint Petersburg, Russia
3Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Department of Neurology, Saint-Petersburg, Russia
Background and Aims: Late admission is a major limitation for systemic thrombolysis in acute ischemic stroke; however, this phenomenon is understudied from the patients’ perspective.
Method: We interviewed acute ischemic stroke patients consecutively admitted to 14 urban stroke units in August-September, 2016.
Results: Of 1114 patients, 291 (29%) started seeking medical aid within 4 h, 94 (9%) within 4–5.5 h, and 635 (62%) within 6–1440h from stroke onset; 94 could not recall onset time. Age, living conditions, previous disability did not differ between early comers (EC; 0–4 h) and late comers (LC; over 4 h). Facial asymmetry, loss of verbal communication and visual disturbances were the most warning stroke signs (24%, 15% and 16% in EC vs. 16%, 6% and 9% in LC, respectively; p < 0.01). Early admission was associated with stroke onset in a public area (14% EC vs.5% LC, p < 0.01), daytime (41% EC vs.28% LC, p < 0.01), presence of witness (72% of EC vs. 61% of LC; p < 0.01), and assistance from co-workers (12% of EC vs. 5% of LC; p < 0.01). Underestimation of the severity of stroke symptoms (47%) and expectation of spontaneous improvement (46%) were the main self-reported reasons of delayed admission. EC demonstrated higher compliance to stroke prevention than LC (compliance with previously prescribed prevention regimen in 44% vs. 35% respectively; p < 0.01).
Conclusion: We conclude that the underlying cause of delayed admission in acute stroke is underestimation of symptoms and noncompliance rather than lack of awareness; this consideration should be addressed by public education strategies. Wide implementation of stroke education at workplace may improve the rate of early admission.
AS08-031
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
FIVE-YEAR SURVIVAL AFTER THROMBOLYSIS: A PROPENSITY SCORE MATCHED STUDY USING THE SOUTH LONDON STROKE REGISTER
W. Muruet1, A. Desikan1, A. Douiri1, A. Rudd2 and C. Wolfe1
1King's College London, Division of Health & Social Care Research, London, United Kingdom
2King's College London, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
Background and Aims: Thrombolysis using recombinant tissue-type plasminogen activator(rt-PA) is currently the only approved treatment for acute ischaemic stroke; nevertheless, little is known about long-term outcomes after its use since the majority of studies evaluate outcomes only up to 12 months. This study aims to assess outcomes up to 5 years after thrombolysis.
Method: We used data from patients included between 1-Jan-2004 and 31-Dec-2015 into the population-based South London Stroke Register of first-ever strokes of an inner London area. We performed propensity score matching using ‘nearest neighbour’ method to pair thrombolysed and non-thrombolysed cases in a 1 to 2 ratio by age, sex, ethnicity, pre-stroke Barthel index, acute phase National Institute of Health Stroke Scale (NIHSS) and stroke subtype. Survival curves and risk of death were estimated with Kaplan-Meier methods and Cox Proportional-Hazard models.
Results: SLSR population: 2,101 ischaemic stroke cases, 13.5% (95% CI [12–15]) received thrombolysis; After matching: 482 controls and 241 treated; thrombolysis significantly improved five-year survival (p = 0.0176). rt-PA therapy improved survival even in the subset of patients >75 years (p = 0.0109). Thrombolytic treatment reduced the risk of all-cause mortality (HR 0.68 [0.54–0.86] when adjusted for age, sex, ethnicity, pre-stroke Barthel, NIHSS and stroke subtype.
Conclusion: In this study, we provided evidence that thrombolytic therapy improves survival at five years. The use of propensity score matching helps to strengthen this argument.
AS08-057
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
LOW THROMBIN GENERATION PREDICTS POOR PROGNOSIS IN ISCHEMIC STROKE PATIENTS AFTER THROMBOLYSIS
Z. Bagoly1, R. Hudák2, E.G. Székely1, K.R. Kovács3, A. Nagy4, G. Hofgárt3, E. Berényi5, J. Kappelmayer2 and L. Csiba3
1University of Debrecen Faculty of Medicine, Division of Clinical Laboratory Sciences, Debrecen, Hungary
2University of Debrecen Faculty of Medicine, Department of Laboratory Medicine, Debrecen, Hungary
3University of Debrecen Faculty of Medicine, Department of Neurology, Debrecen, Hungary
4University of Debrecen Faculty of Public Health, Department of Preventive Medicine, Debrecen, Hungary
5University of Debrecen Faculty of Medicine, Department of Radiology, Debrecen, Hungary
Background and Aims: Thrombolysis by intravenous recombinant tissue plasminogen activator (rt-PA) is an effective therapy in acute ischemic stroke (AIS). Thrombin generation test (TGT) is a global hemostasis test providing information about the speed and amount of generated thrombin in plasma. Here we aimed to find out whether results of this test before the initiation of thrombolysis might predict outcomes.
Method: Study population included 120 consecutive AIS patients, all within 4.5 hours of their symptom onset, who underwent thrombolysis by rt-PA. Blood samples were collected from all patients upon admission and TGT was performed using platelet poor plasma. Clinical data of patients including the NIHSS score were registered at admission, day 1 and 7 after therapy. The ASPECT score was assessed using CT images taken before and 24 hours after thrombolysis. Long-term functional outcome was defined 3 months after the event by the modified Rankin Scale.
Results: Endogenous Thrombin Potential (ETP) and Peak Thrombin were significantly lower in patients with cardioembolic IS. Symptomatic intracranial hemorrhage (SICH) was found in 6 patients and was significantly associated with low ETP and Peak Thrombin levels. A multiple logistic regression model revealed that an ETP result in the lower quartile is an independent predictor of mortality within the first two weeks (OR:6.03; 95%CI:1.2-30.16, p < 0.05) and three months after the event (OR:5.28; 95%CI:1.27–21.86, p < 0.05).
Conclusion: Low levels of ETP and Peak Thrombin parameters increase the risk of therapy associated SICH. A low ETP result is an independent predictor of short- and long-term mortality following thrombolysis.
AS08-061
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
IMPACT OF STROKE CODE: AN ATTEMPT TO IMPROVE INTRAVENOUS THROMBOLYSIS RATE & SHORTEN DOOR TO NEEDLE TIME IN ACUTE ISCHEMIC STROKE
K. Zirpe1, S. Gurav1, R.S. Wadia2, A. Naniwadekar3, A. Deshmukh1, D. Tambe1, D. Kharwade1 and R. Kodagali4
1Ruby Hall Clinic, Neuro-trauma Unit, Pune, India
2RUBY HALL CLINIC, Neurology, Pune, India
3RUBY HALL CLINIC, Radiology, Pune, India
4Boehringer Ingelheim, Medical, Mumbai, India
Background and Aims: Timely intravenous thrombolysis for acute ischemic stroke is associated with better clinical outcome. “Stroke code” (SC) may improve the timeline in delivery of intravenous tissue plasminogen activator (tPA).1,2 This study aimed to measure the impact of “stroke code” on DTN reduction and lysis rates.
Method: Emergency staffs were instructed to activate common number on arrival of patients within 4.5 hr with symptoms of stroke. Total no. of patients who received IV thrombolysis were analysed. Parameters such as “symptom to door time”, “Door to physician time”, “Door to imaging time” and “door to needle (DTN) time” were calculated and compared in pre and post stroke code timeline using Mann Whitney U Test. The severities of acute stroke (NIHS) were calculated and compared within era’s using paired t-test. All statistics were performed using R version 3.2.2
Results:
Conclusion: Stroke Code implementation is associated with an increased rate of thrombolysis and reduced door to needle times in acute ischemic stroke patients presenting in window period and decrease in DTN.
References:
1. Chih-Hao et al, PLoS ONE 9(8):e104862
2. Gregg C et al, JAMA 311(16):1632–1640
AS08-063
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
INFLUENCE OF DEMOGRAPHIC AND CLINICAL CHARACTERISTICS ON TPA-USE OVER TIME: A MULTIVARIATE ANALYSIS OF PATIENT-DATA IN THE AUSTRIAN STROKE-UNIT REGISTRY
M. Marko1, A. Posekany2, J. Ferrari3, P. Sommer4, V. Lang3, W. Lang3 and S. Greisenegger1
1Medical University of Vienna, Neurology, Vienna, Austria
2Danube University Krems, Gesundheit Österreich GmbH, Vienna, Austria
3Krankenhaus Barmherzige Brüder, Department of Neurology, Vienna, Austria
4Krankenanstalt Rudolfstiftung, Department of Neurology, Vienna, Austria
Background and Aims: Iv-thrombolysis is an established treatment in acute ischemic stroke (AIS) and thrombolysis rates are increasing. We analysed the influence of demographic and clinical characteristics on thrombolysis-rates over time in a large cohort of patients with acute ischemic stroke.
Method: We analysed data of tPA-treated patients from 2005–2016 in the Austrian Stroke-Unit Registry. We analysed associations of demographic factors and clinical risk factors with tPA-use at two consecutive time-intervals (2005–2009/2010–2016) by multivariate logistic regression analysis. Model specification was done using bidirectional stepwise variable selection.
Results: Overall, data of 85 947 patients with AIS were implemented in this analysis, of which 14 226 (16.6%) were treated with iv-tPA. Rates of tPA-use increased from 7.5% to 15.5% in 2005–2009 and from 17.0% to 20.9% in 2010–2016.
Pre code era n = 659
Post code era n = 573
P Value
Percentage of patient thrombolysed
6.3% (44)
11.51% (65)
–
Average Door to physician time (in minutes)
32.93
8.94
<0.001
Average Door to imaging time (in minutes)
58.88
26.84
<0.001
Average Door to needle time (in minutes)
104.95
67.77
<0.001
Percentage of patients, DTN ≤60 minutes.
15.90%
53%
<0.001
NIHSS score
Before Thrombolysis 9.80 (±5.19)
After Thrombolysis 8.27 (±10.93)
Before Thombolysis 11.12 (±9.91)
After Thrombolysis 6.0 (±4.82)
Atrial fibrillation (AF) was associated with tPA-treatment in 2010–2016 (OR = 0.67, p < 0.001) but not in 2005–2009 (OR = 0.93, p = n.s.). Peripheral arterial disease (PAD), rural place of residence and transport by helicopter were significantly associated in 2005–2009 but not in 2010–2016 (PAD 2005–2009: OR = 0.55, p = 0.006 versus 2010–2016: OR = 0.88, p = n.s.; rural residence: 1.49, p = 0.003 vs. 0.97, p = n.s.; helicopter-transport: 1.60, p = 0.008 vs. 1.23, p = n.s.). Across both time-periods age >80 years, an onset-to-door-time (ODT) >120 min, pre-stroke disability, posterior circulation stroke, previous stroke and stroke severity were significantly associated with tPA-treatment.
Conclusion: We found decreasing associations of rural place of residence, transport by helicopter and PAD with tPA-use over the last 11 years. Conversely, we detected an increasing association of AF with tPA-treatment over time.
AS08-069
Scientific Communication (Oral Abstract Presentation) Thrombolysis in practice
THE ROLE OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN ISCHEMIC STROKE PATIENTS TREATED WITH TPA THROMBOLYSIS: RESULTS FROM THE MAGIC STUDY
A.M. Gori1, B. Giusti1, B. Piccardi2, P. Nencini3, M. Nesi3, V. Palumbo3, A. Sereni1, G. Pracucci2, E. Sticchi4, R. Abbate1 and D. Inzitari5
1University of Florence, Experimental and Clinical Medicine, Florence, Italy
2University of Florence, NEUROFARBA Department- Neuroscience Section, Florence, Italy
3Careggi University Hospital, Stroke Unit, Florence, Italy
4Careggi University Hospital, Thrombosis Centre, Florence, Italy
5University of Florence, NEUROFARBA Department- Neuroscience Section- Italian National Research Council, Florence, Italy
Background and Aims: Inflammatory mediators are altered in the acute phase of ischemic stroke (IS). Both pro-inflammatory and anti-inflammatory cytokines are involved in the pathogenesis of ischemic stroke and an imbalance [Office1] of which leads to inflammation. Data obtained in clinical settings using pro- and anti-inflammatory biomarkers are still scanty.
This study aimed to evaluate concurrently the effect of pro-inflammatory and anti-inflammatory cytokines on 3-month poor functional outcomes, symptomatic hemorrhagic transformation (SICH) and death in stroke patients treated with i.v. thrombolysis.
Method: Blood was taken before tPA administration (pre-tPA) from 327 patients (mean age 68, mean NIHSS 11). Pro(IL-1Beta, IL-6, IL-8, IL-12, IFN-gamma, IP-10, TNF-alpha and MCP-1)- and anti (IL-1RA, IL-4, IL-10)-inflammatory biomarkers were assessed by Bioplex assay system. Pre-tPA circulating cytokine levels and pro-inflammatory/anti-inflammatory ratios were analyzed according to SICH, death and 3-month mRs.
Results: At logistic regression analysis, after adjustment for major clinical determinants of outcomes, pre-tPA IL-6/IL-1RA ratio resulted to be an independent predictor of death [OR (95% CI) 1.09 (1.02–1.16), p = 0.020]. IL-6/IL-1RA ratio was also independently and significantly associated with a mRS 3–6 [OR (95% CI) 1.09 (1.02–1.16), p = 0.020]. IL-6, and IL-8 levels did not remain as predictors of death, whereas IL-12 levels were significantly and inversely associated with death [IL-12: OR (95% CI) 0.64 (0.43–0.65), p = 0.029].
Conclusion: Our data suggest that balance between pro- and anti-inflammatory cytokines may contribute to the pathophysiological mechanism of IS and poor outcomes after tPA and underline that some pro-inflammatory mediators may have a protective function at early stages of an ischemic injury.
AS16-007
Scientific Communication (Oral Abstract Presentation) Risk Factors
ATRIAL FIBRILLATION IN TIA AND ISCHEMIC STROKE PATIENTS WITH A PRIOR STROKE IN COMPARISON TO THOSE WITHOUT. A SWEDISH STROKE REGISTER (RIKSSTROKE) STUDY
F. Buchwald1, B. Norrving2 and J. Petersson2
1Department of Clinical Sciences- Neurology- Lund University, Neurology- Skåne University Hospital, Malmö, Sweden
2Department of Clinical Sciences- Neurology- Lund University, Neurology- Skåne University Hospital, Lund, Sweden
Background and Aims: A history of stroke is common in patients with transient ischemic attack (TIA) and ischemic stroke (IS) but there are only few reports characterising this group of patients. Atrial fibrillation (AF) is a major risk factor for TIA and IS. We therefore aimed to assess the proportion of prior stroke in patients with TIA and IS, and compare the proportion of AF and oral anticoagulant (OAC) medication at discharge in patients with a history of stroke versus those without.
Method: Hospital-based data on TIA and IS events, registered from July 2011 to June 2013, were obtained from the Swedish Stroke Register (Riksstroke). The item of a previous stroke was not specified as hemorrhagic or ischemic; the item of AF included both previously known and newly diagnosed AF.
Results: A history of stroke was present in 19.3% (2892/15012) of TIA and 24.6% (10853/44169) of IS patients, and its presence increased markedly with age. In all age groups, patients with prior stroke were more likely to have AF (TIA: 27.4% vs 16.4%; p < 0.0001; IS: 36.1% vs 28.0%; p < 0.0001). Among patients with AF, proportions of OAC medication at discharge were lower in patients with prior stroke than those without (TIA: 58.0% vs 66.5%; p < 0.0001; IS: 45.2% vs 52.7%; p < 0.0001).
Conclusion: In TIA and IS, AF is more common in patients with a history of stroke compared to those without. Patients with AF and a previous stroke were less likely to be treated with OAC than those without prior stroke.
AS16-010
Scientific Communication (Oral Abstract Presentation) Risk Factors
WHITE MATTER HYPERINTENSITY MORPHOMETRY PROVIDES NOVEL INFORMATION ABOUT FUTURE RISK OF STROKE
T. Evans1, M.A. Ikram1, M. de Groot2, P. Koudstaal3, M.K. ikram3, W. Niessen4, M. O'sullivan5 and M. Vernooij2
1Erasmus MC, Department of Epidemiology, Rotterdam, The Netherlands
2Erasmus MC, Department of radiology and nuclear medicine, Rotterdam, The Netherlands
3Erasmus MC, Department of Neurology, Rotterdam, The Netherlands
4Erasmus MC, Department of medical informatics, Rotterdam, The Netherlands
5Kings College London, Basic and clinical neuroscience, London, United Kingdom
Background and Aims: A higher volume of white matter hyperintensities (WMH) has been associated with an increased risk of stroke. Recent insights suggests that different morphometry of WMH may reflect different underlying pathology, with smaller WMHs displayed by those with cerebral amyloid angiopathy. A surface-to-volume ratio (WMHSVR) can be calculated to quantify this morphometry, analogous to, but independent of WMH-volume. Lower WMHSVR indicates fewer yet larger lesions in comparison to a similar volume with smaller and more frequent punctate lesions. Whether differences in WMHSVR can identify subgroups within WMH and elucidate more about risk for future events is unknown.
Method: Using the population-based Rotterdam study, 5220 stroke- and dementia-free individuals (> = 45 years) were followed for stroke occurrence for 5.3years. All participants underwent MRI with segmentation of WMH-volume and WMHSVR. Cox proportional hazard models were used to associate WMHSVR with risk of stroke, adjusting for age, sex, intracranial volume, WMH-volume, lacunar infarcts, cerebral microbleeds, and additionally cardiovascular factors.
Results: During follow-up 107 people experienced a stroke. Higher WMHSVR was associated to a decreased risk of stroke (hazard ratio per 0.1 increase in WMHSVR:0.69(p < 0.0001), and adjusting for cardiovascular factors:0.73(p = 0.004)). When categorizing the ratio into quartiles, a hazard ratio of 3.50 for stroke (p = 0.005) was observed for the lowest ratio quartile (ref:highest).
Conclusion: Stroke risk is thus not only associated with WMH-volume but also with WMH morphometry, with lower WMHSVR (i.e. fewer, larger lesions for given WMH volume) having an increased risk of stroke. The WMHSVR could improve identification of those at higher risk of stroke.
AS16-018
Scientific Communication (Oral Abstract Presentation) Risk Factors
GAMMA-GLUTAMYL TRANSFERASE PREDICTS STROKE RISK INDEPENDENT OF ALCOHOL CONSUMPTION: A KOREAN NATIONAL SAMPLE COHORT STUDY
W. Yang1, D.Y. Kim1, C.K. Kim2, D.W. Kang1, H.G. Jeong1, E.S. Park1 and S.H. Lee1
1Seoul National University Hospital, Neurology, SEOUL, Republic of Korea
2Korea University Guro Hospital, Neurology, SEOUL, Republic of Korea
Background and Aims: Gamma-glutamyl transferase (GGT) is generally regarded as an alternative biomarker for alcohol consumption. Recently, an independent role of GGT on vascular diseases is emerging, but is yet to be investigated regarding stroke. To clarify this obscure impact of GGT on stroke, we utilized a large-sized, national, standardized population cohort in Korea.
Method: In Korea, a sole system named the National Health Insurance Service (NHIS) provides full-coverage health insurance service for all citizens, which is unique in the world. From the NHIS, the NHIS-National Sample Cohort (NHIS-NSC), a large-scale cohort was designed by randomly selecting 2% of Koreans in consideration of demographic characteristics. We analyzed eligible individuals from this standardized cohort. The Cox proportional hazards model was used for the longitudinal study investigating the relationship between GGT and stroke.
Results: Among 455,521 eligible participants, 7,745 patients (1.70%) developed incident stroke: 6,003 ischemic strokes (ISs), 1,096 intracerebral hemorrhages (ICHs), and 646 subarachnoid hemorrhages (SAHs). IS and ICH, but not SAH, showed elevated risk with increasing GGT. GGT was independently correlated with increased risk of stroke after adjustment for alcohol consumption and stroke risk factors, and the results were still significant when stratified by alcohol consumption.
Conclusion: In the analysis with standard Korean population, GGT is a novel biomarker independently predicting stroke risk. As the biomarker, GGT is deserved to be re-evaluated in other ethnic groups.
AS16-029
Scientific Communication (Oral Abstract Presentation) Risk Factors
EMBOLIC STROKES OF UNDETERMINED SOURCE IN THE HELSINKI YOUNG STROKE REGISTRY: BASELINE CHARACTERISTICS
N. Martinez-Majander1, K. Aarnio1, J. Pirinen1,2,3, T. Lumikari1, T. Nieminen3, M. Lehto3, J. Sinisalo3, M. Kaste1, T. Tatlisumak1,4,5 and J. Putaala1
1Helsinki University Hospital, Department of Neurology, Helsinki, Finland
2Helsinki University Hospital, Department of Clinical Physiology and Nuclear Medicine HUS Medical Imaging Center, Helsinki, Finland
3Helsinki University Hospital, Department of Cardiology Heart and Lung Center, Helsinki, Finland
4Sahlgrenska University Hospital, Department of Neurology, Gothenburg, Sweden
5Institute of Neuroscience and Physiology The Sahlgrenska Academy at University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden
Background and Aims: Half of young-onset (<50 years) ischemic strokes (IS) remain cryptogenic after a complete diagnostic work-up. We applied the recently proposed embolic stroke of undetermined source (ESUS) criteria to patients in the Helsinki Young Stroke Registry to compare clinical characteristics of ESUS patients to patients with known causes.
Method: Among the first-ever IS patients in our registry, we identified ESUS patients based on clinical and imaging data. We compared them to patients with known causes, i.e. TOAST groups 1 to 4, and separately to those with cardioembolism (CE) from a high-risk source alone (TOAST 2).
Results: Of the eligible 773 patients, we found 201 ESUS patients (26.0%) and 572 (74.0%) patients with defined causes. ESUS patients were younger (median age 40 vs. 45 years, p < 0.001), had less cardiovascular comorbidities (2% vs 17%, p < 0.001) and milder strokes on the NIH Stroke scale (NIHSS, median 2.0 vs 3.0, p < 0.001). They had cortical and large ischemic lesions more frequently (59% vs 42%; 19% vs 15%, respectively, p < 0.001), and more migraine (22% vs 15%, p = 0.015). Furthermore, when compared to those with CE from a high-risk source (median age 44 years), ESUS patients were similarly significantly younger, had lower NIHSS scores and less cardiovascular comorbidities; in contrast, they had smaller and less frequently cortical lesions. Compared to defined causes and specifically to CE, women were overrepresented in the ESUS group.
Conclusion: Clinical characteristics of ESUS patients differ significantly from those with defined causes. Identifying these patients is the first step in developing new treatment strategies.
AS16-059
Scientific Communication (Oral Abstract Presentation) Risk Factors
AMBULATORY BLOOD PRESSURE LEVELS RELATE TO WHITE MATTER HYPERINTENSITIES PROGRESSION IN PRIMARY HIPERTENSIVES. RESULTS FROM THE ISSYS (INVESTIGATING SILENT STROKES IN HYPERTENSIVES: A MRI STUDY)
P. Delgado1, I. Riba-Llena1, J. Jiménez-Balado1, M. Noviembre1, O. Abril1, X. Mundet2, E. Espinel3 and J. Montaner1
1Institut de Recerca Hospital Vall d'Hebron. Universitat Autònoma de Barcelona UAB, Neurovascular Research Lab, Barcelona, Spain
2IDIAP Jordi Gol, Barcelona City Research Support Unit. UAB, Barcelona, Spain
Background and Aims: Hypertension is a risk factor for white matter hyperintensities (WMH) accumulation and poor cognitive outcomes in elderly individuals. We aimed to explore the relation between office and 24-hour ambulatory blood pressure monitoring (ABPM) and the presence of incident infarcts and WMH progression over time.
Method: Data from the ISSYS, a prospective cohort of hypertensive individuals, aged 50 to 70 without prior stroke or dementia. At baseline, all subjects underwent a brain MRI and 24-hour ABPM. WMH progression (periventricular and deep subcortical areas) was rated according to the Rotterdam Progression Scale and classified as none/minor (≤2 points) and marked (>2 points) at follow-up MRI. We explored the relationship between office and 24 hours, daytime and nighttime blood pressure and WMH progression or incident brain infarcts. Odds ratios were obtained by multivariate analysis after adjusting by age, gender, vascular risk factors and baseline WMH or silent brain infarcts.
Results: 220 subjects participated (mean age 64, mean time to follow-up MRI 4 years, mean baseline 24-hour BP 127.3/76.5 mmHg). Among all, 44 (20%) participants showed marked WMH progression and 14 (6.4%) presented incident brain infarcts. Age and the presence of baseline MRI lesions were associated with both WMH progression and incident infarcts. Regarding BP, 24-hours (OR = 1.12; p = 0.002), daytime (OR 1.12, p = 0.002) and nighttime (OR 1.09, p = 0.004) diastolic BP, but not office BP were independently associated with marked WMH progression.
Conclusion: Ambulatory diastolic BP levels were associated with marked WMH progression, which was present in up to 20% of this well-controlled hypertensive cohort.
AS16-079
Scientific Communication (Oral Abstract Presentation) Risk Factors
CEREBRAL ARTERIAL PULSATILITY IS ASSOCIATED WITH LEUKOARAIOSIS AND RECURRENT CEREBROVASCULAR EVENTS INDEPENDENTLY OF AGE AND BLOOD PRESSURE
A. Webb1, L. Li1, S. Mazzucco1 and P.M. Rothwell1
1University of Oxford, Centre for Prevention of Stroke and Dementia- Nuffield Department of Clinical Neuroscience, Oxford, United Kingdom
Background and Aims: Increased cerebral arterial pulsatility is associated with cerebral white matter disease, probably reflecting increased transmission of aortic pulse waves to the brain through stiff conduit vessels, yet the relationship between pulsatility, leukoaraiosis and cerebrovascular events is unclear.
Method: Patients recruited within 4–6 weeks of a TIA or non-disabling stroke (Oxford Vascular Study) had face-to-face follow-up to 5 years. Leukoaraiosis on baseline MRI was categorised by the Fazekas scale. MCA pulsatility (Gosling’s index, MCA-PI) was measured by transcranial ultrasound and aortic pulse wave velocity (PWV), and aortic systolic, diastolic and pulse pressure (SBP, DBP, PP) by applanation tonometry (Sphygmocor).
Results: Among 404 patients, MCA-PI was greatest in those with moderate/severe leukoaraiosis (0.92 vs 0.79, p < 0.0001). Severity of leukoaraiosis was strongly associated with MCA-PI and PWV (Fazekas ordinal OR: MCA-PI 2.10,1.65-2.66, p < 0.001; PWV 2.02,1.63-2.50, p < 0.001) with weaker associations with aortic SBP, DBP and pulse pressure. MCA-PI was the only predictor of recurrent cerebrovascular events (HR per SD: MCA-PI 1.34,1.05–12.5, p = 0.018; PWV 1.23,0.97–1.18, p = 0.09) and all cardiovascular events (MCA-PI: 1.73,1.36–41.3, p < 0.001; PWV 1.28,0.94–1.22, p = 0.12), and the only predictor of recurrent cerebrovascular events independent of haemodynamic measures, BP and age (HR = 1.50,1.04–2.18, p = 0.03). A strong relationship between PWV and risk of death primarily reflected age (unadjusted 1.71,1.21–2.07, p = 0.0002; age-adjusted 1.00,0.56–1.77, p = 0.99).
Conclusion: Although MCA pulsatility and aortic stiffness were both associated with leukoariasis, aortic stiffness primarily reflected the relationship between age and death whilst MCA pulsatility independently predicted recurrent cerebrovascular events. Cerebral pulsatility may be a novel treatment target for preventing progression of cerebrovascular disease, beyond standard BP management.
AS16-081
Scientific Communication (Oral Abstract Presentation) Risk Factors
BASELINE COGNITIVE SCORE AT TIME OF FIRST TIA/STROKE PREDICTS RISK AND SEVERITY OF RECURRENT STROKE: POPULATION-BASED STUDY
S. Pendlebury1, R. Wharton1 and P. Rothwell1
1Nuffield Department of Clinical Neurosciences- University of Oxford, Oxford, United Kingdom
Background and Aims: Cognitive impairment and dementia are risk factors for incident stroke, but associations with recurrent stroke are uncertain. We determined whether degree of baseline cognitive impairment at the time of first TIA/stroke predicted risk or severity of recurrent stroke.
Method: All patients with index TIA or stroke from 2002–2012 in a defined population of 92 728 (Oxford Vascular Study) had baseline clinical and cognitive assessment (MMSE) and follow-up for recurrent stroke to 2017. Risks of recurrent stroke and for severity (NIHSS) of recurrence were determined and stratified by baseline cognitive function (MMSE > 26; MMSE = 24–26; MMSE < 24 or pre-event dementia) adjusted for age/sex and vascular risk factors (diabetes, hypertension, hyperlipidaemia, AF, and smoking).
Results: In 1702 patients (mean/SD age = 73.8/13.1, 855/50% male and 569/33% TIA) risk of recurrent stroke on follow-up ranged from 13.4% (118/883; 95%CI = 11.1–16.0) in MMSE > 26 to 18.9% (100/530; 15.4–23.0) in MMSE < 24/dementia (adjusted HR = 1.59,1.18–2.12; p = 0.006). Recurrent stroke was also more severe (padj = 0.0042) in those with worse baseline cognition: NIHSS ≥ 3 occurred in 67/96 (70%) with MMSE < 24/dementia versus in 46/118 (39%) with MMSE > 26; NIHSS > 10 in 37/96 (39%) with MMSE < 24/dementia versus 17/118 (14%) with MMSE > 26.
Conclusion: Cognitive impairment at the time of TIA/stroke predicts both increased risk and severity of recurrent stroke. Baseline cognitive testing may be a useful addition to prognostic scores in clinical practice.
AS16-083
Scientific Communication (Oral Abstract Presentation) Risk Factors
7 YEAR TRENDS IN SUBDURAL HAEMORRHAGE: INCIDENCE AND ASSOCIATION WITH ANTICOAGULATION USAGE
M. Byrne1, M.T. Cooney2, S. Clarke3, J. Cronin4, M. Barry5 and R. Doyle6
1University College Dublin, School of Medicine and Medical Science, Dublin, Ireland
2St Vincents University Hospital, Department of Geriatrics, Dublin, Ireland
3Health Service Executive, Medicines Management Programme, Dublin, Ireland
4St Vincents University Hospital, Department of Emergency Medicine, Dublin, Ireland
5St James's Hospital, National Centre for Pharmacoeconomics, Dublin, Ireland
6St Columcille's Hospital, Department of Geriatrics, Dublin, Ireland
Background and Aims: More older people now receive anticoagulation, particularly for stroke prevention in atrial fibrillation. The introduction of direct oral anticoagulants (DOACs) and the aging population further increases this number. Our aim was to calculate incidence rate of subdural haemorrhage (SDH) on a background of increasing anticoagulation prescription.
Method: We identified through HIPE, patients in South-East Dublin and (most of) Wicklow presenting to St. Vincent’s University Hospital and St. Columcille’s Hospital between 2009–2015 with first acute SDH. Clinical information including demographics, medical co-morbidities, medications, examination, radiological severity, in-hospital outcome (mortality and disability) and discharge destination, was collected. Rates of SDH were calculated, using the age structure of the catchment area population from the 2011 Census and age-standardised using direct method and the European Standard Population.
Results: 313 patients presented with SDH from a catchment area of 330632 people (mean age 68.68 years, 43.77% women). The age-standardised rate for SDH overall was 11.86; 1.98 for anticoagulant-associated SDH. 25% gave no history of trauma. There was a possible non-significant trend towards increasing rates (p = 0.1) in SDHs overall, however these excess SDHs were trauma-related and occurred in younger people. There was no indication of an increasing trend in anticoagulant-associated SDHs over the 7 years (p = 0.82), see table.
Conclusion: Between 2010 and 2016 anticoagulation usage nationally increased by 53%[1]. However, the expected parallel increase in SDH has not been demonstrated thus far. The shift from warfarin to DOAC (1% DOACs in 2010 compared to 48% in 2016[1]) provides a potential explanation for this, however ongoing monitoring is required.
AS27-019
Scientific Communication (Oral Abstract Presentation) Risk Factors
RUPTURE RISK FOR FAMILIAL COMPARED TO SPORADIC INTRACRANIAL ANEURYSMS
L. Mensing1, Y. Ruigrok1 and G. Rinkel1
1University Medical Center Utrecht, Neurology, Utrecht, The Netherlands
Background and Aims: A 17-times higher rupture rate for patients with familial intracranial aneurysms (IA) compared to patients with sporadic IA has been reported. We aimed to validate these findings in a large independent series of Dutch patients with familial and sporadic IA.
Method: We included patients with untreated unruptured IA (UIA) from our prospectively collected database of the University Medical Center Utrecht between 1994 and 2016. In patients with familial IA, the IA were identified by screening because of a positive family history for subarachnoid hemorrhage (SAH); patients with a prior history of SAH or UIA were excluded. For sporadic IA, we selected patients with an incidental UIA and no family history of SAH or UIA. We assessed the incidence of SAH in the two patient groups with survival analysis and calculated an incidence ratio by dividing the observed incidence in the familial IA patients by the incidence in sporadic IA patients.
Results: We identified 65 familial IA patients with 93 UIA and 434 sporadic IA patients with 580 UIA. Four familial IA patients had SAH during 3239 patient-years of follow-up compared to ten sporadic IA patients during 1483 patient-years of follow-up. The observed incidence of rupture was 0.12 ruptures per patient-year (95% CI 0.03–0.32) for familial IA and 0.67 ruptures per patient-year (95% CI 0.34–1.20) for sporadic IA (incidence ratio 0.18 (95% CI 0.06–0.59)).
Conclusion: In contrast to previous reports, our results suggest that the risk of aneurysmal rupture is comparable for familial IA and sporadic IA.
AS23-006
Scientific Communication (Oral Abstract Presentation) Service Organisation
IMPACT OF TRANSCRANIAL DOPPLER ULTRASOUND ON LOGISTICS AND OUTCOMES IN PATIENTS TREATED WITH INTRAVENOUS THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE. RESULTS FROM THE SITS-ISTR
M. Mazya1, E. Azevedo2, A. Davalos3, L. Dorado3, M. Karlinski4, L. Svetlana5, D. Toni5, N. Ahmed1 and T.P. Moreira1
1Karolinska University Hospital, Department of Neurology, Stockholm, Sweden
2São João Hospital Center- Faculty of Medicine of University of Porto, Department of Neurology, Porto, Portugal
3Hospital Germans Trias i Pujol- Universitat Autònoma de Barcelona, Department of Neuroscience, Badalona, Spain
4Institute of Psychiatry and Neurology, Department of Neurology, Warsaw, Poland
5University of Rome- 'La Sapienza', Department of Neurology and Psychiatry, Rome, Italy
Background and Aims: Transcranial Doppler (TCD) is a valuable tool for diagnosing proximal arterial occlusion in patients with acute ischemic stroke. We aimed to assess how much TCD examination delays initiation of intravenous thrombolysis (IVT) and if pre-IVT TCD influences outcomes in stroke thrombolysis.
Method: We analysed data from the SITS-International Stroke Thrombolysis Register collected between December 2002 and December 2011, when TCD-related data entry was available. Among 31596 ischemic stroke patients treated with IVT, 1701 (5.4%) were examined with TCD prior to IVT initiation. Outcomes were door to needle time (DNT), functional independence (modified Rankin Scale 0–2), mortality at three months and symptomatic intracerebral hemorrhage (SICH).
Results: Patients examined with pre-IVT TCD had higher NIH Stroke Scale scores, 14 versus 12, p < 0.001. The DNT was higher in TCD patients, 74 vs 65 minutes, p < 0.001. There were no significant differences in functional outcomes (38.4% vs. 38.2%, p = 0.87), mortality (14.9% vs. 15.4%, p = 0.63) or SICH (1.5% vs. 1.9%, p = 0.28). Following multivariate adjustment for demographic, clinical and radiological covariates, and centre IVT patient volume, pre-IVT TCD was independently associated with a minor increase in functional independence (adjusted OR 1.2 (95% CI 1.0–1.3), p = 0.018) and lower mortality (adjusted OR 0.8 (95% CI 0.7–1.0), p = 0.049).
Conclusion: In our study, diagnostic TCD before stroke thrombolysis was employed in patients with more severe stroke, and increased the DNT by nine minutes on average. Its use was not associated with deleterious effects on clinical outcomes. Meanwhile, potential influence of unaccounted-for centre effects cannot be excluded.
AS25-020
Scientific Communication (Oral Abstract Presentation) Service Organisation
PREHOSPITAL STROKE SCALE (FAST PLUS TEST) PREDICTS PATIENTS WITH LARGE ARTERIAL VESSEL INTRACRANIAL OCCLUSION
D. Vaclavik1, M. Bar2, L. Klecka3, D. Holes4 and R. Mikulik5
2Faculty of Medicine – Ostrava University, Department of Neurology and Psychiatry, Ostrava, Czech Republic
3City Hospital Ostrava, Primary Stroke Centre, Ostrava, Czech Republic
4Comenius University in Bratislava-Jessenius Faculty of Medicine in Martin, Emergency Health Service Ostrava, Ostrava, Czech Republic
5St. Anne´s University Hospital and Faculty of Medicine- Masaryk University- International Clinical Research Centre- Stroke Research Program, Neurology, Brno, Czech Republic
Background and Aims: Mechanical thrombectomy is indicated for the treatment of occlusions of large cerebral arteries (LVO), it should be provided as quickly as possible, therefore, a test identifying the suspected occlusion in the pre-hospitalisation stage is needed for the patients to be directed to the centre providing mechanical recanalisation. We assume that the patients with clinically severe hemiparesis have a high probability of the presence of LVO. Therefore, the FAST test was modified to the FAST PLUS test. The FAST PLUS has two parts: the first is the well-known FAST test, the second part evaluates only the presence of severe arm or leg motor deficit (scored 0–1) and unilateral occurrence of its motor function deficit (scored 0–1).
Aims: Prospective multicenter study to determine specificity and sensitivity of the FAST PLUS test regarding the occlusion of major arteries in the anterior cerebral circulation confirmed by CT angiography (CTA).
Method: Firstly, paramedics trained in conducting the FAST PLUS test via e-learning. Secondly, in all pre-hospital FAST positive patients, demographic, NIHSS score, brain CT and CTA were recorded. Sensitivity and specificity of the FAST PLUS test were calculated.
Results: During 10 months 2016, 371 patients were enrolled to study. In 125 patients (33%) CT angiography showed the occlusion of intracranial artery. The sensitivity of the test for ICA/MCA occlusion was 93% and specificity 49%, NPV 93%,PPV 48%.
Conclusion: We found high sensitivity of the FAST PLUS test in our work. The test is suitable for prehospital selection of acute patients with suspected ischemic stroke due to LVO.
AS25-043
Scientific Communication (Oral Abstract Presentation) Service Organisation
WHICH HOSPITAL-LEVEL ORGANISATIONAL FACTORS CONTRIBUTE TO THE VARIATION IN MORTALITY FOR STROKE PATIENTS?
L. Paley1, E. Williamson2, B. Bray3, A. Hoffman4, P. Tyrrell5, M. James6, A. Rudd7 and O.B.O.T. SSNAP Collaboration4
1The Royal College of Physicians, CQID, London, United Kingdom
2London School of Hygiene and Tropical Medicine, Medical Statistics, London, United Kingdom
3University College London, Farr Institute of Health Informatics Research, London, United Kingdom
4Royal College of Physicians, CQID, London, United Kingdom
5University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
6Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
7King’s College London, Division of Health and Social Care Research, London, United Kingdom
Background and Aims: Well organised stroke care is associated with better patient outcomes but it is not known which organisational factors are most important.
Method: Data were extracted from Sentinel Stroke National Audit Programme (SSNAP) of adults (aged ≥ 16 years) with acute stroke treated in stroke hospitals in England and Wales between April 2013-March 2015. Multilevel models with random intercepts for hospitals were used to estimate the association of each variable with 30-day mortality in order to estimate the impact of admission to a differently organised hospital.
Results: Of the 143,578 patients with acute stroke admitted to 154 hospitals, 14.4% died within 30 days of admission. In adjusted analyses, admission to a hospital with a higher ratio of swallow-trained nurses to 10 acute beds was associated with reduced odds of death (p = 0.008), with an “elbow” around 2 swallow-trained nurses per 10 acute beds, with patients in hospitals with at least this ratio having the lowest odds of death. The number of patient admissions was also associated with odds of death (p = 0.015), in an “n-shaped” relationship where the highest odds of death were estimated in hospitals with around 450 admissions/year. A higher ratio of registered nurses on duty at 10am on a weekend was associated with lower mortality (p = 0.009), up to approximately 4 nurses per 10 acute beds.
Conclusion: This multiply-adjusted analysis demonstrates that high volume hospitals are not associated with the lowest mortality, but that appropriate staffing ratios are key, particularly the ratio of swallow-trained nurses to acute beds.
AS25-052
Scientific Communication (Oral Abstract Presentation) Service Organisation
BETWEEN AND WITHIN CENTER EFFECTS OF VOLUME ON WORKFLOW AND OUTCOME IN INTRA-ARTERIAL TREATMENT FOR ACUTE ISCHEMIC STROKE: RESULTS FROM THE MR CLEAN REGISTRY
B. Roozenbeek1, M. Mulder2, W. Schonewille3, G. Lycklama à Nijeholt4, J.A. Vos5, J. Boiten6, E. Venema7, V. Chalos1, I. Jansen8, R.J. Goldhoorn9, A. Van der Lugt10, D. Dippel1 and H. Lingsma7
1Erasmus MC, Neurology, Rotterdam, The Netherlands
2Erasmus MC, Neurology and Radiology, Rotterdam, The Netherlands
3St. Antonius Hospital, Neurology, Nieuwegein, The Netherlands
4Medical Center Haaglanden, Radiology, Den Haag, The Netherlands
5St. Antonius Hospital, Radiology, Nieuwegein, The Netherlands
6Medical Center Haaglanden, Neurology, Den Haag, The Netherlands
7Erasmus MC, Public Health, Rotterdam, The Netherlands
8Academic Medical Center Amsterdam, Radiology, Amsterdam, The Netherlands
9University Hospital Maastricht, Neurology, Maastricht, The Netherlands
10Erasmus MC, Radiology, Rotterdam, The Netherlands
Background and Aims: For many interventions, volume positively affects outcome. We aim to assess the effect of volume of intra-arterial treatment (IAT) for acute ischemic stroke on workflow and outcome.
Method: All IAT patients in 17 MR CLEAN centers in the Netherlands have been registered since the final MR CLEAN trial inclusion. We report patients included from March 2014 until June 2016. We analyzed the between-center effect of volume (number of patients treated per year) on workflow (time from ED arrival in the IAT center to groin puncture) and outcome (modified Rankin Scale score at three months). To detect within-center effects of increasing volume, we analyzed workflow and outcome over the subsequent years of inclusion.
Results: We included 1123 patients with complete data on workflow. Median yearly volume was 36 patients (interquartile range: 15–53). Yearly volume was weakly associated with time from ED arrival in the IAT center to groin puncture (adjusted beta -1 minute per 10 patients, p = 0.04), but not with outcome (adjusted odds ratio per 10 patients 0.97, p = 0.284). Within centers there was a positive effect of increasing volume on both time from ED arrival in the IAT center to groin puncture (adjusted beta -11 minutes per year, p < 0.01) and outcome (adjusted odds ratio 1.27 per year, p < 0.01).
Conclusion: Within centers, increasing volume improved workflow and outcome, but there were no differences between larger and smaller centers. This might be explained by selection. Alternatively, since volumes are still relatively low, higher volumes might be needed for between-center effects to become apparent.
AS25-056
Scientific Communication (Oral Abstract Presentation) Service Organisation
VARIATION IN THE USE OF URINARY CATHETERS IN ACUTE STROKE: EXPLORATION OF HEAD POSITION IN STROKE TRIAL (HEADPOST) TRIAL DATA
D. Forshaw1, C. Anderson2, H. Araima2, P. Lavados3, L. Billot2, M. Hackett2, V. Olavarria4, P. Munoz-Venturelli2, A. Brunser5, B. Peng6, L. Cui6, L. Song7, K. Rogers2, S. Middleton8, J. Lim2, M. Woodward2, O. Pontes-Neto9, D.S. Asita10, T. Robinson11 and C. Watkins12
1University of Central Lancashire, Lancashire Clinical Trials Unit- BB423, PRESTON, United Kingdom
2The George Institute, for Global Health, Sydney, Australia
3Clinica Alemana de Santiago, Universaidad del Desarrollo, Santiago, Chile
4Clinica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile
5Clinical Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile
6Peking Union Medical College Hospital, Department of Neurology, Beijing, China
7Shangai 85th Hospital of PLA, Department of Neurology, Shanghai, China
8Australian Catholic University, Nursing Research Institute, Sydney, Australia
9University of Sao Paulo, Ribeirao Preto School of Medicine, Ribeirao Preto, Brazil
10University of Kelaniya, Clinical Trials Unit- Faculty of Medicine, Ragama, Sri Lanka
11University of Leicester, Department of Cardiovascular Sciences, Leicester, United Kingdom
12University of Central Lancashire, Clinical Trials Unit, Preston, United Kingdom
Background and Aims: Urinary incontinence (UI) is common (approximately 50%) post-stroke, whilst evidence for interventions to improve outcomes is lacking, it is recommended that urinary catheters should be avoided to ensure patient safety and avoid urinary tract infections (UTIs) and other complications. UTIs are common post-stroke, and are linked to poorer functional outcomes, disability and death. Catheters are responsible for most UTIs in hospitalised patients and are a leading cause of sepsis. The longer the catheter stays in the greater the risk and reaches 100% after 30 days. This study explores the use of indwelling urinary catheters post-stroke in patients from countries participating in a global trial of head-positioning in acute stroke.
Method: Each centre aimed to recruit consecutive acute stroke patients; there was centralised follow-up with blinded outcome assessment. Data collected: type of stroke, presence of incontinence, use of urinary catheters, date of insertion and discontinuation, and SAEs.
Results: Eight countries contributed 161 centres and 11093 patients. 1166 (10.5%) received a urinary catheter. Proportions receiving a urinary catheter ranged from 4% (Taiwan) to 44.9% (India). Analyses performed and to be presented will explore casemix, process and outcome data to clarify the relationship between patient characteristics, incontinence and urinary catheter use, and SAEs across countries.
Conclusion: There are differences in the use of urinary catheters between countries within this trial population. These differences should be explored further to allow an understanding of variations in the implementation of evidence-based care.
AS25-057
Scientific Communication (Oral Abstract Presentation) Service Organisation
COST-EFFECTIVENESS OF ENDOVASCULAR THERAPY USING MECHANICAL THROMBECTOMY DEVICES FOR ACUTE ISCHAEMIC STROKE
C. Teljeur1, R. Glynn2, P. Harrington1, J. Harbison3, D. Williams4 and M. Ryan1
1Health Information and Quality Authority, Health Technology Assessment, Dublin, Ireland
2Health Service Executive, Public Health & Epidemiology, Dublin, Ireland
3St. James's Hospital, Centre For Medical Gerontology, Dublin, Ireland
4Royal College of Surgeons in Ireland, Geriatric Medicine, Dublin, Ireland
Background and Aims: There is RCT evidence that the addition of endovascular treatment with second-generation mechanical thrombectomy devices to intravenous thrombolysis significantly improves functional outcomes for eligible patients experiencing an acute ischaemic stroke. This study estimated the cost-effectiveness of adding mechanical thrombectomy to established standard-of-care.
Method: A decision-tree model with Markov component was populated with clinical effectiveness data derived from a systematic review and meta-analysis of published RCTs and other parameter estimates derived from the literature and local cost databases. The main outcome was the incremental cost-effectiveness ratios (ICER) at five years. The base case analysis assumed that two additional dedicated bi-planed angiography suites would be required to provide sufficient capacity for a national service.
Results: A national endovascular treatment service would lead to an incremental cost and benefit of €3,840 and 0.15 quality-adjusted life years (QALYs) per eligible patient. The ICER was €25,578 per QALY with a probability of being cost-effective of 34.1% and 85.2% at thresholds of €20,000 and €45,000 per QALY gained, respectively. There was a 4% chance of the intervention being cost saving relative to current care. The parameter with most influence on the ICER was the proportion of patients achieving functional independence. A national service would have substantial organisational implications, particularly for the timely transport of patients to treatment centres.
Conclusion: Assuming clinical outcomes achieved in RCTs can be replicated by a national service, addition of mechanical thrombectomy to standard-of-care would deliver a substantial clinical benefit at an acceptable cost given current Irish willingness-to-pay thresholds.
AS25-059
Scientific Communication (Oral Abstract Presentation) Service Organisation
VARIATION IN THE MANAGEMENT OF VENOUS THROMBOEMBOLISM (DVT AND PE) ACROSS THE WORLD: EXPLORATION OF HEAD POSITION IN STROKE TRIAL (HEADPOST) TRIAL DATA
C.E. Lightbody1, C. Anderson2, H. Araima2, P. Lavados3, L. Billot2, M. Hackett2, V. Olavarria3, P. Munoz-Venturelli2, L. Cui4, L. Song5, S. Middleton6, J. Lim2, M. Woodward2, O. Pontes-Neto7, A. De Silva8, R.T. Lin9, T.H. Lee10, J. Pandian11, T. Robinson12 and C. Watkins1
1UCLAN, Clinical Practice Research Unit, Preston, United Kingdom
2The George Institute, for Global Health, Sydney, Australia
3Clinica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile
4Peking Union Medical College Hospital, Department of Neurology, Beijing, China
5Shanghai 85th Hospital of PLA, Department of Neurology, Shanghai, China
6Australian Catholic University, Nursing Research Institute, Sydney, Australia
7Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil
8University of Kelaniya, Clinical Trails Unit- Faculty of Medicine, Ragama, Sri Lanka
9Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung, Taiwan R.O.C.
10Linkou Chang Gung Memorial Hospital, Department of Neurology, Taoyuan, Taiwan R.O.C.
11Christian Medical College, Department of Neurology, Ludhiana, India
12University of Leicester, Department of Cardiovascular Sciences, Leicester, United Kingdom
Background and Aims: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common (approximately 50%) post-stroke and may be life threatening. Current evidence –based guidance suggests that subcutaneous heparin (SCH) should not be given routinely for VTE prophylaxis, and should only be given to patients at high risk of VTE. However, intermittent pneumatic compression (IPC) sleeves are effective and should be applied as soon as possible (within 72 hours of admission). IPC should only be discontinued when the patient becomes independently mobile, at discharge from hospital or at 30days (whichever sooner) and if the patient develops adverse effects. This study explores the use of SCH and IPC in countries participating in a global trial of head-positioning in acute stroke.
Method: Each centre aimed to recruit consecutive acute stroke patients; there was centralised follow-up with blinded outcome assessment. Data collected: type of stroke, use of subcutaneous heparin and IPC devices, date of initiation and discontinuation.
Results: There were 11093 patients recruited from 161 centres across 8 countries.1895 (17.1%) received SCH and 1493 (13.5%) received IPC. Proportions receiving SCH ranged from 0.6% (Taiwan) to 83.3% (Brazil); and IPC from 0.4% (Brazil and Sri Lanka) to 28.3% (UK). Analyses performed and to be presented will explore casemix, process and outcome data to clarify the relationship between patient characteristics, and SCH and IPC use across countries.
Conclusion: There are differences in use of SCH and IPC between countries within this trial population. These differences should be explored further to allow an understanding of variations in implementation of evidence-based care.
AS25-061
Scientific Communication (Oral Abstract Presentation) Service Organisation
VARIATION IN THE IDENTIFICATION AND MANAGEMENT OF DYSPHAGIA AND PNEUMONIA ACROSS THE WORLD: EXPLORATION OF HEAD POSITION IN STROKE TRIAL (HEADPOST) TRIAL DATA
E. Boaden1, C. Anderson2, H. Araima3, P. Lavados4, L. Billot2, M. Hackett2, V. Olavarria4, P. Munoz-Venturelli2, A. Brunser4, B. Peng5, K. Rogers2, S. Middleton6, J. Lim2, D. Forshaw7, M. Woodward2, R.T. Lin8, T.H. Lee9, J. Pandian10, T. Robinson11 and C. Watkins1
1University of Central Lancashire, Clincial Practice Research Unit, Preston, United Kingdom
2The George Institute, for Global Health, Sydney, Australia
3The George Institute, for Global Healthf, Sydney, Australia
4Clnica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile
5Peking Union Medical College Hospital, Department of Neurology, Beijing, China
6Australian Catholic University, Nursing Research Institute, Sydney, Australia
7University of Central Lancashire, Clinical Trials Unit, Preston, United Kingdom
8Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung, Taiwan R.O.C.
9Linkou Chang Gung Memorial Hospital, Department of Neurology, Taoyuan, Taiwan R.O.C.
10Christian Medical College, Department of Neurology, Ludhiana, India
11University of Leicester, Department of Cardiovascular Services, Leicester, United Kingdom
Background and Aims: Pneumonia is common post-stroke (6-10%), it causes death, poor functional outcome, increases hospital stay and costs. Dysphagia, affecting 37–55% of stroke patients, contributes to pneumonia. Early identification of dysphagia, through screening, assessment, then effective management plans, could reduce pneumonia and other complications. The relationship between UK’s time to screening and assessment of dysphagia and pneumonia has been explored, but results were not interpreted with knowledge of subsequent management. This study explores the relationship between dysphagia screening, assessment, and management, and with pneumonia and 90 days outcome in a large cohort participating in a global trial of head-positioning in acute stroke.
Method: Each centre aimed to recruit consecutive acute stroke patients; there was centralised follow-up with blinded outcome assessment. Data collected: severity of stroke, details of screening, assessment and management of dysphagia, pneumonia (fatal/ non-fatal) and 90 day outcomes; status (dead/ alive) and modified Rankin.
Results: Eight countries contributed 161 centres and 11093 patients. 2042 patients had dysphagia (18.4%) and 411 (3.7%) developed pneumonia. Proportions with dysphagia ranged from 5.7% (Taiwan) to 46% (Brazil); pneumonia ranged from 1% (China) to 11.7% (Brazil). Analyses performed and to be presented will explore casemix, process and outcome data to clarify the relationship between dysphagia screening, assessment, and management, with pneumonia occurrence and 90 days outcomes.
Conclusion: There are differences in the occurrence of pneumonia, but also between country variation in clinical practice. These differences should be explored further to guide and standardise areas of nursing practice where further reliable randomized evidence is required.
AS25-066
Scientific Communication (Oral Abstract Presentation) Service Organisation
HOW USEFUL IS SIMULATION TRAINING
I. Grunwald1, S. Shah2 and P. Guyler3
1Southend University Hospital NHS Foundation Trust- Anglia Ruskin University, Radiology, Southend, United Kingdom
2Southend university hospital, Stroke Medicine, Southend, United Kingdom
3Southend University Hospital NHS Foundation Trust, Stroke Medicine, Southend, United Kingdom
Background and Aims: To assess if an interventional stroke service can be implemented in a hospital without previous neurointerventional experience by training staff on a high-fidelity vascular simulator in a virtual hospital environment.
Method: Key stroke care professionals (ward and cath-lab staff) received training in interventional neuroradiological procedures in a dedicated simulation environment. Training was conducted by an experienced Neurointerventionalist and included patient selection, imaging interpretation, interventional pathways, catheter skills, management of devices, anaesthetic considerations, pre-, peri- and post-interventional patient care, complications and medications.
Results: Joint, interdisciplinary training in the simulation environment allowed the development of a collaborative interventional stroke pathway and subsequent implementation of an interventional stroke service within 1 month of completion of training. Clinical outcomes matched or exceeded those of recently published randomized trials despite a severely affected (mean NIHSS 24), in a non-selected patient group. Mean times from decision to treatment (end of CT angiography) to arterial puncture were 27 minutes within- and 67 minutes out-of- hours. The anaesthetic team was available within a maximum of 3 minutes from decision to treat.
Conclusion: This is the first study demonstrating that Simulation Training enabled implementation of a collaborative, multidisciplinary,interventional stroke service in a hospital without previous neurointerventional expertise. Adoption of our team training strategy can help address the growing need for acute interventional services.
AS01-018
Scientific Communication (Oral Abstract Presentation) Acute intervention
MECHANICAL THROMBECTOMY FOR MINOR AND MILD STROKE PATIENTS HARBORING LARGE VESSEL OCCLUSION IN THE ANTERIOR CIRCULATION: A MULTICENTER CASE CONTROL STUDY
C. Dargazanli1, C. Arquizan2, R. Blanc3, A. Consoli4, B. Gory5, V. Costalat1, F. Turjman5, M. Piotin3 and B. Lapergue6
1Gui de Chauliac Hospital, Interventional Neuroradiology, Montpellier, France
2Gui de Chauliac Hospital, Neurology, Montpellier, France
3Rothschild Foundation, Interventional Neuroradiology, Paris, France
4Foch Hospital, Interventional Neuroradiology, Suresnes, France
5Pierre Wertheimer Hospital, Interventional Neuroradiology, Lyon, France
6Foch Hospital, Neurology, Suresnes, France
Background and Aims: Proximal large vessel occlusion (LVO) is present in up to 30% of minor strokes. There is no proven effectiveness of MT in the subgroup of minor stroke with LVO in the anterior circulation, with optimal management of these patients being yet not definitely addressed. The purpose of this case-control study was to evaluate MT in patients suffering from acute ischemic stroke (AIS) and LVO in the anterior circulation, presenting with minor to mild stroke symptoms (NIHSS < 8).
Method: Case-control study involving 4 comprehensive stroke centers, having two approaches regarding management of patients with NIHSS < 8 harboring LVO in the anterior circulation. An intention-to-treat analysis was conducted. The primary end point was the rate of excellent outcome defined as the achievement of a mRS score of 0 –1 at 3 months.
Results: 301 patients were included, 170 with MT associated to best medical management (BMM, case group) and 131 with BMM alone as first line treatment (control group). Patients treated with MT were younger, more often received intravenous thrombolysis, and had shorter time to imaging. Twenty-four patients (18.3%) belonging to the medical group had rescue MT due to neurologic worsening. Overall, excellent outcome was achieved in 64.5% of patients, with no difference between the two groups. Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size.
Conclusion: Patients having underwent MT or BMM achieve excellent and favorable functional outcome at 3 months in similar proportions. However, baseline differences were between the 2 groups, highlighting the urgent need for randomized trials.
AS01-034
Scientific Communication (Oral Abstract Presentation) Acute intervention
A NON-INFERIORITY, RANDOMIZED TRIAL OF THE SAFETY AND EFFECTIVENESS OF THE PENUMBRA 3D REVASCULARIZATION DEVICE AS AN ADJUNCT TO ASPIRATION IN ACUTE ISCHEMIC STROKE
R. Nogueira1, D. Frei2, J. Kirmani3, O. Zaidat4, M. Lazzaro5, D. Lopes6, A. Turk III7, D. Heck8, B. Mason9 and A. Siddiqui10
1Grady Health System, Dept of Neurology, Atlanta, USA
2Swedish Medical Center, Neurointerventional Surgery, Englewood, USA
3John F. Kennedy Medical Center, Neurocritical Care and Neurointervention, Edison, USA
4Mercy Health, Neuroscience and Stroke, Toledo, USA
5Froedtert Hospital, Neurology and Neurosurgery, Milwaukee, USA
6Rush University Medical Center, Neuroendovascular Surgery, Chicago, USA
7Medical University of South Carolina, Neurointerventional Surgery, Charleston, USA
8Forsyth Medical Center, Interventional Neuroradiology, Winston-Salem, USA
9Physicians Regional Medical Group, Neuroradiology, Naples, USA
10SUNY University at Buffalo & Kaleida Health, Neurosurgery, Buffalo, USA
Background and Aims: The benefits for a revascularization device when used as an adjunct to aspiration versus aspiration alone remain uncertain. The goal of this trial was to determine the safety and effectiveness of the 3D revascularization device when used in combination with the Penumbra Aspiration System (3D/PS) was non-inferior to the Penumbra Aspiration System (PS) alone.
Method: Patients presenting with ischemic stroke symptoms within 8 hours of onset with evidence of a large vessel occlusion (LVO, diameter ≥2.5 mm) and a NIHSS ≥8 were randomized 1:1 to either treatment arm. The primary endpoints were reperfusion of the target vessel at immediate post-procedure where the 3D/PS is non-inferior to PS by 15% or less and incidence of device- and procedure-related serious adverse events within 24 hours. A Core Laboratory evaluated imaging data, a Clinical Events Committee assessed safety events, and a Data Safety Monitoring Board monitored safety.
Results: In total, 198 patients were randomized at 25 sites: 98 to the 3D/PS and 100 to the PS alone arms. Results demonstrated that the 3D/PS was non-inferior to the PS arm in safety and efficacy (difference in mTICI 2–3 = 2.5%, 95% CI: −5.9% to 10.8%). The 3D/PS vs. PS rates for device- and procedure-related SAEs were 4.6% vs. 4.7% and 10.3% vs. 14.0%, respectively. The 90-day mRS 0–2 rates were 41.6% vs. 48.2%.
Conclusion: These findings provide Class 1 evidence for the similarity in safety and efficacy of a revascularization device when used as an adjunct to aspiration versus aspiration alone in acute stroke from LVO.
AS01-040
Scientific Communication (Oral Abstract Presentation) Acute intervention
ECONOMIC EVALUATION ALONGSIDE THE MULTICENTER RANDOMIZED CLINICAL TRIAL OF ENDOVASCULAR TREATMENT FOR ACUTE ISCHEMIC STROKE IN THE NETHERLANDS – MR CLEAN TRIAL
L. van den Berg1, O. Berkhemer2, P. Fransen3, D. Beumer4, H. Lingsma5, C. Majoie2, D. Dippel3, A. van der Lugt6, R. van Oostenbrugge4, W. van Zwam7, Y. Roos8 and M. Dijkgraaf9
1Academic Medical Center, Amsterdam, The Netherlands
2Academic Medical Center, Radiology, Amsterdam, The Netherlands
3Erasmus MC University Medical Center, Neurology, Rotterdam, The Netherlands
4Cardiovascular Research Institute Maastricht, Neurology, Maastricht, The Netherlands
5Erasmus MC University Medical Center, Public Health, Rotterdam, The Netherlands
6Erasmus MC University Medical Center, Radiology, Rotterdam, The Netherlands
7Cardiovascular Research Institute Maastricht, Radiology, Maastricht, The Netherlands
8Academic Medical Center, Neurology, Amsterdam, The Netherlands
9Academic Medical Center, Clinical Research Unit, Amsterdam, The Netherlands
Background and Aims: Endovascular treatment for acute ischemic stroke is expensive, but it may be cost-effective in the long run in comparison to standard care by improving survival and quality of life, and by reducing demands for rehabilitation and nursing home stay. An economic evaluation of endovascular treatment was performed alongside the MR CLEAN trial.
Method: In the economic evaluation we took a societal perspective with a 2-year time horizon. Incremental cost-effectiveness ratios (ICER’s) were calculated as the extra costs per additional patient with good outcome (mRS 0–2) and the extra cost per quality adjusted life year (QALY). Differences in costs and QALYs were displayed by a cost-effectiveness plane (C/E-plane), after non-parametric bootstrapping. The probability of the intervention being cost-effective was calculated for levels of society's willingness to pay (WTP) per QALY up to 100,000 euro’s.
Results: The incremental costs were minus €13,247 per extra patient with mRS 0–2 and minus € 76,937 per gained QALY. Endovascular treatment had a chance of being cost-effective of at least 97% for any WTP per QALY below 100,000 euro's (Figure 1 and 2).
Conclusion: Endovascular treatment in patients with acute ischemic stroke is cost-effective over 2 years.
AS01-056
Scientific Communication (Oral Abstract Presentation) Acute intervention
STRATIS REGISTRY: USE OF GENERAL ANESTHESIA AND IMPACT ON CLINICAL OUTCOME
N. Mueller-Kronast1, O. Zaidat2, M. Froehler3, R. Jahan4, M.A. Aziz-Sultan5, R. Klucznik6, J. Saver7, F. Hellinger- Jr.8, D. Yavagal9, T. Yao10, D. Liebeskind11 and D. Haussen12
1Advanced Neuroscience Network/Tenet South Florida, Neurointerventional Service, Delray Beach, USA
2St. Vincent Mercy Hospital, Neuroscience and Stroke Programs, Toledo, USA
3Vanderbilt University Medical Center, Cerebrovascular Program, Nashville, USA
4University of California Los Angeles, Division of Interventional Neuroradiology, Los Angeles, USA
5Brigham and Women's Hospital, Department of Neurosurgery, Boston, USA
6Methodist Hospital, Department of Radiology, Houston, USA
7University of California Los Angeles, Neurology and Comprehensive Stroke Center, Los Angeles, USA
8Florida Hospital, Interventional Neuroradiology, Winter Park, USA
9University of Miami Hospital, Department of Neurology and Neurosurgery, Miami, USA
10Norton Healthcare, Norton Neuroscience Institute, Louisville, USA
11University of California Los Angeles, Department of Neurology- Neurovascular Imaging Research Core, Los Angeles, USA
12Marcus Stroke and Neuroscience Center- Grady Memorial Hospital, Department of Neurology, Atlanta, USA
Background and Aims: Mechanical thrombectomy (MT) with stent retrievers is now standard of care for large vessel occlusion in acute ischemic stroke. The use of general anesthesia (GA) may impact patient outcomes.
Method: STRATIS is a prospective, multicenter, observational, single-arm registry of patients treated with MT within 8 hours from onset. A post-hoc analysis was performed to compare clinical outcomes in patients who received GA vs. conscious sedation (CS). CS group included patients with rescue GA.
Results: A total of 832 patients were analyzed; 580 (69.7%) received CS, 16 (6.3%) required rescue GA and 252 (30.2%) had GA. The GA cohort had lower mean core lab ASPECTS (7.9 vs. 8.2, p = 0.04), a shorter mean time from onset to puncture (209.8 vs. 235.9 minutes, p = 0.002). The mean NIHSS was similar (17.8 vs. 17.0, p = 0.10). The mean enrolling hospital door to puncture, puncture to reperfusion times, successful reperfusion (TICI ≥ 2b) and rate of symptomatic intracranial hemorrhage (sICH) and pneumonia were not significantly different between groups. The mean length of ICU and hospital stay were similar. The GA group achieved significantly less frequent good clinical outcome (mRS 0–2) at 90 days after adjusting for age, ASPECTS, NIHSS, and onset to puncture time (48.9% vs. 58.7%; OR = 0.67 p = 0.036); mortality was similar.
Conclusion: Mechanical thrombectomy can be safely performed under CS. There was no significant time delay with initiation of GA and time to revascularization. Rates of successful reperfusion, sICH, and mortality were not impacted. The lower likelihood of good clinical outcome in the GA cohort warrants a further randomized study.
AS09-011
Scientific Communication (Oral Abstract Presentation) Acute intervention
MECHANICAL THROMBECTOMY IN PATIENTS WITH ACUTE ISCHEMIC STROKE ON ANTICOAGULATION THERAPY
D. Sanak1, D. Cernik2, P. Divisova1, M. Kocher3, F. Cihlar4, T. Veverka1, A. Prcuchova2, M. Kral1, M. Cerna3, T. Dornak1, V. Prasil3, D. Franc1 and P. Kanovsky1
1University Hospital Olomouc, Comprehensive Stroke Center- Department of Neurology, Olomouc, Czech Republic
2Masaryk´s Hospital, Comprehensive Stroke Center- Department of Neurology, Usti nad Labem, Czech Republic
3University Hospital Olomouc, Comprehensive Stroke Center- Department of Radiology, Olomouc, Czech Republic
4Masaryk´s Hospital, Comprehensive Stroke Center- Department of Radiology, Usti nad Labem, Czech Republic
Background and Aims: Mechanical thrombectomy (MT) can be performed also in acute ischemic stroke (IS) patients using anticoagulation therapy (AT), however reported data has not been still enough consistent. Our aim was assess the safety and efficacy of MT in patients on AT.
Method: All consecutive IS patients treated with MT in both centers were enrolled in the retrospective analysis. In all patients, MT was performed using stent-retrievers, neurological deficit was scored using National Institutes of Health Stroke Scale (NIHSS) and 90day clinical outcome using modified Rankin scale (mRS) with score 0–2 for good outcome. Achieved recanalization was rated using Thrombolysis in Cerebral Infarction (TICI) scale. Symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria.
Results: Out of 750 patients treated with MT, 54 (7 %) patients (44 % of males, mean age 73 years) were on AT with a median of admission NIHSS 17 points. 87 % of patients had atrial fibrillation (AF). Overall recanalization was achieved in 89 % and complete (TICI 3) in 67 % of patients. ICH after MT was detected in 37 % of patients and SICH in 11 % of patients. 29 % of patients had good outcome after 3 months. 7-day mortality was 17 % and 45 % of patients died within 3 months.
Conclusion: MT seems to be safe also in patients on AT. Poor outcome with high 3-month mortality might be associated with presence of AF. Acknowledgment: Supported by grants: IGA LF UP_010_2017, RVO FNOL_00098892_2017 and IGA-KZ-2016-1-2.
AS09-046
Scientific Communication (Oral Abstract Presentation) Acute intervention
SAFETY AND OUTCOME OF INTRA-ARTERIAL TREATMENT FOR MINOR ISCHEMIC STROKE: RESULTS OF MR CLEAN REGISTRY
R.J. Goldhoorn1, M. Mulder2, I. Jansen3, W. Zwam- van4, D. Dippel2, A. Lugt- van der5, C. Majoie3, Y. Roos6, J.A. Vos7, J. Boiten8 and R. Oostenbrugge- van1
1Maastricht UMC+, Neurology, Maastricht, The Netherlands
2Erasmus Medical Center- Rotterdam, Neurology, Rotterdam, The Netherlands
3Academic Medical Center- Amsterdam, Radiology, Amsterdam, The Netherlands
4Maastricht UMC+, radiology, Maastricht, The Netherlands
5Erasmus Medical Center- Rotterdam, radiology, Rotterdam, The Netherlands
6Academic Medical Center- Amsterdam, Neurology, Amsterdam, The Netherlands
7St. Antonius Hospital- Nieuwegein, Radiology, Nieuwegein, The Netherlands
8Medical Center Haaglanden- The Hague, Neurology, The Hague, The Netherlands
Background and Aims: Intra-arterial treatment (IAT) for acute ischemic stroke has recently been shown to be safe and effective. However, insufficient data is available about IAT in patients with minor stroke symptoms (NIHSS 5 or less). Previous studies suggest that about one third of these patients will not reach a modified Rankin Scale score (mRS) <4 when IAT had not been performed. We present complications and functional outcome in patients with minor ischemic stroke who underwent IAT.
Method: The MR CLEAN-registry is an ongoing prospective multicenter observational study. All IAT treated patients in 17 MR CLEAN centers in the Netherlands have been registered since the final MR CLEAN trial inclusion. We report patients included from March 2014 until June 2016, who had an anterior circulation occlusion and were treated within 6.5 hours. Patients with baseline NIHSS 5 or less were included in the present study.
Results: Baseline NIHSS score was available for 1189 of 1221 patients. We identified 62 (5.2%) patients with NIHSS 5 or less. Symptomatic ICH occurred in 1 patient (1.6%). In total, 46/62 patients (74.2%) reached functional independence (modified Rankin Scale (mRS) 0–2) after 3 months, and 54 reached mRS 0–3 (87.1%).
Conclusion: Minor ischemic stroke patients who underwent IAT appear to have low occurrence of symptomatic intra-cranial hemorrhage, and have a high chance of favorable outcome. Therefore, IAT for minor ischemic stroke is justifiable in the absence of precise effect estimates from controlled studies.
AS09-048
Scientific Communication (Oral Abstract Presentation) Acute intervention
ASSOCIATION OF COLLATERAL STATUS ON BASELINE CTA WITH CLINICAL OUTCOME IN ACUTE ISCHEMIC STROKE; RESULTS FROM THE MR CLEAN REGISTRY
I. Jansen1, M. Mulder2, R.J. Goldhoorn3, A. van der Lugt4, W. van Zwam5, Y. Roos6, J.A. Vos7, B. Emmer4, G. Lycklama8, B. van der Kallen8, S. Jenniskens9, M. Sprengers1, A. van Es4, J. Boiten10, R. van Oostenbrugge3, M. van Walderveen11, D. Dippel2 and C. Majoie1
1Academic Medical Center University of Amsterdam, Radiology, Amsterdam, The Netherlands
2Erasmus Medisch Centrum Rotterdam, Neurology, Rotterdam, The Netherlands
3Maastricht University Medical Center, Neurology, Maastricht, The Netherlands
4Erasmus Medisch Centrum Rotterdam, Radiology, Rotterdam, The Netherlands
5Maastricht University Medical Center, Radiology, Maastricht, The Netherlands
6Academic Medical Center University of Amsterdam, Neurology, Amsterdam, The Netherlands
7St. Antoniusziekenhuis, Radiology, Nieuwegein, The Netherlands
8Medisch Centrum Haaglanden, Radiology, Den Haag, The Netherlands
9Radboud University Medical Center, Radiology, Nijmegen, The Netherlands
10Medisch Centrum Haaglanden, Neurology, Den Haag, The Netherlands
11Leiden University Medical Center, Radiology, Leiden, The Netherlands
Background and Aims: Radiological biomarkers can potentially play a key role in patient selection for intra-arterial therapy (IAT) in patients with acute ischemic stroke. The aim of this study was to assess the association of collateral status with clinical outcome on the modified Rankin Scale (mRS) at 90 days, and to determine whether this important radiological biomarker modifies the effect of IAT on mRS.
Method: All IAT treated patients in 17 MR CLEAN hospitals in Netherlands have been registered since the final MR CLEAN trial inclusion. We analyzed patients included from March 2014 until June 2016, who had an anterior circulation occlusion and were treated within 6.5 hours. All patients with available baseline CTA imaging were included (>95% of patients). Collaterals were graded on a 4-point scale, 0 (absent) to 3 (excellent). We investigated the association of collateral status with the modified Rankin Scale score at 90 days. We used propensity weighted and unadjusted ordinal logistic regression to compare outcomes in the MR CLEAN Registry with the treatment and controls arms of MR CLEAN. Also, we explored the influence of time to groin on the relationship of collateral status with mRS.
Results: The results will be presented at the conference and will include approximately 1500 patients.
Conclusion: This study will consist of the largest series examined to date. Insights in treatment benefit and clinical outcome for different collateral grades at different time points will be of direct value for clinical practice.
AS09-056
Scientific Communication (Oral Abstract Presentation) Acute intervention
COMPARISON OF RADIOLOGICAL OUTCOMES IN PATIENTS WITH ACUTE ISCHEMIC STROKE TREATED WITH DIFFERENT THROMBECTOMY TECHNIQUES
A.C. Hesse1, A. Kemmling2, N. Grosse-Hohkamp3, I. Frischmuth4, D. Behme1, J. Liman5, I.L. Maier5, J. Fiehler4, A. Mpotsaris3, P. Schramm2, A. Berlis6, M. Knauth1 and M.N. Psychogios1
Background and Aims: Thrombectomy has become the standard of care for acute ischemic stroke due to large vessel occlusion. Current literature lacks a comparison of different thrombectomy techniques. Aim of this study was to compare the radiological outcome of thrombectomy with aspiration only, stentretriever only and a primary combined approach (PCA).
Method: In this retrospective, multicenter study we analyzed the data of 450 patients with occlusion of the anterior circulation, treated in five high-volume centers from 2013 to 2016. The treatment-techniques were subdivided into five categories: 1. Aspiration only; 2. Aspiration with stentretriever rescue; 3. Stentretriever only; 4. Stentretriever with aspiration rescue; and 5. PCA. The primary endpoints were successful reperfusion (TICI2b/3) and groin-to-reperfusion-time. Secondary endpoints were the number of attempts and occurrence of “emboli-in-new-territory” (ENT). The primary analysis was based on the intention-to-treat-groups (ITT).
Results: The ITT-analysis showed significantly higher reperfusion rates, with 86% of successful reperfusion, in the PCA group compared to 73% in the aspiration group and 65% in the stentretriever group. There was no significant difference in groin-to-reperfusion-time regarding the used thrombectomy technique. The secondary analysis showed an impact of the technique on the number of attempts and the occurrence of ENTs. Lowest ENT rates and attempts were reported with the PCA-technique.
Conclusion: The combined approach of simultaneous deployment of an aspiration catheter and stentretriever was the most effective technique for reperfusion of anterior circulation large vessel occlusion. Our results correlate with the latest single center studies, reporting very high reperfusion rates with PCA variations (e.g. ARTS, SAVE, CAPTIVE etc.).
AS09-057
Scientific Communication (Oral Abstract Presentation) Acute intervention
CLINICAL OUTCOME OF ACUTE ISCHEMIC STROKE PATIENTS WITH EMERGENT ARTERIAL TANDEM OCCLUSIONS BY CERVICAL CAROTID TYPE OF REVASCULARIZATION
L. Dorado1, E. López-Cancio1, M. Hernández-Pérez1, M. Gomis1, N. Pérez de la Ossa1, E. Palomeras1, S. Remollo1, C. Castaño1, M. Terceño1, M. Millán1 and A. Dávalos1
1Health Sciences Research Institute of the “Germans Trias i Pujol”, Neurosciences, BADALONA. BARCELONA, Spain
Background and Aims: Carotid stenting in patients with tandem occlusions who undergo endovascular treatment (EVT) for acute ischemic stroke (AIS) may have higher risk of symptomatic intracranial haemorrhage (SICH) whereas isolated angioplasty may result in reocclusion of residual stenosis.
Method: We reviewed a prospective registry of AIS patients undergoing EVT for acute tandem occlusions (cervical ICA and MCA) from March 2008 to April 2016. We compared clinical (24 h neurological deterioration and mRS at 3 months) and neuroimaging outcomes (posprocedural TICI score, carotid artery reocclusion and SICH at 24 hours) between two groups of patients according to cervical carotid type of revascularization: stenting or angioplasty.
Results: Out of 430 patients with anterior large artery occlusions who received EVT, 77 had tandem occlusions, of which 68 underwent distal thrombectomy plus either carotid stenting+/-angioplasty (28/68, 41.2%) or isolated angioplasty (40/68, 58.8%). Baseline characteristics, NIHSS and ASPECTS score, IV tPA use and post-EVT TICI score were not different between groups. SICH was more frequent in the stenting group (3/28, 10.7% versus 1/40, 2.5%; p = 0.1) and carotid reocclusion in the angioplasty group (2/25, 8% versus 10/34, 29.4%; p = 0.04). In all patients with carotid reocclusion MCA remained recanalized. Both groups showed no significant differences in early neurologic deterioration (4/28, 14.3% vs 6/40, 8.3%; p = 0.9) and favourable outcome (mRS = 0–2) at 3 months (12/25, 48% vs 11/32, 34.4%; p = 0.3).
Conclusion: Reocclusion of cervical ICA after EVT for tandem occlusion was significantly higher after isolated angioplasty than after stenting. However, this did not result in significantly poorer early or late clinical outcome.
AS21-013
Scientific Communication (Oral Abstract Presentation) Imaging
PREDICTORS FOR GOOD COLLATERALS IN 857 PATIENTS WITH ACUTE ISCHEMIC STROKE AND PROXIMAL MIDDLE CEREBRAL ARTERY OCCLUSION
S. Nannoni1, C.W. Cereda2, G. Sirimarco1, D. Lambrou1, A. Eskandari1, A. Maghraoui3, F. Puccinelli4, P. Mosimann4, M. Wintermark5 and P. Michel1
1Centre Hospitalier Universitaire Vaudois and University of Lausanne, Stroke Center and Neurology Service- Department of Clinical Neurosciences, Lausanne, Switzerland
2Ospedale Civico di Lugano, Stroke Center- Neurology Service- Neurocenter of Southern Switzerland, Lugano, Switzerland
3Centre Hospitalier Universitaire Vaudois and University of Lausanne, Division of Clinical Pharmacology, Lausanne, Switzerland
4Centre Hospitalier Universitaire Vaudois and University of Lausanne, Department of Diagnostic and Interventional Radiology, Lausanne, Switzerland
5Stanford University and Medical Center, Department of Radiology- Neuroradiology Division, Stanford, USA
Background and Aims: Collaterals in acute ischemic stroke (AIS) correlate with infarct size, recanalization rate and clinical outcome. We aimed to identify predictors of good collaterals in a large series of AIS with middle cerebral artery (MCA) occlusion.
Method: In the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 2003 to 2016, we identified all AIS with M1 or proximal M2 occlusion on CTA performed <24 hours. Collaterals were scored from 0 (absent) to 3 (100% or more) according to Tan, and were correlated with multiple demographic, clinical, metabolic and radiological variables in a multivariate regression analyses (MVA). We also analysed clinical only and imaging only predictors in separate MVAs.
Results: The 857 included patients had a median age of 72.3 years, admission NIHSS of 16, and 48.4% were female. Better collaterals were associated with hemineglect (OR = 1.32), dyslipidemia (1.57), higher ASPECTS score (1.27) and lower clot burden (1.09). Poorer collaterals were seen with higher age (0.99), visual field defects (0.64), eye deviation (0.58), and decreased vigilance (0.62), and with higher creatininemia (0.99). Using clinical-only data, smoking, higher NIHSS and increasing delay to imaging also predicted poorer collaterals. Using radiological-only data, leukoaraiosis and chronic strokes were additional independent predictors of poorer collaterals.
Conclusion: Younger age, lower stroke severity (except for neglect) and dyslipidemia are predictors of good collaterals in proximal MCA occlusions. On neuroimaging, minor early ischemic changes and lower clot burden correlated with good collaterals. These data may help identify patients for late or aggressive recanalization treatments independently of time windows.
AS21-016
Scientific Communication (Oral Abstract Presentation) Imaging
THE CORE OF INFARCTION IN CT PERFUSION: RELIABLE ESTIMATOR OF REAL INFARCTION?
L. Martínez Vicente1, S. Trillo Senín1, C. Ramos Martín1, C. Aguirre Hernández1, S. Bashir Viturro1, P. Alcántara Miranda1, J. Villacieros Álvarez1, E. Bárcena Ruiz2, J.L. Caniego Monreal2, R. Manzanares Soler2, L. Vega Piris3, Á. Ximénez-Carrillo Rico1 and J. Vivancos1
1University Hospital la Princesa, Neurology, Madrid, Spain
2University Hospital la Princesa, Radiology, Madrid, Spain
3La Princesa Research Institute, Methodology, Madrid, Spain
Background and Aims: The initial infarct volume can be estimated by the cerebral blood volume(CBV) of CT perfusion(CTP). This study compares the initial CBV infarct core (CBV-core)with the final infarction on follow-up CT at 24 hours (24 h-core). The main objective was to characterize the predictive capacity of CTP depending on the time of evolution of cerebral infarction.
Method: Retrospective study of patients with acute occlusion of middle cerebral artery (MCA) treated with endovascular therapy(ET) in our hospital, excluding non-revascularized patients. The volume of CBV-core infarction was compared with the volume of 24 h-core infarction in the same evaluated CT slices. Static core was defined as an accurate estimation, with a difference of less than 10 ml between CBV-core and 24 h-core. The overestimation greater than 10 ml was denominated illusive core. The degree of accuracy of the CBV-core was correlated with the characteristics of the stroke.
Results: 116 patients. Median NIHSS:18(1,29). Mean growth between CBV-core and 24 h-core: 0,2 ml(SD:7,2). Mean time from CT to recanalization: 104,6 min(SD:61). Mean time from onset to CT:195,1 min(SD:169,9). Accurate estimation rate:84,1%. Illusive core rate:8,4%. Underestimation rate:7,6%. A statistically significant association was found between overestimation and early evolution time (p < 0,0001), discordance between CBV-core and initial ASPECTS(p < 0,05), and fibrinolysis(p < 0,05), as well as between growth of cerebral infarction and diabetes(p < 0,05), and poor collateral circulation(p < 0,05).
Conclusion: In our study early evolution time, discordance with initial ASPECTS and fibrinolysis were related to overestimation of infarction in CTP, whereas diabetes and poor collateral circulation were associated with growth of cerebral infarction. Therefore, when used alone CBV-core should be interpreted carefully for patient selection to reperfusion therapies.
AS21-017
Scientific Communication (Oral Abstract Presentation) Imaging
VALIDATING A PREDICTIVE MODEL OF ACUTE ADVANCED IMAGING BIOMARKERS IN ISCHEMIC STROKE
A. Bivard1, C. Levi2, L. Lin2, C. Xing3, R. Aviv4, N. Spratt2, L. Min5, M. Parsons2 and C. Levi2
1University of Newcastle, Newcastle, Australia
2University of Newcastle, Medicine, Newcastle, Australia
3Fudan University, Neurology, Shanghai, China
4University of Toronto, Department of Medical Imaging, Toronto, Canada
5Fudan University, Department of Neurology, Shanghai, China
Background and Aims: Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. The present study aimed to derive and validate a predictive model for functional outcome based on acute clinical and advanced imaging measures
Method: A database of prospectively collected sub-4.5 hour ischemic stroke patients being assessed for thrombolysis from 5 centres who had CT perfusion(CTP) and CT angiography before a treatment decision was assessed. Individual variable cut points were derived from a classification and regression tree analysis. The optimal cut points for each assessment variable were then used in a backwards logic regression to predict mRS 0–1 and 5–6. The variables remaining in the models where then assessed using a receiver operating characteristic curve analysis
Results: Overall 1519 patients were included in the study, 635 in the derivation cohort and 884 in the validation cohort. The model was highly accurate at predicting mRS 0–1 in all patients considered for thrombolysis therapy (AUC 0.91), those who were treated (AUC 0.88) and those with recanalization (AUC 0.89). Next, the model was highly accurate at predicting mRS 5–6 in all patients considered for thrombolysis therapy (AUC 0.91), those who were treated (0.89) and those with recanalization (AUC 0.91). The odds ratio of thrombolysed patients who met the model criteria achieving mRS 0–1 was 17.89 (4.59–36.35, p < 0.001) and for mRS 5–6 was 8.23 (2.57–26.97, p < 0.001).
Conclusion: This study has derived and validated a highly accurate model at predicting patient outcome after ischemic stroke.
AS21-050
Scientific Communication (Oral Abstract Presentation) Imaging
EXTENDING THE TIME FOR THOMBOLYSIS IN EMERGENCY NEUROLOGICAL DEFICITS (EXTEND) – PENUMBRAL CHARACTERISTICS AMONG PATIENTS 4.5-9 HRS AND WAKE – UP STROKE
H. Ma1, B. Campbell2, M. Parsons3, C. Levi3, L. Churilov4, A. Meretoja2, C. Hsu5, S. Davis2 and G. Donnan6
1Monash Health, Neurology, Clayton, Australia
2Royal Melbourne Hospital, Neurology, Melbourne, Australia
3University of Newcastle, Medicine, Newcastle, Australia
4Florey Neuroscience and Mental Health Research Institutes, Statistics, Melbourne, Australia
5China Medical University Hospital, Neurology, Taichung, Taiwan R.O.C.
6Florey Neuroscience and Mental Health Research Institutes, Medicine, Melbourne, Australia
Background and Aims: Background: EXTEND is an ongoing randomised, double-blind, placebo-controlled Phase III trial of intravenous alteplase vs. placebo among patients with ischemic stroke 4.5–9 hours from stroke onset or wake-up-stroke (WUS). There is uncertainty about the extent of salvageable tissue in this crucial time windows.
Objective: To determine the penumbral mismatch and ischaemic core volumes in EXTEND WUS and non-WUS cohort.
Method: Patients with ischemic stroke within 4.5–9 hours from stroke onset and WUS patients are eligible for enrolment. Criteria for trial entry include perfusion-ischemic core mismatch using a perfusion threshold of Tmax > 6 sec and a perfusion:core lesion volume ratio of >1.2. Ischemic core must be <70 mL based on assessment by automated RAPID software on MR or CT platforms (Stanford).
Results: 165 patients have been randomised to date with median age of 77.0 (IQR 65.0, 81.0 yrs), median admission NIHSS of 12.0 (8.0, 18.0). Compared to non WUS, 140 (66%) WUS patients had median NIHSS12.0 (8.0, 18.0) vs 10.0 (5.6, 16.0 p = 0.07), ischemic core volume 19.0 ml (7.0, 37.6 ml) vs 11.0 ml (6.0, 24 = 7.2 ml p = 0.17), perfusion deficit volume 82.0 ml (44.8, 124.8 ml) vs 59.5 ml (34.8, 118.0 ml p = 0.22), mismatch ratio 5.2 ml (2.9, 10.5 ml) vs 5.0 (2.5, 16.4 p = 0.9) and mismatch volume 60.8 ml (36.3, 102.3 ml) vs 51.0 ml (29.8 ml, 90.5 ml p = 0.3).
Conclusion: Within the EXTEND cohort, there is a clinically significant amount of salvageable penumbral tissue within the 4.5–9 hr time window and in WUS patients which has the potential to lead to clinical improvement if salvaged.
AS21-054
Scientific Communication (Oral Abstract Presentation) Imaging
REVISING COLLATERAL SCORING ON SINGLE-PHASE CTA: INSIGHTS GAIN FROM MULTI-PHASE CTA
H. Gensicke1, P. Pordelli2, D. Dowlatshahi3, F. Al Ajlan3, A. Poppe4, J.M. Boulanger5, T. Field6, A. Calleja7, R. Mikulik8, A. Jin9, J. Puig10, M. Hill2, M. Goyal11, A. Demchuk2 and B. Menon2
8St. Anne's University Hospital and Faculty of Medicine- Masaryk University, Neurology, Brno, Czech Republic
9Queen's University, Neurology, Kingston, Canada
10Dr Josep Trueta University Hospital, Radiology, Girona, Spain
11Hotchkiss Brain Institute- Cumming School of Medicine University of Calgary, Department of Clinical Neurosciences and Radiology, Calgary, Canada
Background and Aims: Collateral assessment on single-phase CTA (sCTA) is often dependent on timing of CTA acquisition. Using assessment of Hounsfield Units (HU) within arteries and sinuses, we sought to develop a time-adjusted pial collateral score that can be used for scoring collaterals on sCTA in acute ischemic stroke patients.
Method: Data are from the INTERRSeCT and ESCAPE trials. All patients had proximal anterior circulation occlusion and collaterals assessed on baseline sCTA using the regional collateral score (rCS) (ranging from 0 = absent to 10 = excellent). Acquisition phase of sCTA was determined using assessment of HU in different arterial and venous structures and a previously published template. Primary outcome was ASPECTS [</=4 versus >4)] on 24–48 hrs CT. Regression models were compared using C-statistics, Akaike (AIC) and Bayesian information criterion (BIC).
Results: Among 366 sCTAs, 48 (13.1%) were in early arterial (EA), 135 (36.9%) peak arterial, 155 (42.3%) arterio-venous equilibrium, 15 (4.1%) peak venous (PV) and 13 (3.6%) late venous (LV) phases. Median(IQR) rCS on EA-sCTA was 6(4–8) vs. 8(6–10) in peak arterial- and equilibrium-sCTAs and 10(9–10) in PV/LV-sCTA (p < 0.05). Ability of rCS to predict follow-up ASPECTS was better after excluding EA-sCTAs from analysis (AIC = 342 versus 289;BIC = 350 versus 296). Model fit improved further when collateral scores for prominence on venous-weighted sCTAs were recalibrated to lower scores (10- > 6) (AIC 275 versus 289;BIC 282 versus 296).
Conclusion: Collateral scoring on sCTA is dependent on phase of image acquisition. Excluding early arterial-sCTA from scoring and recalibrating excellent collaterals on venous-weighted-sCTA to moderate, improved validity of sCTA collateral assessments.
AS22-022
Scientific Communication (Oral Abstract Presentation) Imaging
QUANTITATIVE ASSESSMENT OF PLAQUE ENHANCEMENT IN SYMPTOMATIC INTRACRANIAL ATHEROSCLEROTIC LESIONS: A HIGH RESOLUTION MAGNETIC RESONANCE IMAGING STUDY
W. Yang1, X. Chen1, Y.O.Y. Soo1, T.W.H. Leung1, W.C.W. Chu2 and L.K.S. Wong1
1The Chinese University of Hong Kong, Medicine & Therapeutics, Hong Kong, Hong Kong S.A.R.
2The Chinese University of Hong Kong, Imaging & Interventional Radiology, Hong Kong, Hong Kong S.A.R.
Background and Aims: Contrast enhancement evaluated by using high-resolution magnetic resonance imaging (HRMRI) has been considered as an indicator of plaque vulnerability and inflammation in extracranial atherosclerosis, but its role in intracranial atherosclerosis remains unclear. In this study, we aimed to explore the changes of plaque enhancement over time after stroke by quantitatively assessing the enhancement patterns within symptomatic middle cerebral arteries (MCAs) plaques.
Method: We prospectively recruited 56 stroke or transient ischemic attack patients with culprit atherosclerotic plaques over MCAs. Cross-sectional MCAs was obtained before and after contrast media injection, and plaque enhancement indexes were calculated at the site of maximal luminal narrowing.
Results: Thirty-five patients were classified as acute phase (<4 weeks from symptom onset), 10 subacute phase (4–12 weeks) and 11 chronic phase (>12 weeks) (Table 1). The plaque enhancement index decreased gradually as the time of imaging relative to the ischemic event increased (32.7 ± 23.3, 24.5 ± 24.4, and 4.7 ± 12.0 for acute, subacute and chronic phase, respectively; P for trend = 0.001) (Figure 1).
Conclusion: Plaque enhancement in culprit MCA plaques declines during the post-infarct phase, which may reflect the dynamic changes of inflammatory involvement during post-stroke phases. Our findings may provide a promising imaging biomarker for risk stratification and targeted therapy of stroke patients with symptomatic intracranial atherosclerotic lesions.
AS22-023
Scientific Communication (Oral Abstract Presentation) Imaging
CLINICAL CORRELATES, PROGNOSTIC IMPLICATIONS AND ETHNIC DIFFERENCES OF PERIVASCULAR SPACES IN PATIENTS WITH TIA AND ISCHAEMIC STROKE
G.K.K. Lau1,2, L. Li1, C. Lovelock1, G. Zamboni1, T.T. Chan2, C. Ronald2, L. Kin Ting2, W. Kueker1, H. Mak3 and P. Rothwell1
1University of Oxford, Centre for Prevention of Stroke and Dementia, Oxford, United Kingdom
2University of Hong Kong, Division of Neurology- Department of Medicine, Hong Kong, Hong Kong S.A.R.
3University of Hong Kong, Department of Diagnostic Radiology, Hong Kong, Hong Kong S.A.R.
Background and Aims: Perivascular spaces (PVSs) are considered markers of small vessel disease (SVD). However, their long-term prognostic implications in transient ischaemic attack (TIA)/ischaemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown.
Method: Two independent prospective studies were conducted, one comprising predominantly Caucasians with TIA/ischaemic stroke (Oxford Vascular Study) and one predominantly Chinese with ischaemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semi-ovale (CS) PVSs, were studied with adjustment for age, sex, vascular risk factors and scanner strength.
Results: Caucasians with TIA/ischaemic stroke (n = 1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n = 974) (>20 BG-PVSs: 22.4% vs. 7.1%; >20 CS-PVSs: 45.8% vs. 10.4%, p < 0.0001). >20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all p < 0.0001). During 6924 patient-years follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischaemic stroke (adjusted HR compared with <11 PVSs, 11–20 PVSs: 1.15, 95% CI 0.78–1.68; >20 PVSs: 1.82, 1.18–2.80, ptrend = 0.011) but not ICH (ptrend = 0.10) or all-cause mortality (ptrend = 0.16). CS-PVSs were not associated with recurrent stroke (ptrend = 0.57) or mortality (ptrend = 0.072). Prognostic associations were similar in both cohorts.
Conclusion: Over and above ethnic differences in frequency of PVSs in TIA/ischaemic stroke patients, BG and CS-PVSs had similar risk factors, but whilst >20 BG-PVSs was associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not.
AS22-050
Scientific Communication (Oral Abstract Presentation) Imaging
A CLINICAL PREDICTION RULE WOULD ALLOW MORE EFFECTIVE CTA UTILIZATION OF VASCULAR IMAGING FOR SUSPECTED MILD ACUTE CEREBROVASCULAR (ACVS) IN THE EMERGENCY DEPARTMENT
A.M. Penn1, M.B. Bibok2, M. Penn1, K. Votova2,3, R.F. Balshaw4,5, M.L. Lesperance6, B.D. Farrell7 and J.R. Mathieson8
1Island Health Authority, Neurosciences, Victoria, Canada
2Island Health Authority, Research, Victoria, Canada
3University of Victoria, Division of Medical Sciences, Victoria, Canada
4British Columbia Centre for Disease Control, Disease Research, Vancouver, Canada
5University of British Columbia, Statistics, Vancouver, Canada
6University of Victoria, Mathematics and Statistics, Victoria, Canada
7Island Health Authority, Emergency Medicine, Victoria, Canada
8Island Health Authority, Medical Imaging, Victoria, Canada
Background and Aims: Canadian Stroke Best Practice Guidelines (2014) recommend patients suspected of Acute Cerebrovascular Syndrome (ACVS) receive urgent vascular imaging. High requisition rates for non-ACVS patients, however, overburden radiological resources. We hypothesize that our clinical prediction rule (CPR) developed for diagnosis of ACVS could improve CTA utilization.
Method: Patients – consecutive emergency department (ED) referrals to our TIA clinic from 2015–2016. Referral forms captured all data needed for the CPR. For patients who received CTA, orders were placed in the ED or at the TIA clinic upon arrival. McNemar’s test used to compare sensitivity, specificity, and accuracy of our CPR vs. clinician baseline CTA orders for identifying ACVS.
Results: Out of 1978 referrals clinicians ordered 1190 CTAs. Our CPR would have ordered a total of 1208 CTAs for the same patients. The increase in sensitivity, specificity, and accuracy of our CPR over clinician baseline CTA orders is significant, p < 0.001. Overall, CPR would have ordered an additional 18 CTAs over the 2-yr period, while simultaneously increasing the number of imaged-ACVS patients by 125 with imaging 107 fewer non-ACVS patients.
Conclusion: Our CPR would assist ED physicians to practice as per Canadian stroke best practice guidelines, improving ordering of vascular imaging for ACVS patients before ED discharge, while holding institutional numbers of CTAs constant.
AS22-054
Scientific Communication (Oral Abstract Presentation) Imaging
IS INFARCT VOLUME ON CT A USEFUL PROXY FOR FUNCTIONAL OUTCOME? RESULTS FROM THE MR CLEAN TRIAL
H. Lingsma1, K. Companje2, M. Broers3, D. Dippel4, H. Marquering3, A. van der Lugt2 and C. Majoie3
1Erasmus MC, Public Health, Rottedam, The Netherlands
2Erasmus MC, Radiology, Rottedam, The Netherlands
3Amsterdam Medical Center, Radiology, Amsterdam, The Netherlands
4Erasmus MC, Neurology, Rottedam, The Netherlands
Background and Aims: A potential pathway of the favourable effect of intra-arterial treatment (IAT) on functional outcome is a reduction in infarct volume. The aim of this study was to assess whether infarct volume explains the effect of IAT on functional outcome.
Method: We used data of the MR CLEAN trial (n = 500) on IAT in acute ischemic stroke patients with a proximal occlusion in the anterior cerebral circulation. Outcome infarct volume (OIV) was assessed on non-contrast CT scan one week after stroke. Outcome was the modified Rankin Scale at three months. We tested the pathway of IAT, reduced OIV and functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates.
Results: We excluded 52 patients (10%) who died. In 140 patients (28%) without a follow-up scan missing values were replaced with multiple imputation. Patients with IAT had reduced OIV (mean 86 vs 101 ml, p = 0.06). Reduced OIV was associated with better outcome (adjusted common odds ratio (acOR) per 10 ml 0.93, 95%CI 0.91–0.95). Patients with IAT had better outcome (adjusted common odds ratio (acOR) 1.97 (95%CI 1.40–2.77). After adjustment for OIV the effect of IAT on outcome decreased but remained substantial (acOR 1.88, 95% CI 1.34-2.65). Reduced OIV explains 7% of the beneficial effect of IAT on outcome.
Conclusion: The reduction of OIV by IAT explains only a small part of the effect on functional outcome. Before OIV is used as a primary outcome in efficacy trials, improvement of this potentially valuable outcome measure is need.
AS04-011
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
CORTICAL SUPERFICIAL SIDEROSIS IN DIFFERENT TYPES OF CEREBRAL SMALL VESSEL DISEASE
F. Wollenweber1, E. Baykara2, M. Zedde3, B. Gesierich2, E. Jouvent4, A. Viswanathan5, S. Ropele6, H. Chabriat4, R. Schmidt6, C. Opherk7, M. Dichgans2, J. Linn8 and M. Duering2
1Institute for stroke and dementia ISD, Munich, Germany
2Institute for stroke and dementia ISD, Neurology, Munich, Germany
3IRCCS-Arcispedale Santa Maria Nuova- Reggio Emilia- Italy, Neurology Unit, Reggio Emilia, Italy
4University Paris Diderot- Sorbonne Paris Cite´- UMRS 1161 INSERM- Paris- France, Neurology, Paris, France
5Hemorrhagic Stroke Research Program- Harvard Medical School- Boston- USA, Department of Neurology- Massachusetts General, Boston, USA
6Medical University of Graz- Graz- Austria, Department of Neurology, Graz, Austria
8Institut und Poliklinik für Neuroradiologie- Universitätsklinikum Carl Gustav Carus- Dresden- Germany, Neuroradiology, Dresden, Germany
Background and Aims: Cortical superficial siderosis (cSS) has emerged as an important marker of cerebral amyloid angiopathy (CAA). However, it remains unknown if cSS is also present in non-amyloid associated small vessel disease (SVD), and if patients with cSS differ in terms of other SVD imaging features.
Method: 364 CADASIL patients, 372 populations-based controls (PC) and 100 subjects with cSS (fulfilling the modified Boston criteria for possible or probable CAA) were included. cSS and cerebral microbleeds (CMB) were visually rated on T2*-weighted MRI (figure 1a), white matter hyperintensities (WMH) were segmented on FLAIR Images (figure1b). We applied receiver operator characteristic analysis to compare the classification performance of imaging markers.
Results: cSS was absent in CADASIL and present in only 2 (0.5%) PC. CMB were present in 64% of patients with cSS, 34% of CADASIL patients and 12% of PC. Among patients with CMB, lobar location was found in 95% of cSS patients, 48% of CADASIL patients and 69% PC. The spatial distribution of WMH was comparable between cSS and CADASIL samples as indicated by high colocalization coefficients. CMB count and location showed only modest classifier performance.
Conclusion: cSS was absent in CADASIL. In contrast, other SVD imaging features (CMB, WMH) were similar between CADASIL and patients with cSS. Our findings suggest that cSS is highly indicative of CAA.
AS20-006
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
ACUTE ISCHEMIC LESIONS ARE ASSOCIATED WITH CORTICAL SUPERFICIAL SIDEROSIS IN SPONTANEOUS INTRACEREBRAL HEMORRHAGE
P. Revel-Mouroz1, A. Viguier2, V. Cazzola1, L. Calviere2, S. Pastoura1, J.F. Albucher2, J.M. Olivot2, F. Bonneville1 and N. Raposo2
1Toulouse Hospital, Neuroradiology, Toulouse, France
2Toulouse Hospital, vascular neurology, Toulouse, France
Background and Aims: Diffusion-weighted imaging (DWI) detects acute ischemic lesions in 15–25% of patients with intracerebral hemorrhage (ICH). DWI lesions are more common in cerebral amyloid angiopathy (CAA) and are associated with cerebral microbleeds (CMB), white matter hyperintensities (WMH) and centrum semiovale enlarged perivascular spaces. We investigated the relationship between DWI lesions and cortical superficial siderosis (cSS), a strong marker of CAA, in patients with spontaneous supratentorial ICH.
Method: We retrospectively collected data of consecutive patients with acute supratentorial primary ICH and brain MRI performed within 10 days after hemorrhage. MRI scan were analyzed for DWI lesions, cSS and others markers of small vessel disease. Univariate and multivariate analyses were performed to assess the association between DWI lesions and cSS.
Results: Between January 2012 and May 2014, 226 ICH survivors (mean age: 71.1 +/− 13; male: 58%) were included: 126 with lobar ICH (75 with definite or probable CAA) and 120 with deep ICH. DWI lesions were observed in 38 (15.4%) patients. In univariate analysis, DWI lesions were associated with the presence of chronic ICH (p < 0.001), CMB (p = 0.001), cSS (p < 0.001) and the extent of WMH (p = 0.008). In multivariate logistic regression, cSS (Odds Ratio: 3.24; 95% CI: 1.46 – 7.20; p = 0.004) was independently associated with DWI lesions.
Conclusion: In our cohort, cSS is independently associated with DWI lesions after ICH, suggesting that acute ischemic lesions may result from underlying CAA. Further studies are warranted to assess their clinical relevance.
AS20-009
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
LACK OF EARLY IMPROVEMENT PREDICTS POOR CLINICAL OUTCOME FOLLOWING ACUTE INTRACEREBRAL HEMORRHAGE
V. Yogendrakumar1, E. Smith2, A. Demchuk2, R. Aviv3, D. Rodriguez-Luna4, C. Molina4, J.M. Boulanger5, Y. Silva6, I. Dzialowski7, A. Kobayashi8, C. Lum9, G. Gubitz10, V. Padma11, J. Roy12, C. Kase13, R. Bhatia11, M. Ali14, P. Lyden15, M. Hill2 and D. Dowlatshahi1
1University of Ottawa- Ottawa Hospital Research Institute, Medicine Neurology, Ottawa, Canada
11All India Institute of Medical Sciences, Neurology, New Delhi, India
12Apollo Gleneagles Hospitals, Neurology, Kolkata, India
13Boston Medical Center, Neurology, Boston, USA
14University of Glasgow, Cardiovascular and Medical Sciences, Glasgow, United Kingdom
15Cedars-Sinai Medical Center, Neurology, Los Angeles, USA
Background and Aims: Early Neurological Worsening (ENW) is common after ICH, and predicts poor outcome. Yet, there is limited data as to what degree of ENW best relates to outcome. We used two ICH cohorts to refine and validate a definition of ENW that best predicted 90-day outcomes.
Method: We generated a receiver operating characteristic (ROC) curve for the association between 24-hour NIHSS change and ICH outcomes using data from the VISTA collaboration. The primary outcome was poor outcome at 90 days (mRS 4–6); secondary outcomes were mRS ranges: 2–6, 3–6, 5–6, 6. We tested the commonly used NIHSS ≥ 4 definition and employed Youden’s J Index to select optimal cut-points. Independent predictors of poor outcome were determined via multivariable logistic regression. Definitions were validated in the prospectively collected PREDICT-ICH cohort.
Results: Using 552 patients from VISTA, a ROC curve had an area under the curve of 0.75. Youden’s method showed an optimum cut-point at −0.5. ENW defined as >0 (Sens 43%, Spec 91%, PPV 83%, aOR 7.13 [CI:4.05–12.55]), ≥0 (Sens 65%, Spec 73%, PPV 70%, aOR 5.05 [CI:3.25–7.85]), or ≥−1 (Sens 78%, Spec 59%, PPV 65%, aOR 6.04 [CI:3.75–9.71]) all predicted poor outcome. As a continuous variable, a 1 point increase in NIHSS increased the odds of poor outcome by 1.4 (95% CI: 1.28 – 1.50). All definitions independently predicted primary/secondary outcomes and reproduced well in the validation cohort (n = 275).
Conclusion: All NIHSS cut-points for ENW predict clinical outcome, regardless of definition. In particular, lack of clinical improvement at 24 hours robustly predicted poor outcome,
AS20-011
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
ASSOCIATIONS WITH HAEMORRHAGIC TRANSFORMATION IN ACUTE ISCHEMIC STROKE
K.R. van Kranendonk1, A.M.M. Boers2, K.M. Treurniet1, O.A. Berkhemer1, H.A. Marquering2, Y.B.W.E.M. Roos3 and C.B.L.M. Majoie1
1AMC, Radiology, Amsterdam, The Netherlands
2AMC, Biomedical Engineering and Physics, Amsterdam, The Netherlands
3AMC, Neurology, Amsterdam, The Netherlands
Background and Aims: Haemorrhagic transformation (HT) is a serious complication in patients with an acute ischemic stroke and can impair the patient’s clinical outcome. In this study, we assessed the association of clinical and radiological risk factors with HT in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) population to identify risk characteristics.
Method: In this post-hoc analysis we included all patients from the MR CLEAN trial (n = 500). The association between radiological (early ischemic changes (expressed as ASPECTS) and collateral score) and clinical characteristics (such as intra-arterial treatment (IAT), intravenous treatment (IVT) with rtPA, stroke severity (NIHSS) and hyperglycaemia) with HT was analysed using logistic regression. We included all parameters that were associated with HT with a p-value of 0.1 or lower in a multivariable model.
Results: Of the patients in the MR CLEAN population, 39.4% had HT (n = 197). IAT and IVT did not have a significant association with HT. ASPECTS, NIHSS, collateral score and onset to randomization were included in the multivariable model. In the multivariable model, ASPECTS (OR 0.87, 95% CI (0.78 to 0.97) per point), NIHSS (1.04 (1.00 to 1.08) per point), time to randomization (1.003 (1.00 to 1.006) per minute) and collateral score with absent/poor collaterals as reference level; (moderate collaterals (0.74 (0.47 to 1.14) and good collaterals (0.47 (0.28 to 0.78))) were associated with HT.
Conclusion: This study suggests that an absent/poor collateral score, early ischemic changes on CT, more severe strokes and longer time to randomization are risk factors for HT.
AS20-019
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
PREDICTING PRESENCE OF MACROVASCULAR CAUSES IN PATIENTS WITH NON-TRAUMATIC INTRACEREBRAL HAEMORRHAGE BASED ON PATIENT AND HAEMORRHAGE CHARACTERISTICS; THE DIAGRAM PREDICTION SCORE
N. Hilkens1, C. van Asch2, D. Werring3, D. Wilson3, G. Rinkel4, A. Algra5, B. Velthuis6, R. Jager7, J. Greving8, C. Klijn9 and T. DIAGRAM study group4
1UMC Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
2University Medical Center Utrecht- the Netherlands- Kempenhaeghe- Academic Centre for Epileptology- Heeze- the Netherlands, Department of Neurology and Neurosurgery- Brain Center Rudolf Magnus, Utrecht, The Netherlands
3UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery- Queen Square- London- UK, Stroke Research Centre- Department of Brain Repair and Rehabilitation, London, United Kingdom
4University Medical Center Utrecht- the Netherlands, Department of Neurology and Neurosurgery- Brain Center Rudolf Magnus, Utrecht, The Netherlands
5University Medical Center Utrecht- the Netherlands, Julius Center for Health Sciences and Primary Care- Department of Neurology and Neurosurgery- Brain Center Rudolf Magnus, Utrecht, The Netherlands
6University Medical Center Utrecht- the Netherlands, Department of Radiology, Utrecht, The Netherlands
7UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery- Queen Square- London- UK, Neuroradiological Academic Unit- Department of Brain Repair and Rehabilitation, London, United Kingdom
8University Medical Center Utrecht- the Netherlands, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
9Radboud University Medical Center- Nijmegen- Netherlands- University Medical Center Utrecht- the Netherlands, Department of Neurology- Donders Institute for Brain- Cognition and Behaviour- Center for Neuroscience- Department of Neurology and Neurosurgery- Brain Center Rudolf Magnus, Nijmegen, The Netherlands
Background and Aims: To develop and externally validate a prediction model to estimate the probability of finding a macrovascular cause in patients with non-traumatic intracerebral haemorrhage (ICH).
Method: The DIAGRAM study is a prospective, multicentre study, assessing yield and accuracy of CTA, MRI/MRA and intra-arterial catheter angiography to diagnose macrovascular causes in patients with non-traumatic ICH. 298 patients were included, 69 had a macrovascular cause (23%). We considered pre-specified patient and ICH characteristics in multivariable logistic regression models as predictors of a macrovascular cause. We combined independent predictors in a model, which we validated in a cohort of 173 ICH patients (78 macrovascular cause, 44%).
Results: Independent predictors for presence of a macrovascular cause in DIAGRAM were younger age, location of ICH (lobar or posterior fossa versus deep), no small vessel disease (SVD) and a positive or inconclusive CTA. A model combining age, ICH location and absence of SVD showed good performance in the development data (c-statistic 0.83; 95% CI 0.78–0.88), which was moderate in external validation (c-statistic 0.66; 0.58–0.74). When CTA results were added to the model, the c-statistic was excellent (0.91; 0.88–0.94), and good after external validation (0.88; 0.83–0.94). Predicted probabilities varied from 1% in patients aged 51–70 years with deep ICH and signs of SVD, to more than 50% in patients aged 18 to 50 years with lobar or posterior fossa ICH and no SVD.
Conclusion: The DIAGRAM prediction score can help to select patients for further angiographic imaging based on age, ICH location, signs of SVD and CTA.
AS20-025
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
SMASH-U VERSUS H-ATOMIC: A RANDOMIZED HEAD-TO-HEAD COMPARISON FOR THE ETIOLOGIC CLASSIFICATION OF PATIENTS WITH INTRACEREBRAL HEMORRHAGE
J. Martí-Fàbregas1, L. Prats-Sánchez1, D. Guisado-Alonso1, P. Camps-Renom1, A. Martínez-Domeño1 and R. Delgado-Mederos1
1Hospital de la Santa Creu i Sant Pau- IIB Sant Pau Biomedical Research, Neurology, Barcelona, Spain
Background and Aims: Currently there is no consensus for the etiologic classification of patients with intracerebral hemorrhage (ICH). We performed a head-to-head comparison between the two existing classification systems in a series of patients with ICH.
Method: We evaluated consecutive patients with spontaneous ICH admitted to a tertiary university hospital. H-ATOMIC defines seven categories: Hypertension, Amyloid, Tumour, Oral anticoagulants, Malformation, Infrequent, Cryptogenic. For each category, the etiology is scored with three degrees of certainty (possible, probable and definite). Combinations of >1 etiologic category for an individual patient are acceptable. SMASH-U defines 6 categories: Structural, Medication, Amyloid, Systemic, Hypertension, Undetermined. Categories are mutually exclusive and degrees of certainty are not provided.
Six stroke neurologists used both systems in randomized order for the classification of each patient. A subset of patients was evaluated by two investigators to assess interobserver agreement and time spent in each evaluation was calculated. Concordances and discrepancies between both systems were analyzed.
Results: A total of 156 patients (age 72.3 ± 13.5y) were evaluated by one investigator, and 54 of them were evaluated by two investigators. Time to adjudication with SMASH-U was lower than H-ATOMIC (49.8 ± 67.2 vs 84.2 ± 62.2 seconds, p < 0.0001). Percent of interobserver agreement was 85.5% for SMASH-U and 87.6% for H-ATOMIC. Category concordance between both systems was perfect for 62 (39.7%), almost perfect for 68 (43.6%) and discordant for 26 (16.7%) patients.
Conclusion: The H-ATOMIC system requires more time than the SMASH-U criteria. Agreement between investigators is about 85% for both etiologic classifications. Discrepancies between both systems are frequent due to different categories and definitions.
AS20-026
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
IMPLEMENTATION OF AN ACUTE CARE BUNDLE FOR INTRACEREBRAL HAEMORRHAGE: EXPERIENCE AT A UK COMPREHENSIVE STROKE CENTRE AND ASSOCIATED REDUCTION IN 30-DAY CASE FATALITY
A. Parry-Jones1,2, K. Paroutoglou2, L. Cecchini2, J. Rowland1, B. Bray3 and H. Patel1,2
1University of Manchester, School of Medical Sciences, Manchester, United Kingdom
2Salford Royal NHS Foundation Trust, Greater Manchester Neurosciences Centre, Salford, United Kingdom
3University College London, Farr Institute of Health Informatics, London, United Kingdom
Background and Aims: Rapid reversal of anticoagulants, optimal acute blood pressure management and timely access to neurosurgery and critical care can improve outcomes after intracerebral haemorrhage (ICH). From 01/06/2015, we introduced an ICH acute care bundle targeting these processes at our UK comprehensive stroke centre.
Method: We aimed for a door-to-needle time <90 min for anticoagulant reversal, optimised delivery of intensive blood pressure lowering and introduced criteria for referral to neurosurgery. We collected demographic, clinical and imaging data for consecutive ICH patients from 01/07/13 to 31/07/16. We compared survival before and after bundle implementation using Kaplan-Meier analysis and adjusted for case mix with multifactorial Cox regression. A difference-in-difference analysis compared our centre with the rest of England & Wales using data from the Sentinel Stroke National Audit Programme (SSNAP).
Results: 363 ICHs were admitted pre-bundle (01/07/13 to 31/05/15) and 316 post-bundle (01/06/15 to 31/07/16). 30-day case-fatality fell from 35.3% pre-bundle to 25.3% post-bundle (p = 0.002, logrank test). Admission post-bundle was associated with a significantly lower adjusted risk of death (HR 0.7; 95%CI 0.54 to 0.9; p = 0.006). 29,839 ICHs were recorded in SSNAP during our study period. Pre-bundle, our 30-day case fatality was 6.3% above SSNAP (29.0%) but fell to 1.8% below SSNAP (27%) post-bundle (difference-in-difference −8.1%, p < 0.0001).
Conclusion: Introducing an acute ICH care bundle at our centre was associated with a 10% absolute reduction in 30-day case-fatality and is independent of case mix and national secular trends. Further testing of the care bundle in a prospective cluster-randomised trial with functional outcomes is warranted.
AS20-033
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
BETTER FUNCTIONAL OUTCOME AND LOWER RISK OF MORTALITY FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE ON STROKE UNITS COMPARED TO INTENSIVE CARE UNITS AND NORMAL WARDS
M.N. Ungerer1, P. Martus2, P. Ringleb1 and C. Gumbinger1
1University Hospital Heidelberg, Department of Neurology, Heidelberg, Germany
2University of Tübingen, Institute for Clinical Epidemiology and Applied Biometry, Tübingen, Germany
Background and Aims: There is no consensus for the optimal standard of care for patients with intracerebral hemorrhage (ICH). The American Medical Association revised their recommendations to stroke units (SUs) as a treatment alternative from their recommendation to treat ICH only on intensive care units (ICUs). The European guidelines prefer a treatment in SUs compared to normal wards and state that neuro-ICUs are a “convincible” alternative for SUs.
Method: We compared the (adjusted) in-hospital mortality and outcome of over 10,000 (years 2008–2014) consecutive ICH-patients according to treatment ward (normal ward (NW) vs. SU vs. ICU) of the consecutive stroke-database Baden-Württemberg. Favourable outcome was defined as a modified rankin (mRS) of 0–2 at discharge or reaching the prestroke mRS. ICUs were in majority non-neurological ICUs. We excluded patients with coma at admission, patients needing ventilation or who were transferred after diagnosis to another hospital for treatment.
Results: About 14.4% of patients were treated at NW, 30.9% at ICUs and 54.8% at SUs. Treatment on normal wards and on ICUs was associated with a higher risk for achieving an unfavourable outcome (ICU vs. SU: 1.27 [95% CI 1.09–1.46], NW vs. SU: 1.28 [95% CI 1.08 – 1.52]) and mortality (ICU vs. SU: 2.11 [95% CI 1.75–2.56], NW vs. SU: 1.52 [95% CI 1.23–1.87]).
Conclusion: For patients with intracerebral haemorrhage treatment on SUs was associated with better outcome and reduced mortality compared to (interdisciplinary) ICUs and NWs for those patients without coma or ventilation at admission. Our results underline the recommendations of European guidelines to treat ICH-patients on SUs.
AS20-053
Scientific Communication (Oral Abstract Presentation) ICH – Associations and Outcomes
ABSOLUTE RISK AND PREDICTORS OF THE GROWTH OF ACUTE SPONTANEOUS PRIMARY INTRACEREBRAL HAEMORRHAGE: AN INDIVIDUAL PATIENT DATA META-ANALYSIS
R. Lee1, J. Frantzias2, R. Al-Shahi Salman2, A. ICH growth, IPDMA Collaborators1 and A. VISTA-ICH Collaborators3
1University of Edinburgh, Usher Institute of Population Health Sciences and Informatics, Edinburgh, United Kingdom
2University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
3University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
Background and Aims: Intracerebral haemorrhage (ICH) growth is associated with outcome and is a therapeutic target. We sought to determine the absolute risk and predictors of ICH growth.
Method: In a systematic review to 31 December 2015 we identified observational cohorts and randomised trials with repeat scanning protocols (to minimise bias) for patients with acute ICH. We sought individual data for eligible patients: age ≥18 years, with acute primary ICH onset to diagnostic imaging <24 hours, onset to follow-up imaging <6 days, without treatment that reduces ICH growth, and with diagnostic and repeat imaging data available. We estimated the absolute risk and predictors of ICH growth (>6 ml increase in ICH volume on repeat imaging) using multivariable logistic regression models involving 19 categorical or continuous (upper vs. lower quartile) covariates, following a pre-specified protocol (not registered).
Results: 36 (47%) of 77 cohorts provided data on 5,076 eligible patients (60% male, median age 67 years), of whom 20% had ICH growth. Time from symptom onset to baseline scan (odds ratio [OR] 0.50, 95%CI 0.36–0.70), ICH volume on baseline scan (OR 7.18, 95%CI 4.46–11.60), antiplatelet use (OR 1.68, 95%CI 1.06–2.66), and anticoagulant use (OR 3.48, 95%CI 1.96–6.16) were independent predictors of ICH growth (c-index 0.78, 95%CI 0.75–0.82). Addition of CT angiography spot sign (OR 4.46, 95%CI 2.95–6.75) to the model increased c-index by 0.05 (95%CI 0.03–0.07).
Conclusion: The absolute risk of acute ICH growth was 20%. A model using simple predictors had moderate-good discrimination for ICH growth and could be used in clinical practice and randomised trials.
AS07-020
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
LONG-TERM PREDICTORS OF MORTALITY AND FUNCTIONAL OUTCOME AFTER DECOMPRESSIVE HEMICRANIECTOMY FOR MALIGNANT MIDDLE CEREBRAL ARTERY INFARCTION
M. Bodenant1, A. Tuffal1, B. Casolla1, H. Henon1, J.P. Lejeune2, D. Leys1 and C. Cordonnier1
1CHRU de Lille, Department of Neurology, LILLE, France
2CHRU de Lille, Department of NeuroSurgery, LILLE, France
Background and Aims: Decompressive hemicraniectomy (DH) is recommended in patients with a high risk of malignant middle cerebral artery territory infarct. However, predictors of outcome after DH remain unknown. Our objective was to identify predictors of mortality and of functional outcome one year after DH.
Method: We evaluated prospectively consecutive patients who underwent DH between May 2005 and September 2015. We performed logistic regression analyses to identify predictors of mortality, and predictors of poor functional outcome (modified Rankin scale [mRS] 4–5) in survivors.
Results: We included 139 patients [88 men, 63%; median age 49 years, interquartile range 43–57). Twenty-two (16%) patients died in hospital and a total of 28 patients (20%) had died within the first year. The only predictor of in hospital death was an increasing volume of the infarct (measured on DWI sequences) before DH (OR 1.6, 95% CI 1.004–2.6), while the only predictor of mortality at one year was an increasing age (OR 1.08, 95% CI 1.02–1.14). At one year, 43 of the 111 survivors (39%) had a mRS 4–5. Predictors of poor functional outcome were excessive alcohol consumption (OR 6.5; 95% CI 2.1–20.2) and arterial hypertension (OR 8.8; 95% CI 2.7–29.2).
Conclusion: Short term mortality depends only on the volume of diffusion abnormality before surgery, while long-term outcome depends mainly on the pre-existing status of the patient (age, excessive alcohol consumption and arterial hypertension). These findings may help identifying patients who may benefit the most from DH.
AS10-012
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
TIME-COURSE OF EVOLUTION OF FUNCTIONAL RECOVERY AND CAUSE-SPECIFIC MORTALITY AFTER ISCHAEMIC STROKE: IMPLICATIONS FOR TRIAL DESIGN AND INTERPRETATION
A. Ganesh1, R. Luengo- Fernandez1, R.M. Wharton1, S.A. Gutnikov1, L.E. Silver1, Z. Mehta1, P.M. Rothwell1 and O.B.O.T. Oxford Vascular Study1
1University of Oxford- Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom
Background and Aims: Outcome in stroke trials is often based on 3-month modified-Rankin-scale (mRS). How 3-month mRS relates to longer-term outcomes will depend on late recovery, delayed stroke-related deaths, recurrent strokes, and non-stroke deaths. We evaluated 3-month mRS and death/disability at 1-year and 5-years in a population-based cohort study.
Method: In 3-month survivors of ischaemic stroke (Oxford Vascular Study; 2002–2014), we related 3-month mRS to 1-year and 5-year disability (mRS > 2) and/or death rates (age/sex-adjusted). Accrual of disability and index-stroke-related and non-stroke deaths in each post-stroke year was stratified by 3-month mRS.
Results: Among 1,606 patients with acute ischaemic stroke, 181 died within 3-months but 126 index-stroke-related deaths and 320 other deaths occurred during the subsequent 4,866 patient-years of follow-up up to 5-years. Although 69/126(54.8%) post-3-month index-stroke-related deaths occurred after 1-year, mRS > 2 at 1-year strongly predicted these deaths (adjusted hazard-ratio = 21.94,95%CI 7.88-61.09, p < 0.0001). Consequently, 3-month mRS > 2 was a strong independent predictor of death at both 1-year (aHR = 6.67,4.16–10.69, p < 0.0001) and 5-years (2.93,2.38–3.60, p < 0.0001). Although mRS improved by ≥1 point from 3-months to 1-year in 317/1266(25.0%) patients with 3-month mRS ≥ 1, 3-month mRS > 2 still strongly predicted 5-year disability/death (aOR = 34.1,23.6–49.5, p < 0.0001), and improvement in mRS after 1-year was limited (improvement by ≥1 point: 91/858[10.6%]; improvement to mRS ≤ 2: 13/353[3.7%]).
Conclusion: Our results reaffirm use of the 3-month mRS outcome in stroke trials. Although later recovery does occur, extending follow-up to 1-year would capture most long-term stroke-related disability. However, administrative mortality follow-up beyond 1-year has potential to demonstrate translation of early disability gains into additional reductions in long-term mortality, without much erosion by non-stroke-related deaths.
AS17-014
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
DERIVATION AND VALIDATION OF A NOVEL, PARSIMONIOUS, BIOMARKER-BASED PROGNOSTIC SCORE IN ISCHEMIC STROKE: THE CORISK-SCORE
M. Katan1, T. Dankowski2, I.R. König2, C. Foerch3, D. Buhl4, F. Fluri5, R. Kurmann6, O. Findling7, M. Christ-Crain8, M. Arnold6 and G.M. De Marchis9
1University Hospital Zurich, Stroke Center / Neurology, Zurich, Switzerland
2University of Lübeck, Institut für Medizinische Biometrie und Biostatistik, Lündbeck, Germany
9University Hospital Basel, Stroke Center / Neurology, Basel, Switzerland
Background and Aims: Serum copeptin is, so far, the only biomarker fully validated to predict outcome three months after acute ischemic stroke (AIS). Here, we sought to derivate and externally validate a 3-item prognostic model (serum copeptin, age, NIHSS: the “CoRisk-Score”) to predict disability and death within 3 months from AIS.
Method: The derivation cohort consisted of 362 patients with AIS enrolled between 2006 and 2007 at the University Hospital of Basel, Switzerland (COSMOS-Study). The validation cohort consisted of 783 patients with AIS enrolled between 2009 and 2011 at the University Hospital of Bern, Switzerland, and Frankfurt, Germany (CoRisk-Study). All copeptin levels were measured on serum drawn within 24 hours from AIS-onset. Performance of the biomarker-based score was compared to the prognostic model with only age and NIHSS. The combined primary outcome of disability and death was defined as mRs 3–6.
Results: For 3-month combined prediction of disability and death, the CoRisk-score was well calibrated. The calibrated CoRisk-Score correctly classified 79% of patients. The net reclassification improvement between the calibrated CoRisk-Score with and without copeptin was 54%, indicating that copeptin improved prediction in more than half of patients when added to a score with age and NIHSS. For the prediction of 3-month mortality, the model was poorly calibrated, and could not be externally validated.
Conclusion: The parsimonious, biomarker-based CoRisk-Score for the combined prediction of disability and death was well calibrated, could be externally validated, and performed better than a risk-score with NIHSS and age alone, the main outcome predictors after AIS.
AS17-027
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
PERFORMANCE OF THE ORDINAL VERSUS DICHOTOMIZED MODIFIED RANKIN SCALE IN PREDICTING 5-YEAR DEATH, DISABILITY, AND HEALTHCARE COSTS AFTER ISCHAEMIC STROKE: IMPLICATIONS FOR CLINICAL TRIALS
A. Ganesh1, R. Luengo-Fernandez1, R.M. Wharton1, S.A. Gutnikov1, L.E. Silver1, Z. Mehta1, P.M. Rothwell1 and O.B.O.T. Oxford Vascular Study1
1University of Oxford- Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, OXFORD, United Kingdom
Background and Aims: There is disagreement about the merits of ordinal (shift) versus dichotomous analysis of the modified Rankin Scale (mRS) as a primary outcome measure in stroke trials, and about the optimal cut-point for dichotomy. We assessed the predictive power of the three commonly used mRS representations (ordinal versus dichotomized >1 or >2) for long-term outcome after ischaemic stroke.
Method: In 3-month survivors of ischaemic stroke (Oxford Vascular Study; 2002–2014), we related 3-month mRS to 1-year and 5-year disability and death (logistic regressions), and to healthcare costs (generalized linear model), adjusted for age/sex. We compared the area under the receiver-operating-characteristics curve (AUC) and Akaike information criterion (AIC) for the three mRS-representations. We also calculated the proportion of patients in whom pre-morbid mRS already exceeded 1 or 2.
Results: Among 1,425 survivors, the three representations of the 3-month mRS differed (pheterogeneity = 0.001) in prediction of 5-year mortality (AUC = 0.821 for ordinal; 0.814 for 0–2/3–5; 0.798 for 0–1/2–5), with ordinal being clearly superior to 0–1/2–5 (p = 0.0006) and 0–2/3–5 performing somewhat better than 0–1/2–5 (p = 0.02). Results were similar for 5-year disability and 5-year care costs were also best predicted by the ordinal model (AIC relative-likelihood < 0.00001). 30.5% of patients had pre-morbid mRS > 2 (60.7% of those >85years), and 17.1% had mRS > 1 (37.4% of >85).
Conclusion: Ordinal analysis of the 3-month mRS better predicts long-term outcomes of ischaemic stroke than either dichotomy. Dichotomous analyses will also lead trials to exclude of a significant proportion of patients with pre-morbid disability, although the 0–2/3–5 dichotomy is less problematic and more predictive.
AS17-044
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
IMPACT OF ANTI-N-METHYL-D-ASPARTATE-RECEPTOR (NMDAR) NR1 ANTIBODIES ON LONG-TERM FUNCTIONAL OUTCOME IN STROKE PATIENTS
P.S. Sperber1, S.K. Piper1, B. Siegerink1, H. Prüß2, T.G. Liman3 and M. Endres3
1Charité, Center for Stroke Research Berlin CSB, Berlin, Germany
2Charité, German Center for Neurodegenerative Diseases DZNE, Berlin, Germany
3Charité, Department of Neurology with Experimental Neurology, Berlin, Germany
Background and Aims: Seroprevalence of anti-N-Methyl-D-Aspartate-Receptor NR1 antibodies has been reported in healthy and neuropsychiatrically ill subjects. One previous study showed smaller lesions in anti-NMDAR NR1 antibody seropositive ischemic stroke patients compared to those who were seronegative. Whether these antibodies influence the long-term functional outcome remains unclear.
Method: Data were collected from the Prospective Study with Incident Stroke (PROSCISB; NCT01363856). We used multivariable logistic regression to examine the association between anti-NMDAR antibody seropositivity and dichotomised functional outcome defined by the modified Rankin Scale (0 – 2 vs. 3 – 6). Anti-NMDAR NR1 antibodies of IgA, IgM or IgG isotype were measured with cell-based assays of transfected HEK293 cells.
Results: From March 2010 to May 2013, 629 patients with first-ever ischemic stroke were included. 115 were anti-NMDAR NR1 antibody seropositive. Titer levels ranged between 1:10 and 1:1000. Data on antibody levels and functional outcome at 1 year were available in 500 patients. After adjusting for potential confounders (age, sex, aetiology, stroke severity, and comorbidities) we observed no significant association between the presence of anti-NMDAR antibodies and good functional outcome (mRS < 3) at one year after stroke (OR: 0.89 95% CI: 0.47 – 1.66).
Conclusion: Our findings could not support the hypothesis that anti-NMDAR NR1 antibody seropositivity influences the functional outcome of ischaemic stroke patients after one year. However, studies with longer follow-up are warranted.
AS17-046
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
IMPACT OF STROKE ASSOCIATED PNEUMONIA ON MORTALITY, LENGTH OF HOSPITAL STAY AND FUNCTIONAL OUTCOME FOLLOWING ACUTE STROKE
W.H. Teh2, C. Smith3, R. Barlas1, A. Wood1, J. Bettencourt-Silva4, A. Clark5, A. Metcalf4, K. Bowles5, J. Potter5 and P. Myint1
1University of Aberdeen, Institute of Applied Health Sciences, Aberdeen, United Kingdom
2University of Aberdeen, School of Medicine- Medical Sciences and Nutrition, Aberdeen, United Kingdom
3University of Manchester, Faculty of Biology- Medicine and Health, Manchester, United Kingdom
4Norfolk and Norwich University Hospital, Stroke Services, Norwich, United Kingdom
5University of East Anglia, Norwich Medical School, Norwich, United Kingdom
Background: Stroke associated pneumonia (SAP) is common and associated with adverse outcomes. However, long term effect of SAP beyond one year has never been studied.
Methods: A cohort of consecutive stroke admissions over 12 years (January 2003 – April 2015) from UK Regional Stroke Register was examined. Logistic regression models were constructed to examine short-term mortality (in-patient and -90days) and LOS outcome while Cox-regression models were used to examine longer term mortality outcomes at various time periods 90 days-1 year, 1–3 years and 3–10 years for SAP. Effect of SAP on poor functional outcome was assessed using shift analysis.
Results: N = 9,238 [mean age (sd) = 77.61 ± 11.88 years] were included. SAP was present in 11.7% (n = 1,083); 60.8% (n = 658) of them had aspiration pneumonia. After controlling for age, sex, stroke type, Oxfordshire Community Stroke Project classification (OCSP), pre-stroke modified Rankin scale, co-morbidities and acute illness markers, mortality estimates remained significant at three time periods assessed; inpatient (OR 5.87, 95%CI 4.97–6.93]), 0–90 days (4.05;3.45–4.76) and 91–365 days (HR1.31, 1.03–1.67). SAP was also more likely to be associated with worse functional outcome (p < 0.001) and higher odds of long length of hospital stay (1.93;1.67–2.22). The results were not significant for 1–3 years, but SAP was associated with reduced mortality beyond 3 years.
Conclusion: Stroke Associated Pneumonia is linked to increased adjusted mortality up to 1 year post stroke, prolonged LOS and poor functional outcome. Targeted intervention strategies are required to improve longer term outcome in people with SAP who survived to hospital discharge.
AS17-051
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
OUTCOME AFTER POSTERIOR CIRCULATION STROKE – PROPENSITY SCORE MATCHING ANALYSIS FROM THE AUSTRIAN STROKE UNIT REGISTRY
P. Sommer1, A. Posekany2, J. Ferrari3, M. Marko4, E. Fertl1, W. Serles4 and S. Greisenegger4
1Krankenanstalt Rudolfstiftung, Neurology, Vienna, Austria
2Danube University Krems, Department Klinische Neurowissenschaften und Präventionsmedizin, Krems, Austria
3Krankenhaus Barmherzige Brüder, Neurology, Vienna, Austria
4Medical University Vienna, Neurology, Vienna, Austria
Background and Aims: There is limited evidence whether the functional outcome of posterior circulation stroke (PCS) is different compared to anterior circulation stroke (ACS) and whether the outcome is influenced by rtPA-treatment. We analyzed 3-month-outcomes of PCS versus ACS within a nationwide cohort.
Method: We analyzed functional outcome at 3 months measured by the modified Rankin Scale(mRS) of patients with acute ischemic stroke (AIS) enrolled into the Austrian Stroke Unit Registry(ASUR) stratified by infarct localization according to the Oxfordshire Community Stroke Project Classification. Propensity score matching was used to control for covariate imbalances. Based on the score, patients with PCS were matched to ACS. A proportional odds model was calculated based on the matched patients to estimate the influence of the infarct localization and other explanatory variables. Model specification was done using bidirectional stepwise variable selection.
Results: Of 86581 patients with AIS enrolled in the ASUR between 2003 and 2016, 3-month follow-up data was available in a representative subsample of 26491 (22124 ACS/4367 PCS). After stabilizing differences in baseline characteristics with propensity score matching, 4367 with PCS and 4367 with ACS were included in the analysis, of those 862 with rtPA-treatment (431PCS/431ACS). After adjustment for confounding, PCS was a negative predictor of 3-month functional outcome (odds ratio 1.36, 95%confidence interval 1.24–1.5, p < 0.0001). Using a cut-off in the mRS (0–1 vs. 2–6) revealed similar results (OR 1.27, 95%CI 1.15–1.4, p < 0.0001).
Conclusion: In our study PCS was associated with worse functional outcome compared to ACS. This result was independent of stroke severity, rtPA-treatment, demographic or vascular risk factors.
AS17-059
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
COMPARISON OF LONG-TERM SPONTANEOUS FUNCTIONAL RECOVERY AND RESPONSE TO TREATMENT WITH MLC601 BETWEEN CORTICAL AND NON-CORTICAL STROKES – THE CHIMES-E STUDY
N. Venketasubramanian1, C.F. Lee2, C. Chen3 and CHIMES-E Study Investigators4
1Raffles Neuroscience Centre, Neurology, Singapore, Singapore
2The University of Hong Kong, School of Public Health, Hong Kong, China
3National University of Singapore, Pharmacology, Singapore, Singapore
4Philippines- Thailand- Malaysia- Hong Kong- Sri Lanka, Singapore
Background and Aims: Cortical and subcortical strokes have dissimilar recovery patterns in response to interventions primarily because of anatomical and pathophysiological differences.
We aimed to compare the long-term functional recovery and response to MLC601 treatment between strokes with and without cortical signs.
Method: CHIMES-E evaluated the 2-year outcome of subjects aged ≥18 years with ischemic stroke, NIHSS 6–14, and pre-stroke modified Rankin Scale (mRS) ≤1 included in a randomized, double-blind, placebo-controlled trial of MLC601 given for 3 months. Standard stroke care and rehabilitation were allowed throughout the study. Presence of cortical signs were based on baseline NIHSS. mRS was assessed at months 6, 12, 18 and 24.
Results: Baseline characteristics were similar between treatment groups (n = 880, mean age 61.8 ± 11.3 years, 36% women, baseline NIHSS 8.6 ± 2.5). Subjects with cortical signs had lower rates of spontaneous functional recovery (mRS ≤ 1) for all time points compared to subjects with no cortical signs (figure 1). Subgroup analyses showed qualitatively similar effects of MLC601 on subjects with and without cortical signs (figure 2).
Conclusion: Cortical strokes have lower rates of functional independence at two years compared to strokes with no cortical signs. Treatment effect size with MLC601 is similar between the two subtypes.
AS17-083
Scientific Communication (Oral Abstract Presentation) Prognosis – Outcomes
REDUCTION IN MORTALITY AFTER STROKE IN YOUNG ADULTS IN THE NETHERLANDS
J. Verhoeven1, M. Ekker1, K. van Nieuwenhuizen2, E. van Dijk1, I. Vaartjes3, C. Klijn1 and F.E. de Leeuw1
1Radboud University Medical Centre- Donders Institute for Brain- Cognition and Behaviour, Neurology, Nijmegen, The Netherlands
2Brain Center Rudolf Magnus- University Medical Center Utrecht, Neurology and neurosurgery, Utrecht, The Netherlands
3Julius Center for Health Sciences and Primary Care- University Medical Center Utrecht, Neurology, Utrecht, The Netherlands
Background and Aims: The mortality rate is high after stroke in young adults, although data mainly comes from studies that included patients before major changes in acute stroke treatment and secondary prevention occurred. We therefore investigated the time trends in mortality of young stroke in the Netherlands.
Method: Through linkage of the national hospital discharge register, national cause of death register and Dutch population register, using ICD-9 and ICD-10 codes for transient ischemic attack, ischemic- and hemorrhagic stroke, we created a cohort of patients aged 18 to 49 with first-ever stroke. (Change in) cumulative mortality was identified from 1998 to 2010. Additionally, we looked at differences in mortality by stroke-subtype, sex and age.
Results: 23,923 patients (53% women) aged 18 to 49 suffered a first-ever stroke (ischemic-, hemorrhagic stroke or transient ischemic attack) between 1998 and 2010. Thirty day, one year and five year cumulative risk of mortality was 6.1%, 8.2% and 10.6% respectively. One-year cumulative mortality declined from 30.8 to 16.3% (47% reduction) for hemorrhagic stroke and from 10.3 to 5.0% (51% reduction) for ischemic stroke between 1998–2010. Similar reductions were seen for 5-year cumulative mortality.
Conclusion: Cumulative mortality declined by about 50% in 12 years. This is probably due to improved diagnostic techniques for stroke, improved primary and secondary prevention strategies and better stroke care in young adults.
