Abstract
eOral Presentations
O01-O19
ePosters
P01-P17
O01
J Schweizer1; M Arnold1; I König2; A Bicvic3; L Westphal1; V Schütz1; C Inauen1; A Luft1; M Galovic1; M Arnold4; U Fischer3; L Bonati5; GM De Marchis5; T Kahles6; K Nedeltchev6; C Cereda7; G Kägi8; A Bustamante9; J Montaner9; G Ntaios11; C Foerch1 1; K Spanaus1 2; A von Eckardstein1; M Katan1
1 UniversitätsSpital Zürich (USZ); 2 University of Lübeck; 3 Bern University Hospital (Inselspital); 4 Universitätsspital Bern; 5 Basel University Hospital; 6 Canton Hospital Aarau; 7 Cantonal Hospital Lugano; 8 Cantonal Hospital St.Gallen; 9 Vall d’Hebron Institute of Research (VHIR); 11 University of Thessaly; 1 1 Johann Wolfgang Goethe University Medical Center; 1 2 University Hospital of Zurich
Background and aim:
Midregional-proatrial-natriuretic-peptide (MR-proANP) is a promising biomarker to differentiate the underlying etiology of acute ischemic stroke (AIS). We evaluated the incremental predictive value of MR-proANP – a marker of underlying atrial cardiopathy - in identifying cardioembolic stroke (CE), newly diagnosed atrial fibrillation (NDAF), and risk assessment for major adverse cardiovascular events (MACE).
Methods:
In this prospective, observational, multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study we measured MR-proANP levels in AIS patients prospectively collected within 24 hours after symptom onset. Primary outcomes were CE stroke etiology, the identification of NDAF after prolonged cardiac monitoring (PCM) as well as a composite of MACE consisting of recurrent cerebrovascular events, myocardial infarction or cardiovascular death within 1 year. Logistic and sub-proportional hazard regression were applied to assess the association between MR-proANP and outcomes. Additionally, a model for prediction of NDAF was derived and validated in a split dataset as a decision tool for clinical application.
Results:
Between October 2014 and October 2017, we recruited 1759 participants of whom complete follow-up data were available for 1751 patients (99.5%). Log 10 MR-proANP levels were associated with CE stroke (OR 7.96, 95%-CI 4.82-13.14) as well as incidence of NDAF (OR 35.3, 95%-CI 17.6-71.0) or MACE (SHR 2.02, 95%CI 1.32-3.08) during follow up in multivariable models adjusted for relevant covariates. The novel predictive model for NDAF including only age and MR-proANP levels had a good discriminatory capacity with an AUC of 0.81 (95%-CI 0.76-0.86) in the validation set. The model was well calibrated (CITL -0.086, calibration slope 1.053) and yielded higher net-benefit over the full range of decision thresholds compared to validated scores for NDAF (AS5F-Score, CHA2DS2-VASc-Score).
Conclusion:
MR-proANP is a valid, independent biomarker to determine risk of NDAF and MACE in acute ischemic stroke patients. Therefore MRproANP seems to be a good candidate to select patients for prolonged rhythm monitoring.
O02
M Beyeler1; L Weber1; C Kurmann2; T Meinel1; M Goeldlin1; T Dobrocky2; E Piechowiak2; M Arnold1; S Pilgram-Pastor2; M Heldner1; P Mordasini2; J Gralla2; J Kaesmacher2; U Fischer1
1 Department of Neurology and Stroke Center, Inselspital, Bern University Hospital, University of Bern, Switzerland; 2 Department of Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Switzerland
Background:
Mechanical thrombectomy (MT) reduces 3-months mortality in patients presenting with a large vessel occlusion compared to best medical treatment. The degree of reperfusion is one of the most important, modifiable predictors of 3-months functional outcome in patients undergoing MT, but data on long-term follow-up are sparse. Aim of this analysis was to assess the association of angiographic reperfusion success and very long-term mortality.
Material and method:
All consecutive patients undergoing mechanical thrombectomy between 01/2010 and 12/2018 were included. Post MT reperfusion was core-lab adjudicated applying the expanded Thrombolysis In Cerebral Infarction (eTICI) scale. Successful reperfusion was defined as eTICI ≥ 2b50. Vital status was assessed by phone interview and the Swiss register of inhabitants between 08/2019 and 06/2020. Results of multivariate analyses using a cox-regression model, are displayed as Hazard Ratio (HR) and 95% confidence intervals (95% CI). Sensitivity analyses were performed in borderline indication groups (patients with Alberta Stroke Program Early CT Score [ASPECTS] ≤ 5, NIHSS < 5 and medium vessel occlusions).
Result:
Of 1319 screened patients, 55 were lost to follow-up, yielding a study population of 1264 patients with 43028 months of cumulative follow-up. Patients with successful reperfusion had longer survival (68.9 vs 41.9 months, P < 0.01), with gradually increasing survival across the whole eTICI spectrum (eTICI0/1 36.4 months, eTICI2a 46.2 months, eTICI2b 65.4months, eTICI2c/3: 71.6 months, p < 0.001). After adjusting for potential confounders, successful reperfusion was associated with lower mortality rates (HR 0.46, 95%-CI 0.36-0.58). This association was also discernible in patients with ASPECTS 0-5 (HR 0.55, 95%-CI 0.35-0.85), patients with NIHSS < 5 (HR 0.25, 95%-CI 0.06 -1.05) and patients presenting with medium vessel occlusions (HR 0.45, 95%-CI 0.29-0.71)
Conclusion:
Achieving successful and ideally complete reperfusion is associated with long-term mortality reduction in patients undergoing MT for an acute ischemic stroke, also in patients with borderline indication criteria. Technical development geared towards improving angiographic reperfusion may therefore improve long-term survival.
References
1. Van Den Berg LA, Dijkgraaf MGW, Berkhemer OA, et al. Two-year outcome after endovascular treatment for acute ischemic stroke. N Engl J Med. 2017;376(14):1341-1349. doi:10.1056/NEJMoa1612136
2. Dávalos A, Cobo E, Molina CA, et al. Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial. Lancet Neurol. 2017;16(5):369-376. doi:10.1016/S1474-4422(17)30047-9
3. Zhao W, Shang S, Li C, et al. Long-term outcomes of acute ischemic stroke patients treated with endovascular thrombectomy: A real-world experience. J Neurol Sci. 2018;390(March):77-83. doi:10.1016/j.jns.2018.03.004
4. Arakawa M, Suzuki K, Kutsuna A, et al. Good recanalization is associated with long term favorable outcomes in acute stroke patients with large vessel occlusion treated with endovascular therapy. J Neurol Sci. 2020;416(January):117009. doi:10.1016/j.jns.2020.117009
5. Liebeskind DS, Bracard S, Guillemin F, et al. ETICI reperfusion: Defining success in endovascular stroke therapy. J Neurointerv Surg. 2019;11(5):433-438. doi:10.1136/neurintsurg-2018-014127
O03
M Haeberlin; G Narula; C Straessle; E Keller; L Imbach
UniversitaetsSpital Zuerich
Purpose:
The burst suppression pattern in clinical EEG recordings is an important diagnostic tool because of its association with comas of various etiologies, for example with hypoxia, drug related intoxication, anesthesia etc. The detection of bursts and the calculation of burst/suppression ratio are often used to monitor the level of sedation during treatment of status epilepticus. However, manual counting of bursts is a laborious process. Here, we describe a novel unsupervised learning algorithm that detects bursts in a burst-suppression pattern and generates burst-per-minute estimates for the purpose of monitoring sedation level in an ICU setting.
Materials and Methods:
A bipolar 10-channel EEG-montage was recorded at 200 Hz from 16 patients under deep sedation in the ICU. The montage was bandpass filtered into typical EEG rhythms (Delta, Theta, Alpha) and segmented into 2 secs epochs (0.1 s overlap). In each epoch, we computed the empirical covariance matrix. Under a Riemannian metric (Foerstner and Moonen 1999) for covariance matrices, a distance matrix between all epochs was computed using data from the first 20 mins of recording, and subsequently transformed into a similarity matrix using radial basis functions. We used Spectral Clustering (Shi and Malik 2000) to obtain two clusters: Burst and Suppression. We disregarded all bursts that occur within 2.5 seconds of each other. We labelled the rest of the (test) data by training a K-nearest neighbor classifier (5 neighbors) from the labels produced by clustering. The EEG was scored by a neurologist to get ground truth burst annotations in one hour recording period per patient. We computed bursts per minute (BPM) by counting burst labelled epochs in each minute.
Results:
The mean (SD) of absolute error in estimating BPM was 0.94 (1.49) bursts per minute (n = 16 patients). To quantify burst-suppression classification accuracy, we computed the Area under the Receiver-Operator Curve (AUROC) score per patient. The mean (SD) of AUROC was 0.84 (0.14). The latency in estimating BPM was approximately 2 sec / min.
Conclusion:
We present a novel, unique algorithm for automated real-time detection of bursts in burst-suppression coma EEG. The algorithm does not require expert annotation or fine tuning, and learns on each patient’s data independently. Thus, it can adapt to patient specific characteristics.
References
Foerstner, W., & Moonen, B. (1999). A metric for covariance matrices. In Qua vadis geodesia…? Festschrift for Erik W. Grafarend on the occasion of his 60th Birthday (pp. 113-128). Tech. Report of the Dpt of Geodesy and Geoinformatics, Stuttgart University.
Shi, J., & Malik, J. (2000). Normalized cuts and Image Segmentation. IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE LEARNING, 22(8), 888-905.
O04
M Goeldlin1; A Mueller2; B Siepen1; M Mueller1; D Strambo3; P Michel3; M Schaerer4; C Cereda5; G Bianco5; F Lindheimer6; C Berger6; F Medlin7; R Backhaus8; N Peters8; S Renaud9; L Fisch11; J Niederhaeuser11; E Carrera1 1; C Bonvin1 2; R Sturzenegger1 3; T Kahles1 4; K Nedeltchev1 4; G Kägi1 5; J Vehoff1 5; B Rodic1 6; M Bolognese1 7; L Schelosky1 8; S Salmen1 9; M Mono2⁰; L Bonati2 1; A Polymeris2 1; S Engelter2 1; P Lyrer2 1; S Wegener2; AR Luft2 2; W Z’Graggen2 3; D Bervini2 4; B Volbers2 5; T Dobrocky2 6; J Fandino2 7; M Arnold1; U Fischer1; D Seiffge1
1 Department of Neurology, Inselspital, Bern University Hospital and University of Bern; 2 Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland; 3 Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV); 4 Department of Neurology, Buergerspital Solothurn; 5 Neurocenter of southern Switzerland, Regional Hospital Lugano (EOC); 6 Department of Internal Medicine, Spitalregion Rheintal, Werdenberg, Sarganserland, Grabs; 7 Department of Internal Medicine, Unit of Neurology, HFR Fribourg – Cantonal Hospital; 8 Stroke Center Hirslanden, Klinik Hirslanden Zurich; 9 Division of Neurology, Pourtalès Hospital, Neuchâtel; 11 Stroke unit, GHOL, Hôpital de zone de Nyon; 1 1 Stroke Research Group, Department of Clinical Neurosciences, University Hospital and Faculty of Medicine; 1 2 Service de Neurologie, Hôpital du Valais; 1 3 Department of Internal Medicine, Kantonsspital Graubünden; 1 4 Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland; 1 5 Department of Neurology, Cantonal Hospital, St. Gallen; 1 6 Department of Neurology and Stroke Unit, Kantonsspital Winterthur; 1 7 Neurology Department, Luzerner Kantonsspital; 1 8 Division of Neurology, Kantonsspital Münsterlingen; 1 9 Stroke Unit, Spitalzentrum Biel and Department of Neurology, Inselspital, Bern University Hospital and University of Bern; 20 Stadtspitäler Triemli und Waid, Zurich; 2 1 Department of Neurology and Stroke Center, University Hospital and University of Basel; 2 2 Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland and cereneo Center for Neurology and Rehabilitation, Vitznau; 2 3 Department of Neurology and Department of Neurosurgery, Inselspital, Bern University Hospital and University of Bern; 2 4 Department of Neurosurgery, Inselspital, Bern University Hospital and University of Bern; 2 5 Department of Neurology, Inselspital, Bern University Hospital and University of Bern and Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU); 2 6 University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital and University of Bern; 2 7 Department of Neurosurgery, Cantonal Hospital Aarau
Background:
We determined the frequency of different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their association with clinical characteristics and outcomes.
Methods:
We analyzed data from consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014-2019). Etiology of ICH was determined according to prespecified, mutally exclusive categories. We assessed prevalence of ICH etiologies, their association with clinical characteristics, functional independence (modified Rankin Scale 0-2), mortality, recurrent ICH and ischemic stroke at 3 months.
Results:
We included 2584 patients (median age 72y, IQR 64-82, 46.6% female, median NIHSS 10; IQR 3-15). 2037 patients (80%) had hypertension and 553 (22.3%) were on anticoagulants. Distribution of etiologies was as follows: Hypertension (n=1216 patients; 47.1% of all / 56.3% of patients with hypertension), unknown etiology (n=542, 21.0%), antithrombotic therapy (n=225, 8.7% of all / 38% of patients on anticoagulants), cerebral amyloid angiopathy (CAA, n=211, 8.2%), macro-vascular (n=121, 4.7%), other determined etiologies (n=269, 10.4%). Patients with hypertensive ICH had significantly higher NIHSS (median 9; IQR 4-16) and blood pressure levels (median systolic 176; IQR 156-195) on admission. Patients with CAA had significantly lower NIHSS at baseline (median 5; IQR 2-12). Three month follow-up was available for 2109/2584 patients (81.6%). 820 (38.9%) were functionally independent, 658 have died (31.2%). Hypertensive ICH was associated with an increased rate of functional independence (aOR =1.42, 95%CI 1.06 -1.90, p=0.02). 5.2% of patients had a cerebrovascular event within 3 months. CAA was associated with a high risk of recurrent ICH (HR 6.95, 95%CI 3.05-15.84, p < 0.001). The risk of ischemic stroke (2.2%) was higher than that of ICH (1.5%) in patients with hypertensive ICH.
Conclusions:
In Swiss Stroke Units and Centers, one of two patients has ICH from a different cause than hypertension. The rate of functionally independent patients at 3 months seems higher than mortality. Absolute and relative risks of recurrent ICH and ischemic stroke after recent ICH differ among underlying etiologies.
O05
S Thilemann1; S Engelter2; L Bonati2; GM De Marchis2; N Peters2; J Fladt2; F Schaub2; C Nickel2; P Hunziker2; M Lüthy2; S Schädelin3; P Lyrer2
1 Universitätsspital Basel; 2 Universitätsspital Basel; 3 Universität Basel
Background and Aim:
The aim of our telestroke path is to optimize pre-hospital triage using a video link connecting ambulances and a stroke specialist MD to identify (1) patients suffering any stroke and especially (2) LVO as candidates for endovascular treatment using RACE-Score. Those could skip the time-consuming ER-admission and directly proceed to neuroimaging.
Methods:
In this prospective cohort study, we included 97 subjects to prove feasibility of our local telestroke-concept applying the RACE-Score (items: facial palsy, arm & leg motor function, head & gaze deviation, aphasia or agnosia) in authentic settings such as emergency department or ambulance (patient out-of-hospital, stroke doctor in the hospital). A VIDYO®-connection was established between a mobile device (I-Phone 6S®) out-of-hospital and a personal computer, run by the stroke professional in-hospital. A short briefing was followed by the neurological examination, all of which was recorded on an encrypted server. Results of all telestroke-analysis were independently assessed by three raters, and compared to the neuroimaging gold standard in order to identify: (1) strokes out of the population of suspected strokes and (2) LVO out of the population of detected strokes. Presence of a stroke was defined as CTA-proven cerebral vessel occlusion, DWI lesion or any acute intracerebral bleeding. LVO was defined as CCA, ICA, MCA M1/M2 or BA-occlusion in CTA, or referring to the area in perfusion imaging in one case where thrombolysis successfully reopened the occlusion during imaging.
Results:
Of the 97 patients analyzed, 41 strokes could be confirmed via neuroimaging of which 78%, 2 or 3 raters positively identified a stroke. 11 Patients suffered a LVO, which was identified in 73.8% by 2 or 3 raters. The inter rater agreement in the RACE-Score assessment was ICC = 0.82 (intraclass-correlation coefficient).
Conclusion:
These results support our thesis that the local telestroke concept is feasible. It allows (I) stroke and (II) LVO identification and thus has the potential to conduct an efficient pre-hospital triage. The main study is planned for Q4/2020 at University Hospital Basel in collaboration with Rettung Basel Stadt.
O06
T Bremova-Ertl1; L Abel2; M Walterfang3; E Salsano4; A Ardissone4; V Malinova5; M Kolnikova6; J Byarria7; AR Tavasoli8; MR Ashrafi9; Y Amraoui11; E Mengel11; S Kolb1 1; A Brecht1 1; S Bardins1 2; M Strupp1 2
1 Inselspital, Universitätsspital Bern; 2 School of Medicine, Deakin University; 3 Royal Melbourne Hospital, Parkville, VIC, and University of Melbourne & NorthWestern Mental Health, Parkville, VIC, Australia; 4 Fondazione IRCCS Istituto Neurologico “Carlo Besta”; 5 First Faculty of Medicine, Charles University, General University Hospital; 6 Comenius University Children’s Hospital; 7 Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat; 8 Pediatric Center of Excellence, Tehran University of Medical Sciences; 9 Children’s Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences; 11 University Medical Center of the Johannes Gutenberg University und SphinCS Gmbh, Clinical Science for LSD, Hochheim; 1 1 Actelion, a Janssen company of Johnson & Johnsons; 1 2 University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University
Background:
Niemann-Pick type C (NPC) is a rare lysosomal storage disorder with ocular motor involvement. In this study we characterized ocular motor function in 72 patients with NPC from twelve countries by means of video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers.
Methods:
Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls. The Modified Disability Rating Scale, Scale for Assessment and Rating of Ataxia, Spinocerebellar Ataxia Functional Index for neurological status, and Montreal Cognitive Assessment for cognition were also performed. Results Mean saccadic peak velocity to 20° stimulus was 63.5°/s (SD, 95% CIs of the mean: 59.5, [47.9-79.2]) in NPC patients and 403.1°/s (69.0, [392.0-414.2°/s]) in healthy subjects (p < 0.001). In contrast to the common belief that the “downward saccadic system degenerates to greater extent than the upward one”, the saccadic impairment in both directions was similar. Vertical position smooth pursuit gain was 0.649 (0.33, [0.554-0.744]) in NPC and 0.935 (0.149 [0.91-0.959]) in HC (p < 0.001). The number of patient-specific saccadic patterns, incl. slow-pursuit like, hypometric and staircase-pattern saccades suggest varying involvement of the saccadic system with fragmentation of the velocity profile as a sign of omnipause neuron dysfunction. Vertical reflexive saccades were more impaired and slower than self-paced ones. Ocular motor performance depended on age of onset and disease duration.
Results:
We found that peak velocity and latency of horizontal saccades, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials, as they showed the strongest correlation to disease severity. By comparing saccadic with pursuit movements, we showed that 98.2% of patients generated vertical saccades (both up and down) that were below the 95% confidence intervals of the controls’ peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% of healthy controls.
Conclusion:
Vertical supranuclear saccade palsy and not vertical supranuclear gaze palsy is the hallmark of NPC disease. Observed compensating strategies, such as blinks to elicit saccades, head and upper body movements to overcome the gaze palsy, should be used clinically to establish a diagnosis.
O07
JR Mendell; Z Sahenk; K Lehman; C Nease; LP Lowes; NF Miller; MA Iammarino; LN Alfano; J Vaiea; S Al-Zaidy; S Lewis; K Church; R Shell; R Potter; DA Griffin; ER Pozsgai; M Hogan; LR Rodino-Klapac
The Abigail Wexner Research Institute at Nationwide Children’s Hospital
Background & Goals:
Gene transfer therapy is a promising treatment for Duchenne muscular dystrophy (DMD). We designed an adeno-associated virus vector (rAAVrh74) containing a codon-optimized human micro-dystrophin transgene driven by a muscle-cardiac specific promoter, MHCK7. Findings from 4 patients in our open-label, single-dose, Phase I/IIa trial (NCT03375164) are presented.
Material & Methods:
Eligibility criteria were: ambulatory boys (4-7y) with confirmed DMD mutations; creatine kinase (CK) elevations (> 1,000 U/L); ≤ 80% predicted 100-meter timed test (100 m); no AAVrh74 antibodies; and stable steroid dosing (≥ 3 mo). IV infusion (2.0x10^14 vg/kg rAAVrh74.MHCK7.micro-dystrophin) given. Prednisone (1 mg/kg/d) initiated 1d before gene delivery, tapering after 30d. Primary endpoint: safety. Secondary and exploratory endpoints: micro-dystrophin expression by western blot (WB) and immunohistochemistry (IHC); functional outcomes by North Star Ambulatory Assessment (NSAA), 100 m, Time to Rise, 4-Stair Climb; CK.
Results:
No serious adverse events were observed by serum chemistry. Three patients had transiently elevated gamma-glutamyl transpeptidase (resolved with steroids). No adverse immune responses observed. Robust transgene expression was observed in all: mean 81.2% muscle fibers expressing micro-dystrophin (mean intensity 96% at the sarcolemma by IHC). WB showed mean micro-dystrophin expression of 74.3% without fat/fibrosis adjustment and 95.8% when adjusted (Day 90). All patients had confirmed vector transduction and showed robust reductions in CK (mean change baseline to 1 year: -67.3%). Motor function was improved in all, measured by increased ambulatory function (100 m), increased muscle strength (Time to Rise, 4-Stair Climb), and overall motor abilities (NSAA). All 4 patients demonstrated a clinically meaningful improvement on NSAA as early as Day 90.
Conclusions:
rAAVrh74.MHCK7.micro-dystrophin infusion was well-tolerated, demonstrating successful systemic delivery of micro-dystrophin transgene and targeted expression of functional micro-dystrophin protein.
O08
SA Valizadeh1; M Cheetham1; L Jaencke2; R Renzel3; E Efthymiou3; L Imbach3
1 University Hospital and University of Zurich, Department of Internal Medicine, Zurich, Switzerland; 2 University of Zurich, Division Neuropsychology, Institute of Psychology, Zurich, Switzerland; 3 University Hospital and University of Zurich, Division of Epileptology, Department of Neurology, Zurich, Switzerland
Background:
The initial 20-minute standard EEG after first ever unprovoked epileptic seizure has a poor diagnostic yield. The accurate diagnosis of epilepsy is time-consuming, often requiring repetitive standard EEGs or long-term EEG. A reliable and higher yielding screening method for automated epilepsy classification is needed.
Objective:
We tested whether recently developed neural biomarkers based on the temporal dynamics of effective connectivity improve the diagnostic yield of initial EEG. Method: We extracted Granger causality (GC)-based indices of effective connectivity from the interictal resting-state EEG data of N=67 adult patients (acquired after first unprovoked epileptic seizure and without interictal epileptiform discharges), used a feature selection method to identify sets of features that distinguish well between epilepsy and nonepilepsy, and tested a range of machine learning (ML) classifiers for optimal epileptic vs. nonepileptic discrimination. We used accuracy, sensitivity and specificity as evaluation criteria of ML-based classification performance compared with final epilepsy diagnosis.
Results:
Automated ML-based classification achieved 84% specificity, 42% sensitivity and 73% accuracy. Given the high specificity of the ML classifier, a negative result indicates that the first seizure is less likely to be an initial manifestation of epilepsy. The sensitivity was considerably better than that of early standard EEG alone, and the overall accuracy was superior to the diagnostic yield of the first and second long-term EEGs.
Conclusion:
While appropriate cut-off levels need to be determined, the high specificity of this automated method enhances assessment at first standard EEG of whether the first seizure amounts to an initial manifestation of epilepsy. The reported sensitivity could contribute to early risk assessment by helping the clinician to evaluate whether to lower the threshold for commencing AED treatment.
009
E Ménétré; P De Sefano; F Picard; S Vulliemoz; M Vargas; M Seeck
Hôpitaux Universitaire de Genève HUG
Introduction:
Epileptic seizures are the second most frequent neurologic emergency after strokes, which often constitutes a challenge for the diagnosis. In this monocentric prospective study, we analyzed patients presenting symptoms of a first seizure. The purpose was to collect epidemiological data and determine the yield of combined evaluation tools.
Method:
Adult patients (> 16 years) in the Geneva area who presented a probable first seizure between 3/2012 and 3/2017 were included. Obvious non-epileptic, acute symptomatic and withdrawal seizures were excluded. Standard exams were EEG, a blood laboratory and a CT scan. Follow-up exams included an MRI, an overnight EEG if the standard EEG was normal, as well as cardiologic and psychiatric exams depending on the suspected diagnosis. Final diagnosis and outcome after two years were evaluated.
Results:
1011 patients with a possible epileptic seizure were enrolled (44% women; mean age: 53 years). 585 (58%) patients had an epileptic seizure and 475 (47%) were finally diagnosed with epilepsy. Primary generalized epilepsy was reported in 31 patients (3%), while focal epilepsy was diagnosed in 444 patients (44%)(unclear in 68 patients or 7%). Not surprisingly, the diagnostic power of the overnight EEG was superior to standard EEG. Of all patients with probably epilepsy and normal standard EEG (N = 350), 77 underwent LTM-EEG which allowed the identification of epileptiform discharges in an additional 39 patients (51). If standard EEG, overnight EEG and MRI were normal/without discharges (N = 77), 8 patients were nevertheless diagnosed with epilepsy on the basis of a convincing witness report, which represents 0.8% of the total group. Of all patients with epilepsy, 313 (66%) patients remained seizure free after two years.
Conclusion:
If standard EEG and MRI are normal, overnight EEG should be added to the basic work-up of a first seizure given its high yield. Despite swift epileptology and neurosurgical care, 34% of patients experienced recurrent seizures within 2 years. This affected mainly patients with lesional epilepsy, of which 39 (24%) presented evolutive brain diseases. Underdosing and variable compliance could explain the rest of the relapses. True pharmacoresistance was noted in 21%.
O10
LP Westphal1; N Lohaus1; SF Winklhofer1; C Manzolini1; U Held2; K Steigmiller2; J Hamann1; M El Amki1; T Dobrocky3; LD Panos4; J Kaesmacher3; U Fischer4; MR Heldner4; C Stippich1; AR Luft1; J Gralla3; M Arnold4; R Wiest3; S Wegener1
1 UniversitätsSpital Zürich (USZ); 2 Universität Zürich, Zürich, Switzerland; 3 Inselspital - Universitätsspital Bern; 4 Inselspital - Universitätsspital Bern; Universität Bern
Background and Purpose:
An incomplete Circle of Willis (CoW) has been associated with an increased risk of stroke. In acute stroke due to large vessel occlusion (LVO), CoW variants might affect collateral flow. In this study, we investigated the potential impact of CoW variants on functional outcome in patients with LVO stroke receiving endovascular treatment (EVT).
Methods:
The CoW was assessed on Time-of-flight (TOF) magnetic resonance angiography (MRA) in 193 patients with acute middle cerebral artery (MCA)-M1-occlusion treated at the University Hospital Berne and 73 patients with transient ischemic attack (TIA) without LVO treated at the University Hospital Zurich. We created four vascular models of presumed collateral flow for the main CoW variants and correlated them to 3-months functional disability (modified Rankin Scale, mRS) in patients with stroke.
Results:
82.4% (n=159) of patients with MCA-M1-occlusion stroke and 72.6% (n=53) of patients with TIA had an incomplete CoW. In stroke patients, most variants were found in the posterior circulation (77.2%, n=149), while 39.9% (n=77) were anterior variants. Initial stroke severity was similar for patients with and without CoW variants. CoW integrity did not differ significantly between groups with favorable (mRS 0-2) and unfavorable (mRS 3-6) 3-months functional disability. In a logistic regression analysis including the potential confounders age, sex, atrial fibrillation and NIHSS on admission, neither the vascular models of the main CoW variants nor individual anterior or posterior variants were independently associated with outcome.
Conclusions:
CoW variants are frequent in patients with MCA-M1-occlusion stroke. Our data suggest that these variants are not significantly related to clinical outcome in LVO stroke patients receiving endovascular treatment.
O11
SJ Pittock1; A Berthele2; HJ Kim3; K Fujihara4; M Levy5; I Nakashima6; C Oreja-Guevara7; J Palace8; M Terzi9; N Totolyan11; S Viswanathan1 1; K Wang1 2; A Pace1 3; M Yountz,1 3; L Miller1 3; G Sabatella1 3; R Armstrong1 3; DM Wingerchuk1 4
1 Mayo Clinic, Rochester, MN, USA; 2 Technical University of Munich; 3 National Cancer Center; 4 Tohoku University Graduate School of Medicine; 5 Johns Hopkins University; 6 Tohoku University; 7 Hospital Universitario Clinico San Carlos,, Spain; 8 John Radcliffe Hospital; 9 Ondokuz Mayıs University; 11 First Pavlov State Medical University of St Petersburg,; 1 1 Kuala Lumpur Hospital; 1 2 Cheng-Hsin General Hospital,; 1 3 Alexion Pharmaceuticals; 1 4 Mayo Clinic,
Background and Goals:
In the phase 3 PREVENT trial (NCT01892345), eculizumab was well tolerated and significantly reduced relapse risk versus placebo. The time course of relapses in a pre-specified subgroup of patients who did not receive concomitant immunosuppressive therapy (IST) suggested a treatment effect consistent with that in the overall population.
Material and Methods:
Adults with AQP4-IgG+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant IST. A post hoc analysis of the following outcomes using data from patients receiving eculizumab monotherapy or placebo without concomitant IST during PREVENT was performed: relapses, hospitalizations, acute relapse treatment, worsening of Expanded Disability Status Scale (EDSS), Hauser Ambulation Index (HAI) scores.
Results:
Of 34 patients in the no IST subgroup: 10 had never received IST, 14 previously received rituximab (eculizumab monotherapy, 7/21; placebo, 7/13). Adjudicated relapses occurred in 0/21 patients receiving eculizumab monotherapy and 7/13 (53.8%) receiving placebo (p < 0.0001; post hoc analysis). In the placebo group, 6/13 patients (46.2%) were hospitalized for adjudicated relapses and received treatment. EDSS and HAI each worsened in 1/21 patients (4.8%) receiving monotherapy, and in 5/13 (38.5%) and 4/13 patients (30.8%), respectively, receiving placebo.
Conclusion:
These data support the efficacy of eculizumab monotherapy in reducing relapse risk in AQP4-IgG+ NMOSD. Patients receiving eculizumab monotherapy were spared relapse-associated hospitalizations and acute treatments, and the majority (95%) did not experience disability worsening. Long-term results from PREVENT’s open-label extension will be analyzed.
Disclosure Statement:
Funded by Alexion Pharmaceuticals.
O12
F Capecchi, L Imbach
Univeristätsspital Zürich
Purpose:
Stimulus induced repetitive periodic or ictal discharges (SIRPIDs) are a rare EEG pattern in critically ill patients and associated with poor prognosis. However, its clinical significance regarding epileptic risk and anticonvulsive treatment is yet unclear.
Method:
In a retrospective analysis, we reviewed 32 patients with SIRPIDs according to the American Clinical Neurophysiological Society (ACNS) criteria. SIRPIDs occurred after standardized painful stimulus in the hand during a standard 20-minute EEG. These cases were investigated regarding seizures, non-convulsive status epilepticus (according to Salzburg consensus criteria) and mortality.
Results:
In 23/32 patients (71.9%), SIRPIDs were associated with either non-convulsive status epilepticus (20/32, 62.5%) or seizures (3/32, 9.4%). In 75% of the patients with concurrent status epilepticus, SIRPIDs occurred after status epilepticus (on average 6 days later), but in 4 patients (20%) they were observed before a later to come status epilepticus. One patient suffered from non-convulsive status epilepticus two days before and one day after the appearance of SIRPIDs. In 8 patients the status epilepticus was refractory or super-refractory and 3 patients died before resolution of the status epilepticus. The overall mortality in the cohort was 47%. Mortality after occurrence of SIRPIDs was independent from status epilepticus.
Conclusion:
These findings corroborate the hypothesis that SIRPIDs are epileptiform interictal phenomena, commonly co-occurring with non-convulsive status epilepticus. Furthermore, SIRPIDs are associated with therapy-refractory course of status epilepticus. These findings suggest that initiation of prophylactic anticonvulsant treatment for SIRPIDs might be beneficial.
O13
G Disanto1; P Ripellino1; G Riccitelli1; R Sacco1; B Scotti1; A Fucili1; E Pravatà1; J Kuhle2; C Gobbi1; C Zecca1
1 Neurocenter of Italian Switzerland; 2 Basel University Hospital
Background and aims:
Phase II and observational studies support the use of rituximab in multiple sclerosis, Standard protocols are lacking, but studies suggest comparable efficacy between low and high dose regimens. We aimed at evaluating the effectiveness and safety of de-escalating rituximab dose from 1000 to 500 mg/6 months in multiple sclerosis.
Methods:
Patients were switched from rituximab 1000 to 500 mg/6 months and prospectively followed for 12 months. Relapses, disability, occurrence of brain/spinal MRI lesions, serum neurofilament light chain (NfL), CD19+ B cell and IgG concentrations were analyzed.
Results:
Fifty-nine patients were included (37 relapsing-remitting, 22 secondary progressive). No relapses occurred, with no difference in EDSS between baseline (4, [2.5-4.5]) and 12 months (3.5, [2.5-5.5], p=0.284). Overall, 3 new T2 lesions appeared during follow-up. NfL concentration was stable between baseline (7.9, [5.9-45.2] pg/ml) and 12 months (9.1, [5.9-21.3] pg/ml, p=0.120). IgG concentrations decreased with greater rituximab load (coefficient=-0.439, p=0.041). IgG deficient patients had greater risk of infections (OR=6.27, 95%CI=1.71-22.9, p=0.005).
Conclusion:
De-escalating rituximab dose from 1000 to 500 mg/6 months is safe, results in clinical and radiological stability, and does not affect serum NfL over 12 months. RTX load negatively influences IgG concentrations and IgG deficient patients are at higher risk of infections.
O14
M Arnold1; J Schweizer1; C Nakas2; V Schütz1; LP Westphal1; C Inauen1; C Inauen1; T Pokorny1; A Luft1; A Leichtle2; M Arnold3; A Bivic2; U Fischer2; GM De Marchis4; L Bonati4; M Müller4; T Kahles5; K Nedeltchev5; C Cereda6; G Kägi7; A Bustamante8; J Montaner8; G Ntaios9; C Foerch11; K Spanaus1; A von Eckardstein1; M Katan1
1 Univeristätsspital Zürich; 2 Inselspital - Universitätsspital Bern; 3 Insel Spital Bern; 4 Universität Basel & Universitätsspital Basel; 5 Cantonal Hospital Aarau; 6 Cantonal Hospital Lugano; 7 Canton Hospital St. Gallen; 8 Vall d’Hebron Institute of Research (VHIR); 9 University of Thessaly; 11 University Hospital of Frankfurt
Aims:
Lipoprotein(a) (Lp(a)) is a recognized causal risk-factor for atherosclerotic cardiovascular disease but its role for acute ischemic stroke (AIS) is controversial. In this study we evaluated the association of Lp(a) with large artery atherosclerotic (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients.
Methods and Results:
For this analysis of the prospective, observational, multicenter BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1759 AIS patients, collected within 24 hours after symptom-onset. Primary outcomes were LAA-stroke etiology and recurrent cerebrovascular events (ischemic stroke or transient ischemic attack) within one year. We showed that Lp(a) levels are independently associated with LAA stroke etiology (adj.OR 1.48, 95% CI 1.15 - 1.90, per unit log10Lp(a) increase) and identified age as a potent effect modifier (p-interaction = 0.031) of this association. The adjusted OR for LAA stroke in patients aged < 60 years was 3.64 (95% CI 1.76 - 7.52) per unit log10Lp(a) increase and 4.04 (95% CI 1.73 - 9.43) using the established cut-off ≥ 100 nmol/l. For 152 recurrent cerebrovascular events we did not find a significant association in the whole cohort. However, Lp(a) levels ≥ 100 nmol/l were associated with an increased risk for recurrent events among patients who were either < 60 years (adj.HR 2.40, 95% CI 1.05 - 5.47), had evident LAA-stroke etiology (adj.HR 2.18, 95% CI 1.08 - 4.40) or had no known atrial fibrillation (adj.HR 1.60, 95% CI 1.03 - 2.48).
Conclusion:
Elevated Lp(a) was independently associated with LAA-stroke etiology and risk of recurrent cerebrovascular events among individuals aged < 60 years or with evident arteriosclerotic disease.
O15
P Baumgartner1; M Hänsel1; K Geier1; S Petrus1; L Kook2; A Luft1; S Wegener1
1 University Hospital Zurich and University of Zurich; 2 University of Zurich
Introduction:
Intracranial Hypertension (IH) is a life-threatening complication of large vessel occlusion (LVO) stroke. Mortality in this condition is up to 80% if treated conservatively. Therefore, fast diagnosis of IH is imperative for successful surgical treatment. Since invasive intracranial pressure (ICP) monitoring devices are not always feasible, patients are usually followed based on clinical symptoms. However, medications or comorbidities of stroke complicate clinical IH assessment. Therefore, readily available, non-invasive methods to early detect IH in stroke patients are needed. We are investigating whether optic nerve sonography (ONS) is feasible to monitor ICP after stroke.
Methods:
Monitoring of ICP by ONS was achieved through transorbital measurement of the optic nerve sheath diameter (ONSD) which changes according to ICP. Normal ONSD values and interrater reliability were assessed in non-stroke control patients using a Bland-Altman Plot and intraclass correlation (ICC). In patients with LVO and no-large vessel occlusion (NLVO) stroke, ONSD was repeatedly assessed up to 120 hours after symptom onset. Neuroimaging from clinical routine was used to confirm the presence of brain edema.
Results:
Average ONSD in control patients (n = 60 eyes) was 6.1 mm ± 0.6 mm. and showed a very good agreement between investigators. Patients with LVO (n = 17 patients) and NLVO (n = 16 patients) both had an increased ONSD compared to control patients within the first 12 hours after stroke onset, which persisted up to 48 h after stroke on the ipsilateral eye in LVO stroke patients. Brain edema was detected in 10 out of 36 stroke patients between 9 – 31 (median 19) hours after stroke. The subset of stroke patients who developed brain edema had significant higher ONSD values on the ipsilateral eye compared to patients with no development of brain edema. This difference was most prominent within the first 12 hours after stroke and decreased gradually until after 72 hours after stroke no more differences between the groups were found.
Conclusions:
ONS might help to identify stroke patients at risk of brain edema very early. We are now developing an ONSD threshold which warns the clinician that a malignant course of brain edema is likely. Such a threshold could aid in earlier decision making for hemicraniectomy in stroke patients.
O16
Y Naseri1; MT Krüger1; G Kägi1; J Avecillas-Chasin2; F Brugger1; D Brogle1; R Bauer3; S Hägele-Link1
1 Kantonspital St. Gallen; 2 Mount Sinai Hospital New York; 3 Department of Neurosurgery, Cantonal Hospital Aarau, Switzerland
Background:
Holmes tremor (HT) is characterized by the presence of rest and intention tremor at a frequency below 4.5 Hz. Most cases are due to a midbrain lesion affecting ascending dopaminergic and cerebello-thalamic pathways. The optimal target for the treatment of HT with deep brain stimulation (DBS) is still in question. The most commonly reported targets include the ventral intermediate nucleus of thalamus (VIM), globus pallidus internus (Gpi), and subthalamic nucleus (STN). The posterior subthalamic area (PSA) contains the Zona incerta (ZI) and both the cerebellothalamic (CTT) and pallidothalamic tract (PTT), hence structures that effectively suppress ET as well as PD tremor. Lesions placed in the PSA showed high efficacy in tremor reduction in patients suffering from tremor-dominant Parkinson’s disease. The Pallidothalamic Tract (PTT) has been described as a highly efficient target in Parkinson’s disease. We here report our results in three patients who received PTT DBS for HT and describe and compare its effect to VIM, STN and Gpi stimulation.
Methods:
Three patients with HT (two of vascular origin one following traumatic brain injury) and unilateral PTT DBS were included into the study. Two patients had an additional unilateral VIM electrode, one an additional unilateral STN and Gpi electrode.
Tremor analysis with PTT-ON vs. PTT- OFF was performed in 2 patients with Fahn-Tolosa-Marin scale and in 1 patient with Whiget scale to evaluate the clinical effect of the PTT stimulation. Furthermore, the tremor effect of the additional electrodes (VIM, PTT and STN) was evaluated.
Results:
The most effect was seen for PTT stimulation. The tremor severity was reduced by 53.1% on the clinical tremor rating scale. Neither VIM nor Gpi or STN DBS showed a tremor reduction so that ultimately only the PTT electrode was left active in all three patients.
Conclusion:
Targeting the PTT and stimulating in the PSA appears to be promising for the treatment of therapy-resistant Holmes tremor. More studies are needed to confirm these results.
References
Adolfo Ramirez-Zamora et al. Deep brain stimulation for the treatment of uncommon tremor syndromes. Expert Rev Neurother . 2016 Aug;16(8):983-97.
Artusi CA et al. Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming. J Neurol 2018;265:2473–2493.
Juho Joutsa et al. Mapping Holmes Tremor Circuit Using the Human Brain Connectome. Ann Neurol. 2019 Dec;86(6):812-820.
Marc N. Gallay et al. MRgFUS Pallidothalamic Tractotomy for Chronic Therapy-Resistant Parkinson’s Disease in 51 Consecutive Patients: Single Center Experience. Front Surg. 2019; 6: 76.
Andy OJ, Jurko MF, Sias FR. Subthalamotomy in treatment of Parkinsonian Tremor. Journal of Neurosurgery 1963; 20:860–70. doi:10.3171/jns.1963.20.10.0860
O17
K Rosafio1; S Harris2; JQ Tran2; H Southworth3; CM Spencer4; BA Cree4; S Zamvil4
1 Celgene Corporation; 2 Bristol-Myers Squibb Company; 3 Data Clarity Consulting Ltd.; 4 University of California San Francisco
Background and goals:
Ozanimod is a sphingosine 1-phosphate receptor 1 and 5 modulator that causes lymphocyte retention in lymphoid tissues. The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system. The goal of this study was to characterize the effect of ozanimod on circulating leukocyte subsets in patients with relapsing multiple sclerosis (RMS) and compare results obtained using 2 methods of measurement.
Material and methods:
In a phase 1, open-label, pharmacokinetic/pharmacodynamic study, 24 patients with RMS were randomized to oral ozanimod 0.46 (n = 13) or 0.92 mg/d (n = 11) [equivalent to ozanimod HCl 0.5 or 1 mg] for ∼12 weeks following initial 7-day dose escalation (0.23 mg/d x 4 days + 0.46 mg/d x 3 days). Key exclusion criteria included active infection or history of chronic infections or immunodeficiency, recent live vaccination, previous lymphocyte-depleting or immunosuppressant therapy, and absolute lymphocyte count < 1.0 × 109/L. Exploratory analyses used flow cytometry and epigenetic cell counting to characterize leukocyte subsets. Circulating leukocyte subset counts at day 85 (end of treatment [EOT]) were compared with baseline using descriptive statistics. Results are expressed as a geometric mean (95% confidence interval) of the percentage of baseline value at EOT.
Results:
Both flow cytometry and epigenetic cell counting analyses showed that ozanimod was associated with dose-dependent reductions in nearly all cell types analyzed. Circulating B cells and T cells were reduced by >50% and >75% with ozanimod 0.46 and 0.92 mg, respectively, at EOT. Ozanimod 0.92 mg showed greater decreases in CD4+ (T helper) than CD8+ (cytotoxic) T cells. Mean reductions in CD8+ naive T cells with ozanimod 0.92 mg were >85% at EOT. Data on other cell types measured via flow cytometry or epigenetic cell counting will be presented, including cell types for which ozanimod has no appreciable effect.
Conclusions:
In line with its mechanism of action, ozanimod produced dose-dependent reductions in B and T cells in peripheral blood. A differential effect of ozanimod on specific leukocyte subtypes in patients with RMS was observed. Results were consistent for the leukocyte subsets measured using both methodologies, suggesting that epigenetic cell counting may be an acceptable alternative to flow cytometry.
O18
L Steinman1; G Comi2; A Bar-Or3; K Selmaj4; D Arnold5; H Hartung6; X Montalban7; EK Havrdová8; J Sheffield9; N Minton9; A Janjua9; V Huang9; D Silva9; L Kappos11; J Cohen1 1; B Cree1 2
1 Beckman Center for Molecular Medicine, Stanford University Medical Center; 2 San Raffaele Scientific Institute, Vita-Salute San Raffaele University; 3 Perelman School of Medicine, University of Pennsylvania; 4 Center for Neurology Łódz, Poland and University of Warmia and Mazury; 5 NeuroRx Research and Montréal Neurological Institute, McGill University; 6 Heinrich-Heine University; 7 Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d’Hebron; 8 Charles University; 9 Bristol-Myers Squibb Company; 11 University Hospital and University of Basel; 1 1 Mellen Center for MS Treatment and Research, Cleveland Clinic; 1 2 UCSF University of California San Francisco
Background and goals:
Ozanimod, a sphingosine 1-phosphate receptor modulator, was recently approved in the US for the treatment of relapsing forms of multiple sclerosis (RMS) and in the EU for relapsing-remitting multiple sclerosis. Ozanimod has been evaluated for RMS treatment in clinical pharmacology and in phase 2 and 3 efficacy and safety studies. This ongoing open-label extension (OLE) study characterized ozanimod’s long-term safety and efficacy.
Material and methods:
RMS participants who completed 1 of 4 parent trials were eligible for the OLE, where they received ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg). The primary efficacy endpoint, annualized relapse rate (ARR), was calculated via negative binomial regression. Efficacy data were summarized by pooled parent-trial treatment group (ITT population): placebo followed by ozanimod 0.46 mg (equivalent to ozanimod HCl 0.5 mg/d; n = 37) or 0.92 mg/d (n = 35), intramuscular interferon β-1a (IFN) 30 µg/wk (n = 740), or ozanimod 0.46 mg/d (n = 838) or 0.92 mg/d (n = 844). Treatment-emergent adverse events (TEAEs) were monitored.
Results:
This interim analysis (data cutoff 30 June 2018) included 2494 participants with mean (range) ozanimod exposure of 19.0 (0.03–32.5) months in the OLE. In phase 3 parent trials (12–24 months), mean ARR was 0.153 (95% CI, 0.125–0.187) with ozanimod 0.92 mg and 0.246 (0.204–0.297) with IFN. Among participants who received ozanimod 0.92 mg in parent trials, ARR with continued ozanimod 0.92 mg (additional 19.2 months) was 0.126 (0.099–0.161). Among those who received IFN in parent trials, mean ARR was reduced to 0.123 (0.095–0.158) after switching to ozanimod 0.92 mg (mean exposure 18.3 months). In the OLE, 1704 participants (68.3%) had any TEAE, 144 (5.8%) had a serious TEAE, and 30 (1.2%) discontinued due to a TEAE. TEAEs and serious TEAEs were similar in the parent trials. The most common TEAE was nasopharyngitis (11.7%).
Conclusions:
Ozanimod 0.92 mg was associated with a low ARR. Ozanimod was generally well tolerated, with no new safety concerns. These data support ozanimod as a safe and effective therapy for RMS patients.
O19
A Bicvic1; A Brueggemann2; R Kalla3; H Kerkeni3; G Mantokoudis3; M Abegg3; M Kolnikova4; T Bremova-Ertl5
1 University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland; 2 Sonnenhofspital, Lindenhofgruppe, Bern, Switzerland; 3 University Hospital Bern (Inselspital) and University of Bern; 4 Comenius University Children’s Hospital; 5 University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland
Background:
Ataxia telangiectasia (AT) is a rare autosomal recessive disorder characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. There is no authorized treatment, but supportive care1. Thus, the development of specific therapies is of high importance. Acetyl-DL-leucine (AL) is an acetylated derivative of an amino acid leucine. In animals, AL changes the membrane potential of vestibular cells2, activates vestibulocerebellum3, but also shows neuroprotective and anti-inflammatory effects 4–6. Current evidence suggests an improvement of cerebellar ataxia in patients with Niemann-Pick type C (NPC)7 and GM2-Gangliosidosis (GM2)8.
Aims:
We aimed to evaluate the clinical benefits of the treatment with AL in patients with AT. Methods Six AT patients were treated with AL 3 g/day for 1 week and then with 5g/day for 3 weeks. 1 patient was treated for 1 year. Cerebellar ataxia was evaluated by validated scales. Gaze-holding, saccades and smooth pursuit were examined by video-oculography. Measurements took place at baseline, and after 1 month of therapy in 5 patients and after 6 and 12 months in 1 patient.
Results:
Scale for Assessment and Rating of Ataxia (SARA) changed from the baseline (mean, (±SD, Min-Max)) of 22.1 points (5.88, 11-28.5) to 18 points (5.39, 8.5-23.5) after 1 month on medication (p = 0.0028). The 9-Hole Peg Test of the dominant hand gave results that were approaching statistical significance (p = 0.085), with the absolute change of 142.1 s (80.95, 85.38-300) to 130.24 s (84.83, 77.9-300). All patients demonstrated gaze-holding deficits; in 3 patients central-position DBN (CP-DBN) was present. In these 3 patients, the slow-phase velocity (SPV) of CP-DBN with the gaze straight-ahead changed from 5.57°/s (1.8, 3.53-6.99) at baseline to 4.7°/s (0.79, 3.97-5.56) after 1 month on treatment (1.35, -2.56-4.17) (p = 0.046). As a group, SPV of gaze drifts and CP-DBN changed from 1.36°/s (0.86, 0.43-2.31) to 0.5°/s (0.68, 0.01 -1.83) (p = 0.098).
Conclusion:
AL improved ataxia and ocular stability in AT patients. Currently, phase II trials are investigating the effects of AL in both AT (NCT03759678), NP-C (NCT03759639), and GM2 (NCT03759665), respectively. Owing to their overlapping phenotypes, and the mechanism of action of AL, a single master protocol was developed, implementing both an innovative trial design and a novel primary endpoint, better suited to these small, inhomogeneous populations.
References
1. Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: a review. Orphanet J Rare Dis. 2016;11(1):159. doi:10.1186/s13023-016-0543-7
2. Vibert N, Vidal PP. In vitro effects of acetyl-DL-leucine (tanganil) on central vestibular neurons and vestibulo-ocular networks of the guinea-pig. Eur J Neurosci. 2001;13(4):735-748.
3. Günther L, Beck R, Xiong G, et al. N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus. PLoS ONE. 2015;10(3): e0120891. doi:10.1371/journal.pone.0120891
4. Kaya E, Smith DA, Smith C, Boland B, Strupp M, Platt FM. Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease. J Clin Med. 2020;9(4). doi:10.3390/jcm9041050
5. Kaya E, Smith D, Smith C, et al. Acetyl leucine analogues as novel therapeutics for lysosomal storage diseases.
6. Sarkar C, Hegdekar N, Lipinski MM. N-acetyl-L-leucine treatment attenuates neuronal cell death and suppresses neuroinflammation after traumatic brain injury in mice. bioRxiv. Published online September 8, 2019:759894. doi:10.1101/759894
7. Bremova T, Malinová V, Amraoui Y, et al. Acetyl-dl-leucine in Niemann-Pick type C: A case series. Neurology. 2015;85(16):1368-1375. doi:10.1212/WNL.0000000000002041
8. Bremova-Ertl T, Platt FM, Strupp M. Sandhoff-disease: improvement of gait by acetyl-DL-leucine – a case report.
P01
J Stefela1; A Hakim2; U Fischer1; DJ Seiffge1
1 Department of Neurology and Stroke Center, Inselspital, Bern University Hospital, University of Bern, Switzerland; 2 University Institute of Diagnostic and Interventional Neuroradiology, Bern University Hospital, Inselspital, University of Bern, Switzerland
Background:
Haemorrhagic transformation of acute ischaemic stroke is a known complication of acute treatments including intravenous thrombolysis, mechanical thrombectomy or early anticoagulation therapy. Knowledge on prevalence of haemorrhagic transformation on MRI before and independent of any acute therapy is rare.
Material and Methods:
We analysed all consecutive patients with ischaemic stroke and MRI (as first imaging modality prior to any acute treatment) enrolled in our prospective stroke database between 1st January and 31th December 2017. On baseline MRI, we determined presence of haemorrhagic transformation and cerebral microbleeds using susceptibility weighted imaging (SWI) MRI sequence and ischaemic stroke lesions size. Haemorrhagic transformation was classified according to MRI adapted ECASS III classification. We assessed association with lesion size, prior anticoagulation therapy, time from symptom onset to MRI and presence of cerebral microbleeds, using univariate regression analysis.
Results:
We analysed the first 176 of 707 eligible patients (preliminary analysis). The median age was 73 years (IQR 62-82), the median NIHSS on admission was 3 (IQR 1-7) 25 patients (14%) were on prior anticoagulation therapy and 70 patients (40%) were female. The median time from symptom onset to MRI was 372 minutes (IQR 156-936 minutes). Among 176 patients analysed, the majority had single (64 patients, 36%) or multiple (77 patients, 44%) embolic infarcts while 35 patients (20%) had non-embolic strokes. Infarct lesion size was small in 78 patients (45%), moderate in 77 patients (44%) and major in 19 (11%) patients. Ten patients (5.7%) had any haemorrhagic transformation with two patients having parenchymal haematoma (PH I according to ECASS). Among patients with prior anticoagulation, 2 patients (8%) had haemorrhagic transformation. Lesion size (OR 3.4, 95%CI 1.3-8.8; p = 0.013) but not prior anticoagulation (OR 1.6, 95%CI 0.31-7.8, p = 0.592) nor time from symptom onset to MRI (OR 1.6, 95%CI 0.7-3.6, p = 0.255) nor presence of cerebral microbleeds (OR 1.3 95%CI 0.2-5.6, p = 0.878) were associated with haemorrhagic transformation in univariate analysis.
Conclusion:
This preliminary data show haemorrhagic transformation on MRI prior to any acute therapy seems to occur in up to 5% of patients. Further research is needed to determine exact frequency, risk factors and clinical implications.
P02
K Rosafio1; H Hartung2; B Cree3; K Selmaj4; E Havrdová5; G Comi6; J Sheffield7; N Minton7; A Janjua7; N Ding7; A Bar-Or8
1 Celgene Corporation; 2 Heinrich-Heine University; 3 UCSF University of California San Francisco; 4 Center for Neurology, Łódz, Poland and University of Warmia and Mazury; 5 Charles University; 6 San Raffaele Scientific Institute, Vita-Salute San Raffaele University; 7 Bristol-Myers Squibb Company; 8 Perelman School of Medicine, University of Pennsylvania
Background and Goals:
Ozanimod was recently approved in the US for relapsing forms of multiple sclerosis (RMS) and in EU for the treatment of relapsing-remitting multiple sclerosis. By modulating sphingosine 1-phosphate receptor subtype 1, ozanimod reduces circulating lymphocytes, potentially increasing susceptibility to infections. Our objective was to evaluate infection rates with long-term exposure to ozanimod 0.92 mg in clinical trial participants with RMS.
Material and Methods:
SUNBEAM (NCT02294058; ≥ 12 months) and RADIANCE (NCT02047734; 24 months) were multicenter, randomized, double-blind, phase 3 trials comparing oral ozanimod 0.92 and 0.46 mg/d (equivalent to ozanimod HCl 1 and 0.5 mg) with intramuscular interferon β-1a 30 µg/week in adults (18–55 years) with RMS. Participants who completed any ozanimod RMS clinical trial were eligible to enroll in an open-label RMS extension trial (DAYBREAK; NCT02576717) of ozanimod 0.92 mg/d. Infection rates with ozanimod 0.92 mg are compared descriptively in controlled phase 3 trials (SUNBEAM and RADIANCE) and in participants who received ozanimod 0.92 mg in any RMS trial.
Results:
In pooled controlled phase 3 studies, 882 participants received ozanimod 0.92 mg (mean [SD] exposure, 18.1 [6.0] months; 1345.4 person years [PY] on study). The incidence of infections was 35.1% and serious infections was 1.0%. The overall infection rate was 300.5/1000 PY; herpes zoster rate (including varicella zoster virus [VZV] infection) was 3.7/1000 PY. The most common infections were nasopharyngitis (11.1%) and upper respiratory tract infection (5.9%). Opportunistic infections, predominantly herpes related, occurred in 1.8%. With longer term exposure to ozanimod 0.92 mg in any trial (n = 2631; data cutoff 31 January 2019; mean [SD] exposure 32.0 [12.8] months; 7058.5 PY on study), overall infection incidence was 48.6% and serious infections was 1.7%. The overall infection rate was 270.1/1000 PY. Herpes zoster rate (including VZV infection) was 5.3/1000 PY. No serious opportunistic infections occurred.
Conclusions:
In RMS participants with longer ozanimod 0.92 mg exposure, overall infection rates were similar to those with ≤ 24 months’ exposure in controlled phase 3 trials. Non-serious herpes zoster infections were infrequent, but increased over time. No serious opportunistic infections have been reported with ozanimod.
References
1. Brooks BR et al. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293.
2. Agosta F et al. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:1.
3. Cudkowicz ME et al. Lancet Neurol. 2013;12:1059.
4. Ludolph A et al. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:291.
5. Writing Group; Edaravone (MCI-186) ALS 19 Study Group. Lancet Neurol. 2017;16:505.
6. Abe K et al. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610.
7. Atassi N et al. Neurology. 2014;83:1719.
8. Czaplinski A et al. J Neurol Neurosurg Psychiatry. 2005;77:390.
9. Belsh JM. ALS Other Motor Neuron Disord. 2000;1: S57.
10. Ross MA et al. Neurology. 1998;50:768.
11. de Carvalho M. Brain. 2012;135:2581.
12. Swash M. J Neurol Neurosurg Psychiatry. 2012;83:659.
13. de Carvalho M et al. Clin Neurol. 2008;119:497.
14. Johnsen B et al. Clin Neurophysiol. 2019;130:307.
P03
N Braun1; E Macklin2; E Sinani3; A Sherman4; M Weber5
1 Kantonsspital St Gallen; 2 Massachusetts General Hospital; 3 Massachusetts General Hospital; 4 Harvard Medical School; 5 Kantonsspital St. Gallen
Over the past two decades, the El Escorial criteria (EEC) have been used as eligibility criteria in major randomized controlled trials. One of the goals of the revised EEC was to allow earlier diagnosis and, thus earlier trial inclusion by introducing a new category, namely “clinically probable laboratory supported” ALS. This category allowed EMG findings to be taken into account assuming that EMG is more sensitive than the clinical examination in detecting lower motor neuron signs. Recently, Edaravone has been licensed in several countries for the treatment of ALS based on a randomized controlled trial in a selected group of ALS patients excluding the EEC category “clinically probable laboratory supported”. The major reason was that in a post hoc analysis of the first Edaravone trial this group comprised many slow progressors. As it is unclear whether this bias toward slow progressors was a study-specific problem or related to the category itself, we performed an analysis in the PRO-ACT dataset. In the PRO-ACT dataset, progression in ALS patients included at baseline into the “clinically probable laboratory supported” category was significantly slower (– 0.53 in ALSFRS/month) compared to the other EEC categories (– 0.68 in ALSFRS/month; p < 0.001) and exhibited a significantly longer diagnostic delay (13.5 months vs. 11.7 months, p < 0.001). This suggests that the bias toward slow progressors in the “clinically probable laboratory supported” category is an inherent problem of the category and thus does not fulfill the previous goal of earlier diagnosis, raising several questions concerning the application of this category.
P04
B Jin
Department of Neurology, Inselspital
When a patient is referred to the hospital because of a possible epileptic event, the most valuable information is a description of the event itself. Since this is not always possible, diagnostic tools such as EEG and MRI are needed to dichotomize epileptic and non-epileptic events. But often, they provide nonspecific findings or are negative.
The question arises, who could possibly benefit from an antiepileptic treatment already after first seizure. The goal of our study was to assess prospectively, whether EEG and MRI can possibly help the clinician to answer that question.
In the SWISS FIRST study, we collect EEG, MRI and clinical information of patients, who suffered most likely their first epileptic seizure in their life and were referred to one of seven contributing centers. Up to now, 56 patients were recruited in Bern. 47 of those (84%) effectively suffered an epileptic seizure based on the clinical assessment in the emergency setting.
24 of 56 patients (43%) showed EEG alterations, most commonly focal slowings, which are nonspecific findings. In our cohort 5 of the 9 patients (56%), who did not suffer from an epileptic seizure, showed slowings. Of the 47 patients with epileptic seizures, only 3 (6%) showed typical discharges in the initial EEG, which is regarded as the most specific diagnostic finding in the EEG.
In 26 of all included patients (46%), NCI was acquired additionally during the MRI scan, which detects highly synchronized electric activity in the brain. 23 of those 26 (88%) patients were classified as epileptic. In 15 of these 23 patients (65%), we found an effect in NCI. However, also 2 of the 3 (67%) patients without epileptic seizure had detectable NCI abnormalities. 9 of the 23 (39%) epileptic patients showed a pathologic EEG (mostly only slowing), and only 2 of 23 (8%) showed typical epileptic discharges in the EEG.
Our interim findings demonstrate the ultimate need of more precise diagnostics. Two years after the first seizure, we will make the final assessment, whether a patient really had an epileptic event, and determine if and how many recurrences occurred. A retrospective analysis of our prospectively acquired dataset comprising ∼500 patients from Switzerland will reveal, which pattern of findings in the initially performed EEG and MRI were effectively helpful to support the diagnosis and the decision for initialization of treatment.
Jin B et al., Clinical and Translational Neurosciences, 2020, 4
This abstract is related to Abstract ID:6233
P05
J Allum1; H Rust1; N Lutz2; CO Schouenborg2; B Fischer-Barnicol1; V Haller1; T Derfuss1; J Kuhle1; O Yaldizli1
1 University of Basel; 2 Bern University of Applied Sciences
Background and Aims:
Balance impairment is frequent in multiple sclerosis (MS). Previously, we determined that vibrotactile feedback (VTfb) training of trunk sway significantly improves MS patients’ balance control more than training without VTfb [1, 2]. In this study, we aimed to answer 5 questions: 1) How many weeks of VTfb training are required to obtain the best benefit with VTfb? 2) How long does the carry-over benefit last once VTfb training terminates? 3) Is the benefit similar for stance and gait? 4) Is position or velocity based VTfb more effective in reducing trunk sway? 5) Are improvements also observed in patients’ subjective assessments of balance control?
Methods:
Balance control of 16 MS patients was measured with gyroscopes at the lower trunk. The gyroscopes also drove directionally active VTfb in a head-band. The VTfb thresholds were based on individual 90% ranges of roll and pitch trunk sway amplitudes for stance and trunk sway velocity amplitudes for gait tasks. Patients trained twice per week with VTfb for 4 weeks to determine when balance control with and without VTfb stopped improving. Tandem gait was tested with position- and with velocity-based VTfb. After VTfb training ceased, weekly assessments without VTfb over 4 weeks and at 2, 4, and 6 months determined when the carry-over effect ended. Trunk sway differences between the first and subsequent assessments quantified balance control changes.
Results:
A 20% improvement in balance to normal levels occurred with VTfb. The short term (3 days) carry-over effect improved from 15 to 20% (p≤0.001). Medium term (1-4 weeks) carry-over improvement was constant at 19% (p≤0.001). At 4 and 6 months improvement was not significant, 12 and 10%. Most improvement was for lateral sway. Equal improvement occurred when angle position or velocity drove VTfb. Subjective assessments of balance revealed most improvement after 3 weeks of training (range 11 to 32%, p≤0.05).
Conclusions:
This study demonstrated that 3-4 weeks VTfb training yields clinically relevant sway reductions for MS patients during stance and gait. The carry-over effect lasted at least 2 months. Velocity-based VTfb was equally effective as position-based VTfb. Patient assessments of balance capabilities also improved.
Clinical Rehabilitation Impact:
This study provides guidelines on the practical application of VTfb training into regular physiotherapy to improve balance control in MS patients.
References
1. van der Logt RP, Findling O, Rust H, Yaldizli O, Allum JHJ. The effect of vibrotactile biofeedback of trunk sway on balance control in multiple sclerosis. Mult Scler Rel Disord (2016) 8: 58-63.
2. Rust HM, Lutz N, Zumbrunnen V, Imhof M, Yaldizli Ö, Haller V, et al. Benefits of short-term training with vibrotactile biofeedback of trunk sway on balance control in multiple sclerosis. Phys Med and Rehab Res (2020) (in press).
P06
V Urbano1; J Novy1; K Schindler2; S Rüegg3; V Alvarez4; F Zubler2; M Oddo1; JW Lee5; A Rossetti1
1 CHUV Lausanne, Université de Lausanne; 2 Inselspital - Universitätsspital Bern; 3 University Hospital Basel / University of Basel; 4 Hôpital du Valais - Sion; 5 Brigham and Women’s Hospital/Harvard Medical School
Background:
Continuous EEG (cEEG) is increasingly used in critically-ill patients, but it is more resource-intensive and, in the USA, more expensive compared to routine EEG (rEEG). This study analyzes hospital-related reimbursement costs in participants of a Swiss multicenter randomized controlled trial that assessed the relationship of cEEG versus repeated rEEG with outcome.
Methods:
We analyzed data of the CERTA study (NCT03129438), including demographics, clinical variables, and costs (in CHF) for acute hospitalizations after the Swiss Diagnosis Related Groups. In addition to a comparison across EEG intervention groups, we explored correlations with several clinical variables, using uni- and multivariate analyses.
Results:
In total, 366 adults were analyzed (184 cEEG, 182 rEEG); 123 (33.6%) were women, mean age was 63.8 years (+/- 15). Median hospitalization costs were comparable across EEG groups; cEEG: 89’631 CHF (IQR: 45’635 – 159’994); rEEG: 73’017 CHF (IQR: 43’031 – 158’565); p = 0.432. While in univariate analyses increasing costs correlated with longer acute hospitalizations, younger age, hypoxic-ischemic encephalopathy, changes in clinical management within 60 hours, no seizures or status epilepticus detection, and survival at 6 months, only acute hospitalization duration was independently related to costs (p < 0.001).
Conclusion:
There is no significant reimbursement cost difference across critically-ill adults receiving cEEG or rEEG in a Swiss DRG billing system, a system similar to several other countries. Rather, costs correlate with duration of hospitalization.
References
1. Ney JP, van der Goes DN, Nuwer MR, Nelson L, Eccher MA. Continuous and routine EEG in intensive care: utilization and outcomes, United States 2005-2009. Neurology. 2013;81(23):2002-8.
2. Hilkman DM, van Mook WN, van Kranen-Mastenbroek VH. Continuous electroencephalographic-monitoring in the ICU: an overview of current strengths and future challenges. Curr Opin Anaesthesiol. 2017;30(2):192-9.
3. Rossetti AO, Schindler K, Alvarez V, Sutter R, Novy J, Oddo M, et al. Does Continuous Video-EEG in Patients With Altered Consciousness Improve Patient Outcome? Current Evidence and Randomized Controlled Trial Design. Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society. 2018;35(5):359-64.
4. Hirsch LJ, LaRoche SM, Gaspard N, Gerard E, Svoronos A, Herman ST, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version. Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society. 2013;30(1):1-27.
5. Claassen J, Taccone FS, Horn P, Holtkamp M, Stocchetti N, Oddo M, et al. Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM. Intensive care medicine. 2013;39(8):1337-51.
6. Hill CE, Blank LJ, Thibault D, Davis KA, Dahodwala N, Litt B, et al. Continuous EEG is associated with favorable hospitalization outcomes for critically ill patients. Neurology. 2019;92(1): e9-e18.
7. Hilkman DMW, van Mook W, Mess WH, van Kranen-Mastenbroek V. The Use of Continuous EEG Monitoring in Intensive Care Units in The Netherlands: A National Survey. Neurocrit Care. 2018;29(2):195-202.
8. Singh J, Britton J, Alwaki A, Singh P. After-Hours EEG: Relative Value of Emergent Routine Versus Prolonged EEG Recordings. J Clin Neurophysiol. 2019;36(1):32-5.
9. Abend NS, Topjian AA, Williams S. How much does it cost to identify a critically ill child experiencing electrographic seizures? J Clin Neurophysiol. 2015;32(3):257-64.
10. Busse R, Geissler A, Aaviksoo A, Cots F, Hakkinen U, Kobel C, et al. Diagnosis related groups in Europe: moving towards transparency, efficiency, and quality in hospitals? BMJ. 2013;346: f3197.
11. Scheller-Kreinsen D, Quentin W, Busse R. DRG-based hospital payment systems and technological innovation in 12 European countries. Value Health. 2011;14(8):1166-72.
12. Wild V PE, Biller-Andorno N. Les DRG: l’éthique contre l’économie? Bull ASSM. 2009;09(1):1-5.
13. Mathauer I, Wittenbecher F. Hospital payment systems based on diagnosis-related groups: experiences in low- and middle-income countries. Bull World Health Organ. 2013;91(10):746-56A.
14. Schreck RI. Medicare. MSD Manual Professional Edition. Rev Feb 2019
15. Crepeau AZ, Fugate JE, Mandrekar J, White RD, Wijdicks EF, Rabinstein AA, et al. Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest. Resuscitation. 2014;85(6):785-9.
16. Rossetti AO SK, Sutter R, Rüegg S, Zubler F, Novy J, Oddo M, Warpelin-Decrausaz L, Alvarez V. Continuous versus routine EEG in critically ill adults with altered consciousness and no recent seizure: a multicenter randomized trial. JAMA Neurology 2020.
P07
T Badel1; I Savic Pavicin1; V Basic Kes2; S Kocijan Lovko3; S Anić Milošević1; N Lukic4; L Krapac5; D Zadravec2
1 School of Dental Medicine; 2 Sestre milosrdnice University Hospital Center, University of Zagreb; 3 Psychiatry Hospital “Sv Ivan”; 4 Center of Dental Medicine, University of Zürich; 5 Academy of Medical Sciences of Croatia
Introduction & Aims:
The aim of this study was to compare the relationship between clinical characteristics of the patients from the subgroup with osteoarthritis (OA) and disc displacement (DD) of temporomandibular joint (TMJ) related to types of headaches and vertebral column disorders (VCD) with a 9-year-follow-up after treatment.
Materials and Methods:
The patients were divided into two subgroups according to different diagnoses of TMJ disorders; the G1 subgroup consisted of 47 patients with DD of TMJ (mean age ± standard deviation (SD) 29.53 ± 14.16, 76.6% women). These patients were compared to the G2 subgroup of 36 patients who only had OA of TMJ (mean age ± SD: 50.58 ± 16.11, 88.9% women). The patients from both subgroups were treated in the same way using the occlusal splint and physical therapy. Clinical variables were compared between the two groups (G1 and G2) as well as within the total number of patients (G1+G2) for particular clinical features in the period of the first examination (T0) and on recalls after 9 years (T1). Pain on VAS (visual analogue scale) in TMJs, occurrence of headache, and the existence of VCD were recorded. The psychological assessment was carried out by Spielberger’s State-Trait Anxiety Inventory (STAI).
Results:
There was a significant age difference (p < 0.001) between the two subgroups of TMJ diagnoses. There was no difference (p = 0.4674) for pain intensity on VAS measured at T0 and T1 for G-1 and G-2 subgroups. Measuring anxiety showed a significant difference for both score values at T0 (first appointment): for STAI 1 p = 0.029 and for STAI 2 p = 0.006). VCD were found in 17% patients of G-1 and in 66.7% patients of G-2 group. For patients without VCD alone, a statistically significant difference was found between patients’ age (p = 0.0008) and STAI 2 (p = 0.004): G-2 patients were older and with higher scores of anxiety than G-1 patients. Headaches were found in 34% of G-1 and 44% of G-2 patients, and there was no difference for any variables.
Discussion:
Reversible treatments are the primary choice for the treatment of TMJ disorders, with the occlusal splint and TMJ physical therapy both equally successful.
Conclusion:
Patients with OA (G-2) were older and with higher anxiety scores. Patients without VCD with OA (G-2) had higher pain intensity at 9-year-recall.
References
Di Paolo C et al. Pain Res Manag. 2017;2017:3203027.
P08
P Dorin1; J Walch1; MT Krüger1; D Brogle1; G Kägi1; S Mittas2; S Bohlhalter2; S Hägele-Link1; F Brugger1
1 Kantonsspital St. Gallen; 2 Kantonsspital Luzern
Background:
Deep brain stimulation (DBS) is a surgical procedure associated with a perioperative infection rate of approximately 1-2%. Patients under immunosuppressive treatment are arguably more prone to infectious complications, but experience in patients on immunosuppressants who underwent DBS is limited to one anecdotal report (Samii et al. 2005).
Methods:
The first patient has been treated with Mycofenolate-mofetil, Cortisone and Hydroxychloroquine for several years due to systemic lupus erythematosus. He received bilateral DBS in the ventral intermedius nucleus due to medication-refractory essential tremor. The second patient was under immunosuppressive therapy with Tacrolimus and Mycofenolate after renal transplant due to polycystic kidney disease. He suffered from Parkinson’s disease for > 10 years. Due to pronounced wearing-offs and peak-dose dyskinesia he received bilateral DBS in the subthalamic nucleus.
Results:
The peri- and postoperative course in the first patient was favourable without any wound or lead infections. Three months after implantation an ischemic cerebral infarction of the small vessels occurred. A few months after implantation, the patient died from a septic shock due to aspiration pneumonia. Both events were considered as unrelated to DBS implantation. The second patient did not suffer from any peri- or postoperative wound or lead infections. Because of an infected hepatic cyst he developed a transient renal failure due to a bacteremia two weeks after surgery. However, the long-term outcome was favourable with a good recovery. Immunosuppressive therapy was continued in both patients.
Conclusion:
In our two patients on immunosuppressive treatment we did not observe any wound or lead infections. Our observation is in line with one published case report on this topic, which did not show any perioperative complications either. However, the postoperative course was complicated by severe comorbidities. We consider DBS implantation in immunosuppressed patients as feasible, but multidisciplinary management is required. In order to provide more reliable evidence on this issue, systematic studies are warranted.
P09
N Binder1; W Middleham1; N Pranculeviciute1; C Glück2; M Wyss3; B Weber4; M El Amki1; S Wegener1
1 Universitätsspital Zürich; 2 Univeristät Zürich; 3 Universität Zürch; 4 Universität Zürich
Context and Objectives:
Propagation of waves of cortical spreading depolarization (CSD) during stroke promotes infarct expansion. During CSD, the cerebral cortex undergoes different waves of hemodynamic responses known as spreading hyperaemia (SH). Here, we analysed the different SH patterns after stroke in mice and their association with outcome.
Methods:
For induction of stroke, thrombin was injected into the left middle cerebral artery (MCA) of Balb-C mice. After stroke induction, cortical perfusion was measured using laser speckle contrast imaging (LSCI) for 120 minutes. Functional deficits were assessed until day 7. On day 7, animals were euthanized. Triphenyl-tetrazolium chloride (TTC) was used to stain brain slices for infarct size quantification.
Results:
Analysis of LSCI in the first moments after ischemic stroke revealed that three different patterns of SH occurred in the cortex: SH covering the full hemisphere including the infarct core and the peri-infarct area (FHSH); SH occurring only in the peri-infarct area (PSH); or lack of SH (no-SH). Amplitude and duration of SHs were considerably increased in FHSH compared to PSH mice. When confined only to peri-infarct regions (PSH), CSDs were associated with progressive tissue damage while FHSHs indicated a beneficial infarct outcome and potential viability of the infarct core. Most notable, the no-SH group showed intermediate infarct sizes, mortality and frequency of haemorrhages.
Conclusion:
In our stroke model, we observed that mice displaying FHSH had the best outcome after stroke. Our data suggest that SH does not necessarily predict bad outcomes.
In conclusion, extension and shape of SH occurring a few minutes after stroke onset predict severity and extent of the lesion.
P10
S Crippa1; M Fett1; G Kägi2; P Kohler3; P Meyer Sauteur4; L Graf5
1 Kantonspital St. Gallen; 2 Kantonsspital St Gallen; 3 Kantonsspital St. Gallen; 4 UniversitätsSpital Zürich (USZ); 5 Zentrum für Labormedizin St. Gallen
We describe a previously healthy 24-year-old man who presented with acute paresthesia, arm weakness, homonymous hemianopsia, hemiataxia all left-sided and gait instability (NIHSS 4). Further he had noted a fever of 38.5°C, nausea and headache since 24 h but denied any respiratory symptoms. Chest radiograph was unremarkable; C-reactive protein was 13mg/L (reference < 8mg/L). Cerebral imaging (CT and MRI) showed ischemic stroke in the territory of the right posterior cerebral artery with persisting rest thrombus (P1/2 segment) with embolic pattern. Polymerase chain reaction (PCR) from nasopharyngeal swab and stool were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR from blood and spinal fluid remained negative. Despite complete evaluation no concurrent etiology was detected (no source of cardiac embolism or PFO in transesophageal echocardiography and long-term-ECG (30 days), no signs of vasculitis or cns infection in blood work and CSF). Coagulation work-up 3 days after admission revealed markedly elevated factor VIII (fVIII; 321%; reference range 50-150%) and von Willebrand factor (vWF)-activity (198%; reference range 65-145%), but no signs of systemic blood coagulation activation (non-elevated d-dimers and prothrombin fragments) suggesting vascular endothelial dysfunction. Hereditary thrombophilia, lupus anticoagulant and antiphospholipid-antibodies were excluded. The patient was treated with acetylsalicylic acid, enoxaparin and hydroxychloroquine. We present the case of a young adult with stroke in the context of very mild coronavirus disease 2019 (COVID-19). Ischemic stroke has been reported in association with COVID-19, particularly among the elderly and those with a severe disease course [1-2]. Coagulopathy and vascular endothelial dysfunction have been discussed as complications of COVID-19 [3]. In our patient, results of hematologic work-up suggest SARS-CoV-2-induced endotheliitis. SARS-CoV-2 has been shown to attack angiotensin converting enzyme-2 receptors in endothelial cells causing endotheliitis, thereby disrupting the integrity of the blood vessel wall [4]. To conclude, this case illustrates the possibility of stroke in healthy SARS-CoV-2-infected patients without hyperinflammatory state or excessive systemic coagulation activation. We recommend measuring fVIII and vWF levels as signs of endothelial activation in case of cryptogenic stroke associated with COVID-19.
References
1. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. Epub 2020 Apr 10.
2. Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. New England Journal of Medicine. 2020;0: e60.
3. Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. New England Journal of Medicine. Massachusetts Medical Society; 2020;382: e38.
4. Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell. Epub 2020 Apr.: S0092867420303998.
P11
C Achtnich, A Felbecker, S Zimmerer
Kantonsspital St Gallen
Background:
Steroid responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is a rare condition leading to subacute encephalopathy. The presence of anti-thyroid antibodies is characteristic. As in Hashimoto-Thyroiditis women are more frequently affected than man. The clinical presentation has a wide range including seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal. The diagnosis must be suspected in investigation-negative encephalopathies after exclusion of other metabolic, toxic, paraneoplastic or infectious encephalopathies. MRI findings are often non-specific, as for example leukoencephalopathy-like or limbic encephalitis-like manifestations.
Case report:
We describe the case of a 75 year old woman, who presented to our memory clinic with complaints of cognitive decline over several months and a right sided headache. The neuropsychological tests showed deficits in episodic memory and executive functions. The cerebral spinal fluid showed normal cell count, slightly elevated protein levels (0.62g/l), no oligo-clonal bands, beta-amyloid 1-42 was low (318pg/ml) and Phospho-tau was normal. The anti-TPO-Antibodies were significantly elevated (1932U/l) but thyroid function was normal, additionally there was a multinodular thyroid. On several MRI there were changing and growing PML-like lesions in the Gyrus cinguli, frontal lobe, parietal lobe and the occipital lobe manly in the white matter involving the cortex, no signs of vasculitis, no involvement of the hippocampus despite a slight atrophy shown on volumetry. After exclusion of other types of encephalopathies on laboratory testing including screening for limbic encephalitis and a tumour scanning we made the diagnosis of SREAT.
Results:
4 weeks after treatment initiation with Prednisone beginning with 1mg/kg/KG and tapering over the following weeks we performed an MRI where there was subtotal resolution of the lesions with persisting innumerable microbleeds. Another neuropsychological test showed slightly improved results with persisting deficits in episodic memory and executive functions. The headache was gone.
Conclusion:
Steroid responsive encephalopathy and associated autoimmune thyroiditis represents a rare and treatable cause of a rapidly progressive dementia which responds well to steroids and therefore is important to recognize.
References
CH Lauren et al. Autoimmun rev. 2016 15(12):1129-1133
R Mocellin et al. CNS Drugs 2007 21(10):799-811
J Wang et al. PLoS one 2013 8(2): e55758
P12
M Spiegelberg, A Hünerwadel, M Wu, A Tarnutzer
Kantonsspital Baden AG
Background:
Benign paroxysmal positional vertigo (BPPV) is the most common episodic triggered vertigo. With targeted treatment available, prognosis is usually excellent. However, rarely, other dangerous conditions may mimic BPPV. Thus, performing an extended diagnostic work-up in cases when treatment fails is important.
Case description:
A 44-year-old male patient presented to the emergency department with a 10-day history of brief dizzy spells (lasting 1-2 minutes) triggered by head-position changes and accompanying gait imbalance. On history taking further complaints were denied. Clinical neuro-otologic examination was normal except for mild dizziness triggered in the 90°-supine-roll maneuver to the right side, followed by a left beating spontaneous nystagmus when returning to supine position. Provocation maneuvers performed on a rotating chair the same day showed a persistent apogeotropic horizontal nystagmus in 90°-supine roll position (left>right), accompanied by intense vertigo. Diagnosis of cupulolithiasis of the right lateral canal (apogeotropic variant) was made and repositioning maneuvers were initiated. The next day the patient reported partially resolved symptoms, but as he continued to show the same nystagmus pattern repositioning maneuvers were repeated. On subsequent provocation maneuvers for the lateral canals no pathologic nystagmus or vertigo was triggered any more. With reemerging apogeotropic nystagmus when testing the lateral canals on the following day, an MRI was ordered, demonstrating multiple cerebral and cerebellar space-occupying, cystic lesions with perifocal edema. Resection of the largest cerebellar lesion was performed at another hospital, providing the diagnosis of an TTF1-positive adenocarcinoma originating from the lung. The patient received palliative radiation of the brain and the bone metastases.
Conclusion:
Central paroxysmal positional vertigo (CPPV) may closely mimic lateral canal BPPV with regards to triggers, nystagmus beating direction and transient disappearance after repositioning maneuvers. While rare, the identification of CPPV is critical for further diagnostic steps. An extended workup should be initiated if a) focal neurologic signs are identified, b) isolated positional nystagmus without vertigo/dizziness is observed, c) the pattern of nystagmus is atypical for the provocation maneuver performed, d) the nystagmus does not respond to repositioning maneuvers or e) reemerges on three or more treatment session
P13
V Fuchs1; M Kutza2; S Wischnewski2; N Deigendesch1; L Lutz1; L Kulsvehagen1; G Ricken3; S Hametner3; L Kappos1; A Tzankov1; S Frank1; L Schirmer2; A Pröbstel1
1 Universität Basel & Universitätsspital Basel; 2 Medizinische Fakultät Mannheim, Universität Heidelberg; 3 Medizinische Universität Wien
Background:
Although primarily targeting the respiratory system, coronavirus disease 2019 (COVID-19) also manifests with central nervous system (CNS)-related symptoms. Yet, little is known about the clinical course of CNS autoimmune disease and concurrent SARS-CoV-2-infection. Whether multiple sclerosis (MS) renders patients more susceptible to CNS involvement and / or infection during COVID-19 and the impact of SARS-CoV-2 infection on disease activity remain elusive.
Objective:
Here, we assessed whether an impaired blood-brain barrier in MS facilitates viral CNS entry, and whether COVID-19 infection is associated with MS disease exacerbation.
Methods:
To that end, we combined an in-depth histopathological assessment with spatial transcriptomic analysis using multiplex in situ hybridization analysis for immune and SARS-CoV-2 transcripts in autoptic brain tissue of an untreated MS patient, who died from COVID-19-associated respiratory failure, compared to a cohort of non-MS COVID-19, non-MS non-COVID-19, and non-COVID-19 viral encephalitis controls.
Results:
Despite a general microglia activation in COVID-19 brain parenchyma, we found neither evidence for active demyelinating activity nor presence of SARS-CoV-2 transcripts in COVID-19 MS lesions.
Conclusions:
We conclude that neither clinical and morphological signs of MS disease exacerbation nor presence of viral transcripts in MS brain lesions are observed in COVID-19 patients and that no SARS-CoV-2-specific abnormalities are present in MS COVID-19 and non-MS COVID-19 patients. Future studies will yield further insights into the risk profile of COVID-19 in MS and related CNS autoimmune diseases.
P14
V Petroulia1; BZ Jin1; C Rummel2; M Reyes3; M Seeck4; R Wiest1
1 Inselspital, University Hospital and University of Bern; 2 Inselspital, University of Bern, Bern, Switzerland; 3 University of Bern / Insel Data Science Center, Inselspital, Bern, Switzerland; 4 University Hospitals of Geneva and University of Geneva
Background:
“SWISS FIRST” is a Switzerland-wide prospective observational study. We aim to segregate patients presenting with an epileptic vs. non-epileptic seizure with the aid of EEG, MRI and clinical information and assess whether EEG and MRI can answer that question.
The goal of neuroimaging in the setting of a first seizure is the identification or exclusion of a structural epileptogenic lesion associated with an increased risk of seizure recurrence and manifestation of an epilepsy.
We report on the prevalence of structural epileptogenic lesions, incidental findings, diffusion- (DWI) and susceptibility-weighted (SWI) abnormalities as well as perfusion abnormalities in our patient sample thus far.
Materials and Methods:
In the SWISS FIRST study, we collect EEGs, MRIs and clinical information of patients, who suffered their first epileptic seizure in their life and were referred to one of seven contributing centers. Up to now, 56 patients were recruited in Bern.
Results:
The mean age of the patients was 48.6 years (range: 20 – 83 yrs) with males comprising 57% of the total sample (32 male, 24 female).
In the visual assessment of the MRI scans 12 out of 56 (21%) patients showed no structural epileptogenic lesions. Twenty patients (36%) had white matter lesions (WML), i.e. cerebral small vessel disease.
24 patients (43%) showed possible epileptogenic lesions, with post-ischemic gliosis seen in seven patients (12.5%). Four patients (7%) revealed FCD or juxtacortical lesions. Brain tumors were found in four patients (7%) and two patients (3.6%) had a first seizure in the setting of a CNS infection. Three patients (5%) showed vascular anomalies as epileptogenic cause (arteriovenous fistula, cavernoma, post-traumatic brain injury). Single cases of demyelinating disease and unilateral volume decrease of Hippocampus without signal alteration were observed.
Peri-ictal imaging abnormalities were observed in 22 patients (39%), 13 of them (23%) with abnormalities in DWI and 4 of them (7%) with alterations in the oxygenation of cortical veins in SWI. Perfusion abnormalities were found in 15 patients (27%).
Conclusion:
Our findings are in keeping with current literature and demonstrate the need for further studies to assess the diagnostic yield of advanced neuroimaging in the setting of a first seizure as well as the risk of seizure recurrence in abnormal brain scans established by a fixed long-term follow up of the patients.
Further Information:
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Wiest, R., & Beisteiner, R., Current Opinion in Neurology, 2019:32(4), 530–538.
Williams, J. A. et al., Seizure, 2017: 50, 19–32.
P15
L Bitzi1; D Lehnick2; E Wilder-Smith3
1 Universität Bern; 2 Universität Luzern; 3 Luzerner Kantonsspital
Background:
Despite advances in the understanding of small fibre neuropathy (SFN), many questions are still open concerning epidemiology, demographics and clinical characteristics of SFN.1 Up until today there is only one study from the Netherlands pertaining to incidence and prevalence showing incidence rates of 11.73 cases/100,000 inhabitants/year and prevalence rates of 52.95 cases/100’000 inhabitants.2 This research analyzes data from medical records to calculate epidemiology, demographics, clinical characteristics and etiology of SFN.
Method:
An observational study with retrospective data analysis of sequential patients diagnosed with definite SFN (typical clinical features, normal nerve conduction, combined with abnormal epidermal nerve fibre density)3 from the end of November 2016 to the middle of July 2019 (2 2/3 years) at the Cantonal Hospital Lucerne, central Switzerland.
Results:
84 patients (64.29% female) with a mean age of 54.68 years were analyzed. Duration of symptoms at time of first contact was 4.83 years. A length dependent clinical pattern was seen in 79.76%. All patients complained of sensory discomfort. Etiological alignment was not possible in 35.71% of patients. The second largest associated etiology was with a variety of inflammatory diseases including the category of apparent autoimmune SFN followed by different individual etiologies known to induce small nerve fibre dysfunction. The minimum incidence over 2 2/3 years was 4.87 cases/100.000 inhabitants/year. The minimum prevalence was 12.98 cases/100.000 inhabitants. In this paper we discuss the various approaches to obtain a representative prevalence in particular by taking into account long duration of the disease.
The comparison of the three largest etiological groups showed that the age at diagnosis was significantly higher in the metabolic group compared with the idiopathic group (61.46 years versus 50.63 years, p = 0.007). Compared to the idiopathic group, patients with an immunological cause have more severe pain (p = 0.04).
Conclusion:
This retrospective sequential cohort study highlights clinical features and etiology of SFN in central Switzerland and shows high incidence and prevalence rates. Compared to the Dutch study, the incidence and prevalence rates in our cohort were somewhat lower.2 This may be due to the fact that the disease is not yet as well known in Switzerland. We suspect that many patients with SFN remain undiagnosed.
References
1. Chan AC. et al. Muscle Nerve 2016:53:671.
2. Peters MJ. et al. Neurology 2013:81:1356.
3. Tesfaye S. et al. Diabetes Care 2010:33:2285.
P16
M Baldauf1; M Kapauer1; M Jörger1; L Flatz1; R Rodriguez1; S Frank2; B Tettenborn1; A Felbecker1; T Hundsberger1
1 Kantonsspital St. Gallen; 2 Universitätsspital Basel
Die onkologische Immuntherapie, insbesondere mit Immuncheckpoint-Inhibitoren (ICPI), revolutioniert die Therapieoptionen für verschiedenste Tumorarten. Durch die Aktivierung des Immunsystems treten als Nebenwirkungen ICPI-assoziierte autoimmune Störungen wie Pneumonitis, Kolitis und Thyreoiditis auf. Sehr viel seltener sind neurologische Nebenwirkungen oder Vaskulitiden. Das Spektrum der ICPI-assoziierten Störungen erweitert sich zunehmend durch den breiten Einsatz und die Zulassung bei weiteren Tumorentitäten.
Ausgehend vom klinischen Phänotyp einer Mononeuritis multiplex erfolgte eine multimodale paraklinische Diagnostik (Nervensonographie, ENMG, Haut- und N. suralis-Biopsie mit histologischer und immunhistochemischer Analyse).
Eine 61-jährige Patientin entwickelte rasch progrediente schmerzhafte und asymmetrische sensomotorische distale Ausfälle, betont an beiden Beinen und der rechten Hand. Elektrophysiologisch zeigte sich eine schwere axonale Neuropathie in den Versorgungsgebieten der klinisch betroffenen Nerven (Nn. peroneii, rechter N. suralis und N. radialis). Sonographisch stellten sich faszikuläre Schwellungen in den betroffenen Nerven dar. Der Verdacht einer Mononeuritis multiplex bei Kleingefässvaskulitis konnte durch die N. suralis-Biopsie und eine Hautbiopsie gesichert werden. Die Lymphozytencharakterisierung zeigte eine Prädominanz von CD8+-T-Zellen.
30 Monate vor dieser Symptomatik wurde ein malignes pleurales Mesotheliom diagnostiziert und nach Progredienz unter einer Chemotherapie über mehrere Monate mit Pembrolizumab behandelt. Nach einer fraglichen Kolitis erfolgte bei erneuter Progression eine Pembrolizumab-Reexposition über wenige Zyklen.
Trotz Einsatz von hochdosiertem Methylprednisolon, einer Pulstherapie mit Cyclophosphamid und einer analgetische Triple-therapie (Pregabalin, Amitriptylin, Methadon) war das Hauptsymptom der schmerzhaften Allodynie initial nur schwer beherrschbar.
Durch den breiten Einsatz der ICPI treten neue autoimmune Nebenwirkungen im Kontext onkologischer Behandlungen auf. Zwar sind neurologische Nebenwirkungen eher selten (1%), jedoch in Ihrem Verlauf schwerwiegend. Der hier dargelegte Fall einer vaskulitischen Mononeuritis multiplex erweitert das neurologische Nebenwirkungsspektrum von Immuntherapien und unterstreicht den potentiell schweren Verlauf dieser Erkrankungen. Die Kenntnis dieser seltenen Nebenwirkung ist wichtig, um die moderne, multidisziplinäre Versorgung von Tumorpatienten zu verbessern.
P17
B Rodriguez; R Hoepner; A Salmen; N Kamber; W Z’Graggen
Inselspital, Bern University Hospital
Introduction and aim:
The postural tachycardia syndrome (POTS) is a chronic form of autonomic dysfunction characterized by symptoms of orthostatic intolerance often accompanied by additional sudomotor dysfunction as well as gastrointestinal dysmotility. The prevalence is estimated to be between 0.2% and 1% with a strong predominance of young females. Symptoms can be disabling and may compromise the patients’ educational and professional functioning as well as their quality of life. POTS is considered a heterogeneous clinical syndrome that may include different systemic and chronic disorders resulting in a final common phenotype. In recent years, evidence has accumulated that in a subset of patients, the pathogenesis of dysautonomia may be immune-mediated.
The aim of the current report was to evaluate the use of intravenous immunoglobulin (IVIG) treatment in patients with progressive and/or refractory POTS presenting with strong serological evidence for autoimmunity.
Method:
We assessed the effect and tolerance of monthly administered repeated IVIG in n = 6 patients using thorough autonomic function testing, standardized symptom questionnaires and patients’ symptom diaries each before and six months into immunomodulatory treatment.
Results:
The present results show an objective improvement in autonomic functioning after six months of IVIG, which was paralleled by an improved subjective symptom experience and functionality in everyday life reported by patients. Autonomic function testing showed improved cardiovascular functioning by almost 60% and a reduction of anhidrotic areas by one third. According to the symptom questionnaire, the severity of symptoms in everyday life was reduced by nearly 40%. All patients responded to immunomodulatory treatment, regardless of disease duration. However, we generally observed an unusually poor tolerance of IVIG treatment with very pronounced side effects, which in some patients even required hospitalization. Side effects could be reduced by pre-medication with steroids and additional i.v. hydration.
Conclusion:
Using for the first time standardized objective measures, the present case series describes very promising effects of immunomodulatory treatment with IVIG in patients with immune-mediated dysautonomia, typically presenting with POTS.