Abstract
AL061
Trigeminal nerve: functional brainstem somatotopy during nociception
L. M. Sturm1, H. Basedau1, J. Mehnert1, A. May1
1Institute of Systems Neurosciences, Hamburg, Hamburg, Germany
Objective
The trigeminal nerve plays a crucial role in the pathogenesis of primary headache disorders. Its three branches (V1, V2, V3) distribute peripherally in U-shaped dermatomes and enter the brainstem in somatotopic order from ventral (V1) to dorsal (V3). Besides the peripheral dermatomes (V1-V3), animal studies suggest an alternative dermatome in the central presentation within the spinal trigeminal nucleus (STN). Fibers of perioral regions are represented more rostrally and those of the periauricular regions more caudally in the STN (“onion-shaped pattern”). In our current study we investigated the somatotopic arrangement of the trigeminal nerve within the brainstem in human beings.
Methods
A 3-Tesla functional magnetic resonance imaging (fMRI) study was conducted in 26 healthy volunteers. Four areas on the left hemiface were stimulated with nociceptive electrical stimulation. Stimulated areas were chosen based on their representation within in the brainstem to ensure adequate spatial resolution between each other within the STN.
Results
We found distinct blood oxygen level-dependent (BOLD)-signal activation for each stimulus site within the spinal trigeminal nucleus.
Conclusion
Our results provide non-invasive, functional evidence in humans to support the long hypothesized somatotopic arrangement along the rostro-caudal axis within the brainstem with an onion -shaped pattern in the face.
AL062
K. P. Peng1, H. Basedau1, T. Oppermann1, A. May1
1University Medical Center Hamburg-Eppendorf, Department of Systems Neuroscience, Hamburg, Germany
Background
Antibodies to the calcitonin gene-related peptide and its receptor (CGRP-mAb), are emerging migraine treatments. We hypothesized that the CGRP-mAb, galcanezumab, modulates peripheral pain processing and that possible differences of sensory thresholds discriminate clinical responses.
Methods
Twenty-six migraine patients were recruited. Quantitative sensory tests over the right V1 dermatome and forearm were tested before and 2–3 weeks after galcanezumab administration. A clinical responder was defined as having at least a 30% reduction in headache frequency after 3 months of treatment. Predictors for clinical response were calculated using binary logistical regression models.
Results
Heat pain threshold (HPT) and mechanical pain threshold (MPT) increased significantly (p < 0.05) after galcanezumab exclusively in the V1 dermatome, but not on the forearm. These changes over time (i.e., between 1st and 2nd measurement) did not differ regarding clinical response. Baseline HPT (before galcanezumab) predicted a clinical response and inversely correlated with the baseline headache frequency.
Conclusion
Galcanezumab modulates pain thresholds specifically in the V1 dermatome, but this modulation is independent of clinical response. Instead, baseline (heat) pain threshold predicts clinical response, suggesting that clinical response may be associated with individual susceptibility and disease activity.
AL063
C. Ernstsen1, S. Christensen1, R. Rasmussen1, B. Nielsen1, I. Jansen-Olesen1, J. Olesen1, D. M. Kristensen12
1Danish Headache Center, Department of Neurology, Glostrup, Denmark
2University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), Rennes, France
Objective
Calcitonin gene-related peptide (CGRP) antagonizing drugs signify a major advance in migraine treatment. Yet, ≥50% of patients do not benefit from monoclonal antibodies against CGRP or its receptor. We test the hypothesis that a closely related peptide, pituitary adenylate cyclase-activating peptide (PACAP-38), works independently of CGRP and thus might represent a new alternative drug target.
Methods
We used mouse models of provoked migraine-like pain based upon multiple stimulations and subsequent measurement of tactile sensitivity responses. Genetically modified mice lacking either functional CGRP receptors (Ramp1 knockout) or TRPA1 channels (Trpa1 kockout) were used together with CGRP-targeting antibodies and chemical inhibitors. Ex vivo myograph studies were used to measure dilatory responses to CGRP and PACAP-38 in mouse carotid arteries.
Results
PACAP-38 provoked significant hypersensitivity and dilated the carotid arteries independently of CGRP. In contrast, glyceryl trinitrate (GTN)-induced hypersensitivity is CGRP dependent. Contrary to other migraine-inducing substances like GTN, cilostazol, and levcromakalim, PACAP-38-induced hypersensitivity worked only partially through KATP channel inhibition.
Conclusion
These findings establish the PACAP-38 pathway as distinct from the migraine provoking agents CGRP and GTN. PACAP antagonism may therefore be a novel therapeutic target, of particular interest in patients unresponsive to CGRP antagonists.
AL064
M. Kurnukhina1, E. Semina2, V. Cherebillo1
1First Pavlov State Medical University of St. Petersburg, Neurosurgery, St. Petersburg, Russian Federation
2First Pavlov State Medical University of St. Petersburg, Medical Faculty, St. Petersburg, Russian Federation
Summary
Pain syndrome is one of the most frequent complaints of patients with pituitary adenoma before and after surgery. Correlation between the severity of pain syndrome and the degree of invasion of pituitary adenoma into the cavernous sinus has not been studied in the literature before.
Purpose
Assessment of the impact the degree of invasion into the cavernous sinus according to the Knosp Scale(KS) on the pain syndrome.
Methods
A clinical study of 200 patients was conducted. All the studied patients underwent transsphenoidal endoscopic resection of pituitary adenoma. The analysis of changes in pain syndrome was carried out before and after surgery. The subjects were aged 18–64 years (median 42,4 years). We used scale VAS, EORTC QLQ-C 30 questionnaire (pain scale), KS.
Results
We found a significant decrease in headache complaints after surgical treatment (diffuse headaches–74,8% and 8,6%, headache of a certain localization – 9.8% and 1,4% – before and after surgery, accordingly)(p < 0,05). Patients Grade III-IV KS noted a decrease in the severity of pain syndrome from 7 ± 2,2 to 1,2 ± 0,8; 9,2 ± 3,4 to 2 ± 1,4 points on the VAS scale (p < 0,05) according, after surgery. According to the EORTC QLQ-C 30 in the late postoperative period, patients Grade IV KS had a more pronounced pain syndrome (r = 0.38; p < 0,05).
Conclusion
Patients Grade III-IV KS are more likely to report pain syndrome. Transsphenoidal resection leads to a significant decrease in the severity of the pain syndrome.
AL065
O. I. Ogunlaja1, P. J. Goadsby12
1NIHR-Wellcome Trust King’s Clinical Research Facility, London, United Kingdom
2University of California, Department of Neurology, Los Angeles, CA, United States
Objectives
Nummular headache (NH) is an uncommon primary headache disorder characterised by a small, round or elliptical, well circumscribed area of intermittent or continuous cranial pain. We set out to determine in how many cases the presence of associated features questioned the diagnosis.
Methods
We audited cases of patients seen at King's College Hospital headache clinic who met ICHD 3 criteria for the diagnosis of NH, as well as those with headache in a nummular distribution. Three met ICHD 3 criteria for NH and two had a diagnosis of migraine.
Results
The mean age of onset in patients with NH was 35 (range, 12–54), while the two patients with a nummular type distribution of pain were age 34 and 59 at headache onset. Location varied and multifocal areas of nummular pain were present in three of the patients: 2 with NH, 1 with migraine. Notably, in all three patients with NH, the pain was episodic while in those with migraine it was chronic and persistent. Of the three patients who met diagnostic criteria for NH, one had onset in pregnancy, and this resolved following delivery. The second, had onset 6 months after puberty and the condition markedly improved at age 18 while they were on testosterone for gender transition.
Conclusion
The pathophysiology of NH is uncertain. Some cases overlap phenotypically with other primary headache disorders and may represent an endophenotype other disorders.
AL066
S. Younis1, A. Hougaard1, C. E. Christensen1, M. B. Vestergaard2, O. B. Paulson3, H. B. W. Larsson2, M. Ashina1
1Danish Headache Center, Neurology, Glostrup, Denmark
2Functional Imaging Unit, Clinical Physiology, Glostrup, Denmark
3Neurobiology Research Unit, Neurology, Copenhagen, Denmark
Objective
In the pons, glutamatergic mechanisms are involved in regulating inhibitory descending pain modulation, serotoninergic neurotransmission as well as modulating the sensory transmission of the trigeminovascular system. Migraine involves altered pontine activation and structural changes, and biochemical, genetic and clinical evidence suggests that altered interictal pontine glutamate levels may be an important pathophysiological feature of migraine abetting to attack initiation.
Methods
Thirty-four migraine without aura patients were scanned outside attacks using a proton magnetic resonance spectroscopy protocol optimized for the pons at 3T. The measurements were performed on two separate days to increase accuracy and compared to similar repeated measurements in 16 healthy controls.
Results
We found that interictal glutamate levels in the pons of migraine patients were not different from healthy controls (p = 0.098), while total creatine levels were markedly increased in patients (9%, p = 0.009). There was no correlation of glutamate or total creatine levels to migraine frequency, days since the last attack, or usual pain intensity of attacks.
Conclusion
Migraine is not associated with altered interictal pontine glutamate levels. However, the novel finding of increased total creatine levels suggests that disequilibrium in the pontine energy metabolism could be an important feature of migraine pathophysiology.
AL067
S. K. Kim1, S. Kim1, M. K. Chu2, B. K. Kim3, P. W. Chung4, M. J. Lee5, Y. Choi6, J. W. Park7, B. S. Kim8, K. Oh9, H. S. Moon4, T. J. Song10, J. Y. Ahn11, J. H. Sohn12, K. S. Lee13, K. Y. Park14, J. M. Chung15, C. S. Chung5, S. J. Cho16
1Gyeongsang National University College of Medicine, Department of Neurology, Jinju, South Korea
2Severance Hospital, Seoul, South Korea
3Eulji University, Seoul, South Korea
4Kangbuk Samsung Hospital, Seoul, South Korea
5Neuroscience Center, Samsung Medical Center, Seoul, South Korea
6Presbyterian Medical Center, Jeonju, South Korea
7Uijeongbu St. Mary’s Hospital, Uijeongbu, South Korea
8Bundang Jesaeng General Hospital, Seoul, South Korea
9Korea University College of Medicine, Seoul, South Korea
10Ewha Womans University School of Medicine, Seoul, South Korea
11Seoul Medical Center, Seoul, South Korea
12Chuncheon Sacred Heart Hospital, Chuncheon, South Korea
13Seoul St. Mary’s Hospital, Seoul, South Korea
14Chung-Ang University Hospital, Seoul, South Korea
15Inje University College of Medicine, Seoul, South Korea
16Dongtan Sacred Heart Hospital, Hwaseong, South Korea
Background and Objective
The objective of this study was to identify the factors affecting QoL in Cluster headache (CH) patients during the active periods.
Methods
The CH patients were enrolled from September 2016 to February 2021 in 16 headache clinics in Korea. The questionnaire conducted questions about their QoL using EQ-5D-3L with the time trade-off (TTO) method. The age-sex matched control groups consisted of patients with migraine were recruited.
Results
A total of 425 CH patients during an active period were included. The CH patients had lower median scores of EQ-5D than healthy control and migraine patients (0.88 ± 0.43 vs. 0.99 ± 0.33 and 0.99 ± 0.43, p < 0.000). Fifty-eight (13.6%) CH patients scored moderate to severe QoL impairment by the TTO method. The QoL states in CH patients were associated with current smoking, the severity, frequency, and duration of pain, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Headache impact test-6, and Allodynia Symptom Checklist-12 scores. Multivariate logistic regression analyses revealed that the QoL states in CH patients were negatively correlated with the daily frequency of headache, duration of active periods, GAD-7, and PHQ-9 scores.
Conclusions
Our results show that CH patients have a poorer QoL during active periods than the healthy control and migraine patients. Their QoL might be is associated with daily headache frequency, duration of active periods, anxiety, and depression.
AL068
H. Bolay1, O. Karadaş2, B. Öztürk2, R. Sonkaya2, B. Taşdelen3, T. Bulut1, Ö. Gülbahar1, A. Özge3, B. Baykan4
1Gazi University, Medical Biochemistry, Ankara, Turkey
2University of Health Sciences, Neurology, Ankara, Turkey
3Mersin University, Neurology, Mersin, Turkey
4Istanbul University, Neurology, Istanbul, Turkey
Aim
Pathogenesis of COVID-19 -related headache is unknown, we investigated key systemic circulating inflammatory molecules and their clinical relations with headache.
Methods
This cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied.
Results
The mean ages of 48 COVID-19 patients with headache and 40 COVID-19 patients without headache were comparable. COVID-19 patients with headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar. Ang II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels.
Conclusion
Stronger inflammatory response is associated with COVID-19 headache. Increased levels of the circulating inflammatory/nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and headache secondary to SARS-CoV-2 infection.
AL069
H. Basedau1, L. M. Sturm1, J. Mehnert1, K. P. Peng1, M. Schellong1, A. May1
1University Medical Center Eppendorf, Hamburg, Department of Systems Neuroscience, Hamburg, Germany
Monoclonal antibodies (mAb) targeting calcitonin gene-related peptides (CGRP) are a novel treatment for migraine prevention. Based on a previous functional magnetic resonance imaging (fMRI) study with the CGRP receptor mAb (erenumab), we hypothesised that galcanezumab, CGRP ligand mAb, would also alter trigeminal central pain processing and that responders to galcanezumab treatment would show specific (hypothalamic) modulation in contrast to non-responders. This study was pre-registered in the Open Science Framework.
We conducted an fMRI study in 26 migraine patients with an established trigeminal nociceptive paradigm with gaseous ammonia, in the same way as the previous erenumab study, and studied the patients before and 2–3 weeks after the administration of galcanezumab. We have found that galcanezumab reduces hypothalamic activation, this was also prominent in responders against non-responders. Erenumab and galcanezumab show different changes to trigemino-nociceptive central responses. The activity of the spinal trigeminal nucleus (STN) followed by trigemino-nociceptive stimulation before treatment covaries with the response to galcanezumab. Furthermore the connectivity between the STN and the hypothalamus is altered after galcanezumab administration.
Our results suggest that despite the impermeability of the blood-brain barrier to CGRP-mAb, treatment with mAb induces specific effects in the brain that may be part of its mechanism of efficacy in migraine treatment.
AL070
B. S. Winsvold123, A. V. E. Harder45, C. Fourier6, R. Noordam7, E. O’Connor8, C. Ran6, J. Vandrovcova8, J. A. Zwart129, H. Houlden8, G. M. Terwindt4, M. Matharu10, A. van den Maagdenberg45, A. C. Belin6, C. Int. Consortium for Cluster Headache Genetics1
1Oslo University Hospital, Department of Research and Innovation, Division of Clinical Neuroscience, Oslo, Norway
2Norwegian University of Science and Technology (NTNU), K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Trondheim, Norway
3Oslo University Hospital, Department of Neurology, Oslo, Norway
4Leiden University Medical Center, Department of Neurology, Leiden, Netherlands
5Leiden University Medical Center, Department of Human Genetics, Leiden, Netherlands
6Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden
7Leiden University Medical Center, Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden, Netherlands
8University College London, Department of Neuromuscular Diseases, Institute of Neurology, London, United Kingdom
9University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, Norway
10UCL Queen Square Institute of Neurology, Headache and Facial Pain Group, London, United Kingdom
Objective
To identify genetic risk variants for cluster headache (CH).
Methods
Two parallel genome-wide association studies (GWAS) of CH were conducted based on 1443 CH cases and 6748 controls from Sweden and UK, and 984 CH cases and 3257 controls from the Netherlands and Norway, respectively. Subsequently, the studies were combined in a first attempt to meta-analyse the data of the two initiatives.
Results
The two studies independently identified four genetic risk loci (p < 5 × 10–8) on chromosome (chr) 1 near the gene DUSP10, chr 2 near MERTK, chr 2 near SATB2 and chr 6 near FHL5, with odds ratios around 1.5 (range 1.30–1.61). A first meta-analysis of the two studies suggested three additional loci on chr 7 near ASZ1, chr 10 near PLC1 and on chr 19 near KIR3DX1.
Conclusion
The discovery of four risk loci for CH provides robust evidence that the disease has a genetic basis. Effect sizes are larger than those typically seen in GWAS of complex traits. The identification of the FHL5-locus, an established risk locus for migraine, besides loci specific to CH, may suggest a partly overlapping genetic basis for both disorders. Downstream analyses to obtain insight into disease mechanisms will require larger sample sizes. To this end, we have established the International Consortium for Cluster Headache Genetics, aiming to gather interested researchers and available samples for a large-scale GWAS meta-analysis of CH.
AL071
N. Noory1, E. A. Smilkov2, J. L. Frederiksen3, T. B. Heinskou1, A. S. S. Andersen1, L. Bendtsen1, S. Maarbjerg1
1Danish Headache Center, Department of Neurology, Glostrup, Denmark
2Rigshospitalet-Glostrup, Department of Radiology, Glostrup, Denmark
3Rigshospitalet-Glostrup, Department of Neurology, Glostrup, Denmark
Objective and Background
A demyelinating plaque and neurovascular contact with morphological changes have both been suggested to contribute to the etiology of trigeminal neuralgia secondary to multiple sclerosis (TN-MS). The aim of this study was to confirm or refute whether neurovascular contact with morphological changes is involved in the etiology of TN-MS.
Methods
We prospectively enrolled consecutive TN-MS patients from the Danish Headache Center. Clinical characteristics were collected systematically. MRI scans were done using a 3.0 Tesla imager and were evaluated by the same experienced blinded neuroradiologist.
Results
Sixty-three patients were included. There was a low prevalence of neurovascular contact with morphological changes on both the symptomatic side (6 (14%)) and the asymptomatic side (4 (9%)), p = 0.157. Demyelinating brainstem plaques were more prevalent on the symptomatic side compared to the asymptomatic side (31 (58%) vs. 12 (22%), p < 0.001). A demyelinating plaque was highly associated with the symptomatic side (odds ratio = 10.6, p = 0.002).
Conclusions
The primary cause of TN-MS is demyelination along the intrapontine trigeminal afferents. As opposed to classical trigeminal neuralgia, neurovascular contact does not play a role in the etiology of TN-MS. Microvascular decompression should generally not be offered to patients with TN-MS.
AL072
N. Karsan1, P. J. Goadsby12
1King’s College, Headache Group, London, United Kingdom
2University of California, Los Angeles, CA, United States
Objective
We aimed to audit the reporting of voice change and throat swelling as potential cranial autonomic symptoms (CAS) associated with headache.
Methods
Clinic letters of patients seen between 2016-May 2021 containing “voice” (n = 65) or “throat” (n = 151) were selected; those mentioning voice change and/or throat swelling as CAS were included for analysis (n = 64). Patient age, headache diagnosis, pain site, preventive use and CAS phenotype were collated and analysed in IBM SPSS 27.
Results
Subjects were 72% female, age range 23–83 (median 49, IQR 21). Headache diagnoses were chronic migraine (50%), chronic cluster headache (11%), undifferentiated continuous lateralised headache (9%), SUNCT/SUNA (8%), hemicrania continua (8%), episodic migraine (8%), episodic cluster headache (3%) and trigeminal neuropathies (3%). Most (89%) described pain in the trigeminal distribution; 25% involving all three divisions and 67% including V3. Throat swelling was reported by 54, voice change by 17 and both by 7. Between 1–11 CAS were reported (median 6, IQR 3); the most common were lacrimation (n = 47), facial swelling (n = 45) and rhinorrhoea (n = 37). There was significant agreement between the co-reporting of throat swelling (χ21 = 7.59, P = 0.013) and voice change (χ21 = 6.49, P = 0.02) with aural fullness.
Conclusion
Voice change and throat swelling may be parasympathetically-mediated CAS. They may be co-associated and associated with aural fullness, suggesting a broadly somatotopic endophenotype.
AL073
P. Wilbrink1, I. de Coo2, P. Doesborg2, W. Mulleners3, O. Teernstra4, E. Bartels2, K. Burger5, F. Wille6, R. Dongen7, E. Kurt8, G. Spincemaille4, J. Haan2, E. Zwet2, F. Huygen9, M. Ferrari2
1Zuyderland Medical Centre, Neurology, Heerlen, Netherlands
2Leiden University Medical Center, Neurology, Leiden, Netherlands
3Canisius Wilhelmina Hospital, Neurology, Nijmegen, Netherlands
4Maastricht University Medical Centre, Maastricht, Netherlands
5Alrijne Hospital, Anaesthesiology, Leiderdorp, Netherlands
6Diakonessenhuis Hospital, Anaesthesiology, Zeist, Netherlands
7Radboud University Medical Centre, Anaesthesiology, Nijmegen, Netherlands
8Radboud University Medical Centre, Neurosurgery, Nijmegen, Netherlands
9Erasmus University Medical Center, Anaesthesiology, Rotterdam, Netherlands
AL074
G. L’Italien1, E. Popoff2, K. Johnston2, D. McGrath1, C. M. Conway1, L. Powell2, L. Harris1, N. Kowalczyk1, R. Croop1, V. Coric1
1Biohaven Pharmaceuticals, New Haven, CT, United States
2Broadstreet Health Economics & Outcomes Research, Vancouver, Canada
Objective
The objective of this study was to describe long-term reductions in monthly migraine days (MMD) associated with rimegepant 75 mg oral tablet, when taken as needed (PRN) as an acute treatment.
Methods
Eligible subjects were a subset of the BHV3000-201 trial (NCT03266588): adults with ≥1 year migraine history and ≥6 MMD at baseline, treated with rimegepant 75 mg PRN up to once daily, for up to 52 weeks. Kaplan-Meier analyses were used to assess median time to ≥30% and ≥50% reduction in MMDs from baseline. Cluster analyses were used to identify 3 clusters based on MMD over the study period.
Results
Among 1,044 subjects, the median time to ≥30% reduction in MMDs was 12 weeks (IQR; 4–40 weeks); median time to ≥50% reduction was 32 weeks (IQR; 12-NR weeks). MMD reduction was observed over time regardless of baseline migraine frequency, including low-frequency (baseline MMD 8.7), moderate frequency (baseline MMD 11.5) and high-frequency (baseline MMD 14.8) cluster groups (Figure 1). Higher baseline MMD were associated with a longer time to achieving ≥30% or ≥50% MMD reduction.
Conclusions
In subjects presenting with ≥6 MMD, PRN acute treatment over 52 weeks with oral rimegepant 75 mg conferred clinically significant migraine reductions. There was no evidence of medication-related MMD increases with long-term PRN rimegepant use. These findings are consistent with preventive benefits of rimegepant 75 mg shown in a placebo-controlled study.
AL076
C. Gaul1, R. Riesenberg2, C. Stroud3, Y. Dong3, T. Myers Oakes3
1Headache Center, Frankfurt a. M., Germany
2Atlanta Center for Medical Research, Atlanta, GA, United States
3Eli Lilly and Company, Indianapolis, IN, United States
AL077
B. Klein1, R. Miceli2, L. Severt2, P. McAllister3, L. Mechtler4, J. McVige4, M. Diamond5, M. J. Marmura6, H. Guo2, M. Finnegan2, J. M. Trugman2
1Abington Neurological Associates, Ltd., Abington, PA, United States
2AbbVie, Madison, NJ, United States
3New England Institute for Neurology & Headache, Stamford, CT, United States
4DENT Neurologic Institute, Amherst, NY, United States
5Diamond Headache Clinic, Chicago, IL, United States
6Thomas Jefferson University, Department of Neurology, Philadelphia, PA, United States
Background and Objective
A phase 3 trial, ADVANCE (NCT03777059), demonstrated that atogepant, an oral, CGRP receptor antagonist dosed once daily, results in a clinically meaningful reduction in mean monthly migraine days. This open-label extension for ADVANCE trial completers evaluated the long-term safety and tolerability of atogepant over 40 weeks.
Methods
Participants in this trial (NCT03939312) rolled over from the lead-in ADVANCE trial and were treated with atogepant 60 mg once daily for 40-weeks, with a 4-week safety follow-up period. Only safety data were collected.
Results
685 participants took at least one dose of study drug, 74.6% completed the 40-week treatment period; mean age of 41.8 years, 88.2% female, 84.4% white, and mean BMI of 30.58 kg/m2. Mean (SD) treatment duration was 233.6 (89.32) days. Overall, 62.5% of participants experienced a treatment-emergent adverse event (TEAE), with 8.8% considered treatment-related by the investigator; serious adverse events (SAEs) occurred in 3.4% of participants, none were treatment-related. Table 1 reports the most frequent AEs leading to discontinuation; Table 2 reports the most frequent TEAEs observed. No deaths and no hepatic safety issues were observed.
Conclusion
These safety results are consistent with the known safety profile of atogepant from previous trials and support the long-term safety and tolerability of once daily dosing of atogepant 60 mg.
AL078
E. Schäfer1, M. Arzt1, I. Meyer1, A. Gantenbein2
1Novartis Pharma Schweiz AG, Neuroscience, Rotkreuz, Switzerland
2Zurzach Care, Neurology, Bad Zurzach, Switzerland
Objective
To present real-world effectiveness data of erenumab from the SQUARE (Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population) study.
Methods
SQUARE is a non-interventional study which provides clinical effectiveness data on erenumab in a post-marketing setting from both migraine care specialist centers and general neurologists in Switzerland. Migraine patients receiving Aimovig® in accordance with the Swiss label were included if willing and able to participate, with the exception of patients with prior use of any medications targeting the calcitonin gene-related peptide (CGRP) pathway or recent use of investigational drugs. Patients were observed over a period of 24 months.
Results
A total of 173 adult patients were included in 19 centers. Here, we will present real-world effectiveness data of erenumab at month 6 compared to baseline, including scores of Headache Impact Test (HIT-6), modified (monthly) migraine disability assessment test (mMIDAS), and impact of migraine on partners and adolescent children (IMPAC).
Conclusion
These are among the first prospectively collected data on erenumab under routine medical care. Results from the SQUARE study will provide insights into the effectiveness of a CGRP receptor-based therapy in a real-world scenario.
P0405
A. Cordeiro1, E. Silva1, M. Grunho1, L. Pereira1
1Hospital Garcia de Orta, Department of Neurology, Almada, Portugal
Objective
Epicrania fugax (EF) is a primary headache consisting of brief stabbing head pain, following a linear or zigzag trajectory across the scalp, through the territories of different nerves. Although rarely, some cases of coronal radiation of pain have been described.
Methods
Clinical case.
Results
A 48-year-old woman with a history of migraine without aura presented to the emergency department with new onset headache: stabbing, severe (10/10 on the visual analog scale), describing a linear trajectory on the coronal plane from the right temporal to the left temporal scalp, lasting 1–40 seconds, multiple times a day, preventing sleep. Neurological examination revealed right hemicrania hypoesthesia. Laboratory tests were unremarkable, and brain magnetic resonance imaging exhibited dilated Virchow-Robin perivascular spaces (PVS) in the left hemi-midbrain. Pregabalin 25mg twice a day was started with immediate pain relief and complete resolution by the sixth day.
Conclusion
We believe this to be a case of atypical EF with coronal radiation, raising awareness that patients can present with linear pain of different trajectories across the scalp. Despite the presence of dilated PVS, they are unlike to be causal due to their nature, lateralization and absent relation with the trigeminal nucleus and other relevant pain matrix structures. Early diagnosis of these atypical cases is essential to provide the proper treatment.
P0406
A. Telesca1, A. Proietti Cecchini1, M. Consonni1, S. Piacentini1, S. Usai1, G. Lauria Pinter12, L. Grazzi1
1IRCCS Foundation “Carlo Besta” Neurological Institute, Neuroalgology, Milan, Italy
2University of Milan, Biomedical and Clinical Sciences “Luigi Sacco”, Milan, Italy
Chronic Cluster headache (CH) patients are usually comorbid to mood spectrum disorders, psychopathological symptoms and personality disorders, but the role of psychopathological aspects is still insufficiently explored. Our aim is to verify, by a data driven approach, if CH patients may be classified on the basis of personality trait disorders. We applied hierarchical cluster analysis (HCA) to classify 60 patients suffering from CH, based on values of the clinical personality pattern scales of the Millon Clinical Multiaxial Inventory-III (MCMI-III). Subgroup comparison on demographical data and clinical features where subsequently performed. The outcome of HCA revealed the existence of 3 groups of patients with different personality traits. Two groups had unique patterns. Group 1 (n = 20) had distinctive
P0407
I. Velichko1, M. Barabanova1, G. Muzlaev1
1Kuban State Medical University, Neurology and Neurosurgery, Krasnodar, Russian Federation
Background and objective
Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) is a trigeminal autonomic cephalalgia presenting as unilateral periorbital pain with autonomic symptoms. We are reporting a patient with SUNA syndrome who transformed from trigeminal neuralgia.
Methods
Case report.
Results
The 33-year-old man with no medical history or family history of headache first became ill 2 years ago. Initially, there were attacks of severe stabbing pain as “electric shock” in the right supraorbital and zygomatic areas, both spontaneously and caused by light touch in the same areas. Attacks lasting 10–15 sec occurred 3–10 times a day. Idiopathic trigeminal neuralgia was diagnosed by a neurologist, and carbamazepine significantly reduced the pain. After 8 months, the attacks recurred; the pain was strictly in the right orbital periorbital area, lasting 60–120 sec and a frequency of about 12–13 per day. The attacks were accompanied by intense unilateral сonjunctival injection. There was moderate interictal pain. Clinical and diagnostic examinations did not reveal any abnormalities. Carbamazepine, gabapentin, topiramate were not beneficial. Lamotrigine (100 mg/day) significantly reduced the frequency and intensity of the pain.
Conclusion
This observation suggests that SUNA is probably more closely linked to trigeminal neuralgia than to other unilateral headache syndromes.
P0408
R. Riesenberg1, C. Gaul2, C. Stroud3, T. Myers Oakes3, Y. Dong3, M. Bangs3, R. Wenzel3, J. Martinez3
1Atlanta Center for Medical Research, Atlanta, GA, United States
2Headache Center, Frankfurt a. M., Germany
3Eli Lilly and Company, Indianapolis, IN, United States
P0409
D. W. Bae1, S. J. Cho2, S. H. Cho3, H. S. Moon4, M. K. Chu5, B. K. Kim6
1St. Vincent’s Hospital, Neurology, Suwon, South Korea
2Dongtan Sacred Heart Hospital, Neurology, Hwaseong, South Korea
3Uijeongbu Eulji Medical Center, Neurology, Uijeongbu, South Korea
4Kangbuk Samsung Hospital, Neurology, Seoul, South Korea
5Severance Hospital, Neurology, Seoul, South Korea
6Nowon Eulji Medical Center, Neurology, Seoul, South Korea
Methods
Four patients with cluster headache were enrolled during their cluster period. There were three treatment protocols; 1) oral abortive medication 2) two oxygen concentrators connected to non-rebreathing mask using Y-tube 3) one oxygen concentrator connected to non-rebreathing mask. Four enrolled patients documented total 50 treated attacks (22 attacks treated with oral medication, 20 attacks treated with two oxygen concentrator, 8 attacks treated with one oxygen concentrator). Among the three treatment options, two oxygen concentrator showed superior pain free response rate at 30 minutes (65%) compared to one oxygen concentrator (62.5%) and oral medication (4.5%). Attack duration in two oxygen concentrators was also shortest among the three treatment protocols (29 ± 1.4min).
Conclusion
This study is going to provide the evidence of oxygen concentrator therapy in the acute treatment of cluster headache. Further randomized controlled trial is in progress.
P0410
J. Lee1
1BuCheon U-RI General Hospital, Seoul, Korea, Department of Neurology, Bucheon-si, South Korea
Background and objective
We investigate whether vertigo is correlated with clinical relevance in headache according to age spectrum.
Methods
From May 2020 to February 2021, 925 patients, aged ≥ 7 years and participants who met the inclusion criteria were enrolled from the neurology clinics. We re-analyzed patients who experience headache with/without vertigo symptoms and two groups were studied according to the patient's age. Logistic regression analysis was used to evaluate the association between headache and vertigo. First, we reviewed vertigo with diagnosed 281 and 570 headache patients, and 31 vertiginous headache. Second, common types of primary headache patients were included. Third, the vertigo was classified into 2 groups: peripheral or central types.
Results
Of the 925 outpatient, headache of 570(61.6%) and vertigo of 281(30.3%) were reported. In this study, prevalence of headache of 200(35.1%) in men and 370(64.9%) in women was expected. The frequency of vertigo in headache patients was significant relationship with ageing{Ages 0 to 9:0, 10 to 19:2, 20 to 29:5, 30 to 39:2, 40 to 49:3, 50 to 59:8, 60 to 69:7, 70 to 79:1,80 to 89:3}. Total 31 headache related vertigo patients were divided into two groups{peripheral(n = 27), central(n = 4) type} and proportion of peripheral vertigo has a positive relevance with headache.
Conclusions
The findings of our study may provide direction for useful diagnostic and therapeutic approach to the vertigo attack in headache patients.
P0411
L. Grazzi1, D. D’Amico1, A. Telesca1, P. Rizzoli2
1IRCCS Foundation “Carlo Besta” Neurological Institute, Neuroalgology, Milan, Italy
2Harvard Medical School, J Graham Headache Center, Brigham & Faulkner Hospital, Boston, MA, United States
Chronic Migraine (CM)is a disabling condition that affects the 2% of migraine population often complicated by Medication overuse (MO) and withdrawal is often needed for these patients. Clinical results can be improved when traditional therapies are combined with behavioral approaches (mindfulness). As the emergency situation due to the COVID-19 pandemic, the regular clinical practice adopted for patients with CM-MO changed and the traditional program for withdrawal has been modified. We run a pilot study to enforce the application of a Home-withdrawal procedure and the use of web technology so that patients could continue their therapeutic process by using behavioral support (mindfulness). We enrolled 30 CM-MO patients. A withdrawal program at home, by oral administration of therapies, with specific instructions and education, was organized. Instructions for behavioral approach (mindfulness) were given: daily 12-minutes standardized mindfulness sessions on their smartphone have been combined with weekly 60-minutes-video-on line-sessions for 6 weeks. A face-to-face follow-up was scheduled every 3 months until 12 months. 15 patients achieved the 3 months follow-up: days of migraine/month, medication intake/month, catastrophizing attitude decreased significantly (PCS: 21.5 ± 6.7 vs 9 + 8.7; 22.1 ± 5.7 vs 7.9 ± 8.6; 28 ± 11.4 vs 21 ± 10.9). Results seem to encourage toward the application of this approach in emergency condition and in regular clinical practice too.
P0412
L. Grazzi1, A. Telesca1, P. Rizzoli2
1IRCCS Foundation “Carlo Besta” Neurological Institute, Neuroalgology, Milan, Italy
2Harvard Medical School, J Graham Headache Center, Brigham & Faulkner Hospital, Boston, MA, United States
Chronic Migraine is frequently associated with medication overuse that makes this condition difficult to treat. Prior investigations confirmed the efficacy of withdrawal, and clinical results are enhanced when traditional therapies are combined with behavioral approaches, in particular mindfulness. At the Besta Institute, after a medication withdrawal, patients follow a specific prophylaxis for migraine, and a program for mindfulness practice, administered for 6 weekly-45 minutes sessions in small groups. During the COVID-19 pandemic, technology (smartphones) has been used to treat patients practicing the mindfulness approach.
P0413
V. Gallardo López1, R. E. Shapiro2, E. Caronna1, P. Pozo-Rosich1
1VHIR, Neuroscience, Barcelona, Spain
2University of Vermont, Department of Neurological Sciences, Burlington, United States
Objective
To study the prevalence of headache as a prognostic factor for mortality in COVID-19 inpatients.
Background
COVID-19 has not impacted people uniformly. This disparity has prompted investigations to identify clinical and genetic predictors of COVID-19 mortality. Headache, a COVID-19 symptom, has been associated with positive disease prognosis.
Methods
Following PRISMA guidelines, we conducted a systematic literature search (April 1 to December 22, 2020) of COVID-19 clinical inpatients series that reported headache as a symptom of the disease. Random-effects pooling models were computed in order to estimate the effect size of the presence of headache in survived vs. non-survived COVID-19 cohorts. Quality of studies was assessed with Newcastle-Ottawa Scale (NOS). PROSPERO registration number: CRD42021260151.
Results
From a total of 48 full-text peer-reviewed meta-analyzed publications, the estimated prevalence of headache as a symptom among COVID-19 inpatients was 10.4% [8.3%–12.9%]. We observed higher risk ratio (RR) of headache among COVID-19 inpatients who survived, compared to those who did not (RR: 1.90 [1.46–2.47], p < 0.0001). In sensitivity analyses, excluding studies with lower quality (NOS score < 7), headache RR increased without a statistically significant heterogeneity between studies (RR: 2.60 [2.03–3.32], p < 0.0001; I2 = 23.6%, p = 0.180).
Conclusion
Headache as a COVID-19 symptom is associated with enhanced survival in hospitalized patients.
P0414
K. M. N. Joy1, R. Mahmud2, G. Rabbani3, M. K. Islam4, M. I. Khalil1, N. C. Kundu1
1Shaheed Suhrawardy Medical College, Department of Neurology, Dhaka, Bangladesh
2Dhaka Medical College Hospital, Department of Neurology, Dhaka, Bangladesh
3University of Dhaka, Department of Statistics, Dhaka, Bangladesh
4Dhaka Medical College Hospital, DEPARTMENT OF MEDICINE, Dhaka, Bangladesh
Objective
We investigated the prevalence of mask/PPE associated headache among Bangladeshi physicians during COVID 19 pandemic along with the risk factors and headache characteristics. Headache severity was assessed by the Headache Impact Test (HIT-6).
Methods
This is a cross-sectional, online Google form based study among 200 physicians from different hospitals in Dhaka conducted from December 2020 to April 2021.
Results
Majority participants were male (129, 64.5%) with mean (SD) age of 35.4(7.5) years. Filter masks (146, 73%) were mostly used along with other PPE (139, 69.5%). Headache prevalence was 71% and 59.9% developed new onset headache. Doctors working in the COVID unit [OR: 2.47, 95% CI: 1.18–5.18; P = 0.017] had the highest risk of developing headache. Headache occurrence was independently associated with previous primary headache [OR:5.40, 95% CI: 2.03–14.41; P = 0.001] and combined mask & all PPE usage [OR: 2.48, 95%CI: 1.31–4.23; P = 0.006] for ≥6 months [OR: 2.05, 95%CI: 1.05–3.99; P = 0.036]. Most headaches were dull aching (33.8%), lasted for 1–4 hours (58.5%) & relieved within 1 hour of mask removal (43.6%). Headache Impact Test (HIT-6) score was substantial to severe among the doctors with previous headaches [OR: 2.91, 95%CI:1.43–5.92; P = 0.003] and those having moderate to severe stress levels [OR: 2.56, 95%CI: 1.19–5.55; P = 0.017].
Conclusions
Most physicians with previous primary headache develop mask/PPE associated headache with considerable impacts on daily life.
P0415
R. A. Garcia Santos1, M. S. Rodríguez Rodríguez1, A. S. Ramírez García Luna1, D. S. López Gonzalez1
1National Institute of Respiratory Diseases, Neurology, Mexico City, Mexico
Our objective is to report headache during and post COVID-19 in hospitalized COVID-19 survivors.
Three neurologists examined and analyzed the presence of headache on 273 patients admitted at a single medical center of COVID-19 three months after their hospital discharge, in Mexico City, from November 1st 2021 to June 1st 2021. All patients were positive for SARS-CoV-2 RT-PCR.
Most of the patients were men (63.4%). 65.2% intubated with mean intubation of 19 days. 49.5% experienced headache during COVID-19, being holocranial (36.3%) and oppressive. Duration ranged from 1 to 5 days, (mean of 3 days). Patients with headache during COVID-19, had a higher frequency of post COVID-19 fatigue (85.2%), this difference was statistically significant among groups (p = 0.02). Cognitive complain at the time of neurological evaluation was frequent in patients with headache during COVID-19 (71.1%).
41.8% patients experienced post COVID-19 headaches, holocranial oppressive headache was the most common (27.2%) with a frequency of twice a week in 28.3%. Most patients with post COVID-19 had headache during COVID-19 (73.3%), this difference was statistically significant among groups (p = < 0.001). Patients who presented with post COVID-19 headache, had a higher frequency of post COVID-19 fatigue (74.2%), with statistically significance (p = 0.01). Almost half of the patients presented depressive symptoms at the time of evaluation, with no difference among headache groups regarding these symptoms.
P0416
E. Pucci123, M. Q. Falvo123, V. Nava123, M. Lagorio123
1Università di Pavia, Department of Brain and Behavioral Sciences, Pavia, Italy
2University Of Pavia, Graduate School of Geriatrics and Gerontology, Pavia, Italy
3ASP – IDR S. Margherita, Alzheimer’s Nucleus, Pavia, Italy
Background and objective
Headaches represent at the same time the symptom and the disease, while the secondary ones are the expression of an ongoing pathology that can be systemic. The aim of this study is to determine the prevalence rate in the workplace in a ward during the period of Sars-COV2 infection. This survey was carried out using 2 questionnaires: work activity and headache sheet according to IHS criteria.
Methods
All health personnel belonging to the Alzheimer Nucleus of the IDR S. Margherita di Pavia were subjected to compilation of questionnaires during the Sars-COV2 infection period.
Results
From the analysis of the questionnaires administered, it was found that out of 15 workers, 10 women and 5 men. 4 (all women had migraines without aura) and 7 tension-type headaches (5 women and 2 men). Before the Sars-COV2 period, only 2 workers had migraine without aura and 2 tension-type headaches (all women). All 11 workers reported stress, insomnia, and concern for family members and their own health. None of the workers at the time of testing had been vaccinated.
Conclusions
Factors related to the work environment are able to increase the frequency and/or intensity of pre-existing headaches. It is also likely that particular situations can give rise to or cause some forms of headache under certain working conditions. Excessive responsibility or, on the contrary, disaffection and incongruous work rhythms should be considered among the occupational risk factors.
P0417
E. Pucci123, M. Q. Falvo123, V. Nava123, M. Lagorio123
1Università di Pavia, Department of Brain and Behavioral Sciences, Pavia, Italy
2University Of Pavia, Graduate School of Geriatrics and Gerontology, Pavia, Italy
3ASP – IDR S. Margherita, Alzheimer’s Nucleus, Pavia, Italy
Background and objective
Migraine without aura is the most frequent of the forms of migraines (about 60–80% of all forms of migraines). There are many causes that can trigger migraines, including infections (IHS ICDH-3).
Methods
69 year old woman. Professional nurse. Family history of migraine (maternal line). Arising in school age. Diagnosis made according to the IHS ICDH-3 criteria. The patient presented 2–3 crises/month with pulsating pain in the bilateral frontotemporal region, medium-strong intensity, associated with photo-phonophobia, nausea, sometimes vomiting. Duration 24–36 hours. Triggering factors: menstruation and psychophysical stress. After menopause (49 years) reduction of intensity, duration and frequency with 1–2 cris/month related stress lasting 12–24 hours and responsive to NSAID intake. No preventive therapy performed.
Results
On 29.11.2020 episode of atypical headache (described as different from other episodes) with very strong, throbbing, stabbing, burning pain in the bilateral front-temporal region. Duration 24 hours. No other symptoms reported, apiretic. 30.11.2020: TNF fast: +. Molecular TNF: positive for SARS COV 2. During the period of infection headache present whenever the patient had fever and was unresponsive to paracetamol.
Conclusions
In our case report, atypical migraine can be considered a sentinel symptom of an initial infection. The patient works as a professional nurse in the ward which had become Covid on 3.11.2020.
P0418
O. Grosu1
1Diomid Gherman Institute of Neurology and Neurosurgery, Headache center, Chisinau, Moldova
Objective
The aim of the study was to characterize the Moldovan cohort of headache and COVID 19 infection patients.
Methods
A survey of people with COVID 19 and headaches from January till June 2021 was done. The study sample consists of 138 volunteers, mean age 36.74 ± 8.16, 89.6% female, that complete online a questionnaire about demographics, comorbidities, clinical signs of COVID 19 infection, headache before, during, and after COVID 19, screening for anxiety, depression, and sleep disorders.
Results
the study showed that 58.3% of the respondents had different forms of headache before COVID 19 infection and 17.9% severe forms. During the period of COVID 19 infection – 91% of respondents had bouts of headache attributed to COVID 19 infection and 54.5% severe forms with increased intensity, generalized localization (30.9%), associated with vertigo (64.8%), nausea (54.1%), peripheral vegetative signs (22.4%), accompanied with pronounced asthenia (80%) and pain with another localization (85.5%). Persistent headaches after COVID presented 62.7% of respondents, being severe for 16.7% of them with associated vertigo (34.7%), nausea (25.2%), and phonophobia (39.9%).
Conclusion
The percentage of patients with a headache in the post-COVID period is worryingly high, it increases the degree of functional disability of patients and the individual and social burden, respectively.
P0419
O. Grosu1
1Diomid Gherman Institute of Neurology and Neurosurgery, Headache center, Chisinau, Moldova
Background
Medication overuse in patients with headaches is the most important risk factor for chronification and persistence.
Methods
An online survey, launched through social media channels from January till June 2021, was completed by patients with headaches and COVID 19 disease. Validated questionnaire gathered data on demographics, COVID infection, the characteristics of headache before, during, and after COVID 19 infection, abortive headache medication, behavior, sleep disorders, anxiety, and depression.
Results
The study included 131 participants: 14 men (10.6%) and 117 women (89.31%), mean age – 37 ± 8,16 years. Before COVID 19 infection participants used analgesic drugs on 3.67 ± 2.96 days/month, during the COVID 19 infection month – 10.44 ± 8.81 days/month, and in the post-Covid period – 12.27 ± 9.73 days/month. From the study group, 9.1% of patients had medication overuse before COVID 19, during the Covid 19 period – 43%, and after the Covid 19 – 33%.
Conclusion
The study proved an increased analgesic consumption during and after the COVID 19 infection, possibly due to the association of a secondary headache namely headache attributed to infection. The other factors will be elucidated in further research.
P0421
J. Al-Hashel12, F. Abokalawa2, R. Alroughani3, M. Alenezi4, S. Farouk Ahmed25
1Kuwait University, Medicine, Kuwait, Kuwait
2Ibn Sina Hospital, MOH, Neurology, Kuwait, Kuwait
3Amiri Hospital, MOH, Neurology, Kuwait, Kuwait
4Farwanya hospita, MOH, Medicine, Kuwait, Kuwait
5Faculty of Medicine, Minia University, Neuropsychiatry, Minia, Egypt
Background
Headache is a common symptom during and after acute respiratory syndrome coronavirus 2 (SARS-COV-2).
P0422
A. Dubey1, S. Dubey2
1GMC & Hamidia Hospital Bhopal, Bhopal, India
2MMCH & RI, Department of Neurology, Kanchipuram, India
Objective
Covid-19 pandemic has had a major impact on the health of people globally. Mucormycosis has come up as an important challenging epidemic in India in patients recovered from Covid-19 and with immunocompromised states like diabetes mellitus. We describe a case of rhino-orbital-cerebral mucormycosis here.
Methods
A 47 year old diabetic male was admitted in Covid unit for pulmonary symptoms. He received steroids along with the standard treatment and was discharged in a stable state. 15 days after discharge, he developed left sided dull aching headache of moderate intensity and increasing in the next 3 days and being unresponsive to analgesics.
Results
Examination showed tenderness over left cheek, reduced touch sensations over left upper face with mild ptosis in left eye. Lateral movements were restricted from left eye. These findings suggested left 3rd, 5th and 6th cranial nerve involvement. MRI brain and paranasal sinuses showed left cavernous sinus thrombosis with internal carotid artery thrombosis and left maxillary and ethmoid sinusitis. Considering the ongoing epidemic of mucormycosis in covid rcovered patients, endoscopic sinus biopsy was taken which showed aseptate hyphae consistent with mucormycosis.
Conclusion
Mucormycosis is an important post Covid complication especially in diabetic patients treated with steroids. Careful history and examination are needed for any such patient presenting with isolated headache.
P0423
S. Rahman1, D. Buchholz2, B. Imbiakha2, H. Aguilar-Carreno2, A. Luebke1
1University of Rochester, Biomedical Engineering and Neuroscience, Rochester, MN, United States
2Cornell University, Ithaca, United States
In December 2019, the coronavirus disease (COVID-19) caused by SARS CoV-2 was identified. COVID-19 causes a respiratory illness like the flu with symptoms such as fever, cough, headache, chills, and nausea. The FDA has approved BiohavenPharmaceuticals to proceed to a clinical trial of its CGRP-receptor antagonist to treat patients with severe COVID-19, suggesting that the neuroinflammatory reaction that is initiated by CGRP in response to SARS-CoV-2 could be a therapeutic target for treating severe COVID-19. We were interested in testing if a CGRP receptor antagonist (olcegepant) would mitigate COVID-19 symptoms in mice. As a readout of SARS-CoV-2 infection symptoms, we have assessed weight loss, O2 saturation, temperature in young and old mouse models with CGRP receptor antagonized by olcegepant (2 mg/kg/day/SQ). In ongoing experiments, we will be also monitoring the presence of a nausea-like state by assessing hypothermic responses to provocative motion. To date, we have determined that CGRP receptor antagonism is only protective in older C57B6 mice, as there was no significant difference between CGRP receptor antagonism and placebo controls in younger mice. Ongoing studies will determine if CGRP antagonism is similarly protective against nausea – like symptoms. Information gained from these studies will provide a direct assessment of whether a CGRP-receptor antagonist can mitigate both mild and severe symptoms associated with SARS-CoV-2 infection.
P0424
S. Dubey1, V. Ramakrishnan1, A. Dubey2, C. Mutharasu1
1MMCH & RI, Department of Neurology, Kanchipuram, India
2Gandhi Medical College, Department of Medicine, Bhopal, India
Background and objective
The coronavirus disease 2019 (COVID-19) pandemic has led to a large number of morbidity as well as mortality across the world. Out of its many complications, COVID-19 Associated Mucormycosis (CAM) has also emerged to be an important one. We here present an interesting case of CAM with headache.
Methods
A 77 year old diabetic man presented with history of cough, breathlessness and fever. He was diagnosed to be COVID positive. HRCT chest showed 85–90% lung involvement with CT severity score 23/25. He was treated with oxygen, remdesivir and corticosteroids. During his stay, he started complaining of unilateral (right sided) headache.
Results
There was nasal stuffiness with blackish discharge from nostrils along with right sided facial tenderness. CT head revealed heterogenous soft tissue lesion showing few hyperdense foci within the right maxillary sinus with associated thinning and rarefaction of medial wall of maxillary sinus and bones of ethmoidal sinus and sclerosis of lateral wall of maxillary sinus, suggestive of fungal sinusitis. Biopsy confirmed mucormycosis. He underwent surgical debridement and received amphotericin B and is currently on improving course.
Conclusions
Any new headache during COVID-19 infection should be dealt with immediately. Mucormycosis cases associated with and after COVID infection have been on a rise lately probably because of immunocompromised states including diabetes and corticosteroid use.
P0425
A. Gusev1, M. Kurnukhina1, V. Cherebillo1
1First Pavlov State Medical University of St. Petersburg, Neurosurgical, St. Petersburg, Russian Federation
Summary
Trigeminal neuralgia is one of the most persistent pain syndromes in clinical neurology. If there is no effect on the background of drug therapy, various surgical methods of treatment are used. One of the possible methods of surgical treatment is to perform microvascular decompression, which ensures a more stable regression of the pain syndrome.
Materials and methods
A clinical study of 40 patients aged 21 to 78 years (median 52,5 years) was conducted. The study of patients was carried out at three stages:before the operation, in the early and late postoperative periods. Retrosigmoid access was used. To assess the effectiveness of surgical treatment, the McGill pain intensity questionnaire, the SF-36 were used.
Conclusion
Microvascular decompression leads to an improvement in the quality of life in the late postoperative period and is an effective treatment method for patients with trigeminal neuralgia.
P0426
I. Velichko1, M. Barabanova1, G. Muzlaev1
1Kuban State Medical University, Neurology and Neurosurgery, Krasnodar, Russian Federation
Objective
Ocular myositis is a rare inflammatory disorder of single or multiple extraocular eye muscles. We report a woman presenting with ocular pain caused by inflammation of extraocular muscle.
Methods
Case report.
Results
A 40-year-old woman presented to the department of neurology because of onset of diplopia and ocular pain on the left. The onset of the disease occurred about 2 months ago with a headache in the left temporal region. Neurological examination revealed limited and painful adduction of the left eye. Pupillary light reflexes and dilated fundus examination were normal. Complete blood count, biochemical profile, erythrocyte sedimentation rate, and thyroid function tests were within normal limits. Antinuclear antibodies were negative. Magnetic resonance imaging (MRI) showed left medial rectus muscle enlargement. The endocrinologist and rheumatologist ruled out the pathology. Based on clinical characteristics, MRI results, the ophthalmologist diagnosed orbital myositis. Intravenous therapy with prednisolone was carried out, followed by oral administration of the drug at a dose of 60 mg per day with a gradual dose reduction. The treatment resulted in complete remission and pain relief within a few weeks.
Conclusion
Diagnosis, assessment and management of facial pain requires the cooperation of neurologists and ophthalmologists in order to achieve the best patient outcomes.
P0427
A. Muñoz-Vendrell1, S. Teixidor-Panella1, J. Sala-Padró2, S. Campoy13, M. Huerta13
1Hospital de Bellvitge – IDIBELL, Headache Unit. Neurology Department., L’Hospitalet de Llobregat, Spain
2Hospital de Bellvitge – IDIBELL, Epilepsy Unit. Neurology Department., L’Hospitalet de Llobregat, Spain
3Hospital de Viladecans, Neurology Department., Viladecans, Spain
Objective
The aim of this descriptive study is to evaluate the efficacy and security of intravenous lacosamide (LCM) and phenytoin (PHT) in the treatment of acute pain caused by trigeminal neuralgia (TN).
Methods
We reviewed clinical records of patients who attended the emergency department at a tertiary hospital in Barcelona between 2012 and 2020 due to acute pain exacerbations related to TN and were treated for the first time with either intravenous PHT or LCM. We analyzed demographic features, TN characteristics and registered follow-up for at least 6 months. Primary endpoints were pain relief (defined as report by the patient, absence of further rescue medication and hospital discharge under 10 hours since treatment) and adverse effects during the hospital stay. We compared these variables between groups using Fisher's exact test.
Results
We recorded 117 episodes from 95 patients (median age 59"2 years, 65"3% women). TN etiology was secondary in 10"5%. Out of 59 LCM infusions, pain relief was observed in 76"3% of cases with a 1"7% of adverse effects. Out of 58 PHT infusions, pain relief was observed in 75"9% with a 13"8% of adverse effects, all of them mild. There was no difference in pain relief between groups, but the percentage of adverse effects was significantly different (p = 0.017).
Conclusion
Intravenous LCM and PHT can be effective and safe treatments for acute pain in trigeminal neuralgia. According to our series though, LCM might be better tolerated than PHT.
P0428
C. Venda Nova1, J. M. Zakrzewska1, S. R. Baker2, R. Ni Riordain13
1University College London, Eastman Dental Institute, London, United Kingdom
2Sheffield University, School of Clinical Dentistry, Sheffield, United Kingdom
3Cork University Dental School and Hospital, Oral Medicine, Cork, Ireland
There are multiple treatment options in Trigeminal Neuralgia (TN) however, consensus is lacking as to what the important outcomes of treatment should be. Additionally, there is no clear choice for the correct measurement instrument to illustrate the impact of treatment. The objectives of these systematic reviews (SRs) were to summarize all the outcomes, patient reported outcomes (PROs) and their psychometric properties published in the literature to date. Two SRs were completed by searching multiple databases for a) all the TN studies with a surgical and/or a medical intervention to summarise the outcomes used to date mapped to the Initiative on Methods. Measurement, and Pain Assessment in Clinical Trials guidelines (IMMPACT); b) all the TN studies assessing psychometric properties of instruments based on Consensus-based Standards for the selection of Health Measurement Instruments guidance (COSMIN). In the intervention studies (n = 467), most collected data on the impact of treatment on pain (n = 459) and on side effects (n = 386). A small number of studies collected data on the impact of treatment on physical (n = 46) and emotional functioning (n = 17). Of the 6 studies assessing psychometric properties of 5 PROs, the Penn Facial Pain Scale-Revised (Penn-FPS-R) was the only demonstrating promising content validity results. The lack of clearly defined outcomes and the poor psychometric performance of PROs creates difficulties in comparing studies and prevents the standardized reporting of results.
P0429
N. Noory1, E. A. Smilkov2, T. B. Heinskou1, A. S. S. Andersen1, J. B. Springborg3, P. Rochat3, J. L. Frederiksen4, L. Bendtsen1, S. Maarbjerg1
1Danish Headache Center, Department of Neurology, Glostrup, Denmark
2Rigshospitalet-Glostrup, Department of Radiology, Glostrup, Denmark
3Rigshospitalet-Glostrup, Department of Neurosurgery, Copenhagen, Denmark
4Rigshospitalet-Glostrup, Department of Neurology, Glostrup, Denmark
Background and Objective
Trigeminal neuralgia (TN) is relatively common among patients with multiple sclerosis (MS). There is a lack of high-quality scientific evidence regarding efficacy of surgery in patients with TN secondary to MS (TN-MS). Such studies are crucial to counterbalance the potential gain from surgery and the risk of surgical complications.
Methods
Surgically treated patients with TN-MS were included from 2012 to 2019. The procedures were microvascular decompression, glycerol rhizolysis and balloon compression. Preoperatively, all patients underwent 3.0 Tesla MRI, a clinical examination including a semi structured interview. All patients were followed for 12 months and surgical complications were classified according to a predefined protocol.
Results
We included 18 TN-MS patients. Seven patients underwent microvascular decompression. Five (71%) had an excellent or good outcome. Three (43%) patients suffered major complications. Eleven patients underwent balloon compression and glycerol rhizolysis. Six (54%) patients had excellent or good outcome. Two patients (18%) had major complications.
Conclusions
Microvascular decompression was efficient in the majority of TN-MS patients, but the rate of major complications was high. Percutaneous procedures were effective in half of the operated patients. We recommend the use of percutaneous procedures in medically refractory TN-MS patients and microvascular decompression in well-selected patients.
P0430
S. Singhota12, N. Tchantchaleishvili34, J. Wu5, L. Zrinzo3, L. Thorne3, J. M. Zakrzewska16
1Royal National ENT & Eastman Dental Hospitals, London, United Kingdom
2Medical School, University of Birmingham, Birmingham, United Kingdom
3The National Hospital for Neurology and Neurosurgery, London, United Kingdom
4University of Bordeaux, Bordeaux Neurocampus, Bordeaux, France
5School of Dentistry, University of Leeds, Leeds, Germany
6Pain Management Center, London, United Kingdom
Background
Trigeminal Neuralgia (TN) is an episodic severe neuralgic pain resulting in significant impact on quality of life. It can be managed both medically and surgically.
Aim
To review all patients who attended a joint neurosurgeon and physician Multi-Disciplinary Team (MDT) clinic over a 11-year period and determine what treatments they underwent and their outcomes.
Methods
Using electronic health records, data was transferred to an excel spreadsheet to analyse a) patient demographics, referrer details, duration of TN, and drugs used at the time of referral b) pain status and drugs used: prior to the MDT, at the time of MDT, and at the last visit to the service c) the type and total number of surgical procedures. Surgical complications were classified according to the Ibanez model.
Results
337 patients attending the MDT between 2008–2019 were analysed of which 49 had previous surgery and were analysed separately. Of the remaining patients, 53% opted to have surgery following the MDT. At the last reported visit 55% of patients who opted to have surgery were pain free and off drugs, compared to 15.3% of medically managed patients. Surgical complications were mostly attributable to numbness and was temporary.
Conclusion
The MDT clinic offers an opportunity for shared decision making with patients deciding on their personal care pathway. In this cohort more than half of patients opted for surgery, and subsequently had better pain control and less drug therapy.
P0431
A. Yakubova1, R. Giniatullin2
1Kazan Federal University, Kazan, Russian Federation
2A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
TRPV1 receptors expressed in trigeminal neurons are implicated in migraine pain. Recent genetic studies suggested that the single nucleotide polymorphism (SNP) 1911A > G affects functional activity of the receptors and is involved in different pain conditions. However, this SNP has not been tested in migraine.
Here was evaluated the frequency distribution of AA, AG and GG variants of 1911A > G in the TRPV1 gene in healthy individuals and patients with episodic (EM) and chronic migraine (CM) to test the influence of the SNP on susceptibility to these forms of migraine.
The study included 106 patients with migraine (32 EM and 24 CM) and 50 healthy controls. DNA from peripheral blood was used to test TRPV1 SNP using allele-specific PCR.
The genotype frequency distribution in EM was comparable with that in controls (AA-38%, AG-53%, GG-9% and AA-34%, AG-46%, GG-20%, respectively, p = 0.467) but a tendency of GG variant frequency reduction is noticeable. In CM the distribution differed significantly from control and EM (p = 0.012 and p = 0.049): the AA genotype doubly increased, whereas the GG variant was completely absent, AA-67%, AG-33%, GG-0% (Fig.1).
This is first indications of distinctive involvement of TRPV1 1911A > G genotypes in EM and CM. Our data reveal a different predisposition to chronic pain in migraine and give a new look at the nature of its chronification, proposing that the absence of GG genotype may be considered as potential biomarker of migraine chronification risk
P0432
A. Scutelnic1, V. Petroulia2, L. Schraml3, S. Jung4, M. Branca5, M. Beyeler4, U. Fischer4, R. Wiest2, N. Slavova2, C. Schankin1
1Inselspital Bern, Neurology, Bern, Switzerland
2Inselspital Bern, Neuroradiology, Bern, Switzerland
3Inselspital Bern, Internal Medicine, Bern, Switzerland
4Inselspital Bern, Neurology, Bern, Switzerland
5University of Bern, Bern, Switzerland
Objective
To assess the relevance of the “index vein” (IV) for making the correct diagnosis of migraine with aura (MwA) in patients with acute neurological deficits. We tested the hypothesis that the prevalence of the IV differs between migraine aura, epilepsy, ischemic stroke, and controls.
P0433
P. Zhang1
1Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
Background
International Classification of Headache Disorders (ICHD3) provides definition of headache disorders that can be used to construct a mathematical basis for headache classification. We seek to construct a theoretical framework for such a construction.
Methods
Headache and facial pain conditions are interpreted as bundles of phenotypes. ICHD3 diagnoses are then defined as sets. We proceed to show that observations, in the form of theorems, can be proved with our set theoretic construction for the ICHD3.
Results
In order for our set theoretic construction to be mathematical consistent, the all-present “not accounted for by another ICHD3 diagnosis” criterion must be excluded. Furthermore, our system can be used to construct a categorical approach to headache medicine in the tradition of category theory.
Conclusions
Mathematical interpretation of ICHD3 is possible and may provide significant implication for understanding the structure and organization of headache diagnostic classification.
P0434
M. A. Ruiz Yanzi1, M. V. Nagel1, S. Crema1, M. Grandinetti1, D. Calvo1, M. Olivier1, N. Larripa1, M. T. Gutiérrez1, S. Cavanagh1, L. Bonamico1, F. Dorr2, D. Fernández Slezak23, M. Farez4, M. T. Goicochea1
1Fleni, Buenos Aires, Argentina
2Entelai, Buenos Aires, Argentina
3UBA, Facultad de Ciencias Exactas, Buenos Aires, Argentina
4CEBES, Buenos Aires, Argentina
Objective
to implement an artificial intelligence (AI) based software as a tool for standardizing headache consultations.
Methods
Prospective study in collaboration with Novartis. Between May and November 2019, in the Headache Section of our institution, an AI software (ENTELAI PRE-DOC) was implemented. Patients completed an electronic survey in the waiting room registering sex, age, MIDAS (Migraine Dissability Assessment Scale), HIT-6 (Headache Impact Test), and clinical characteristics of headache.
The AI software estimated a diagnosis. This information was used by the headache specialist during consultation.
Results
757 patients were included (84.3% women). Average age 41 years. Migraine was the main diagnosis (90.9%), and of those, 39% were chronic.
29.4% described hemicranial pain, only 29.8% pulsatile pain, 65.6% photophobia and phonophobia, 69.3% nausea/vomiting, and 59% worsening of pain with exercise. 66.9% of patients had MIDAS scores higher or equal to 11 (moderate to severe disability) and 73.1% had HIT-6 scores higher or equal to 56 (severe impact).
Conclusions
ENTELAI PRE-DOC facilitated recollection of standardized data for diagnosis and assessment of functionality in headache patients. In our population, headache was highly disabling and had an important impact in functionality.
This software could be useful when access to headache specialists is difficult, and to generate standardized data collection for a better analysis of headache.
P0435
G. Guler Aksu1, O. Kayar2, A. Özge3
1Mersin University, Department of Child and Adolsecent Psychiatry, Mersin, Turkey
2Çankırı Karatekin Univeristy, Department of Psychology, Çankırı, Turkey
3Mersin University, Department of Neurology, Mersin, Turkey
Despite many findings from studies, there is still unknown points why migraine and psychiatric disorders are highly comorbid, what is the underlying pathophysiology in this comorbidity, how do we treat. Moreover, schemas which is the basic structure of cognition is understudied although cognitive behavioral therapy based studies are more. This study examined gender effect on early maladaptive schemas (EMS) and migraine in adolescent migraineurs. It comprised 171 adolescents (67.3% girls, n = 115) aged 12–18 years. The migraine clinic characteristics, accompanying symptoms and EMS were evaluated by gender. Differences were tested controlling for psychopathology and abuse. Mean age was 15.37 ± 1.87 in girls; 15.23 ± 1.98 in boys (p = 0.672). There was no difference the migraine clinic characteristics and except from dizziness all other accompanying symptoms were similar between genders. As schema domain, disconnection and rejection in females, impaired limits in males are more frequent. Also defectiveness/shame, emotional deprivation, abondanment/instability, dependence/incompetence, vulnerability harm or illness schemas were more frequently in females, insufficient self-control/self-discipline schemas so were in males more. This concluded EMS was different in females and males in earlier times before the clinical presentation of migraine was not differentiated in adolescents. EMS may have an effect the clinical presentation of migraine and prognosis potentially chronification.
P0436
H. M. S. Thorud1, R. Aurjord1, H. K. Falkenberg1
1University of South-Eastern Norway, Department of Optometry, Radiography and Lighting Design, Kongsberg, Norway
Musculoskeletal pain and headache are leading causes of years lived with disability, and an escalating problem in school children. Children spend increasingly more time reading and using digital screens, and increased near tasks intensify the workload on the precise coordination of the visual and headstabilizing systems. Even minor vision problems can provoke headache and neck- and shoulder (pericranial) pain. This study investigated the association between headaches, pericranial tenderness, vision problems, and the need for glasses in children. An eye and physical examination was performed in twenty 10–15 year old children presenting to the school health nurse with headache and pericranial pain (pain group), and twenty age-and-gender matched classmates (control group). The results showed that twice as many children in the pain group had uncorrected vision and needed glasses. Most children were hyperopic, and glasses were recommended mainly for near work. Headache and pericranial tenderness were significantly correlated to reduced binocular vision, reduced distance vision, and the need for new glasses. That uncorrected vision problems are related to upper body musculoskeletal symptoms and headache, indicate that all children with these symptoms should have a full eye examination to promote health and academic performance. Thorud, H. S., Aurjord, R. & Falkenberg, H. K. Headache and musculoskeletal pain in school children are associated with uncorrected vision problems and need for glasses: a case-control study. Sci Rep
P0437
T. Hikita1, H. Goda2, Y. Ogawa2, T. Kudo2, K. Ito2
1Hikita Pediatric Clinic, Kiryu City, Japan
2Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan
Background
Caffeine is sometimes used for headache treatment. On the other hand, caffeine consumption is a risk factor for chronic migraine.
Aim
We evaluated correlations among urine caffeine concentration, sleep time, and headache severity in patients.
Methods
Study subjects were 41 patients who came to Hikita Pediatric Clinic for headache treatment. Informed consent was obtained, and study design was approved by Musashino University Ethics Committee. Urine caffeine concentrations were determined by LC-MS/MS, and data were collected for age, sleep time, HIT-6, PedMIDAS, and headache severity score (range 0–10).
Results
Subjects’ ages ranged from 5 to 19 yrs (median 13). Diagnoses and #s of cases were: Migraine without aura (MWO) 22, Migraine with aura (MWA) 4, Orthostatic disease (OD) 3, MWO+OD 3, Probable MWO 3, Other 6. Significant correlations were observed for HIT-6 and PedMIDAS scores (ρ: 0.56), and for HIT-6 and headache severity scores (ρ: 0.65), but not for other combinations of factors. There were 8 urine caffeine-negative (level < 0.0625 μM) cases, and 33 urine caffeine-positive cases. For these two groups, respective median values for parameters were: age 12.5 vs. 13 yrs; weekday sleep time 9 vs. 7.75 hrs; weekend sleep time 9.75 vs. 9 hrs; HIT-6 score 61.5 vs. 64, PedMIDAS score 13 vs. 20, headache severity score 4 vs. 5.
Conclusion
Headache severity was greater for urine caffeine-positive than for urine caffeine-negative cases.
P0438
Y. Levinsky1, T. Eidlitz-Markus1
1Schneider Children’s Medical Center, Givaat Shmuel, Israel
Background and objective
Studies have shown that Duchenne and Becker muscular dystrophies are associated with chronic pain, but headache in particular has not been investigated. The aim of the study was to evaluate the prevalence and features of headache in Duchenne and Becker muscular dystrophies.
Methods
The cohort included 68 male patients aged 3–18 years (mean 3.8 ± 9.0 years with Duchenne (n = 49) or Becker (n = 20) muscular dystrophy attending a tertiary neuromuscular clinic in 2015–2019. The parents and older patients completed demographic and headache questionnaires followed by the Strengths and Difficulties Questionnaire (SDQ). Patients reporting headache were referred for further evaluation.
Results
Twenty-two of the 68 patients (32.4%) reported headaches: 10 (45.5%) were subsequently diagnosed with migraine and 12 with tension-type headache. Patients with headache were older than patients without headache (p < 0.001) and had a higher rate of pain in other organs (p < 0.01), higher score on the emotional problems scale of the SDQ (p = 0.001), and higher rate of parental headache (p < 0.001).
Conclusions
Headache occurs in about one-third of patients with muscular dystrophy and is associated with older age, more emotional problems in SDQ scale, higher rate of pain in other organs, and higher rate of parental headache
P0439
S. Jong-Hee1, L. Sang-Hwa1, C. Byoungchul1, K. Jong-Ho2, K. Young-Suk2
1Chuncheon Sacred Heart Hospital, Department of Neurology, Chuncheon, South Korea
2Chuncheon Sacred Heart Hospital, Department of Anesthesiology and Pain Medicine, Chuncheon, South Korea
Background
Headache, especially migraine, has been associated with various vestibular symptoms and syndromes. Also, tinnitus and hearing impairment are prevalent among migraine patients. But, it is not yet clear whether headache including migraines are related to cochlear disorders. Thus, we sought to investigate possible associations between headache and cochlear disorders.
Methods
We analyzed clinical data from the smart CDW from 2011 to 2021. In patients with migraine and non-migraine headache, MD, BPPV, vestibular neuronitis (VN) and cochlear disorders, such as hearing loss and tinnitus, were collected and compared to clinical data from controls who had health check-ups without headache.
Results
Participants included 15,128 with migraines, 76,773 patients with non-migraine headache and controls were identified based on propensity score matching (PSM). After PSM, the odds ratios (ORs) in subjects with migraine versus controls were 2.59 for MD, 2.05 for BPPV, 2.98 for VN, 1.74 for hearing loss, and 1.97 for tinnitus, respectively (p < 0.001). The OR for MD (1.77), BPPV (1.73), VN (2.05), hearing loss (1.40), and tinnitus (1.70) in patients with non-migraine was also high after matching (p < 0.001).
Conclusions
Our findings suggest that migraine and non-migraine headache are associated with an increased risk of cochlear disorders, in addition to vestibular disorders.
P0440
J. R. Chaudhuri1, T. K. Banerjee2, R. Kulkarni3, S. Singh4, S. Gokhale5, S. Anand5, S. Thakur6, A. Thorat6
1Yashoda Hospitals, Neurology, Hyderabad, India
2National Neurosciences Centre, Neurology, Kolkata, India
3Deenanath Mangeshkar Hospital and Research Centre, Neurology, Pune, India
4Agrim Institute of Neurosciences, Artemis Hospitals, Neurology, Gurugram, India
5Novartis Healthcare Private Limited, Market Access, Mumbai, India
6Novartis Healthcare Private Limited, Medical Affairs, Mumbai, India
Objective
Migraine prevalence peaks in Indian patients during their most productive years leading to an economic burden. There are no scientific tools or literature to uncover this burden and is often ignored. We developed an evidence-based tool estimating migraine related costs associated with productivity loss, resource utilization and symptom burden
Methods
Work productivity and activity impairment data specific to India (N = 263) was adopted from MyMigraineVoice online survey conducted from Sept-2017 to Feb-2018 in patients having at least four monthly migraine days and a failure on prophylactic therapy. Literature review was conducted to get insights about local epidemiology and costs. Tool enables user to input patient numbers, preventive treatment failure (no preventive treatment, no failure, 1 failure and 2+ failures), time horizon (1–12 months) and earnings per day to present cost estimates in Indian rupees (₹)
Results
Tool dynamically demonstrates total cost of migraine based on user provided inputs. Productivity loss was attributed to absenteeism and presenteeism. Resource utilization included costs associated with overnight hospitalizations and emergency visits. Expenses related to brain scans and pharmacological management were considered as symptom burden
Conclusion
In a self-pay market like India, this tool will enable decision makers to make an evidence-based decision. Increasing cost burden in migraine can be reduced by optimal preventive treatment
P0441
R. B. Lipton12, A. M. Nelson3, R. A. Nicholson3, A. Zagar3, Y. Kim3, J. Pascual4, S. Evers5, K. Hirata6, E. Pearlman3
1Albert Einstein College of Medicine, Bronx, United States
2Montefiore Medical Center, Bronx, United States
3Eli Lilly and Company, Indianapolis, IN, United States
4University Hospital Marqués de Valdecilla, University of Cantabria and IDIVAL, Santander, Spain
5Krankenhaus Lindenbrunn, Coppenbrügge and University of Münster, Munster, Germany
6Dokkyo Medical University, Mibu, Tochigi, Japan
Objective
Quantify migraine diagnosis rates and burden among respondents to an ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME).
Methods
Web-based OVERCOME country-specific surveys were fielded in 2020–2021 in US, Spain, Germany, and Japan. Respondents who met modified ICHD-3 criteria for migraine via a validated diagnostic screener were identified. Respondents self-reported if they had a medical diagnosis (SR-MD) of migraine. Migraine-related disability (MIDAS), interictal burden (MIBS-4), and work productivity and activity impairment due to migraine (WPAI-M) were assessed for each country and internationally (equally weighted by country). Descriptive statistics were conducted.
Results
Among respondents (N = 57,837), 52,382 (91%; country-specific range: 82–97%) met ICHD-3 criteria for migraine. Among those (mean age 40.3 years; 66% female), 52% (range: 47–54%) had SR-MD of migraine; 55% (range: 37–67%) reported at least mild disability (i.e., being disabled by migraine, on average ≥2 days/month); 42% (range: 30–48%) had severe interictal burden. Respondents reported on average, 47.0% (range: 37.7–52.8%) overall work impairment and 41.3% (range: 37.9–43.2%) activity impairment due to migraine.
Conclusion
Across countries, just over half of OVERCOME respondents had SR-MD of migraine, although the majority were at least mildly disabled and had substantial overall work and activity impairment due to migraine. 
P0442
B. Benkli1, W. Zhang2, G. Dumkrieger3, M. J. Burish4
1UT Health Neuroscience, Neurology, Houston, TX, United States
2Department of Biostatistics and Data Science, UTHealth School of Public Health, Public Health, Houston, TX, United States
3Mayo Clinic, Neurology, Scottsdale, AZ, United States
4UT Health Neuroscience, Neurosurgery, Houston, TX, United States
Objective
To determine the pain intensity of migraine and its relationship with cranial autonomic features.
Methods
The analysis included 1108 migraine patients who were enrolled in the American Registry for Migraine Research (ARMR) between February 2016 and June 2019. Patients completed the 0–10 numerical rating scale for pain intensity, as well as questions about associated features including all cranial autonomic features listed for cluster headache in the International Classification of Headache Disorders (ICHD) edition 3 beta. Patients also completed Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-4 (PHQ-4) and Migraine Disability Assessment Scale (MIDAS) questionnaires.
Results
Average pain intensity was 6.0 ± 1.7, and 92.7% of patients in ARMR had moderate or severe pain. Higher pain intensity correlated significantly with higher GAD7, PHQ4, and MIDAS scores (p < 0.0015). At least one cranial autonomic symptom was present in 83.8% of patients, and higher pain intensity correlated significantly with a higher rate of conjunctival injection, eyelid edema, and miosis (p < 0.0005) along with increased restlessness (p = 0.0001) and vomiting (p = 0.0014).
Conclusions
Pain intensity in migraine correlates with headache burden (mood and disability scores) in a large clinical dataset, similar to population studies. A graded response of the trigeminal autonomic reflex appears to be a feature of not only cluster headache, but also migraine.
P0443
S. Evers1, T. Panni2, H. P. Hundemer2, D. Novick2, T. Treuer2, G. Dell Agnello2, J. Pascual3
1University of Münster, Munster, Germany
2Eli Lilly and Company, Indianapolis, IN, United States
3Hospital Universitario Marqués de Valdecilla, Santander, Spain
Objective
Migraine is a chronic neurological disease with a considerable economic and societal burden. The objective of this study is to describe the demographics, quality of life, levels of treatment satisfaction and barriers to treatment for people with migraine.
Methods
Descriptive data is provided from the European ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE; OVERCOME (EU), a large, cross-sectional, population level, web-based survey of adults (≥18 years) with migraine in Spain and Germany (Oct 2020 – Feb 2021).
Results
Overall, 20,756 respondents were evaluated, 57.6% had a migraine diagnosis, mean age of respondents was 40.4 years and 60.3% were female. With respect to Migraine Disability Assessment scores 39.4% of respondents reported little to no disability, 19.2% mild disability, 19.3% moderate disability and 22.2% severe disability. The top 3 barriers to taking preventative medication were i) efficacy of acute medication, ii) migraine not being serious enough for treatment and iii) concerns regarding side-effects. Of the patients taking preventative medications 21.1% found their medications to be a little efficacious, 37.7% somewhat, 22.9% a lot, and only 9.8% reported experiencing complete efficacy.
Conclusion
These results provide a unique insight into the levels of disability, satisfaction with currently available preventative treatments and existing barriers to treatment experienced by people with migraine in the EU.
P0444
J. Pascual1, T. Panni2, H. P. Hundemer2, D. Novick2, T. Treuer2, G. Dell Agnello2, S. Evers3
1Hospital Universitario Marqués de Valdecilla, Santander, Spain
2Eli Lilly and Company, Indianapolis, IN, United States
3University of Münster, Munster, Germany
Objective
Migraine is a chronic neurological disease with a considerable economic and societal burden. The objective of this study is to describe the demographics, clinical characteristics, and care seeking behaviors of people with migraine.
Methods
Descriptive data is provided from the European ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE; OVERCOME (EU), a large, cross-sectional, population level, web-based survey of adults (≥18 years) with migraine in Spain and Germany (Oct 2020 – Feb 2021).
Results
In total 20,756 respondents were evaluated, 57.6% had a migraine diagnosis (mean age at diagnosis, 24.2 years), 60.3% were female and the overall mean age was 40.4 years. A total of 13,759 (66.3%) respondents reported 0–3 headache days per month (HD/month), 4,203 (20.2%) 4–7, 1,730 (8.3%) 8–14 and 1,064 (5.1%) 15+ HD/month. The most frequently reported comorbidities were allergies/hay fever (38.8%), anxiety (26.2%) and depression (24.0%). In the preceding 12 months 59.1% of participants visited a general practitioner, 39.4% a pharmacist, and 16.6% a general neurologist. The most severely affected individuals were more likely to have consulted a headache/pain specialist in the previous 12 months, 39.1% of total visits were made by individuals with Migraine Disability Assessment scores of 21+ (MIDAS IV).
Conclusion
This real-world study provides a unique insight into the demographics and care-seeking behaviors of people with migraine in the EU.
P0445
T. Adoukonou1, M. Agbetou1, E. Dettin1, O. Kossi1, D. Houinato1, T. J. Steiner23
1Department of Neurology, University of PARAKOU, BORGOU, Parakou, Benin
2Lifting The Burden, 21–27 Lamb’s Conduit Street, United Kingdom
3Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway, Trondheim, Norway
Headaches disorders globally are common and disabling. The aim of this study, within the Global Campaign against headache, was to determine their prevalence and attributabled burden in the general population of Benin. Disorders of interest, because of their public health importance, were migraine, tension-type headache (TTH) and disorders characterised by headache occuring on ≥15days/month (H15+) including probable medication-overuse headache (pMOH). In a cross-sectional study we randomly selected 2400 adults aged 18–65years from two regions of the country, one in the north and one in the south, taking rural (70%) and urban (30%) dwellers from each. In home visits, we interviewed each participant using HARDSHIP structured questionnaire applying ICHD-3 diagnostic criteria and several measures of burden. The study was approved by the ethics committee of biomedical research of University of Parakou. The mean age of participants was 32.1+/−11.2years. The overall 1-year prevalence of headaches was 76.5% (95%CI: 74.7–78.1). Adjusted for age and gender, the prevalence of migraine was 26.1%, of TTH 46.2% and H15+ 3.3% (including pMOH 2.2%). One-day prevalence (Headace yesterday) was 15.4%, implying that almost one in six adults had headache on any day. Attributed burden was measurable especially in lost productive time and impaired quality of life. The prevalence of headaches reported in Benin is similar to those reported in Ethiopia and Zambia and higher than averages.
P0446
O. Hensel1, P. Burow1, T. Kraya2, S. Nägel1
1University of Halle, Neurology, Halle, Germany
2St. Georg Hospital Leipzig, Neurology, Leipzig, Germany
Objective
There is an ongoing debate regarding the relevance of arterial changes in migraine, as plenty but inconclusive evidence exists. We investigate whether alterations of the vertebrobasilar arteries occur in patients with migraine retrospectively analyzing MRI angiographies.
Methods
In 63 patients with episodic and chronic migraine (30.6 ± 8.9 years, 84% women) and 126 age- and sex-matched controls, we determined the outlet angle of the superior cerebral artery (SUCA) in a coronal TOF-MRI (see Figure).
Results
Across all patients, the SUCA outlet angle was reduced in patients with migraine compared to controls (159 ± 26° vs. 169 ± 29°, p = 0.020). However, this appears to be driven by a subset of the patients, as not all migraine patients have decreased SUCA outlet angles. Analyzing only the patients with reduced SUCA outlet angles (1st cut-off: median of patients 160°, 2nd cut-off: mean-standard deviation of controls 140°) shows that patients with chronic migraine have lower SUCA angles compared to patients wih episodic migraine (1st cut-off: 125 ± 25° vs.142 ± 12°, p = 0.025; 2nd cut-off: mean-SD 110 ± 20 vs. 131 ± 6; p = 0.004).
Conclusion
Migraine patients showed reduced SUCA outlet angle. This only appears to be relevant in a subset of patients, which could reflect different genetic constitution and correspond to a dilation of longitudinal vessel wall structures.
P0447
H. Basedau1, K. P. Peng1, A. May1, J. Mehnert1
1UKE, Institute for Systems Neuroscience, Hamburg, Germany
Objective
Non-invasive imaging studies of the trigemino-vascular system are limited by either spatial or temporal resolution. Multimodal imaging techniques – simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) – may solve this issue.
Methods
We conducted a – visual and trigeminal pain paradigm in 34 healthy volunteers in standalone EEG and fMRT sessions. Additionally, 17 volunteers participated in a simultaneous EEG-fMRI session. We then validated a novel non-parametric fusion technique, which exploits trial-to-trial variance.
Results
We reproduced previous findings and show correlations between both modalities. EEG power changes in theta-band induced by trigeminal pain correlate with fMRI activation within the brainstem, whereas those of gamma band correlate with cortical areas.
Conclusion
Our study validates a trigeminal nociceptive paradigm for EEG-fMRI fusion using standalone sessions and a visual paradigm as control. Power changes of the theta band induced by trigeminal nociception correlated with the nociceptive and anti-nociceptive pain processing systems in the brainstem while gamma band activity related to pain cortical networks of nociception and saliency. While our findings on the experimental side should be extended to headache patients, our analytical approach can be adapted to any multimodal analysis.
P0448
D. Y. Wei12, O. O’Daly3, F. O. Zelaya3, P. J. Goadsby12
1King’s College, NIHR Wellcome Trust King’s Clinical Research Facility, London, United Kingdom
2King’s College, Headache Group, Wolfson Centre for Age-Related Diseases, London, United Kingdom
3King’s College, Centre for Neuroimaging Sciences, Department of Neuroimaging, London, United Kingdom
P0449
E. Ekusheva1
1Academy of Postgraduate Education of the Federal Research and Clinical Centre for Specialized Medical Care and Medical Technolog, Neurology and Neurorehabilitation, Moscow, Russian Federation
There are many controversial and unclear issues with chronic tension-type headache (CTTH), in particular, the pathogenetic mechanisms of the development and chronization of the disease.
Material and methods
84 patients (39.2 ± 6.1) with CTTH and 25 healthy subjects comparable in age were examined. Clinico-neurological examination, nociceptive flexor reflex (RIII reflex), blink reflex, and transcranial magnetic stimulation (TMS).
Results
All patients with CTTH were simultaneously examined clinically and neurophysiologically before the course of therapy with drugs with proven efficacy taken at therapeutic doses for 3months. After the 3month course of treatment all patients were divided into 2 groups: 1 group (1) – with a good response to the therapy (decrease in the frequency and intensity of headache) and 2 group (2) – with minimal effect or its absence. A comparative neurophysiological analysis of the data obtained in patients of these groups before the course of preventive treatment, showed significant differences between them.
P0450
M. S. Mykland1, M. Uglem12, J. P. Neverdahl1, T. W. Meisingset12, L. R. Øie12, T. Sand12, P. M. Omland12
1Norwegian University of Science and Technology, Department of Neuromedicine and Movement Science, Trondheim, Norway
2St. Olavs Hospital, Department of Neurology and Clinical Neurophysiology, Trondheim, Norway
There is a well-known but unexplained association between sleep and migraine. In this blinded longitudinal study, we measured the effect of sleep restriction on Cortical Silent Period (CSP) as a measure of intracortical inhibition.
Fifty-five episodic migraine patients and 30 controls underwent two sessions of Transcranial Magnetic Stimulation (TMS). A 24-hour limit for pre- and postictal phase left 47 migraine patients with at least one interictal recording. Every session was preceded by two nights of either sleep restriction (4 hours) or normal sleep (8 hours) in randomized order. CSP was recorded from the abductor pollicis brevis muscle during approximately 50% of maximum muscle force with TMS intensity of 120% of the resting motor threshold.
We used a linear mixed model of CSP with sleep condition and diagnose as fixed effects and found a trend for interaction between sleep condition and diagnosis (95% CI −24.0, 0.4; p = 0.058). The corresponding interaction was significant when achieved sleep time replaced sleep condition in the model (p = 0.034). Controls had an increase in mean CSP duration from normal sleep (137.3 ms) to sleep restriction (141.7 ms), while interictal migraine had an opposite pattern of decrease in CSP from normal sleep (147.8 ms) to sleep restriction (140.3 ms).
These findings indicate that migraine pathophysiology may encompass a dysfunction of the cortical regulatory response to sleep restriction involving altered GABA mediated cortical inhibition.
P0451
N. Meylakh1, K. Marciszewski1, L. Henderson1
1University of Sydney, School of Medical Sciences, Sydney, Australia
Objective
Although mechanisms underlying migraine pathogenesis remain hotly debated, there is a growing body of evidence suggesting that brain function alters dramatically within the 24 hours preceding a migraine headache. It is possible that altered function, particularly in brainstem and hypothalamic sites, may either trigger or facilitate a peripheral trigger to activate higher cortical areas evoking pain. The aim of this series of investigations was to determine brainstem and hypothalamic function in the 24 hours preceding a migraine, in both a cross-sectional and longitudinal study.
Methods
In 8 migraineurs preceding (within 24 hours) a migraine and 78 pain-free controls, and in 3 migraineurs and 5 pain-free controls, we measured resting blood oxygen level dependent functional magnetic resonance imaging (fMRI) (180 volumes, TR = 2 seconds) over the entire brain.
Results
There was significant increased infra-slow oscillatory activity in brainstem regions encompassing the spinal trigeminal nucleus and dorsal pons, as well as the hypothalamus in the 24-hour period preceding a migraine headache between individuals. Interestingly, alterations in these brainstem sites were found in the same period within individual migraine cycles.
Conclusion
These findings provide evidence that in the 24-hour lead up to a migraine, the activity of the hypothalamus and brainstem is disturbed. How these regions are involved in migraine initiation and expression are yet to be fully understood.
P0452
M. Filipchuk1, T. Castro Zamparella1 M. Carpinella1, D. M. Conci Magris1, M. Lisicki1
1Conci Carpinella Institute, Neuroscience Unit, Córdoba, Argentina
Objective
To evaluate cortical activity in episodic and chronic migraine patients compared to healthy controls.
Methods
One-minute artifact free resting-state electroencephalogram segments from 25 healthy controls and 74 migraine patients (25 ictal, 25 inter-ictal, and 24 chronic) were analyzed using eLORETA. Subject-normalized delta (1–3Hz), theta (4–7Hz), alpha (8–12Hz), beta (13–30Hz) and gamma (31–45Hz) cerebral activity was compared (whole brain, voxel-wise) between groups. Afterwards, activity from specific ROIs (data driven) was extracted to build statistical models.
Results
Marked differences in resting-state cerebral activity were consistently observed in the sub-callosal (BA25), parahippocampal (BA28, BA34, BA35, BA36), and precuneus (BA7) regions. A multivariate statistical comparison showed significant differences for the interaction group-region-frequency band.
Conclusion
Electrophysiological differences in resting-state cortical activity between healthy controls and migraine patients involve several regions, some of which have been previously linked to the disease under alternative approaches. In contrast with other neuroimaging tools, eLORETA directly evaluates brain functioning and not indirect markers like blood flow or metabolism. In addition, band-specific information could provide valuable clues regarding different levels of neural hierarchy. Further research is required to help explain the pathophysiological significance of these observations.
P0453
I. Corbelli1, A. Chiappiniello2, A. Di Renzo3, G. Guercini4, R. Tarducci2, P. Calabresi5, P. Sarchielli1, G. Coppola6
1S.M. Misericordia Hospital – University of Perugia, Department of Medicine, Perugia, Italy
2Azienda Ospedaliera di Perugia, Medical Physics Department, Perugia, Italy
3IRCCS Fondazione Bietti, Rome, Italy
4ServiOspedale S.M. Misericordia, Università degli Studi di Perugia, Servizio di Neuroradiologia, Perugia, Italy
5Università Cattolica del Sacro Cuore, Institute of Neurology, Rome, Italy
6University of Rome Polo Pontino, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy
Background
An involvement of the visual system in the pathophysiology of migraine with aura (MA), is well known and observed in both neurophysiological and functional neuroimaging studies. With this last method in particular, some studies have seen an involvement of different extrastriate networks during visual stimulation.
Methods
We acquired functional MRI at rest in 21 MA patients and 18 healthy controls (HCs) before and after 4 minutes of visual stimulation. For each group we extracted independent resting-state networks correlating the change in network connectivity strength with clinical disease variables.
Results
In HCs, visual stimulation significantly increases functional connectivity between the independent components pair left dorsal attention system (DAS) and executive control network (ECN), and between right DAS and ECN. In MA patients, visual stimulation significantly increased functional connectivity between the independent components pair salience network (SN) and left DAS, and between left DAS and ECN. Correlation test reveals that after light stimulation the slope of the regression line between pre and post visual stimulation Z-scores of the ECN correlated negatively with the monthly frequency of aura.
Conclusions
In HCs visual stimulation involves more the attentional and executive systems, while in MA patients, visual stimulation also involves the SN with the executive one, that is considered a function of the average monthly frequency of the aura.
P0454
E. Caronna1, V. Gallardo Ló pez1, D. Pareto2, A. Alpuente1, M. Torres-Ferrus1, A. Rovira2, P. Pozo-Rosich1
1Vall d’Hebron University Hospital, Neurology, Barcelona, Spain
2Vall d’Hebron University Hospital, Neuroradiology, Barcelona, Spain
Objective
The objective was to describe the differences between patients with migraine and healthy controls (HC) in the total amount of accumulated structural brain changes and their correlation with specific clinical features of the disease.
Methods
We included right-handed patients with migraine (chronic/high frequency episodic) and HC who underwent a 3T brain MRI study. Cortical thickness values were analyzed for each area (31 per hemisphere), calculating the corresponding Z-scores and defining the areas with threshold −/+ 1.96 as abnormal. We compared the two groups and we analyzed the correlations between abnormal areas and migraine clinical variables.
Results
We included 26 patients with migraine and 26 HC, with no differences in age, gender, anxiety/depression. In the migraine group, we observed a higher proportion of brain structural changes (migraine 14.5% vs. 4.0% HC, p < 0.0001). The areas with significant differences between groups were: paracentral (p < 0.0001), isthmus cingulate (p < 0.0001), postcentral (p = 0.006), inferior parietal (p = 0.005) and parahippocampal (p = 0.006). The presence of isthmus cingulate changes was associated with longer disease evolution (p = 0.017) and longer chronification (p = 0.013).
Conclusions
Migraine correlates with a greater load of structural brain changes as a marker of disease burden.
P0455
M. Vila-Pueyo1, K. Johnson2, P. J. Goadsby1, P. R. Holland1
1King’s College, Wolfson Centre for Age Related Diseases, London, United Kingdom
2Eli Lilly and Company, Indianapolis, IN, United States
Objective
Galcanezumab binds to and inhibits calcitonin gene-related peptide (CGRP) signalling and is approved for migraine and cluster headache treatment. To understand better its mechanisms of action, we have studied the effects of galcanezumab in preclinical models of migraine and trigeminal autonomic cephalalgias (TACs) including cluster headache.
Methods
Male Sprague-Dawley rats (N = 32) were anesthetized with isoflurane and maintained with propofol infusion (33–50mg/kg/h). Trigeminovascular afferents and the trigeminal autonomic system were activated by electrical stimulation of the meningeal afferents surrounding the dural vasculature or the superior salivatory nucleus (SSN), respectively. Neuronal responses were recorded in the trigeminocervical complex (TCC). Following baseline responses, animals were intravenously infused with human control IgG or galcanezumab (10mg/kg) and responses were recorded for 270 mins.
Results
Treatment with galcanezumab significantly inhibited spontaneous neuronal activity in the TCC from 3h after administration (F2.8,39 = 8.69,P < 0.05). Additionally, galcanezumab significantly reduced durovascular-evoked nociceptive activation in the TCC (F5.4,76 = 26.47,P < 0.05), starting 150 mins post-infusion. Finally, galcanezumab significantly reduced SSN-evoked nociceptive activation in the TCC (F3.7,48 = 5.44,P < 0.05), starting at 225 mins post infusion.
Conclusion
The results demonstrate a clear effect of galcanezumab in preclinical models of migraine and TACs.
P0456
P. Sureda-Gibert1, M. Vila-Pueyo1, S. Hirschberg2, T. Pickering2, P. J. Goadsby13, P. R. Holland1
1King’s College, Wolfson Centre for Age-Related Diseases, London, United Kingdom
2University of Bristol, School of Physiology & Pharmacology, Bristol, United Kingdom
3King’s College, NIHR-Wellcome King’s Clinical Research Facility (CRF), London, United Kingdom
Background and objective
Migraine patients commonly report head pain, marked fatigue and lack of concentration as hallmarks of their attacks. Noradrenergic locus coeruleus (LC) activity has been shown to have divergent roles on nociceptive durovascular-evoked neuronal responses in the trigeminocervical complex (TCC). We sought to optimise a chemogenetic strategy using a Canine adenoviral vector (CAV) with the PRS promoter (CAV2-PRS-hM3D(Gq)-mCherry) to selectively target noradrenergic projections from the LC, and investigate their role on teminal nociceptive processing.
Methods
Twenty 4-week-old rats underwent targeted unilateral stereotaxic administration into the LC of either an active CAV2-PRS-hM3D(Gq)-mCherry (n = 11) or a control non-PRS CAV (CAV-CMV-mCherry) (n = 9). Allowing three weeks to recover, dural nociceptive-evoked neural responses and spontaneous activity were measured in the spinal cord TCC C1 level. Responses were assessed before and after administration of a specific chemogenetic ligand: Clozapine-N-Oxide (CNO) (3mg/kg).
Results
Dural-evoked responses significantly decreased in the active group (p = 0.0042), at time points: 60, 90 and 150min post-CNO, but not in the control group (p = 0.098). Spontaneous activity significantly decreased in the active group (p = 0.0391) post-CNO, but not within the control group(p = 0.7303).
Conclusions
In vivo activation of LC Noradrenergic projections uncovered an inhibitory influence over trigeminal/migraine-associated nuclei.
P0457
D. Moreno-Ajona1, M. D. Villar-Martínez1, N. Futter1, J. Hoffmann1, P. J. Goadsby1
1King’s College, NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College London, London, United Kingdom
Objectives
Medication overuse headache (MOH) is a cause of chronic daily headache. MOH biological explanation is unresolved. ICHD-3 defines medication overuse as an intake of more than 10 days of opioids, more than 15 days of paracetamol or NSAIDs, or more than 10 days of combined analgesics. We sought to explore medication overuse in rheumatology patients to examine links between headache and the regular intake of analgesics.
Methods
Data from patients seen at the Rheumatology Clinic, King's College London, were retrospectively analysed. Clinical letters were checked for the presence of headache and regular intake of opioids, paracetamol and naproxen. Headache prevalence was compared using the Pearson's chi-squared test.
Results
Data was found for 9288 patients. The total prevalence of headache was 11% (1025 patients). After exclusion of patients taking combined analgesics (2789), the prevalence of headache in patients taking regular opioids (566) was 15.7%, 15.3% for paracetamol (850) and 7.2% for naproxen (805). The difference with the total headache prevalence was significant for all groups (Chi2 opioids vs total: P = 0.001; paracetamol P = 0.001; naproxen: P = 0.007; paracetamol vs naproxen: P < 0.00001).
Conclusion
Regular intake of opioids and paracetamol was associated with higher headache prevalence. In contrast, the findings suggest that naproxen may not cause MOH and may even have a protective effect. These observations should be confirmed in a prospective clinical study.
P0458
R. Bertz1, M. S. Anderson2, J. L. Collins1, J. Stringfellow3, J. Madonia1, R. Bhardwaj2, J. A. Finley1, D. A. Stock1, V. Coric1, R. Croop1
1Biohaven Pharmaceuticals, New Haven, CT, United States
2Certara USA, Princeton, NJ, United States
3Navitas Data Sciences, Pottstown, PA, United States
Objective
Clinically significant drug interactions can limit the utility of medications used for the acute and preventive treatment of migraine. This study evaluated the effect of strong inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pharmacokinetics (PK) of rimegepant in healthy adults.
Methods
This single-center, open-label, randomized study had 2 parts. Part 1 was a 2-period, 2-sequence, crossover evaluation of the effect of cyclosporine (1 oral 200 mg dose), a strong inhibitor of both P-gp and BCRP, on the PK of rimegepant 75 mg. Part 2 was a 2-period, 2-sequence, crossover evaluation of the effect of quinidine (1 oral 600 mg dose), a strong selective P-gp inhibitor, on the PK of rimegepant 75 mg.
Results
Fifteen subjects completed Part 1; 12 subjects completed Part 2. Coadministration with cyclosporine increased rimegepant AUC0-inf and Cmax; geometric mean ratios (90% CI) versus rimegepant alone were 160% (149, 172) and 141% (127, 157). In Part 2, the evaluation with quinidine increased rimegepant AUC0-inf and Cmax similarly; geometric mean ratios (90% CI) versus rimegepant alone were 155% (140, 172) and 167% (146, 191).
Conclusions
Strong P-gp inhibitors (cyclosporine, quinidine) moderately increased rimegepant exposures (>50%, <2-fold). The similar effect of cyclosporine and quinidine on rimegepant exposure suggests that BCRP inhibition minimally influences rimegepant exposure.
P0459
N. Nunes Rabelo1, E. Peixoto2
1University of São Paulo, Department of Neuroloy, São Paulo, Brazil
2Federal University of São Paulo, São Paulo, Brazil
Objective
To report the use of a non-invasive sensor to assess intracranial compliance in the management of patients complaining of migraine.
P0460
L. Al-Hassany1, T. de Vries1, J. A. Carpay2, A. Maassen van denBrink1
1Erasmus University Medical Center, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands
2Tergooi Hospital, Department of Neurology, Hilversum, Netherlands
A need exists for effective preventive medication of migraine, a highly disabling disorder. Recently, antimigraine drugs targeting calcitonin gene-related peptide (CGRP) or its receptor have been approved for use in the clinic. Here, we present a case of a 54-year-old Caucasian male patient suffering from migraine with aura and who was administered a subcutaneous loading dosage of 240 mg galcanezumab, a monoclonal antibody targeting CGRP, and 120 mg each month thereafter. The patient reported erectile dysfunction (ED) as a possible side effect of the treatment. Interestingly, his potency recovered after discontinuation of the treatment. His general practitioner did not find any plausible (other) explanation for this temporary ED. Considering that CGRP is involved in the mammalian penile erection, ED is a conceivable, and possibly underreported, side effect associated with inhibition of CGRP. The reversibility of ED after cessation of galcanezumab treatment hints towards a causal association between the use of galcanezumab and ED. Yet, future studies should elucidate the actual incidence of ED in patients using drugs targeting CGRP or its receptor, and should determine whether such causal relationship between CGRP inhibition and ED exists. This would be relevant not only because of the direct sexual consequences of ED, but also considering the potential cardiovascular consequences of CGRP blockade and the association of both migraine and ED with cardiovascular disease.
P0461
S. Taborda1, F. Villa1, L. Henao1, V. Dominguez1, Y. Giraldo1
1CES University, Neurology, Medellín, Colombia
Objective
To determine the utility and real risks of adding steroids to pericranial blocks in chronic migraine.
Methods
Prospective, descriptive study, case series type; 22 patients with a diagnosis of chronic migraine were evaluated, who had received at least 2 first-line preventive drugs without improvement, and who were given, for the first time, a pericranial block with bupivacaine/lidocaine/dexamethasone.
Results
One month after intervention, there was a median difference in the average headache intensity of 2 on the visual analog pain scale (p = 0.019 confidence interval or CI: 0.4–3.6), the median difference in the number of days of the month with migraine before and after the block was 10 days (p = 0.001, CI 4.5–15–5); There was no change regarding the duration of the headache episodes, use of abortive medications, or the number of days absent from work per month. Regarding adverse effects, 75% of the patients denied any adverse effect associated, 10% reported pain for more than one day, 5% drowsiness, 5% itching, and 5% persistent dizziness. It is important to note that none of the patients reported alopecia or aesthetic alteration during follow-up.
Conclusion
The combination of local anesthetics with dexamethasone produced a significant decrease in the number of days with pain and in the median intensity of the headache, without producing alopecia or aesthetic alteration, the latter being a frequently feared complication due to the use of steroids.
P0462
S. Cavanagh1, V. Nagel1, M. Olivier1, N. Larripa1, M. T. Gutiérrez1, M. Grandinetti1, D. Calvo1, L. Bonamico1, M. T. Goicochea1
1Fleni, Headache, Buenos Aires, Argentina
Methods
Transversal study. We evaluate adult patients with migraine for 30 consecutive days through a survey. Diagnoses, actual use of preventive, patients with indication of preventive treatment and patients who failed at least 2 preventive treatments. Study approved by ethics committee.
Results
602 patients with migraine diagnosis.20 were excluded.582 patients were analyzed.88% women, mean age 41 years. Diagnoses: high frequency episodic migraine (17%), chronic migraine (30%), overuse headache (13%), migraine with aura (10%). 216 (46%) patients use preventive treatment. Topiramate (42%), amitriptyline (25%), valproic acid (8%), botulinum toxin (8%), beta blockers (5%), venlafaxine (4%), flunarizine and others (3%). From the group without preventive treatment(315 patients), 138 (44%) needed one and 52% had used it before.16.5% had failure to at least 2 preventive treatments.
Conclusion
We have a high proportion (30%) of patients with chronic migraine because we are a specialized center. Topiramate was the most used. Most of our population received or needed preventive treatment (70%) and 16.5% could benefit with new preventive treatments such as CGRP monoclonal antibody.
P0463
F. Cheng1, M. Hussain1, V. Wilkinson1, M. Khalil1, F. Ahmed1
1Hull University Teaching Hospital, Department of Neurology, Hull, United Kingdom
Objective
To evaluate fremanezumab efficacy in refractory chronic migraine (CM).
Methods
Adult CM patients attending the Hull Migraine clinic were prescribed fremanezumab and followed up prospectively. Patients maintained a headache diary for at least 1 month prior to and continuously after commencing fremanezumab. All patients tried and failed at least 6 treatments from amitriptyline, propranolol, topiramate, candesartan, flunarizine, greater occipital nerve block and onabotulinumtoxinA. We measured monthly headache days (MHD), migraine days (MMD), headache-free days (HFD), analgesia medication (AMD) and triptan days (TD) and Headache Impact Test-6 (HIT6) scores at baseline and monthly during treatment.
Results
289 patients (215 F, 74 M), mean age 48.6 years (range 21–75), commenced fremanezumab between November 2020–April 2021. 182 patients (119 F, 63 M) at 3-month follow-up so far had baseline MHD, MMD and HFD of 28, 17 and 2 days, improving to 15, 6 and 15 days respectively. Mean MHD and MMD decreased by 37.7% and 57.0% from baseline (p < 0.001). 57.7%, 38.5% and 17.0% patients achieved ≥30%, ≥50% and ≥75% MHD reduction. 79.4%, 68.1% and 41.8% achieved ≥30%, ≥50% and ≥75% MMD reduction. 55.5% and 41.8% increased baseline HFD by ≥2 and ≥3-fold. AMD and TD improved from 10 and 2, to 4 and 0 days (p < 0.001). Mean HIT6 improved from 68.0 to 55.0 (p < 0.001).
Conclusion
We report significant improvement with fremanezumab as a 7th prophylactic treatment in the real-life setting.
P0464
A. Berdnikova1, N. Latysheva2, E. Filatova2, M. Naprienko2, N. Kadymova3
1Federal State Budgetary Educational Institution of Higher Education «A.I. Evdokimov Moscow State University of Medicine and Dent, Neurology, Moscow, Russian Federation
2I.M. Sechenov First Moscow State Medical University, Neurology, Moscow, Russian Federation
3Alexander Vein Headache Clinic, Moscow, Russian Federation
Objective
The effect of CGRP monoclonal antibodies (MAT) may be based on the reduction of peripheral sensitization. The aim of this study is to evaluate the effect of MATon central sensitization (CS) in migraine.
Methods
We recruited 19 patients with episodic (n = 6) and chronic migraine (n = 13) who received 3 monthly injections of erenumab70 mg. All patients filled in the Central Sensitization Inventory (CSI), GAD-7 anxiety questionnaire, Beck Depression Inventory (BDI), and the HIT-6 disability questionnaire. Pressure pain thresholds were measured monthly at 3 sites bilaterally with the Pain Test algometer (Wagner Instruments, USA), temporal summation of pain (wind-up) – with the Neuropen (Owen Mumford, UK). Concomitant treatment of migraine (if any) remained unchanged throughout the study.
Results
Monthly headache days (MHD) decreased significantly from 20.4 ± 9.2 to 12.0 ± 8.6 (p = 0.001), headache intensity was also reduced (p = 0.0001) after 3 months of treatment. 53% of patients reached at least a 50% decrease in MHD. The level of depression but not anxiety decreased significantly (p = 0.004 and p = 0.27, correspondingly). The HIT-6 disability level improved dramatically (p = 0.0001). We observed a significant decrease in the CSI score (p = 0.04) and an increase in the pressure pain score (p = 0.004).
This is the first study measuring the CSlevel during MAT treatment. The effect of erenumab on headache frequency and intensitymay be mediated by its ability to reduce the severity of CS.
P0465
A. Alpuente12, M. Torres-Ferrus1, E. Caronna2, E. Gine-Cipres3, V. Gallardo Ló pez2, P. Pozo-Rosich12
1Vall d’Hebron University Hospital, Headache Unit, Neurology Department, Barcelona, Spain
2Autonomous University of Barcelona, Medicine Department, Barcelona, Spain
3Vall d’Hebron University Hospital, Neurology Department, Headache Unit, Barcelona, Spain
Objectives
To analyze which patient-related outcome scale (PROs) is better correlated with an improvement in treatment response measures after 3-months.
Methods
Prospective study including migraine patients candidates for CGRP-mAbs. They completed an eDiary as well as PROs at baseline and after 3-months: MIDAS, HIT-6, MSQ and PGIC. Treatment response measures were reduction in monthly migraine days (MMD), monthly headache days (MHD), pain intensity (INT, from 0 to 3) and days of acute medication intake (AMD). We analyzed the correlation between PROs improvement and treatment response measures through the Spearman correlation coefficient (rs).
Results
263 patients completed 3-months. All treatment response measures as well as PRO scores were significantly reduced. Only the improvement of the total score from MSQ reflected the improvement in all the treatment response measures: MHD (rs = 0.243; p < 0.0001); MMD (rs = 0.321; p < 0.0001); INT (rs = 0.285; p < 0.0001) and AMD(rs = 0.172; p = 0.004). The role function-restrictive (RFR) of the MSQ was the only domain with statistically significant correlation with all the treatment response measures.
Conclusions
MSQ (RFR) is the PRO significantly correlated with an improvement in all the treatment response measures after 3-months of CGRP-mAbs. It gives clues on which PROs better reflects a global improvement, which scale to use when evaluating treatment response and, probably, which domain of migraine-burden CGRP-mAbs have higher impact.
P0466
A. Alpuente12, M. Torres-Ferrus1, E. Caronna2, E. Gine-Cipres3, V. Gallardo Ló pez2, P. Pozo-Rosich12
1Vall d’Hebron University Hospital, Headache Unit, Neurology Department, Barcelona, Spain
2Autonomous University of Barcelona, Medicine Department, Barcelona, Spain
3Vall d’Hebron University Hospital, Neurology Department, Headache Unit, Barcelona, Spain
Objectives
To analyze which patient-related outcome scale (PROs) more accurately determines the continuation of CGRP-mAbs after 3-months.
Methods
Prospective study including patients candidates for CGRP-mAbs. They continuously completed an eDiary as well as different PROs at baseline and after 3- months of treatment: MIDAS, HIT-6, MSQ and PGIC. A stepwise logistic regression was used in order to identify which PROs were independently associated with treatment continuation at 3-months. A ROC analysis was performed in order to identify the most clinically valid cut-off point for the relative change (%Δ) of the independent PROs identified in relation to the continuation of treatment.
Results
263 patients completed 3-months and 83.3% (219/263) further continued treatment. %Δ in total MSQ (MSQT) (OR[95%]: 7.676[1.821–36.140]; p = 0.047) and PGIC were the only scales being statistically significant independent factors associated with treatment continuation. The ROC analysis for the MSQT %Δ in relation to the continuation of treatment showed an AUC of 0.725 (95% CI, 0.640–0.809; p = 0.003), suggesting that a mean reduction of −11.7% in MSQT significantly predicted treatment continuation.
Conclusions
A change in the MSQ score and PGIC scale is the most accurate way of determining the continuation of CGRP-mAbs treatment at 3-months. This finding focuses on which scale is better to manage treatment and help us decide on whether to continue treatment or not.
P0467
M. Torres-Ferrus12, A. Alpuente12, E. Gine-Cipres12, E. Caronna12, V. Gallardo Ló pez2, P. Pozo-Rosich12
1Vall d’Hebron University Hospital, Neurology, Barcelona, Spain
2Vall d’Hebron Research Institute, Headache Research Group, Barcelona, Spain
Objective
To describe patterns of start and consistency of the response to anti-CGRP MAb after 3 and 6 months of treatment.
Methods
We included consecutive resistant migraine patients treated with erenumab/galcanezumab. Demographic, clinical and migraine variables were collected at baseline and after 3 (M3) and 6 (M6) months of treatment. The response was categorized according to ≥50% or <50% reduction in headache days/month (HDM) and migraine days/month (MDM). We defined 4 response patterns: Maintained-Response with ≥50% reduction at M3 and M6; Short-Response with M3≥50% and M6 < 50% reductions, Late-Response with M3 < 50% and M6≥50% reductions or Partial-Response with M3 and M6 < 50% reductions. The baseline characteristics associated with response patterns were analyzed.
Results
222 patients started treatment (44 stopped treatment at M3). 178 patients were included (68.5% erenumab, 31.5% galcanezumab). Baseline frequency was 21.7 ± 6.6 HDM and 16.2 ± 6.7 MDM. The distribution according to response (DCM/DMM) was: Mantained-Response 36.0/48.9%; Short-Response 10.7/12.9%; Late-Response 16.3/12.4% and Partial-Response 37.1/25.8%. Short-response patients have less medication overuse (p < 0.05). No other significant baseline clinical differences were found including diagnosis or the anti-CGRP MAb used.
Conclusions
One fourth of patients do not have a consistent response to anti-CGRP MAb treatment at 3 and 6 months. Baseline characteristics do not predict the pattern of response.
P0468
M. D. Villar-Martínez1, D. Moreno-Ajona1, J. Hoffmann1, N. Vandenbussche2, P. J. Goadsby13
1King’s College, London, United Kingdom
2Ghent University Hospital, Neurology, Ghent, Belgium
3University of California, Neurology, Los Angeles, CA, United States
Phenotyping of primary headache disorders is an inexpensive tool, essential to diagnosis. Our aim was to identify any potential factors in clinical history that could serve as a predictor of efficacy to treatment with erenumab. Data were prospectively collected from headache patients seen at King's College Hospital. Two authors independently reviewed patients” letters and classified them into 3 phenotype groups: pure chronic migraine and new daily persistent headache fulfilling ICHD-3 criteria, and chronic migraine-plus for those fulfilling the chronic migraine criteria that shared features with other headaches. Differences in headache days were transformed into a 57-limited-outcome-scale. Modelling was performed using negative binomial distribution with multiple imputation. The pure phenotype had lower total and severe headache days (21 ± 8 vs 28 ± 3, and 21 ± 7 vs 25 ± 10, respectively) and was predictive for reduction in total headache days, B = 0.314 (0.194, 0.434, P < 0.001) treated with erenumab. Longer treatment and shorter disease duration were predictors of reduction in severe headache days, B = −0.019 (−0-030, −0.007, P = 0.001) and B = 0.014 (0.003, 0.023, P = 0.016), respectively. Reduction in headache and migraine days may be more prominent in patients with a more typical migraine phenotype. Patients with complex migraine phenotypes and new daily persistent headache may still benefit from a reduction in severe headache days, which may also be related to the duration of the treatment.
P0469
P. Ruedi1, J. Arribas1
1Instituto Chileno de Neurología, Santiago, Chile
Objective
To provide the best treatment in migraine prevention we carried out a descriptive study in patients with migraine history, evaluating the response to preventive treatment with the first monoclonal antibody arrived in Chile, Erenumab, that targets CGRP receptor and has evidence of effectiveness in double blind controlled studies. Our purpose is describe the patients response and compare it with international experience in migraine treatment.
Methods
We considered patients older than 18 years having episodic or chronic migraine with or without aura and history of prior preventive treatment failure. The headache had to be disabling due to frequency or intensity. During the monthly 70mg Erenumab use, previous indicated prophylactic treatment was not suspended until there was no significant change in the pain course. For the effectiveness analysis we considered two objectives: the decrease in monthly migraine days (MMD) and the percentage of patients who achieved a reduction ≥50% from their MMD. For both, the comparisson was between the MMD recorded the month prior to Erenumab start and the month after the third dose.
Results
From 51 patients, 36 were considered on final analysis. The average decrease of MMD was 13.3 days and 75% of the patients achieved a reduction ≥50% on their initial MMD.
Conclusion
Even though methodological limitations, our study supports the evidence for Erenumab use as an effective migraine prevention drug, being a hope for many patients.
P0470
A. R. Gonçalo Pinheiro1, Â. Abreu1, E. Parreira1
1Hospital Prof. Dr. Fernando Fonseca, Neurology, Lisbon, Portugal
Introduction
CGRP is a neuropeptide with a pivotal role in the pathophysiology of migraine and may also play a role in the modulation of platelet function in humans. The experience arising from the increased real-world usage of anti-CGRP therapies leads to the description of possible new adverse effects. Recently there was a report of extensive ecchymoses in a Danish patient taking erenumab and fish oil supplements. We also describe a case of recurrent ecchymoses during erenumab treatment.
Conclusion
Since CGRP inhibits platelet aggregation, its antagonism, through the action of calcitonin gene-related peptide receptor antibodies, can work as a transient modulator of platelet function, which may increase the risk of subcutaneous hemorrhage.
P0471
S. D. Silberstein1, J. M. Cohen2, M. Driessen3, B. Muresan3, L. J. Krasenbaum2, A. Johnston4, M. J. Seminerio5, K. Carr5, H. Akçiçek3, J. Dever4
1Thomas Jefferson University, Jefferson Headache Center, Philadelphia, PA, United States
2Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, United States
3Teva Pharmaceuticals, Amsterdam, Netherlands
4Medical Decision Modeling, Indianapolis, IN, United States
5Teva Pharmaceuticals USA, Inc., Parsippany, NJ, United States
Objective
To assess relative efficacy for fremanezumab (225mg monthly [MLY]; 675mg quarterly [QLY]), atogepant (10/30/60mg daily [QD] or 30/60mg twice daily [BID]), and rimegepant (75mg every other day [QOD]) for prevention of episodic migraine (EM).
Methods
A targeted literature review (excluding studies only in patients with prior preventive failure) was conducted. A fixed-effect Bayesian network meta-analysis (NMA) indirectly compared ≥50% reduction in monthly migraine days (MMD) and mean change from baseline (CFB) in MMD at a 12-week follow-up. Relative efficacy was assessed with pairwise odds ratios (OR) and CFB differences with 95% credible intervals (CrIs).
Results
Six studies were included. Fremanezumab MTY showed a significantly higher ≥50% reduction in MMD vs rimegepant (OR, 2.14 [CrI, 1.38, 3.31]), significantly higher CFB reductions vs rimegepant and atogepant QD, and numerically higher CFB reductions vs atogepant BID (
Conclusions
Both fremanezumab doses showed better efficacy on both outcomes vs rimegepant. Fremanezumab MTY also showed significantly higher reductions in MMD vs all atogepant QD doses; fremanezumab QLY showed significantly higher reductions in MMD vs atogepant 10/30mg QD doses.
P0472
A. R. Gonçalo Pinheiro1, Â. Abreu1, E. Parreira1
1Hospital Prof. Dr. Fernando Fonseca, Neurology, Lisbon, Portugal
Objective
Evaluate the course of migraine after discontinuing erenumab treatment in the group of responders.
Methods
From a prospective study of 28 months of follow-up of erenumab treated patients in our hospital, we performed a sub-analysis of the group of responders. We recorded frequency and severity of attacks, analgesic intake and several patient reported outcome measures.
Results
From a total of 35 migraine patients treated with erenumab, 9 patients, that had stopped due to sustained response, were included. They had an average age of 50,2 years. Prior to erenumab treatment, 33% had chronic migraine. The median duration of treatment was 11 months ranging from 6 to 12 months. Erenumab had led to a reduction in migraine frequency of more than 50% in all of them. After discontinuing treatment, 6 patients (67%) had a progressive increase in headache frequency with 4 even reporting a possible rebound effect. 3 and 5 months after erenumab discontinuation we recorded a median increase in attack frequency of 5 and 11-days per month, respectively. In 5 patients, erenumab had to be restarted. In all 5, the second course of treatment led to a quick improvement. This positive response persisted at 6-month follow-up.
Conclusion
We highlight that in this group, suspension of erenumab led not only to a progressive worsening of migraine but also to a possible rebound effect. This might indicate that in this group, anti-CGRP therapy didn't exhibit a disease-modifying effect.
P0473
F. Golshan1, M. Mikleborough1
1University of Saskatchewan, Psychology, Saskatoon, Canada
Background and Objective
Migraine is a prevalent primary headache disorder with incapacitating neurological characteristics. With respect to the disability and adversity caused by migraine by and large, there is a need for examining noninvasive treatments that can have efficacy on migraine management in the long run. Meditation is a well-recognized umbrella term including different mental training techniques which are shown to be efficient in helping individuals cultivate their core psychological capacities, such as attention and affective self-regulation, and improve resilience towards their physical pain. Based on the dichotomy of meditation into Open Monitoring and Focused Attention subgroups in the neuroscience approach, this presentation will specifically review and suggest how bottom-up and top-down modulation of migraine pain can be facilitated via the two groups of meditation. Subsequently, Open Monitoring and Focused Attention techniques are compared with regards to their attentional and affective control before and during a migraine attack. Further suggestions are made for a migraine symptom checklist in order to optimize the efficacy of the selected meditation practice.
P0474
R. Boinpally1, D. McGeeney1, L. Borbridge2, M. Butler1, L. Severt1
1AbbVie, Madison, NJ, United States
2AbbVie, Irvine, CA, United States
Objective
To evaluate the potential for pharmacokinetic (PK) drug-drug interactions between atogepant and topiramate.
Methods
Phase 1, single-center, open-label, multiple-dose study. Healthy adults (18–45 y) were randomized to cohort 1 to evaluate the effect of topiramate (mild CYP3A4 inducer) 100mg twice daily on the PK of atogepant (CYP3A4 substrate) 60mg once daily, or cohort 2 to evaluate the effect of atogepant 60mg once daily on the PK of topiramate 100mg twice daily. Blood samples were collected to evaluate the potential for PK drug-drug interactions. Safety was monitored throughout the study.
Results
A total of 28 and 25 participants were enrolled in cohorts 1 and 2, respectively. For atogepant, overall systemic exposure (AUC0-tau) and maximum plasma concentration (Cmax) were reduced by 25% and 24%, respectively, with topiramate coadministration. Atogepant median Tmax was the same when administered alone or with topiramate (2h). For topiramate, AUC0-tau and Cmax were reduced by 5% and 6%, respectively, with atogepant coadministration. Topiramate median Tmax was delayed by 0.5h when coadministered with atogepant. Administration of atogepant and topiramate, alone and in combination, was safe and well tolerated.
Conclusion
Atogepant AUC0-tau and Cmax decreased by 25% and 24% when coadministered with topiramate. Given the wide effective dose range for atogepant, these changes are not expected to be clinically significant and no dose adjustments are needed.
P0475
U. Reuter12, P. J. Goadsby34, M. Ferrari5, G. Paiva da Silva Lima6, S. Mondal7, S. Wen8, T. Stites8, M. Arkuszewski9, M. Lanter-Minet1011, S. Pandhi9
1Charité University Hospital Berlin, Neurology, Berlin, Germany
2Universitätsmedizin Greifswald, Greifswald, Germany
3King’s College, NIHR-Wellcome Trust, London, United Kingdom
4University of California, Neurology, Los Angeles, CA, United States
5Leiden University Medical Center, Neurology, Leiden, Netherlands
6Amgen Inc., Thousand Oaks, CA, United States
7Novartis Healthcare Pvt. Ltd., Hyderabad, India
8Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
9Novartis Pharma AG, Basel, Switzerland
10Université Côte d’Azur, Pain Department and FHU InovPain, Nice, France
11Auvergne University, INSERM U1107 Migraine and Trigeminal Pain, Clermont-Ferrand, France
Objective
Efficacy of erenumab 140mg has been demonstrated in the 12-week double-blind treatment phase (DBTP) of the LIBERTY study. Efficacy and safety of erenumab at completion of the 3-year open-label extension phase (OLEP) are reported.
Methods
Patients completing the DBTP (N = 240) continued into OLEP, receiving monthly erenumab 140mg for ≤3 years. Outcomes measured at Week 168 were ≥50% and ≥75% reduction in monthly migraine days (MMD); change from baseline (BL) in MMD, Headache Impact Test (HIT-6™) total score, Migraine Physical Function Impact Diary (MPFID), Everyday Activities (EA), Physical Impairment (PI) and safety.
Results
Of 240/246 (97.6%) patients entering OLEP (118 continuing erenumab, 122 switching from placebo), 169 (70.4%) completed 3-year OLEP. Discontinuations were mainly due to lack of efficacy (12.5%, n = 30), patient decision (10.8%, n = 26) and adverse events (AEs; 4.6%; n = 11, single case per AE). The ≥50% and ≥75% responder rate at 3-year completion was 52.3% and 33.1% (Table). Mean (SD) change from BL at 3-year completion was −4.4 (3.9) in MMD. Mean (SD) change from BL at 3-year completion was –9.7 (8.9), –6.1 (8.2) and –5.1 (7.6) for HIT-6, MPFID-EA and -PI scores. Common AEs ( > 10%) were nasopharyngitis, influenza and back pain.
Conclusions
Efficacy was sustained over 3 years in patients with difficult-to-treat EM who failed 2–4 prior migraine preventives. Erenumab was well-tolerated, with no new safety signals reported after long-term exposure.
P0476
M. Ashina1, U. Reuter23, D. W. Dodick4, F. Zhang5, S. Ritter6, T. Stites6, G. Paiva da Silva Lima5, M. Arkuszewski7, P. J. Goadsby89
1Rigshospitalet-Glostrup, Department of Neurology, Danish Headache Center, Faculty of Health and Medical Sciences, Glostrup, Denmark
2Charité University Hospital Berlin, Department of Neurology, Berlin, Germany
3Universitätsmedizin Greifswald, Greifswald, Germany
4Mayo Clinic, Department of Neurology, Scottsdale, AZ, United States
5Amgen Inc., Thousand Oaks, CA, United States
6Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
7Novartis Pharma AG, Basel, Switzerland
8King’s College, NIHR-Wellcome Trust, King’s Clinical Research Facility, London, United Kingdom
9University of California, Department of Neurology, Los Angeles, CA, United States
Background and objective
To assess the long-term safety of erenumab using pooled data from the double-blind treatment phases (DBTP) and open-label extension phases (OLEP) of two clinical trials in episodic migraine (NCT03096834, NCT01952574).
Methods
The incidence of adverse events (AEs) were summarized as exposure-adjusted patient incidence rates per 100 patient-years (r). Anti-erenumab antibodies were detected using a validated bridging electrochemiluminescence immunoassay.
Results
Of 729 patients randomized across both studies, 502 received erenumab (70 or 140 mg) or placebo in the 12-week DBTP and 623 received erenumab (70 or 140 mg) in the 3- or 5-year OLEP. The cumulative duration of exposure to erenumab during the DBTP and OLEP was 54.3 and 1899.5 patient-years, respectively. Overall exposure-adjusted AE incidence rates were similar in the DBTP and OLEP; no new AEs emerged over time (
Conclusions
Erenumab demonstrated a consistent favorable safety and tolerability profile with long-term exposure.
P0477
M. Empl1, S. Löser2, P. Spille2, A. Rozwadowska3, R. Ruscheweyh4, A. Straube4
1Practice, Ludwig-Maximilians-University, Department of Neurology, Munich, Germany
2Introvision e.V., Hamburg, Germany
3kbo Klinikum, Neurology, Haar, Germany
4Ludwig-Maximilians-University, Neurology, Munich, Germany
Objective
Migraine is a brain disorder with recurrent headache attacks and altered sensory processing. We examined the effect of introvision, a self-regulation method based on a mindfulness-like perception technique developed at the university Hamburg in migraine prevention.
P0478
G. Kennedy1
1Sunderland Royal Hospital, Neurology, Newcastle, United Kingdom
Background and objective
Chronic migraine is underdiagnosed and not all patients suitable for NICE-approved therapies are identified. Headache diaries help clarify the headache diagnosis, identify eligible patients for NICE-approved treatments and recognise medication overuse. A headache diary app is likely to improve compliance with diary completion and provide a platform to monitor patients remotely which has become a requirement during the COVID pandemic restrictions and the introduction of home-based CGRP antibody treatments. This study assesses patient and clinician feedback to assess the feasibility of using the HEIDI app to support headache service s.
Methods
Fifty patients receiving botulinum toxin treatment for chronic migraine were enrolled to use the HEIDI app. Patient reported outcomes on accessibility, speed, accuracy, usefulness and user satisfaction at 3 and 6 months.
Results
The vast majority of patient users preferred the HEIDI app to paper diaries. The HEIDI app was associated with improved diary accessibility, data accuracy and patient satisfaction.
Conclusions
The HEIDI app is a superior method to paper diaries in monitoring chronic headache conditions. It offers the unique function of remote patient monitoring which can lead to reduced inappropriate appointments and more efficient patient assessments which can be performed remotely. It is an appropriate up-to-date digital tool that can support headache services.
P0479
N. A. A. Ain1, W. A. W. Sulaiman1
1Universiti Putra Malaysia, Department of Medicine, Faculty of Medicine and Health Sciences, Serdang, Malaysia
Migraine is a disabling primary headache disorders, which has an annual prevalence of 15%. Migraine is regarded as a polygenic disease and serotonergic pathways and calcitonin gene related peptide (CGRP) appear to play a major role in its pathogenesis. We had conducted a case control study to determine the association of serotonin and CGRP polymorphism gene with migraine among a multi-ethnic Malaysian population. The gene polymorphisms were analysed in 113 migraine patients and 163 control subjects. Serotonin and CGRP polymorphism were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study found that there were significant difference between serotonin and CGRP polymorphism among individuals with migraine as compared to the control (p < 0.005). Hence, the study support possibility of involvement of the serotonin and CGRP in migraine among multi-ethnic Asian population in Malaysia.
P0480
K. Gallop1, S. H. Lo1, K. Shepard1, L. Powell2, T. Smith3, L. Harris4, G. L’Italien4
1Acaster Lloyd Consulting Ltd., London, United Kingdom
2Broadstreet Health Economics & Outcomes Research, Vancouver, Canada
3StudyMetrix Research, Missouri, United States
4Biohaven Pharmaceuticals, Connecticut, CT, United States
Little is known about the interictal (between attack) burden of migraine. Despite many treatment options, patients are often not satisfied with treatment. This study explored the impact of migraines on patients” quality of life (QoL), including the interictal burden, and patients” treatment satisfaction. Semi-structured interviews were conducted with migraine patients in the US, UK and Canada. Interviews explored migraine symptoms, QoL impact and treatment satisfaction. Qualitative data were analysed using thematic analysis. Participants (n = 35) had migraines on average 12 (SD: 8; range 1–30) days per month, reporting impacts of migraine attacks on daily life, work/study, emotional wellbeing, social/leisure activities and relationships. The interictal burden included lifestyle changes, being unable to plan, reducing/stopping work, avoiding migraine triggers and feeling anxious about migraines. Participants discussed their treatment experience and satisfaction, including efficacy, side effects, treatment administration and convenience. Most used both acute and preventative treatments and, when prompted, 30 were interested in exploring the use of a single medication for both purposes. Among participants with experience of injectable preventative treatment, some reported wearing off effects between injections and reduced efficacy over time. This study highlights the burden of migraines both during and between attacks and underlines the unmet treatment needs of migraine patients.
P0481
E. J. Choi1, C. A. Lim2, D. G. Lee2
1Gumi Hospital, Soonchunhyang University, Neurology, Gumi, South Korea
2University of British Columbia, Neurology, Vancouver, Canada
Objective
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal vascular growths leading to arteriovenous malformations (AVM) in various organs. Pulmonary AVM is a common presentation of HHT which can result into pulmonary arteriovenous fistula leading to neurologic complications such as chronic headache, brain abscess and meningitis. We report a case of silent pulmonary AVM leading to brain abscess in a previously undiagnosed HHT patient.
P0482
W. Horta1, M. Horta1
1University of Pernambuco, Department of Neurology, Recife, Brazil
The most prevalent hereditary cerebral angiopathy is the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, known worldwide as (CADASIL). It is a disease caused by a mutation in the NOTCH3 gene on chromosome 19.
P0483
J. Juhl Korsbaek1, D. Beier2, L. Dehghani Molander3, S. Malm Hagen4, R. H. Jensen1
1Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, Glostrup, Denmark
2Odense University Hospital, Department of Neurology, Odense, Denmark
3Odense University Hospital, Department of Ophthalmology, Odense, Denmark
4Rigshospitalet-Glostrup, Department of Ophthalmology, Glostrup, Denmark
Objective
To investigate the prevalence of psychiatric disease in patients with idiopathic intracranial hypertension (IIH).
Methods
This study is a prospective cohort study of 111 patients with new-onset IIH. A structured medical history was taken, and the prevalence of psychiatric disease was compared with the age and sex specific prevalence in the population. We compared IIH without psychiatric disease (IIH-P) and IIH with psychiatric disease (IIH+P) at baseline and 6 months for: BMI, visual fields (perimetric mean deviation), headache, employment and surgical intervention.
Results
In total, 45% of IIH patients had a psychiatric co-morbidity. Major depressive disorder (24.3% in IIH, 1.8–3.3% in the population) and emotionally unstable personality disorder (6.3% in IIH, 2.1% in the population) were highly prevalent compared to the general population. Visual fields were poorer in IIH+P at baseline (−8.6 vs. −6.0, p = 0.02) and 6 months (−5.5 vs. −4.0, p < 0.01). Medication related to weight gain was used by 28% of IIH+P (3.3% of IIH-P, p < 0.001).
Conclusion
Psychiatric co-morbidities, particularly major depressive disorder and emotionally unstable personality disorder, are highly prevalent in IIH. Patients with IIH+P have significantly worse visual fields at baseline and 6 months. We speculate that co-morbid psychiatric disease is related to underlying disease pathophysiology or exposure to medication. A reasonable approach is to include psychiatrists in IIH-teams.
P0484
B. S. Kim1
1Bundang Jesaeng General Hospital, Neurology, Seongnam, South Korea
Backgrounds
Despite the fact that most stabbing headaches are primary, stabbing headache could be occasionally a main manifestation of serious intracranial abnormalities.
Case
A 56-year old man visited our outpatient headache clinic due to newly developed stabbing headache in the right posterior head 4 days ago and following ipsilateral tinnitus and decreased hearing 2 days ago. Audiograms of the patient revealed sensorineural hearing loss of ≥30dB in the right audiogram, suggestive of sudden sensorineural hearing loss (SSNHL). Therefore, he undertook brain magnetic resonance imaging (MRI) to investigate intracranial pathology related to his SSNHL. Diffusion-weighted imaging showed multiple acute infarctions in the right posterior cerebral artery and superior cerebellar artery territories. In perfusion MRI, there was an extensive perfusion delay in the cerebellum and mid to lower brainstem. Magnetic resonance angiography and conventional angiography showed tapered thrombotic occlusion between right V3 segment of the vertebral artery and mid-basilar artery. After anticoagulation therapy using intravenous heparin, there were no new symptoms, and his tinnitus and decreased hearing improved.
Conclusions
This is an uncommon case of secondary stabbing headache accompanying with ear symptoms due to acute intracranial VAD. We should be careful of such occasional presentation of secondary stabbing headaches in clinical practice.
P0485
L. Grazzi1, C. Bernstein2, E. Sansone1, A. Raggi1, E. Grignani1, M. Searl2, F. Andrasik3, P. Rizzoli2
1IRCCS Foundation “Carlo Besta” Neurological Institute, Neuroalgology, Milan, Italy
2Harvard Medical School, J Graham Headache Center, Brigham & Faulkner Hospital, Boston, MA, United States
3Memphis University, Psychology, Memphis, TN, United States
Patients with High Frequency Migraine without Aura (9/14 attacks per month) (HF-M/A) are particularly exposed to the risk of chronification and medication overuse. A multidisciplinary approach is suitable for these patients before than a chronic condition is induced. Recently, non-pharmacological approaches as Acceptance Commitment Therapy (ACT), showed efficacy in treatment of pain conditions and migraine, comparable to pharmacological prophylaxis at long-term, by promoting psychological flexibility and cultivating positive psychological capacities. Our aim was to assess the effectiveness of ACT model for HF-M/A. 35 patients were included and randomized for the study. Two treatment conditions: 1) TAU (Treatment as Usual): pharmacological prophylaxis (17 patients); 2) TAU + ACT (13 patients). ACT consisted of six 90-minutes weekly sessions, and 2 booster sessions, every 15 days; small groups of patients (7–10 patients each). Sessions included: psycho-education, mindfulness, experiential exercises, home assignments. At 12 months follow-up, results showed a decrease in days of headache/month in both groups; a decrease of medications intake/month in the ACT group, and a slight decrease in the TAU group. In conclusion, ACT seems beneficial for these patients. An integrated and flexible treatment program combining different approaches may be more effective than drugs alone to alleviate pain and reinforce clinical improvement.
P0486
S. Singhvi1, P. Singh1
1Smt. NHLMMC and SVP Hospital, Ahmedabad, India
P0487
A. Shahid1, M. Abbasi1, J. Arturo Larco1, Y. Liu1, S. Madhani1, C. Robertson2, L. Savastano1, C. C. Chiang2
1Mayo Clinic, Neurosurgery, Rochester, MN, United States
2Mayo Clinic, Neurology, Rochester, MN, United States
Background
Occipital nerve stimulation (ONS) and occipital surgical decompression (OSD) have been reported to be effective for medically refractory migraine. We conducted a systematic review and meta-analysis to analyze the efficacy and safety of ONS and OSD for the treatment of migraine.
Methods
We searched PubMed, Scopus, and Ovid Medline from 1990-January 2021 using keywords: occipital nerve surgery, occipital nerve stimulation, and migraine. Studies were included if mean change in headache frequency, intensity, and complication rate were reported. Studies were excluded if indications were not migraine and no interventions in the occipital region.
Results
11 studies (306 patients) on ONS and 6 studies (531 patients) on OSD reporting the change in headache frequency and intensity were included in the meta-analysis. There was no significant difference in mean decrease in headache frequency and headache intensity between ONS and OSD [frequency: 7.06 (CI 95%; 5.08–9.05) vs 8.31 (CI 95%; 1.13–15.50), p = 0.74; intensity 3.20 (CI 95% 2.25–4.15) vs 4.73 (CI 95% 3.27–6.18), p = 0.08]. Complication rate was 33.6% (CI 95% 21.7%–47.9%) in ONS and 7.6% (CI 95% 1.3%–33.7%) in OSD, p = 0.06).
Conclusion
We did not find a significant difference between the efficacy and safety of ONS and OSD for migraines. More data is needed to establish their role in refractory migraine. Standardized endpoints should be utilized for future studies, especially surgical intervention for migraine.
P0488
E. Melhado1, S. Ozima Filho1, T. Eschiapati1, A. Gonçalves1, A. de Matos1, J. Picolo1, J. Abdo1, J. Christofoletti1, P. Craice1
1Unifipa, Neurology, Catanduva, Brazil
Background
Headache is a common symptom during the menstrual cycle. The primary trigger of Menstrually Related Migraine (MRM) seems to be the modifications in the estrogen levels. The present study seeks to associate headache with the menstrual cycle, specifically with Premenstrual Syndrome (PMS), relating its causes and aggravating factors.
P0489
S. Dubey1, Y. Sailaja1, V. Ramakrishnan1, C. Mutharasu1
1MMCH & RI, Department of Neurology, Kanchipuram, India
Background and objective
Any young non hypertensive woman with risk of hypercoagulability presenting as worst headache of life and hemiparesis, despite the possibility of subarachnoid hemorrhage(SAH), MRI is the choice of neuroimaging to rule out cerebral venous thrombosis (CVT).
Methods
A 25 year old female presented with intolerable, disabling worst first headache of life, maximal at the onset since 2 days, 2 episodes of vomiting and associated with a staring look with impaired awareness for 5 min, followed by weakness of right upper and lower limbs, clinically suspected as an aneurysmal SAH. She was on hormonal therapy for polycystic ovary syndrome(PCOS) for few months.
Results
On neurological examination, there was right UMN facial palsy, 4/5 power in the right limbs. In view of the worst headache (SAH) and also to rule out any possibility of complications of hypercoagulable state, we opted MRI. MRI brain showed T2 FLAIR hyperintense foci in the sulcal spaces in both hemispheres. MR Venography showed no flow signals in the superior sagittal and transverse sinuses suggestive of cerebral venous thrombosis with subarachnoid hemorrhage.
Conclusions
In a non hypertensive and non traumatic case with risk of hypercoagulability presenting with first worst headache suspicious as SAH, we should maintain a high index of suspicion to rule out combination of other causes of life threatening headache like CVT. In these difficult circumstances, MRI is the choice of neuroimaging.
P0490
M. Mammadova1, S. Mirzayev2
1Scientific Research Institute of Medical Rehabilitation, Clinical-neurophysiological laboratory, Baku, Azerbaijan
2MediClub Clinic, Emergency, Baku, Azerbaijan
Background and objective
The lack of unified protocols for a headache diary creates a problem for the clinician to choose the right diary, to process data for maintaining the headache register. The purpose of our research was to develop and implement a headache diary for Azerbaijani patients in their native language.
Methods
For patients (n = 30) with various forms of chronic headache, we used the headache diary developed by us in the Azerbaijani language in the form of a printed brochure. Patients noted diary items throughout the month. All signs were encoded with the abbreviation of a symptom or condition.
Results
Among the 33% of patients who did not complete the diary, the reasons for noncompliance were a misunderstanding of filling items, failure to follow instructions (30%), late observation, and then forgetting symptoms (24%); the inconvenience of a printed brochure to fill out at work (46%). The identification of headache triggers in patients after using the diary was considered a positive result (15%).
P0491
A. M. Logan1, R. Hallett2, M. Edwards1, N. Greenwood3
1St George’s University of London, London, United Kingdom
2The Open University, Milton Keynes, United Kingdom
3Faculty of Health, Social Care and Education, St George’s University of London and Kingston University, London, United Kingdom
Objective
Self-management interventions for migraine are known to reduce pain and disability compared with usual care but there is a lack of understanding about the components of those interventions.
This systematic review aimed to identify the active components of face to face migraine group self-management interventions, describing the underlying theory, design and Behaviour Change Techniques.
Methods
Five electronic databases were searched in January 2020 following PRISMA guidelines. Randomised controlled trials in English, of adult participants were included. Data were extracted using the Behaviour Change Taxonomy v1 for behaviour change techniques, Painter Criteria for theoretical content and recording intervention duration, timing, settings and outcomes.
Results
Three studies were included; one with high risk of bias, two studies with some concern. The studies were atheoretical, with heterogeneous outcomes and more than twelve years old. The results showed key behaviour change techniques used; Instruction on how to perform a behaviour, Credible Source. Two studies reported significant reductions in headache frequency and disability but trial design limited conclusions.
Conclusions
The review suggests self-management may be beneficial but there is a need for theoretically informed studies, identifying the active components of group self-management interventions for migraine.
P0492
K. Satpute1, K. Parekh1, T. Hall2
1Smt. Kashibai Navale College of Physiotherapy, Musculoskeletal Physiotherapy, Pune, India
2Curtin University, Perth, Australia
Objectives
The C0–C2 axial rotation test (ART) is a measure of upper cervical rotation range of motion (ROM), reported to be reliable in a headache free population. The objective of this study was to determine intra- and inter-rater reliability of the C0–C2 ART and report normal values in people with a diagnosis of cervicogenic headache (CGH) or episodic migraine.
Methods
Two therapists independently evaluated rotation during the C0–C2 ART and flexion- rotation test (FRT) in 70 subjects (mean age 37.7 SD 11.6 years) with a diagnosis of CGH (35 subjects) or episodic migraine (35 subjects). An electrogoniometer was used to evaluate ROM. The FRT was assessed in supine with maximal neck flexion. Rotation ROM was assessed to each side. The C0–C2 ART was performed in sitting, neck in neutral, and rotation ROM assessed to each side with C2 vertebra stabilized.
Results
Reliability of the C0–C2 ART was moderate to high (ICC > 0.70). The standard error of measurement and minimum detectable change for this test were at most 2°. In subjects with CGH mean ROM to the most restricted side was 9.3° (1.9) and 8.8° (2.1) for rater 1 and 2 respectively. In subjects with episodic migraine, mean ROM to the restricted side was 13.7° (1.6) and 13.6° (2.0) for rater 1 and 2 respectively.
Conclusion
The C0–C2 ART has at least moderate levels of reliability and correlates well with mobility determined by the FRT indicating the possibility of using this test when the FRT is not available.
P0493
K. Satpute1, N. Bedekar2, T. Hall3
1Smt. Kashibai Navale College of Physiotherapy, Musculoskeletal Physiotherapy, Pune, India
2Sancheti College of Physiotherapy, Pune, India
3Curtin University, Perth, Australia
Objective
To identify cervical neuromusculoskeletal impairments those distinguish people with cervicogenic headache (CGH) from asymptomatic controls.
Methods
Eight databases were searched for studies which assessed subjects with CGH. Risk-of-bias and quality of evidence were assessed. Meta-analyses were performed for outcome measures of cervical neuro-musculoskeletal impairments using Review Manager 5.3.
Results
16 studies out of 20 were rated as low risk of bias. In comparison with headache free controls the subjects with CGH presented with reduced combined cervical flexion-extension range of motion (ROM) (MD: −17.17, 95% CI: −19.16, −15.13, I2 = 87%), side flexion ROM (MD: −10.38, 95% CI: −11.92, −8.84, I2 = 92%), and rotation ROM (MD: −14.91, 95% CI: −16.84, −12.98, I2 = 96%), and upper cervical rotation ROM determined by the flexion-rotation test (MD: −14.98, 95% CI: −16.47, −13.48, I2 = 30%). Similarly cervical flexor (MD: −33.70, 95% CI: −47.03, −20.37, I2 = 0%) and extensor strength (MD: −60.23, 95% CI: −81.78, −38.68, I2 = 0%) was reduced in subjects with CGH. In contrast, no difference was found in posture and kinaesthetic sense between symptomatic and asymptomatic people.
Conclusion
There is moderate to very low levels of evidence that subjects with CGH have restricted cervical ROM and reduced cervical flexor and extensor strength, endurance, and motor control, but lack postural abnormalities or loss of kinaesthetic sense.
P0494
L. Apostolakopoulou1, A. Tountopoulou1, S. Vassilopoulou1, G. Velonakis2, D. Mitsikostas1
1Eginition Hospital, First Department of Neurology, Athens, Greece
2National and Kapodistrian University of Athens, Second Department of Radiology, Athens, Greece
Objective
MI is a rare migraine complication. As ISRM we characterize the ischemic stroke that does not fulfill the strict MI criteria but is temporally related to a migraine attack. The objective is clinical and imaging correlation of a patient series with MI and ISRM aiming to expand current knowledge.
Methods
We describe seven patients with a history of migraine with aura, who exhibited a migraine attack with neuroimaging demonstrating ischemic infarction in a relevant area, while diagnosis was not better attributed to another ICHD-3 diagnosis. Medical history was obtained and clinical examination, complete stroke work up and magnetic resonance imaging were performed.
Results
The patients' median age was 41 years and 71,4% were women, while 28,6% smoked and had patent foramen ovale. Aura types were visual in 28,6%, sensory and dysphasic in 57,1% and basilar in 14,3%. Ischemic lesions were located on one vascular territory, 71,4% posteriorly, 28,6% anteriorly, 57,1% being isolated, 42,9% multiple. Clinically, all patients exhibited mild neurological deficit and there was a consecutive reduction of migraine attack frequency and severity.
Conclusion
Current theories separate the mechanisms generating migraine related ischemia from thrombotic generated classic ischemia. This study does not provide data favoring one particular theory, but studying more cases of MI and ISRM will elucidate the pathophysiological basis and determine risk factors, prognosis and treatment.
P0495
A. Malik1
1LCMD, Medicine, Karachi, Pakistan
P0496
T. Eidlitz-Markus1, Y. Levinsky1
1Schneider Children’s Medical Center, Headache clinci day hospitaliztion, Petach Tikva, Israel
Background
Adult abrupt severe non-traumatic headache (thunderclap) is often related to serious underlying etiologies such as subarachnoid hemorrhage. However, data are sparse regarding thunderclap headache in the pediatric population.
Objective
The aim of the study was to evaluate the prevalence, characteristics and causes of thunderclap headache in the pediatric and adolescent population, aged 6–18 years, presenting to a pediatric emergency department.
Methods
The electronic database of a tertiary care pediatric emergency department was searched for children presenting with acute headache during 2016–2018. Headache severity was defined by pain scales, either a visual analogue scale or by the Faces Pain Scale–Revised.
Results
Thunderclap headache was diagnosed in 19/2290 (0.8%) of the included patients, all of them with a pain score of 10/10. All the patients had a benign course. Primary headache was diagnosed in 15/19 (78.9%), Six patients had migraine and eight were diagnosed with primary thunderclap headache. Four of the 19 patients were diagnosed with secondary headache: three with infectious causes and one with malignant hypertension.
Conclusions
Thunderclap headache is rare among children and adolescents presenting to the emergency department. This headache is generally of a primary origin Extensive evaluation is still needed to rule out severe diagnosis problem.
P0497
M. D. Villar-Martínez1, P. J. Goadsby12
1King’s College, London, United Kingdom
2University of California, Neurology, Los Angeles, CA, United States
Headache frequency reduction is key aim any preventive treatment. Finding an appropriate statistical model to analyse the difference in monthly headache or migraine days as a marker of treatment response can be challenging due to the presence of non-positive integers, which cannot be easily handled by certain models. Our aim was to provide a simple approach to quantifying headache days for statistical analysis. Headache days are natural numbers by definition. When calculating treatment effects in a preventive study some subjects may have no effect, i.e. treatment difference zero, while others may worsen, i.e. negative treatment difference. Given headache days provides a discrete rather than continuous variable, the choice of a distribution is thus constrained. A transformation was considered that preserved the underlying metric and facilitated a suitable discrete distribution, such as the negative binomial distribution. Headache days over four weeks were transformed to a scale of 57 by adding 29 to the original number of days. These outcomes would start at number 1 (−28 days + 29) to number 57 (+28 days + 29). The value 0 would also be included as number 29 (0 days +29). Change over the treatment period is thus always a natural number. By transforming the number of days into natural numbers we eliminated non-positive integers without altering the metric in terms in outcome.
P0498
Y. Woldeamanuel1, R. Cowan1
1Stanford University School of Medicine, Stanford Headache and Facial Pain Division, Stanford, CA, United States
Objective
To summarize and critically appraise all published studies involving computerized migraine diagnostic tools.
Methods
PubMed, Web of Science for [((computerized) AND diagnosis) AND migraine; ((automated) AND (migraine) AND diagnosis] was used to include articles in English that evaluated a computerized/automated migraine diagnostic tool. Development, sample size, sensitivity, specificity, reference diagnosis, quality of studies (QUADAS) were summarized.
Results
38 studies (median sample size = 461 participants; median age = 42 years; 76% female) were included. Most (60%) tools were developed based on ICHD criteria, half were self-administered, and 88% were evaluated in headache centers using reference face-to-face interview-diagnosis (82%). The machine learning programs involved case-based reasoning, deep learning, classifier ensemble, ant-colony, artificial immune, white and black box combinations, hybrid fuzzy expert systems. The median diagnostic accuracy was: concordance = 75% (range 4–100%), sensitivity = 85% (33–100%), specificity = 83% (28–100%). 94% studies lacked random patient sampling. All studies avoided case-control designs. Most (74%) reference tests exhibited low risk of bias. Patient flow and timing showed low risk of bias in 81%.
Conclusions
Different computerized-automated migraine diagnostic tools are available with high accuracies. Random patient sampling and head-to-head comparison may improve their utility.
P0499
R. Cowan1, A. Rapoport2, J. Blythe3, J. Rothrick4, K. Knievel5, A. Peretz1, E. Ekpo6, B. Sanjanwala1, Y. Woldeamanuel1
1Stanford University School of Medicine, Stanford Headache and Facial Pain Division, Stanford, CA, United States
2UCLA, Los Angeles, CA, United States
3Information Sciences Institute, Los Angeles, CA, United States
4George Washington University, Washington, DC, United States
5Barrow Neurological institute, Phoenix, AZ, United States
6UC Davis, Sacramento, CA, United States
Objective
To assess the concordance in migraine diagnosis between an online, self-administered, computer-based, digital diagnostic tool (DDT) and semi-structured interview (SSI) by a headache specialist, both using ICHD-3 criteria.
Methods
Participants completed two evaluations: phone interview conducted by headache specialists using the SSI and a web-based expert questionnaire, DDT. Participants were randomly assigned to one or the other protocol, with the second following one week after the first. The concordance in migraine/probable migraine (M/PM) diagnosis between SSI and DDT was measured using Cohen's kappa statistics. The diagnostic accuracy of DDT was assessed using the SSI as reference standard.
Results
212 participant completed both SSI and DDT [median age = 32 years, female:male = 3:1]. Concordance in M/PM diagnosis between SSI and DDT was: κ = 0.832. DDT diagnostic accuracy: sensitivity = 90.1%, specificity = 95.8%. Positive and negative predictive values = 96.7% and 86.6%, respectively, using identified migraine prevalence of 60%.
Conclusions
The SSI and DDT have excellent concordance in diagnosing M/PM. Positive DDT helps rule in M/PM, through high specificity and positive likelihood ratio. A negative DDT helps rule out M/PM through high sensitivity and low negative likelihood ratio. DDT that mimics SST logic is a reliable and scalable tool for migraine diagnosis
P0500
E. Semina1, M. Kurnukhina2, V. Cherebillo2
1First Pavlov State Medical University of St. Petersburg, General Medicine, St. Petersburg, Russian Federation
2First Pavlov State Medical University of St. Petersburg, Neurosurgery, St. Petersburg, Russian Federation
Purpose
Assessment of changes in the quality of life of patients with pituitary apoplexy pituitary adenoma after transsphenoidal endoscopic removal.
Materials and methods
Our study included 200 patients with pituitary adenoma. Pituitary apoplexy was found in 2% of operated patients with recurrent pituitary macroadenomas. The subjects were aged 18–64 years. We used scale VAS,EORTC QLQ-C30.
Results
All patients with pituitary apoplexy complained of a pronounced diffuse headache in the preoperative period. The pain syndrome changed from 9,2 ± 0,4 to 3 ± 1,2 in the postoperative period. The study revealed a correlation between the pain syndrome and the indicators of various scales of the EORTC QLQ-C30. Before surgery patients with more pronounced pain syndrome more often indicated a deterioration in physical, cognitive, social, emotional functioning and general health (p < 0,05). After surgery, the severity of headaches decreased in patients (before −82,1 ± 16,4; after −17,2 ± 8,1). After the removal of the formation, the patients, as well as before the operation, noted physical functioning with severe headaches (p < 0,05).
Conclusion
Transsphenoidal removal in patients with pituitary apoplexy leads to an improvement in the quality of life, a decrease in the severity of pain syndrome.
P0501
S. E. Martín Pérez12, P. E. Barrera Singaña3, S. Pettineo3, R. Translateur Grynspan3, J. L. Alonso Pérez12, E. A. Sánchez Romero2
1Universidad Europea de Canarias, Musculoskeletal Pain and Motor Control Research Group, Faculty of Health Sciences, La Orotava, Spain
2Universidad Europea de Madrid, Musculoskeletal Pain and Motor Control Research Group, Faculty of Biomedical and Health Sciences, Villaviciosa de Odon, Madrid, Spain
3Universidad Europea, Faculty of Biomedical and Health Sciences, Villaviciosa de Odon, Madrid, Spain
Background and objective
Tension-type-headache (TTH) is a condition characterized by a dull, non-pulsating, diffuse band-like pain in the head, scalp, or neck produced by an active myofascial trigger point (MTP). Our objective was to update the available evidence about the effectiveness of manual therapy (MT) in combination with exercise therapy (ET) to manage TTH.
Methods
A systematic review was carried out according to PRISMA statement in database MEDLINE (PubMed), PEDro, ScienceDirect, and Cochrane using MeSH and free terms “Tension-type headache”, “musculoskeletal manipulations”, “exercise therapy”, “myofascial pain syndrome” “manual therapy” and “training”. Methodological quality and Risk of Bias were conducted by an independent researcher using PEDro Scale and ROB 2.0 tool.
Results
16 RCTs (n = 1078, W:835; M:183; Mean Age: 35.7) were included with excellent interrater reliability (k = 0.822). Robust evidence showed combining MT (joint mobilization and suboccipital myofascial release) and ET (aerobic and strength exercise and relaxation training and postural reeducation) decreased intensity of pain and reduced TTH episodes frequency. In addition, MT was effective in increasing pain pressure threshold (PPT), and range of motion (ROM). The combination of MT and ET improved disability and quality of life in the long term.
Conclusion
MT showed to be effective on intensity, frequency, PPT, and ROM but its combination with ET improved disability and quality of life.
P0502
A. V. E. Harder12, B. S. Winsvold345, R. Noordam6, L. Vijfhuizen2, S. Børte347, T. Hansen8, J. A. Zwart347, G. M. Terwindt1, A. van den Maagdenberg12
on behalf of the Cluster Headache Working Group2
1Leiden University Medical Center, Department of Neurology, Leiden, Netherlands
2Leiden University Medical Center, Department of Human Genetics, Leiden, Netherlands
3Oslo University Hospital, Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo, Norway
4Norwegian University of Science and Technology, K.G. Jebsen center for genetic epidemiology, Department of public health and nursing, Faculty of Medicine and health sciences, Trondheim, Norway
5Oslo University Hospital, Department of Neurology, Oslo, Norway
6Leiden University Medical Center, Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden, Netherlands
7Oslo University Hospital, Institute of Clinical Medicine, Faculty of Medicine, Oslo, Norway
8Rigshospitalet-Glostrup, Danish Headache Center, Department of Neurology, Glostrup, Denmark
Objective
Identifying common genetic variants that confer genetic risk for cluster headache.
Methods
We conducted a case-control study with cases from the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO) (n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell-derived RNA-sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses.
Results
Four independent lead SNPs (r 2 < 0.1) were identified in relation to cluster headache with genome-wide significance (p < 5 x 10−8) and notably large effect sizes, rs11579212 (odds ratio (OR) = 1.51, 95% CI 1.33–1.72 near RP11-815M8.1), rs6541998 (OR = 1.53, 95% CI 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the total variance of cluster headache. SNPs rs11579212, rs10184573 and rs976357, as proxy SNP for rs2499799 (r 2 = 1.0), replicated in the Norwegian sample (p < 0.05).
Conclusion
This GWAS identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders.
Author Index
A
Abbasi, M.P0487
Abdo, J.P0488
Abokalawa, F.P0421
Aguilar-Carreno, H.P0423
Ahn, J.-Y.AL067, P010, P011
Ain, N. A. A.P0479
Akçiçek, H.P0471
Al-Hashel, J.P0421
Alenezi, M.P0421
Alonso Pérez, J. L.P0501
Alroughani, R.P0421
Anand, S.P0440
Andersen, A. S. S.AL071, P0189
P0193, P025, P0429
Anderson, M. S.P0458
Andrasik, F.P0485
Apostolakopoulou, L.P0494
Arkuszewski, M.P0475, P0476
Arribas, J.P0469
Arturo Larco, J.P0487
Arzt, M.AL078
Aurjord, R.P0436
B
Bae, D. W.P0409
Baker, S. R.P0428
Banerjee, T. K.P0440
Bangs, M.P0408, P095
Barabanova, M.P0407, P0426
Barrera Singaña, P. E.P0501
Bartels, E.AL073
Basedau, H.AL061, AL062
AL069, P0447
Bedekar, N.P0493
Belin, A. C.AL070
Bendtsen, L.AL071, IL040, P0189
P0193, P025, P0429
Benkli, B.P0442
Berdnikova, A.P0464
Bernstein, C.P0485
Bertz, R.P0458
Beyeler, M.P0432
Bhardwaj, R.P0458
Blythe, J.P0499
Boinpally, R.P0474
Bolay, H.AL068, IL04, P02
Borbridge, L.P0474
Buchholz, D.P0423
Bulut, T.AL068
Burger, K.AL073
Burish, M. J.P0442
Butler, M.P0474
Byoungchul, C.P0439
Børte, S.P0502
C
Calabresi, P.P0453
Campoy, S.P0427
Carpay, J. A.P0460, P07
Carpinella, M.P0452
Carr, K.P0471
Castro Zamparella, T.P0452
Cavanagh, S.P0434, P0462
Chaudhuri, J. R.P0440
Cherebillo, V.AL064, P0128, P0194
P0392, P0425, P0500
Chiappiniello, A.P0453
Cho, S.-J.AL067, P010, P011
P0141, P0157, P0409
Cho, S. H.P0409
Choi, E. J.P0481
Choi, Y.AL067
Christensen, S.AL063
Christofoletti, J.P0488
Chu, M. K.AL067, P010, P011
P0141, P0409, P043
Chung, J. M.AL067, P010, P011
Chung, P.-W.AL067, P010, P011
Collins, J. L.P0458
Conci Magris, D. M.P0452
Consonni, M.P0406
Corbelli, I.P0453
Cordeiro, A.P0405
Cowan, R.P0498, P0499
Craice, P.P0488
Crema, S.P0434
D
de Coo, I.AL073, P07
de Matos, A.P0488
Dehghani Molander, L.P0483
Dettin, E.P0445
Dever, J.P0471
Diamond, M.AL077
Doesborg, P.AL073, P07
Dominguez, V.P0461
Dong, Y.AL076, P0265, P0408
Dongen, R.AL073
Dorr, F.P0434
Dubey, A.P0422, P0424
Dubey, S.P0422, P0424, P0489
E
Edwards, M.P0491
Eidlitz-Markus, T.P0438, P0496
Ekpo, E.P0499
Ekusheva, E.P0449
Empl, M.P0477
Ernstsen, C.AL063
Eschiapati, T.P0488
Evers, S.P0441, P0443
P0444, P092
F
Falkenberg, H. K.P0436
Falvo, M. Q.P0416, P0417
Farez, M.P0434
Farouk Ahmed, S.P0421
Fernández Slezak, D.P0434
Ferrari, M.AL073, P0475, P07
Filatova, E.P0464
Filipchuk, M.P0452
Finley, J.-a.P0458
Finnegan, M.AL077, P0294, P0295
P0296, P0301, P0382, P089
Frederiksen, J. L.AL071, P0429
Futter, N.P0457
G
Gallop, K.P0480
Gantenbein, A.AL078
Garcia Santos, R. A.P0415
Gaul, C.AL076, IL073, P0144
P0308, P0325, P0408
Gine-Cipres, E.P0465, P0466, P0467
Giniatullin, R.P0431
Giraldo, Y.P0461
Goda, H.P0437
Gokhale, S.P0440
Golshan, F.P0473
Gonçalves, A.P0488
Greenwood, N.P0491
Grignani, E.P0485
Grosu, O.P0418, P0419
Grunho, M.P0405
Guercini, G.P0453
Gülbahar, Ö.AL068
Guler Aksu, G.P0435
Guo, H.AL077, P0295, P0296
Gutiérrez, M. T.P0434, P0462
H
Haan, J.AL073
Hall, T.P0492, P0493
Hallett, R.P0491
Heinskou, T. B.AL071, P0189
P0193, P025, P0429
Henao, L.P0461
Henderson, L.P0451
Hensel, O.P0446
Hikita, T.P0437
Hirschberg, S.P0456
Hoffmann, J.P0457, P0468
Holland, P. R.P0455, P0456
Horta, M.P0482
Horta, W.P0482
Hougaard, A.AL066, IL061, P080
Houinato, D.P0445
Huerta, M.P0427
Hundemer, H.-P.P0443, P0444
Hussain, M.P0463
Huygen, F.AL073
I
Imbiakha, B.P0423
Int. Consortium for Cluster
Headache Genetics, C.AL070
Islam, M. K.P0414
Ito, K.P0437
J
Jansen-Olesen, I.AL063, P053, P057
Johnson, K.P0455
Johnston, A.P0471
Johnston, K.AL074, P0282
P0339, P0340
Jong-Hee, S.P0439
Jong-Ho, K.P0439
Joy, K. M. N. I.P0414
K
Kadymova, N.P0464
Karadaş, O.AL068, P02
Karsan, N.AL072
Kayar, O.P0435
Kennedy, G.P0478
Khalil, M. I.P0414
Khalil, M.P0463
Kim, B.-K.AL067, IL07, P010
P011, P0157, P0319, P0409
Kim, B.-S.AL067, P0484
Kim, S.AL067
Kim, S.-K.AL067, P011
Kim, Y.P0441
Klein, B.AL077
Kossi, O.P0445
Kowalczyk, N.AL074
Kudo, T.P0437
Kulkarni, R.P0440
Kundu, N. C.P0414
Kurnukhina, M.AL064, P0128, P0194
P0392, P0425, P0500
Kurt, E.AL073
L
Lagorio, M.P0416, P0417
Lanter-Minet, M.P0475
Larsson, H. B. W.AL066, P084
Lauria Pinter, G.P0406
Lee, D. G.P0481
Lee, J.P0410
Lee, K.-S.AL067, P011
Levinsky, Y.P0438, P0496
Lim, C. A.P0481
Lisicki, M.P0452
Liu, Y.P0487
Lo, S. H.P0480
Logan, A.-M.P0491
López Gonzalez, D. S.P0415
Löser, S.P0477
Luebke, A.P0423
M
Maarbjerg, S.AL071, P0189
P0193, P025, P0429
Madhani, S.P0487
Mahmud, R.P0414
Malik, A.P0495
Malm Hagen, S.P0483
Mammadova, M.P0490
Marciszewski, K.P0451
Marmura, M. J.AL077, P0323
Martín Pérez, S. E.P0501
Martinez, J.P0408
May, A.AL061, AL062
AL069, P0447
McAllister, P.AL077, P0106
P0294, P0316, P0320
McGeeney, D.P0474
McGrath, D.AL074
McVige, J.AL077, P0299, P099
Mechtler, L.AL077, P0299
P0327, P099
Mehnert, J.AL061, AL069, P0447
Meisingset, T. W.P0450
Melhado, E.P0488
Meyer, I.AL078
Meylakh, N.P0451
Miceli, R.AL077, P0294, P0295
P0296, P0301, P089
Mikleborough, M.P0473
Mirzayev, S.P0490
Moon, H.-S.AL067, P010
P011, P0157, P0409
Moreno-Ajona, D.P0457, P0468
Mulleners, W.AL073
Muñoz-Vendrell, A.P0427
Muresan, B.P0471
Mutharasu, C.P0424, P0489
Muzlaev, G.P0407, P0426
Myers Oakes, T.AL076, P0408
Mykland, M. S.P0450
N
Nagel, V.P0462
Naprienko, M.P0464
Nava, V.P0416, P0417
Nelson, A. M.P0441
Neverdahl, J. P.P0450
Ni Riordain, R.P0428
Nicholson, R. A.P0441
Nielsen, B.AL063
Noory, N.AL071, P0189
P0193, P025, P0429
Novick, D.P0443, P0444
Nunes Rabelo, N.P0459
O
O’Daly, O.P0448
Ogawa, Y.P0437
Ogunlaja, O. I.AL065
Oh, K.AL067, P010, P011
Omland, P. M.P0450
on behalf of the Cluster
Headache Working Group, .P0502
Oppermann, T.AL062
Özge, A.AL068, P02, P0435
Ozima Filho, S.P0488
Öztürk, B.AL068
P
Panni, T.P0443, P0444
Parekh, K.P0492
Pareto, D.P0454
Park, J.-W.AL067
Park, K.-Y.AL067, P011
Paulson, O. B.AL066
Pearlman, E.P0441
Peixoto, E.P0459
Peng, K.-P.AL062, AL069, P0447
Pereira, L.P0405, P042
Peretz, A.P0499
Petroulia, V.P0432
Pettineo, S.P0501
Piacentini, S.P0406
Pickering, T.P0456
Picolo, J.P0488
Popoff, E.AL074, P0282
P0339, P0340
Powell, L.AL074, P0282
P0339, P0340, P0480
Pucci, E.P0416, P0417
R
Rabbani, G.P0414
Raggi, A.P0485
Rahman, S.P0423
Ramakrishnan, V.P0424, P0489
Ramírez García Luna, A. S.P0415
Rapoport, A.P0499
Rasmussen, R.AL063
Riesenberg, R.AL076, P0408
Ritter, S.P0476
Rizzoli, P.P0411, P0412, P0485
Robertson, C.P0487
Rodríguez Rodríguez, M. S.P0415
Rothrick, J.P0499
Rovira, A.P0454
Rozwadowska, A.P0477
Ruedi, P.P0469
Ruiz Yanzi, M. A.P0434
S
Sailaja, Y.P0489
Sala-Padró, J.P0427
Sánchez Romero, E. A.P0501
Sand, T.P0450
Sang-Hwa, L.P0439
Sanjanwala, B.P0499
Sansone, E.P0485
Sarchielli, P.P0453
Satpute, K.P0492, P0493
Savastano, L.P0487
Schäfer, E.AL078
Schellong, M.AL069
Schraml, L.P0432
Scutelnic, A.P0432
Searl, M.P0485
Semina, E.AL064, P0500
Severt, L.AL077, P0292, P0293
P0294, P0295, P0296, P0299
P0301, P0474, P089
Shahid, A.P0487
Shapiro, R. E.P0413
Shepard, K.P0480
Silva, E.P0405
Singh, P.P0486
Singh, S.P0440
Singhota, S.P0430
Singhvi, S.P0486
Slavova, N.P0432
Smilkov, E. A.AL071, P0189
P0193, P0429
Smith, T.P0480
Sohn, J.-H.AL067, P010, P011
Song, T.-J.AL067, P011
Sonkaya, R.AL068
Spille, P.P0477
Spincemaille, G.AL073
Steiner, T. J.P0445
Stites, T.P0475, P0476
Stringfellow, J.P0458
Stroud, C.AL076, P0408
Sturm, L.-M.AL061, AL069
Sulaiman, W. A. W.P0479
Sureda-Gibert, P.P0456
T
Taborda, S.P0461
Tarducci, R.P0453
Taşdelen, B.AL068
Tchantchaleishvili, N.P0430
Teernstra, O.AL073
Teixidor-Panella, S.P0427
Telesca, A.P0406, P0411, P0412
Thorne, L.P0430
Thorud, H. M. S.P0436
Tountopoulou, A.P0494
Translateur Grynspan, R.P0501
Treuer, T.P0443, P0444
Trugman, J. M.AL077, P0262, P0263
P0281, P0294, P0295
P0296, P0301, P0382, P089
U
Uglem, M.P0450
Usai, S.P0406
V
Vandrovcova, J.AL070
Vassilopoulou, S.P0494
Velichko, I.P0407, P0426
Velonakis, G.P0494
Venda Nova, C.P0428
Vestergaard, M. B.AL066
Vijfhuizen, L.P0502
Vila-Pueyo, M.P0455, P0456
Villa, F.P0461
Villar-Martínez, M. D.P0457
P0468, P0497
W
Wei, D. Y.P0448
Wiest, R.P0432
Wilbrink, P.AL073
Wilkinson, V.P0463
Wille, F.AL073
Woldeamanuel, Y.P0498, P0499
Wu, J.P0430
Wu, Q.P0463
Y
Yakubova, A.P0431
Young-Suk, K.P0439
Younis, S.AL066
Z
Zagar, A.P0441
Zakrzewska, J. M.P0428, P0430
Zelaya, F. O.P0448
Zhang, W.P0442
Zrinzo, L.P0430
Zwet, E.AL073
Øie, L. R.P0450