The International Headache Congress – IHS and EHF joint congress 2021: late breaking abstracts

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 Galcanezumab changes somatosensory perception exclusively in the face, whereas heat pain threshold before treatment predicts efficacy K. P. Peng, H. Basedau, T. Oppermann, A. May University Medical Center Hamburg-Eppendorf, Department of Systems Neuroscience, Hamburg, Germany Correspondence: K. P. Peng The Journal of Headache and Pain 2021, 22(Suppl 2):AL062

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 nonresponders. 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
International Consortium for Cluster Headache Genetics: two initiatives report first genome-wide association hits B. S. Winsvold 1,2,3 , A. V. E. Harder 4,5 , C. 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 metaanalysis of CH. 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. 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 (Σ21= 7.59, P=0.013) and voice change (Σ21= 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
Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial P. Wilbrink 1 , I. de Coo 2 , P. Doesborg 2 , W. Mulleners 3 , O. Teernstra 4 , E. Bartels 2 , K. Burger 5 , F. Wille 6 , R. Dongen 7 , E. Kurt 8 , G. Spincemaille 4 , J. Haan 2 , E. Zwet 2 , F. Huygen 9 , M. Ferrari 2 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. (ClinicalTrials.gov NCT01151631). Findings We enrolled 150 patients and randomised 131: 65 for 100% and 66 for 30% ONS. Median (IQR) weekly MAF in the total population was decreased to 7. 38 (2.50, 18.50; p<0.0001) in weeks 21-24, a median change of -5.2 (IQR -11.18, -0.18; p<0.0001) attacks per week, without difference between treatment arms. In the blinded phase, there were 129 (100% ONS) and 95 (30% ONS) adverse events (AEs). Interpretation In patients with MICCH ONS substantially reduced attack frequency and was safe. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action. 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. . Participants received GMB 300mg subcutaneously up to once monthly. Efficacy-related objectives assessed the effect of GMB on the PGI-I, the EQ-5D-5L Health State Index scores and EQ-VAS Current Health score. Spearman correlation coefficients between PGI-1 and EQ-5D-5L scores mean change from baseline at 1 month (m) were also calculated.
Results Of the 165 participants enrolled, 164 received at least 1 dose of GMB and 163 had ≥ 1 post baseline assessment. Findings are summarized in the table. Majority of participants (≥80%) reported their CH status as very much/much/a little better in PGI-I at 1, 6, and 12 m. The US Health State Index and VAS generally improved from baseline to 1, 6, and 12m. Correlations between mean change in PGI-I and mean change value in EQ-5D-5L Health State Index Scores and VAS Current Health score at 1m were associated and ranged from -0.28 to -0.37. Conclusion Majority of participants reported their CH condition to be very much/much/a little better, as measured using the PGI-I, at 1, 6, and 12m. EQ-5D-5L Health State Index scores (US and UK) and the EQ-VAS Current Health score improved from baseline to 1,6, and 12m. 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
Real-world effectiveness data of erenumab-treated migraine patients 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 (mMI-DAS), 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. Fig. 1 (abstract AL077). See text for description 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
Clustering personality traits in chronic cluster headache patients: a data driven approach A. 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. Background & Objective: Oxygen therapy is the established acute treatment of cluster headache, but there are many obstacles that prevent widespread use by patients. Oxygen therapy using cylinder needs continuous replacement of oxygen and some difficulties in storage and delivery. Oxygen concentrator supplied oxygen at concentration of more than 90% and at flow rates up to 6L/min. We report four patients with episodic cluster headache who were treated with oxygen therapy from one or two oxygen concentrators. 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 nonrebreathing 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
Association study between headache and dizziness according to age spectrum for patients J. 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.    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. 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  Background: Headache is a common symptom during and after acute respiratory syndrome coronavirus 2 (SARS-COV-2). Objective: To study headache character in relation to SARS-COV-2 infection.
Methods: This was a cross-sectional study include patients who had SARS-COV-2 infection presented to headache clinic within 3 months after the onset of infections. Patients were diagnosed as primary headache disorders according to Headache characters were reported before and after SARS-COV-2 infections. Results: A total of 121 patients who recovered from SARS-COV-2 infections were included. 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, O 2 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. 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.  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. Results and discussion.The patients showed positive dynamics in the late postoperative period in the form of a significant decrease in the sensory,affective and evolutional scales of the McGill pain intensity questionnaire (p˂0,05).After surgery positive dynamics were revealed on all scales of the SF-36 questionnaire for all 40 patients:an increase in physical,role, social,emotional functioning,a significant decrease in the intensity of pain syndrome(p˂0,05).Only in 6,8% of cases, we noted a regression of the pain syndrome in the first 3 months after surgical treatment.
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. 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.

Disclosure of Interest
The authors declare no conflicts of interest.

P0427
Intravenous lacosamide and phenytoin as treatment of acute pain exacerbations in trigeminal neuralgia: a retrospective analysis A. Muñoz-Vendrell 1 , S. 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
Outcomes of treatment and psychometric performance of patient reported outcomes in Trigeminal Neuralgia -two Systematic Reviews C. 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  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
A joint medical and surgical multidisciplinary trigeminal neuralgia service eleven-year evaluation S. Singhota 1,2 , N. Tchantchaleishvili 3,4 , J. Wu 5 , L. Zrinzo 3 , L. 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
Episodic and chronic migraine differ in 1911a>g polymorphism of trpv1 gene: a possible biomarker of migraine chronification? 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
The Index Vein is a highly specific sign for migraine with aura in the emergency setting 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. Methods: The IV was defined according to our previous work (Slavova et al. Neurology;94(24):e2577-e2580): a single prominent vein in susceptibility weighted imaging draining the cortical area of the neurological deficit in the absence of diffusion abnormality and occlusion in angiography. For this retrospective study, 400 patients were included when they (i) presented at our emergency department with an acute neurological deficit, (ii) had a brain MRI within eight hours after the symptoms stopped, and (iii) had a discharge diagnosis of migraine aura, ischemic stroke, epilepsy or none of these (controls, n=100 per group). The primary hypothesis was that there is a difference distribution of IV in the four conditions (chi-square test). Results: Compared to stroke (n=2), epilepsy (n=5) and controls (n=1), the IV is more prevalent in migraine aura (n=17, chi-square 27.8, p<0.001). Although the sensitivity is low (17%), we found the IV to be highly specific for migraine aura (specificity 97%, 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.  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
Early maladaptive schemas is maybe a good predictor of adolescent migraine G. . 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
Headache and musculoskeletal pain in school children are associated with uncorrected vision problems and need for glasses: a case-control study H. M. S. Thorud 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-andgender 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 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, PedMI-DAS, 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.  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 Fig. 1 (abstract P0438). See text for description 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%; countryspecific 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. Sponsor: Eli Lilly and Company. 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. 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. 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).

P0443
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
EEG-informed fMRI reveals rhythm specific activations during trigeminal pain processing H. Basedau 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
Depicting areas of cerebral blood flow changes in nitroglycerininduced cluster headache attacks using arterial spin labelling D. Objectives: To investigate cerebral blood flow (CBF) changes during nitroglycerin (NTG) triggered attacks in cluster headache patients, using arterial spin labelling (ASL). Methods: Subjects attended screening visits to receive intravenous NTG infusion. Those for whom NTG successfully triggered attacks attended two scanning visits. They received either intravenous NTG (0.5mg/kg/min) or an equivalent amount of 0.9% sodium chloride over a 20-minute infusion. Whole-brain CBF maps were acquired using a 3 Tesla MRI scanner at "baseline" and post-infusion "headache". This study was approved by an NHS Research Ethics Committee. Results: Eighteen subjects completed the scanning visits. In a wholebrain analysis, we identified regions of elevated CBF in the medial frontal gyrus, superior frontal gyrus, inferior frontal gyrus and cingulate gyrus, ipsilateral to the attack side, during NTG triggered attack compared with the placebo session. We also identified significantly reduced CBF in the precuneus, cuneus, superior parietal lobe and occipital lobe contralateral to the attack side. Both the hypothalamus and ipsilateral pons showed higher CBF in a region of interest analysis. Conclusion: Increases in regional cerebral perfusion were observed in several brain regions, including the hypothalamus and pons. These data contribute to our understanding of cluster headache pathophysiology; and suggest that ASL may be valuable in future mechanistic studies of this debilitating condition. Fig. 1 (abstract P0446). See text for description 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. Cliniconeurological 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. The conclusion. The findings of this study suggest a comprehensive neurophysiological examination prior to the course of preventive therapy and the possible use of drugs from the group of anticonvulsants in the hyperexcitability of neurons of the motor cortex, especially in the refractory course of CTTN, however, these issues require further study. 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. 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. 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 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. 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.

Conclusions
Migraine correlates with a greater load of structural brain changes as a marker of disease burden.

P0455
Galcanezumab effectiveness in preclinical models of migraine and trigeminal autonomic cephalalgias M. Vila-Pueyo 1 , K. Johnson 2 , P. J. Goadsby 1 , P. 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  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. 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. 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 (Pgp) 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, 2sequence, 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 AUC 0-inf and C max ; geometric mean ratios (90% CI) versus rimegepant alone were 160% (149, 172) and 141% (127, 157). In Part 2, the evaluation with Fig. 1 (abstract P0456). See text for description Objective: To report the use of a non-invasive sensor to assess intracranial compliance in the management of patients complaining of migraine. Methodology: This is a case report on the use of a noninvasive sensor to assess intracranial compliance (ICC) in a patient complaining of migraine in the late postoperative period of pseudotumor cerebri. Results: Female patient, 34 years old, diagnosed with pseudotumor cerebri, with an opening pressure initial of 60 cm H2O. Obese, a non-adjustable lumboperitoneal shunt was chosen. Two years after surgery, the patient complained of headache, a noninvasive monitoring was performed, which showed a curve with an altered ICC, a P2/P1 ratio of 1.2, suggesting a reduction in the ICC, but no change in the opening pressure, magnetic resonance imaging maintained the same previous findings and hemodynamic control remained stable. A diagnosis of migraine was made, under treatment with topiramate and propranolol, with total improvement after treatment. Conclusion: The use of non-invasive sensor helped the medical team to understand the information obtained by the ICP curve in the office and in the management of patients with headache complaints, supporting clinical decision making, improving the quality of care, correlated with underlying diseases and procedural and patient safety.
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
Pericranial nerve blocks with local anesthetics and steroids in chronic migraine: impact and adverse effects of the addition of dexamethasone in patients without prior response to 2 preventive treatments, experience in Colombia S. Taborda 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.  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. 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
Correlation between patient-related outcome scales (PROs) and CGRP-mAbs treatment response at 3-months in migraine patients A. Alpuente 1,2 , M. .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. Fig. 1 (abstract P0465). See text for description Fig. 1 (abstract P0466). See text for description 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  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±8vs28±3, and 21±7vs25±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. 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. 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. Clinical Case: A 40-year-old woman, with chronic migraine, after discontinuing 3 different prophylactic drugs due to adverse effects, started treatment with Erenumab 70mg. She completed 27 months of treatment with marked clinical improvement. However, on the day of erenumab injection or on the following day, after minor trauma or spontaneously, she developed ecchymoses in several body locations, unrelated to injection site. Laboratory tests, including platelet count, antiplatelet antibodies and coagulation tests were unremarkable. Despite being alerted for the potential seriousness of this adverse effect, the patient repeatedly requested to continue treatment. After stopping erenumab no new ecchymosis appeared. 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. 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).
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. 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
Migraine 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 wellrecognized 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. Objective: To evaluate the potential for pharmacokinetic (PK) drugdrug 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 (AUC 0-tau ) and maximum plasma concentration (C max ) were reduced by 25% and 24%, respectively, with topiramate coadministration. Atogepant median T max was the same when administered alone or with topiramate (2h). For topiramate, AUC 0-tau and C max were reduced by 5% and 6%, respectively, with atogepant coadministration. Topiramate median T max 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 AUC 0-tau and C max 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. 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 (Table). The most common AE for the erenumab treatment groups (presented as n [r], whereby n = number of subjects reporting ≥1 AE) was nasopharyngitis (DBTP,11 [20.9] 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. Methods: Migraineurs with at least 5 headache days per month were block-randomized to the experimental group (EG) or waiting list group (WL), the latter starting 6 weeks after the EG. Participants learned introvision in 6 weekly on-site group sessions with video-conference support followed by three individual videoconference sessions. Headache parameters were assessed before introvision and three months after the last individual introvision session. Results: 53 patients completed the study. The primary outcome, headache days of the EG after introvision compared to the WL before the introvision, showed no significant effect (11,3+/-7,8, n=22; vs. 10,9 +/-6,2, n=29, p=0,63; Mann-Whitney-U-Test. The secondary outcome, comparing pooled EG and WL data before and after introvision, showed significant reduction of headache days (11,5+/-6,4 vs. 9,8+/-7,0;, p=0,003; Wilcoxon-paired-Test) medication intake, HIT-6 scores and increased self-efficacy. Introvision was recommended by 97 % of participants. Conclusion: The study did not reach its primary endpoint. However, secondary outcome parameters showed an improvement of migraine after the intervention, with a decrease in monthly headache days by 1.7 days/month.

P0478
The 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 Fig. 1 (abstract P0476). See text for description Page 30 of 43 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. 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 multiethnic Malaysian population. The gene polymorphisms were analysed in 113 migraine patients and 163 control subjects. Serotonin and CGRP polymorphism were genotyped by polymerase chain reactionrestriction 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 multiethnic Asian population in Malaysia.

P0480
Understanding the patient experience and disease burden of migraine: a qualitative interview study 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. 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. Methods: This is a case of a pulmonary AVM and concomitant frontoparietal brain abscess in a 48-year-old female with HHT treated with antibiotics and wedge resection. Results: A 48-year-old female with chronic headache presents with epistaxis and right leg weakness. Familial history was suspicious for HHT with the imaging findings. CT Chest revealed a right lower lung AVM and brain MRI showed a large frontoparietal brain abscess. The brain abscess was treated with antibiotics and the pulmonary AVM surgically managed with wedge resection. The patient made complete neurological recovery after initiation of appropriate antibiotics. Conclusions: The patient above had chronic headahce with recurrent epistaxis but otherwise a silent pulmonary AVM leading to brain abscess and therefore, presentation of neurologic symptoms. this case illustrates the significance of screening for pulmonary AVM in patients with HHT suggestive symptoms to prevent further neurological sequelae.
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. Objective: To identify migraine as an initial symptom of CADASIL. Method: Patients diagnosed with CADASIL Results: The proportion of migraine in patients with CADASIL is 5 times higher than the general population. The first symptoms usually occur before the age of 20, with the average age of appearance being 30. Migraine precedes other symptoms by many years, and resonance images may still be normal, leading to delays and diagnostic errors. The relationship between migraine and CADASIL can be justified by the identification of genetic abnormalities that occur on chromosome 19, the same chromosome as familial hemiplegic migraine. The characteristic of CADASIL migraine is the presence of aura symptoms, the most prevalent being the visual symptoms, followed by the sensory ones. Some individuals have atypical auras. A possible mechanism for the increased prevalence of aura in patients with CADASIL is the increased susceptibility to cortical spreading depression. Conclusion: Migraine, especially if there are symptoms of aura, can be an initial symptom of CADASIL disease, and should be considered as a differential diagnosis, especially when dealing with younger individuals. 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 newonset 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.

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. 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. 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
Prevalence and comparison of depression rates in the geriatric population of an old age home and a community, and its association with demographic factors S. Singhvi Background and objective -Depression is the most common mental health problem in the elderly. This adds severe burden on the patient, also affecting their families and their financial situation. Finding out the prevalence of depression among older adults living in an old age home and a community provides information about the impetus one should give on mental health. Therefore, the results of this study will help the entire health care community to understand the severity of depression in the geriatric age group, find the leading causes of depression and help with the intervention of the linkage. Methods -A cross section study of the geriatric group of population was performed, two sections of the geriatric group were taken for the study-geriatric population residing in an old age home (80) and geriatric population residing in a community (80). There were two forms used for data collection -a Geriatric Depression Scale (GDS), a standardized tool used to assess the level of depression and a demographic form was used to collect the demographic information. To find the association between different factors, the statistical method of Chi-square test and P-value was taken.

Results -Given in the Tables below
Conclusion -Increased attention to mental health care, especially in the geriatric population, should be encouraged. Further, multiple factors were found associated with depression and therefore preventive management of such factors should be our goal.  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.
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. Objective: Verify if, among medical students with PMS, there is a higher prevalence of migraine headache; as well as assessing whether female students with headache have a higher   prevalence of premenstrual syndrome. Method: Cross-sectional cohort study carried out on 189 women using a questionnaire. Results: Sample was by 189 young, single participants, students of higher education, users of contraceptives, similar ages of onset of PMS and headache (about 15 years old). It was observed 41% of the women presenting menstrual migraine "latu sensu". Association was observed between headache and PMS, which is called comorbidity (close to 80% has headache and 81.5% has migraine). The risk of PMS was estimated to be 2.54 times higher in the population with headache. It was observed the link between PMS and menstrual migraine, with greatest occurrence of menstrual migraine in women with PMS. The association between HIT and the DSM-V was observed, so that the greatest number of PMS symptoms are observed among those with HIT => 50. Conclusion: Association between PMS and migraine is significant and high. These disorders are comorbid in the population studied. Neither MRM is not a risk fator for PMS, nor PMS is a risk factor for MRM. 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 Fig. 1 (abstract P0488). See text for description Fig. 1 (abstract P0489). See text for description 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%). Conclusion The use of the resource in the native language was convenient for patients, but not portable. The creation of a mobile application for the developed diary in the native language will eliminate the problems that have arisen and speed up the formation of the register, and the placement of items on the visual interface will increase the interest of respondents and the sensitivity of the diary. 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
The C0-C2 axial rotation test -Reliability and correlation with the flexion-rotation test in people with cervicogenic headache and migraine K. 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
Cervical neuro-musculoskeletal impairments in people with cervicogenic headache: A systematic review and meta-analysis -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
Clinical and Imaging Correlation in a Patient Series with Migrainous Infarction (MI) and Ischemic Stroke Related to Migraine (ISRM) L. Apostolakopoulou 1 , A. Tountopoulou 1 , S. Vassilopoulou 1 , G. Velonakis 2 , D. Mitsikostas 1 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. Background: Headache disorders are amid the peak 10 causes of disability. Migraine, tension-type headache, cluster headache and medication-overuse headache are essential in primary care; responsible for almost all headache-related burden. Management of these belongs largely in primary care. The prevalence of headache disorders in Pakistan is high and would be at least on par with that reported in other parts of the world, although no data are available for this country. With a population of 210 million, there would be at least 31 million patients with migraines alone (assuming a 15% prevalence). Methods: To form treatment guidelines for common headache disorders, reviewed available guidelines, so as to develop own guidelines, specific to the needs of Pakistan.
Results: National guideline consists of: The globally IHS accepted definition and classification of common headache disorders with a simplified step wise approach to a patient with different types of primary headaches in Pakistan. Tables selecting the right drug with evidence-based references keeping in mind the cost/availability in Pakistan. Selection of medications in special populations e.g. young women, children and elderly. Use of onabotulinumtoxinA and the calcitonin gene related peptide antibodies for migraine prevention. Tables/Appendixes for easy access.
Conclusion: The guideline aims to provide the medical fraternity treating patients with common headache disorders with a step wise cost effective approach

P0496
Severe abrupt (thunderclap) non-traumatic headache at the pediatric emergency department T.  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. 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. 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-toface interview-diagnosis (82%). The machine learning programs involved case-based reasoning, deep learning, classifier ensemble, antcolony, 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
Can 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. 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 MED-LINE (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.