key: cord-0937217-gxiriza7
authors: nan
title: The International Headache Congress – IHS and EHF joint congress 2021: Virtual. 8-12 September 2021
date: 2021-09-07
journal: J Headache Pain
DOI: 10.1186/s10194-021-01293-9
sha: 519634fbfe3123c09ef5b6531635b0ff1b24231f
doc_id: 937217
cord_uid: gxiriza7

nan

Objective: Previous structural imaging studies in cluster headache (CH) used either volume-(VBM) or surface-based morphometry (SBM) to evaluate related morphological changes. A study combining both methods may provide further insights. Methods: 94 CH (47 during in-bout [CH-in] , and 47 during out-ofbout period [CH-out] ) and 47 healthy controls (CTL) were analyzed. VBM and SBM were applied to investigate between-group differences. Averaged volumes or cortical thicknesses from regions showing group differences were correlated with clinical parameters. Results: Compared with CTL, VBM showed reduction of gray matter volume (GMV) in multiple areas, confined to the pain matrix, in patients with CH (CH-all), CH-in and CH-out. Increased GMV at bil putamen was observed in CH-all and CH-in, but not CH-out, suggesting this effect may be derived from CH-in. SBM revealed a reduction of cortical thickness in ant/mid cingulate, and bil insula cortices in CH-all and CH-in, but not CH-out, suggesting CHin contributed to this effect. Additionally, the cortical thickness at right insula correlated negatively with disease duration in CH-in group. Conclusion: CH-in and CH-out showed distinct morphological changes. Both groups showed reduced GMV in regions within the pain-processing network, while CH-in additionally presented with reduced cortical thickness over bil insular and cingulate cortices, and increased volume in bil putamen. These changes may be related to trait-and state-dependent effects. Objective: Headache is the most common neurological symptom during COVID-19 and a frequent adverse event after viral vaccines. We aimed to investigate the frequency and clinical associations of COVID-19 vaccine-related headache. Methods: We developed a detailed web-based questionnaire screening headache following vaccination in healthcare professionals who received at least one dose of COVID-19 vaccine. We investigated the associations of this headache with primary headache disorders, main comorbid conditions, headache history during COVID-19 or following influenza vaccine. Results: A total of 1247 participants (mean age, 47.6±12.3 years;860 females) contributed to the survey;131 (10.5%) had been infected with COVID-19, being asymptomatic or mildly symptomatic in 111 (84.7%). Nearly one-third of all participants (386;31%) had headache after vaccination; 99(25.6%) experienced headache lasting more than two days. The diagnosis of primary headache disorders and migraine were significantly more frequent in participants having COVID-19 vaccine-related headache (p<0.000; p<0.000). The rates of headache during COVID-19 or following influenza vaccine were also significantly higher (p= 0.003 and p<0.000). Thyroid diseases showed also a significant association(p=0.001). Conclusion: Headache is a frequent adverse event following the COVID-19 vaccine and mostly experienced by people with primary headache disorders, having headache during COVID-19 or headache related to other viral vaccines. Objectives: We aimed to provide data on the effectiveness of onabo-tulinumtoxinA (BT-A) for chronic migraine (CM) in men compared with women. Methods: We performed a retrospective analysis on patients with CM treated with BT-A in 16 European centers. We reported the proportion of patients with a ≥50% decrease in monthly headache days (MHDs) -"responders"during the first 3 BT-A cycles compared with baseline. We also recorded the absolute numbers of MHDs. We then performed exact propensity score matching between men and women, considering age, CM duration, MHDs at baseline, and medication overuse as matching variables. Results: We included 522 men and 2357 women; men were older than women ( Conclusion: Our data suggest that response to BT-A might be lower in men than in women, although significant in both sexes. Sexspecific response to CM treatments merits further study. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six migraine without aura patients were randomly allocated to receive an infusion of MaxiPost or placebo on two study days separated by at least one week. The primary endpoint was the difference in incidence of migraine attacks after MaxiPost compared to placebo. The secondary endpoints were the difference in incidence of headaches and the difference in area under the curve (AUC) for headache intensity scores (0-12 hours), for middle cerebral artery blood flow velocity (VMCA) (0-2 hours), and for superficial temporal artery (STA) and radial artery (RA) diameter. Twenty-two patients completed the study. Twenty-one of 22 (95%) developed migraine attacks after MaxiPost compared with none after placebo (P ˂ 0.0001); the difference of incidence is 95% [95% confidence interval (CI) 86-100%]. The incidence of headache over the 12 hours observation period was higher after MaxiPost day (n= 22) than after placebo (n= 7) (P ˂ 0.0001). We found a significant increase of middle cerebral artery blood flow velocity and superficial temporal and radial arteries diameter. Because BKCa channel opening initiate migraine attacks, we suggest that BKCa channel blockers could be potential candidates for novel anti-migraine drugs.

Alterations of resting-state periaqueductal gray matter connectivity in tension-type headache K. Gecse 1,2 , D. Dobos 1, 2 , D. Baksa 1,2 , C. S. Aranyi 3 , M. Emri 3 , G. Kökönyei 1, 2, 4 , G. Bagdy 1,5 , G. Juhász 1, 2 Objective: Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP) Methods: Thirty-six migraine without aura patients were enrolled in a randomized, double-blinded, two-way, cross-over, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on two different experimental days. Furthermore, translational studies in cells and mouse models, and rat and human tissue samples were conducted. Results: Thirty patients (88%) developed headache after pramlintide infusion, compared to thirty-three (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine-like attacks after pramlintide infusion, compared to nineteen patients (56%) after CGRP (p = 0.180). The pramlintide-induced migraine-like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Interpretation: Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. Objective To assess the pathophysiologic changes in spontaneous intracranial hypotension (SIH) based on measures of CSF dynamics and on the duration of symptoms. Methods: We included consecutive patients from 2012 to 2018. CSF leak was confirmed if extrathecal contrast spillage was seen on imaging after intrathecal contrast application, or dural breach was detected intraoperatively. We divided patients with a CSF leak into 3 groups depending on the symptom duration: ≤10, 11-52, and >52 weeks. Clinical characteristics and measures of CSF fluid dynamics obtained by computerized lumbar infusion testing (LIT) were analyzed over time. Results: Among the 137 patients included, 69 had a confirmed CSF leak. Whereas 93.1% with <10 weeks of symptoms displayed typical orthostatic headache, only 62.5% with >10 weeks of symptoms did (p = 0.004). LIT revealed differences between groups with different symptom duration for CSF outflow resistance (p < 0.001), lumbar baseline pressure (p = 0.013), lumbar plateau pressure (p < 0.001), pressure-volume index (p = 0.001), elastance (p < 0.001), and CSF production rate (p = 0.001). Compared to the reference population, only patients with acute symptoms showed a significantly altered CSF dynamics profile. Conclusion: A CSF leak dramatically alters CSF dynamics in the acute phase of SIH, but these dynamics normalize with long lasting symptoms. There was an association between the clinical presentation and changes in CSF dynamics. Background: Limited data exists to guide treatment of idiopathic intracranial hypertension (IIH). We examined the effects of therapeutics on reducing intracranial pressure (ICP) in IIH. Methods: Randomised, sequential, open label trial in women with active IIH. Participants received 2 weeks of acetazolamide (2g), amiloride (10mg), furosemide (80mg), spironolactone (200mg) and topiramate (100mg). Treatment order was randomised, minimum 1 week drug washout between rounds. ICP was recorded before and after with telemetric, intraparenchymal ICP monitors (Raumedic, Hembrechts, Germany). Headache frequency and severity were recorded by diary. Analysis was by hierarchical regression. Results: 14 participants were recruited. BMI 38.1(6.2) kg/m2, ICP 30.6(5.1) cmCSF at baseline. ICP fell significantly with 4 drugs acetazolamide mean -3.31mmHg(SE 0.95), p=0.0009, furosemide -3.03(0.88), 0.0011, spironolactone -2.71(0.88), 0.0033, topiramate -2.29(0.85), 0.0095. There was no significant difference between drugs. There was no significant improvement in headache. Side-effects were common with acetazolamide (92%) and topiramate (92%). Conclusions: Acetazolamide, furosemide, spironolactone and topiramate marginally reduced ICP, but there was no statistical difference between treatments and no improvement in headache. There were significant side-effects, especially with acetazolamide and topiramate. Therapeutics with greater efficacy and less side effects are an unmet need in IIH.

Objective: Calcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraineurs. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and is thus disease modifying. Methods: This interim analysis includes fifteen episodic migraineurs (14 female, 48±13 years old), who completed all study visits until March 2021 and received assessments of the nociceptive blink reflex (R2 component, 10 trials, 6 stimuli/trial) before (V0) and three months (V1) after treatment with CGRP antibodies started. The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) of the stimulated/non-stimulated side (_s/_ns) following repeated supraorbital stimulation provide a direct readout of brainstem excitability and habituation as key mechanisms in migraine. Results: All patients showed a substantial reduction of headache days/month (V0: 12.3±3.7, V1: 5.9±4.0) and disability (HIT-6, V0: 65.1± 2.9, V1: 55.2±8.6). R2a significantly decreased (R2a_s: -46%, p=.038; R2a_ns: -39%, p=.014) and R2h significantly increased (R2h_s: β=-.33, p=.016; R2h_ns: β=-2.6, p=.041) from V0 to V1. Conclusion: We provide novel evidence that treatment with CGRP antibodies is disease modifying. The nociceptive blink reflex may provide a biomarker to monitor central disease activity.

Long-term Fremanezumab Treatment Over 6 to 12 Months Shows No Effect on Blood Pressure in Migraine Patients S. Nägel 1 , J. M. Cohen 2 , Y. Kessler 2 , V. Ramirez Campos 2 , X. Ning 2 , S. Barash 2 , S. J. Nahas 3 Objective: To assess long-term effects of fremanezumab on blood pressure (BP) in clinical trial participants (CTPs) from a 12-month (mo) long-term extension study (HALO LTS) and 6-mo study (FOCUS) Objectives: To estimate the effectiveness of detoxification in multiresistant chronic migraine (CM) with medication overuse headache (MOH) patients who start prophylaxes with Botulinum Toxin A(BTA) or Anti-CGRP mAb. Method: Prospective analysis of all CM with MOH patients with at least 28 monthly headache days (MHD) who started a prophylaxis with either BTA or Anti-CGRP, with or without detoxification at the beginning of treatment, at Bologna Headache Center. We evaluated CM remission and MHD at three months. Results: 89 patients were included; 50 started BTA and 39 Anti-CGRP.

In the BTA group, 29 patients started prophylaxis immediately after detoxification (PAD) and 21 prophylaxis alone (PA). At 3-months, we observed conversion to episodic migraine in two (9.5%) of the 21 PA patients and in six (20.6%) of the 29 PAD patients (p 0.28). Mean MHD at three months were 26.9 in the PA group versus 22.7 in the PAD group (p 0.03) In the Anti-CGRP group, 13 patients started PAD and 26 PA. At 3months we observed clinical conversion to episodic migraine in five of the 26 PA patients (19.2%) and five of the 13 PAD (38.4%) (p 0.1). Mean MHD were 22.2 in the PA group and 16.3 in the PAD group (p 0.11) Conclusion: Detoxification seems to maintain a key role in preventive treatment of CM patients with MOH, also in the era of new prophylaxes. Larger samples are warranted to obtain definitive results.

Erenumab demonstrated significant reduction in migraine frequency in short-term studies. Here, we report the long-term efficacy and safety of erenumab in episodic migraine patients who completed a 5-year open-label treatment phase (OLTP; NCT01952574). Following a 12-week placebo-controlled, double-blind treatment period (DBTP), 383 patients continued into the OLTP, receiving erenumab 70mg every 4 weeks, and increasing to 140mg after a protocol amendment (after~2 years in OLTP). Overall, 214 patients completed the 5-year OLTP; 138 patients had efficacy data at Week 268 (end of 5-year OLTP) and were included in this analysis. At Week 268, the mean(SD) change from the DBTP baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication (AMSM) days was −5.3(3.9) and −4.4 (3. 3), respectively.

Other efficacy results are presented in Table 1 . Exposure-adjusted patient incidence of adverse events (AEs) and serious AEs during OLTP was 91.6 and 2.8 per 100 subject-years, respectively; this was lower than that observed for erenumab 70mg during DBTP. One fatality occurred during the safety follow-up period when no erenumab was administered and was considered unrelated to study drug by the investigator. Patients receiving erenumab over 5-years demonstrated consistent and sustained response. Safety was comparable to that observed in patients who received erenumab 70mg during the randomised phase of the trial.

Objective: To evaluate efficacy of fremanezumab during the 12-week double-blind (DB) period (DBP) and 12-week open-label extension (OLE) of the phase 3b FOCUS study in patients (pts) with pain or psychiatric comorbidities and inadequate response to 2-4 prior migraine preventive medication classes. Methods: Pts were randomized to quarterly (QTY) or monthly (MLY) fremanezumab or placebo (PBO) for DBP. All pts completing DBP entered the OLE and received MLY fremanezumab. OLE outcomes are summarized by DB randomization group. Changes from baseline (BL) in monthly migraine days (MMD) and monthly headache days of at least moderate severity (MHD) were evaluated in pt subgroups with pain or psychiatric comorbidities. Results: For pts with pain comorbidities (n=95) in the PBO, QTY, and MLY fremanezumab groups, respectively, least-squares mean (LSM) changes from BL in MMD were 0.3, −1.2, −1.5 (P≥0.13 vs PBO) during DBP, and mean changes were −3.1, −5.9, and −3.7 during OLE. For pts with psychiatric comorbidities (n=207) in the PBO, QTY, and MLY fremanezumab groups, LSM changes from BL in MMD were −0.9, −3.7, and −4.2 (P<0.001 vs PBO) during DBP, and mean changes were −4.6, −4.0, and −5.1 during OLE. Similar reductions in MHD were observed in pts with pain or psychiatric comorbidities.

Conclusion: Fremanezumab demonstrated efficacy over up to 6 months of treatment in migraine pts with pain or psychiatric comorbidities and inadequate response to 2-4 prior preventive medication classes.

Changes in the Number of Non-headache Days and Functioning on Those Days With Fremanezumab Treatment in Patients With Migraine: A Pooled Analysis J. VanderPluym 1 , J. M. Cohen 2 , X. Ning 2 , V. Ramirez Campos 2 , L. Janka 2 , D. C. Buse 3 Objective: Assess the onset of migraine preventive treatment efficacy with rimegepant, an oral small molecule CGRP receptor antagonist, during each of the first 4 weeks of treatment with an every other day dosing regimen. Methods: Multicenter, randomized, double-blind, placebo-controlled trial (NCT03732638) enrolled adults with a history of 4-18 monthly migraine attacks of moderate to severe pain intensity. After a 4-week observation period (OP), subjects were randomized to rimegepant 75 mg or placebo every other day for 12 weeks. This post-hoc analysis assessed mean changes from the OP in number of weekly migraine days during Weeks 1 through 4. P values are uncorrected for multiple comparisons. Results: In total, 741 subjects were treated with study medication (rimegepant n=370, placebo n=371). Mean age was 41.2 years; 82.7% of subjects were female, and 23.3% had chronic migraine. Rimegepant and placebo-treated subjects, respectively, had 2.6 and 2.5 mean weekly migraine days at baseline. Rimegepant was more Objective: Compare the efficacy, safety, and tolerability of rimegepantan orally administered, small molecule calcitonin generelated peptide receptor antagonist with demonstrated efficacy in the acute treatment of migrainewith placebo for the preventive treatment of migraine. Methods: Randomized, double-blind, placebo-controlled trial (NCT03732638) in adults with a history of 4-18 moderate-severe migraine attacks/month. After a 4-week baseline observation period, subjects were randomized to oral rimegepant 75 mg or placebo every other day for 12 weeks. The primary efficacy endpoint was change from the 4-week observation period in the mean number of migraine days per month (MMD) during Weeks 9-12. Results: In total, 741 subjects were treated (rimegepant n=370 placebo n=371; mean age 41.2 years, 82.7% female, 81.5% white, 23.3% chronic migraine), and 695 were evaluated for efficacy (rimegepant n=348 placebo n=347). Rimegepant was superior to placebo for the primary endpoint and secondary endpoints of ≥50% reduction in the mean number of moderate or severe MMDs during Weeks 9-12 and change in the mean number of total MMDs during Weeks 1-12 ( Table  1 ). The incidence of adverse events was similar in the rimegepant and placebo groups (35.9% vs 35.8%; Table 2 ). Conclusions: Rimegepant 75 mg taken every other day was effective for the preventive treatment of migraine. Tolerability was similar to placebo, with no unexpected or serious safety issues. Objective: In this post-hoc analysis of the HER-MES trial, we compared the efficacy of erenumab vs. topiramate using multiple imputation. Background: HER-MES is the first study to compare a CGRP-AB to one of the most commonly used migraine prophylactic drugs in a randomized, controlled trial. Design/Methods: HER-MES is the first head-to-head double-blind, double-dummy trial comparing the tolerability and efficacy of erenumab to topiramate in a German cohort ofpatients with at least 4 monthly migraine days (MMD). HER-MES comprised a 24-week treatment epoch (DBTE) in which patients received (1) either 70 mg or 140 mg subcutaneous erenumab/ oral placebo or (2) s.c. placebo/ maximally tolerated dose of topiramate (50-100 mg/daily). This posthoc analysis compares the efficacy of erenumab and topiramate over months 4, 5, and 6 regarding the 50 % responder rate (RR) and change in monthly migraine days from baseline using a multiple imputation model. Results: For both outcomes, 50 % RR and change in MMD from baseline in month 4, 5, and 6 erenumab proved to be superior to topiramate. Conclusion: This analysis displays a hypothetical scenario in which all patients stayed on drug throughout the 24-weeks treatment phase, despite AE and ineffective response. The results of this post-hoc analysis complement the efficacy results from the HERMES primary analysis and further support the benefits of erenumab over topiramate in the prevention of migraine. Background: The CEFALY device is a non-invasive neuromodulation treatment which stimulates the bilateral supraorbital nerves transcutaneously to provide pain relief by targeting the trigeminal nerve. Methods: We conducted a randomized, double blind, shamcontrolled, multicenter study at 10 sites in the United States. 538 adults diagnosed with 2-8 migraine headache days per month were randomized to active or sham stimulation. Neurostimulation was applied for a 2-hour, continuous session. Migraine pain levels and most bothersome migraine-associated symptom (MBS) were recorded at baseline, 2 hours and 24 hours using a paper diary. The primary endpoints for the study were pain freedom at 2 hours and freedom from the MBS at 2 hours. The secondary endpoints were pain relief at 2 hours, absence of all most bothersome migraine-associated symptoms (MBSs) at 2 hours, acute medication use within 24 hours after treatment, sustained pain freedom at 24 hours and sustained pain relief at 24 hours. Results: Active stimulation was more effective than sham stimulation in achieving pain freedom at 2 hours with a therapeutic gain of 7.2% (25.5% versus 18.3%, p=0.043). MBS freedom at 2 hours was also higher in the activegroup compared to the sham group (56.4% versus 42.3%, p= 0.001). Conclusion: External trigeminal nerve stimulation with the CEFALY device was found to be superior to a sham device in providing pain freedom and freedom from the MBS at 2 hours 90.5% reported they were likely to continue using ubrogepant.

Analyses of prior and current acute medication use with ubrogepant suggest reductions in opioids (-80%), barbiturates (-58%), ergots (-93%), triptans (-65%), NSAIDs (-47%), and other acute medications (-32%) use. Conclusions: Ubrogepant users reported high satisfaction with pain relief, ability to think clearly, return to normal function and most indicated that they were likely to continue its use. Ubrogepant use was also associated with reductions in opioid and barbiturate use suggesting additional clinical benefits for users.

Clinical profile of chronic cluster headache (CCH) in a regional headache center in Japan S. Kikui 1 , J. Miyahara 1 Background: CCH is a refractory headache that lowers quality of life, but little is known about the characteristics of CCH in Japan.

Object & Methods: 19 consecutive patients with CCH visiting at a tertiary headache center (Tominaga hospital) from February 2011 to July 2020. Patients with CCH were interviewed using standardised questionnaires during a consultation. Results: Patients with CCH accounted for 4.2% (19/420) of CH.

The demographic characteristics of the study participants are shown in Table 1 . Patients with CCH in Japan had later age of CH onset. Nine (47.4%) patients had CCH from onset of CH (primary CCH), and in the remaining 10 (52.6%) patients, CCH had evolved from episodic CH (secondary CCH). There were more smokers in the secondary CCH group. In one primary CCH patient, CH attacks had disappeared. Two secondary CCH patients migrated to episodic CH. Seven patients have persistent CCH. The detailed treatment results are provided in Tables 2. In 6 cases, quality of life has been improved by the combined use of HOT and subcutaneous sumatriptan injection. Conclusions: prevalence of CCH in our study is low as in other Asian regions. Patients with CCH in Japan had later age of CH onset of and the duration of evolution in patients with secondary CCH is a long interval after CH onset. There are many cases of CCH that can be controlled with HOT and sumatriptan subcutaneous injection. Drug control may be better in many CCH cases in Japan.

Clinical characteristics and burden of a large series with cluster headache from Turkey P. Yalınay Dikmen 1 , C. ARI 2 , E. Sahin 3 Objective: To present results from a cluster headache (CH) survey from Turkey regarding clinical characteristics, diagnostic delay, triggers, treatment and personal burden. Methods: The survey was composed of 76 questions. Participants diagnosed with CH according to IHS criteria were recruited from headache centers.

Results: A total of 209 individuals with a mean age of 39. 8 (11.3) completed the survey (176 males; 188 episodic, 21 chronic). The mean age at onset was 28.6 (10.2). Diagnostic delay was 4.9 years. Incorrect diagnosis before CH was 57.9%. Of participants, 9.1% reported a positive family history for CH and 54.5% had a history of current/prior tobacco exposure. Strikingly, 26.8% noted an aura before a CH attack. The most common cranial autonomic symptoms were lacrimation in 79.9 %, followed by nasal congestion 55%, agitation 55 %, eyelid swelling 50.2 %. Of episodic CH patients, 72.7% had ≥ 1 bout per year. The mean duration of CH attack with and without medication was 40.9 (31.6) and 91.8 (58) minutes, respectively. A positive response to high-flow oxygen was observed in 67% of the participants. The most commonly used prophylactic agent was verapamil (72.7%). In this study, 48% of CH patients reported significant personal burden (episodic 47.3% vs. chronic 62.5%; p=0.80). Conclusion: Diagnostic delay and incorrect diagnosis were still frequent before a proper diagnosis. The significant burden was reported by patients regardless of chronicity. Objectives: This study aimed to identify the role of sphenopalatine ganglion (SPG) in symptoms laterality and treatment response in patients with cluster headache (CH). Methods: We prospectively recruited patients with side-locked episodic CH from our clinic and collected their medical records, headache questionnaires, and data of treatment response. All patients received brain MRI including specialized protocol focusing on SPG during the in-bout period. We compared the SPG volume between pain and non-pain sides and analyzed the association between SPG volume and acute treatment response to sumatriptan nasal spray (NS) . Results: In this study, 34 in-bout CH patients underwent brain MRI. The SPG volume (mean ± SD) was larger at the pain side (pain side vs. non-pain side:36.0±15.5 vs. 30.0±13.2μL, p=0.011). Responders to sumatriptan NS tended to have a larger SPG volume at the pain side (responder vs. non-responder: 43.4±18.3 vs. 31.9±12.4μL, p=0.037). Patients with SPG volume ≥40μL have a higher response rate to sumatriptan NS (≥40 vs. <40μL: 61.5% vs. 19.0%, p=0.012). Conclusion: Using the specialized protocol for measurement of SPG volume, our study showed the CH patients had a larger SPG over the ipsilateral side. In addition, larger SPG volume predicted a higher response rate to sumatriptan NS, suggesting the potential "direct" effect of sumatriptan on the SPG. The SPG volumetry provides insights for future research in the pathophysiology and treatment of cluster headache. Background and objective: Studies regarding cerebrovascular reactivity (CVR) using vasodilatory stimuli in patients with migraine have yielded conflicting results. We aimed to investigate the effect of chronic caffeine use and caffeine cessation on CVR in patients with migraine. Methods: We prospectively recruited patients with episodic migraine who were 18 -50 years of age and free of vascular risk factors at the Samsung Medical Center. Patients were classified into caffeine users and non-users at baseline, and caffeine users were instructed to discontinue caffeine intake. We measured transcranial Doppler (TCD) breath-holding index (BHI) in all the included patients at baseline and followed up after 3 months. We compared BHIs in cerebral arteries between caffeine users and non-users, and analyzed BHI changes according to the caffeine cessation. Results: Among 84 patients completed the study protocol, the baseline PCA-BHI was lower in caffeine users (n=56) than that in nonusers (n=28, p=0.030). In the longitudinal analysis, caffeine quitters showed a significant improvement in the PCA-BHI (p=0.034), whereas continuous users and non-users did not. Multivariable analysis showed an independent effect of caffeine cessation on the changes in the PCA-BHI (unstandardized beta=0.294, 95% CI 0.047-0.541, p= 0.020). Conclusions: In patients with migraine, caffeine use is associated with reduced CVR in the PCA, and caffeine cessation might be beneficial in improving the CVR. Objectives: Digital health applications have the potential to improve patient empowerment and quality of care, though retention is challenging. Six-month retention rates of good-in-class solutions range between 30 and 40%. We evaluated the impact of interactive data sharing in the MigraineManager® solution (Neuroventis, Belgium) between patients connected with their physician compared to patients who did not connect. Methods: Belgian patients with headache or migraine having signed up to the app between 01-Jan-2019 and 31-Aug-2020 were enrolled. We compared retention rates at three and 6 months and reported headache days per 100 active app days per patient (unconnected versus connected). Results: 1007 patients were enrolled. Three and 6 month-retention rates for standalone headache app users were 34% and 20% compared to 67% and 50% for connected patients, respectively. Up to 90% of connected patients reported at least 1 headache episode, compared to 75% unconnected patients. Side effects were reported by 10% of connected users, 3.3 times more frequent than unconnected ones. The average number of reported headaches per 100 active app days was 21 for connected and 7 for standalone users. Conclusion: Interactive data sharing in MigraineManager® increased retention rates and exceeded observations of good-in-class solutions. Future research needs to address how this patient-physician connection impacts outcomes or reflects differences in demographics or headache characteristics. Background: Obese individuals have an increased risk of migraine chronification and headache comorbidities. This study aims to quantify the Body Mass Index (BMI) of new university headache patients and analyze if high BMI is associated with increased migraine chronification and other common comorbidities. Methods: Patients referred to our clinic complete a detailed intake questionnaire prior to their first visit. This questionnaire asks about headache characteristics, sleep, depression, anxiety, and stress. All patient data are analyzed by headache providers, BMI and ICHD-3 headache diagnosis are added. Results: Our study shows 3611 unique patients were diagnosed with migraine. Statistical analysis shows that BMI is higher in chronic migraine. Patient with BMI ≥ 30 have more headache days per month and greater headache severityhigher perception of stress scores (P< 0.0001) that correlates with higher anxiety, have higher PHQ4 (P< 0.0001) that correlates with depression than patients with a normal BMI. Patients reporting sleep problems have higher BMI than patients not reporting sleep problems. Conclusion: Data suggest that BMI ≥ 30 correlates with increased migraine chronification, headache days per month, and headache severity. BMI ≥ 30 also significantly correlates with measures of migraine comorbidities, such as anxiety, depression, and difficulty with sleep. Normalizing BMI may be protective against migraine chronification and improve all migraine comorbidities.

Increased visual sensitivity in cluster headache, as quantified by the Leiden Visual Sensitivity Scale (L-VISS): a cross-sectional study R. Brandt 1 , V. Cnossen 1 , P. Doesborg 1 Background and objective: Abnormal sensitivity to light and patterns is typically associated with migraine. Increased visual sensitivity has also been reported in cluster headache, contributing to confusion with migraine, sometimes delaying the diagnosis. We aim to asses visual sensitivity in episodic (ECH) and chronic cluster headache (CCH).

Methods: Participants filled out the Leiden Visual Sensitivity Scale (L-VISS), assessing their visual sensitivity during an attack, between attacks, and -in ECH -outside a bout. Data were analyzed using a linear mixed model and one-way ANOVA with sex and age included as covariates.

Results: Higher L-VISS scores were observed: (i) in all CH patients during attacks vs between attacks (ECH: 11.9 vs. 5.2, CCH: 13.7 vs 5.6; p = .000); (ii) in ECH patients between attacks inside a bout vs outside a bout (5.2 vs 3.7, p = .000); (iii) in all CH patients during and between attacks vs healthy controls (12.6 vs 5.3 vs 3.6, p = 0.000). Subjective visual hypersensitivity was reported by 110/121 (91%) cluster headache patients; in 70/110 (64%) patients (mostly) unilateral and, in all but one case, ipsilateral to the pain. Conclusions: Patients with CH have an increased visual sensitivity during and between attacks that is in almost two third of the cases ipsilateral to the pain. This is an important clinical realization that might contribute to a reduced diagnostic delay.

Insights into real-world treatment of Cluster Headache through a large Italian database: prevalence, prescription patterns and costs V. Favoni 1 , P. Carlo 2 , G. Ronconi 2 , L. Dondi 2 , S. Calabria 2 , A. Pedrini 2 , A. P. Maggioni 2 , I. Esposito 3 , A. Addesi 3 , G. Pierangeli 1, 4 , P. Cortelli 1, 4 , S. Cevoli 1 , N. Martini 2 This study aimed to analyze the relationship between headache and sleep in pediatric migraine. We evaluated differences in migraine frequency and intensity, presence of migraine equivalents, use of attack and prophylactic medications in subjects with and without sleep disorders based on the results of standardized sleep assessment questionnaires. The parents of 140 children and adolescents with migraine completed the Children's Sleep Habits Questionnaire (CSHQ) and the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) and answered questions about headache characteristics in their children. The CSHQ revealed a sleep disturbance in 72.9% of subjects, but only 5.0% had already received a diagnosis of sleep disorder. We found statistically significant higher headache frequency (p=0.002) and prevalence of migraine equivalents (p=0.007) in patients with sleep disorders. A higher CSHQ total score was associated with higher severe attacks frequency (p=0.012) and lower acute drug efficacy (p=0.003). Significant positive correlations of sleep onset delay, sleep duration and nightwakings subscales with migraine frequency emerged. Our findings indicate that sleep disorders are highly prevalent in pediatric migraine and frequently associated with a higher headache severity, but remain underdiagnosed in many cases. Given the relationship between sleep and migraine characteristics, improving sleep quality could help to reduce migraine intensity and disability and vice versa.

Characteristics of pre-cluster symptoms in cluster headache S. Cho 1 Background: In this study, we investigated characteristics of precluster symptoms in patients with cluster headache. Methods: In this multi-center study, 190 patients with cluster headache patients (184 episodic and 6 chronic cluster headache) were recruited between October 2018 and December 2020. Patients were asked about the prediction of upcoming cluster bout. For the characteristics of pre-cluster symptoms, we selected the 20 relevant symptoms and signs. If patients have had other symptoms which were not included in the list, they could describe them in their own words.

Results: Pre-cluster symptoms were predictable in 36.8%. When present, pre-cluster symptoms occurred at a median of 7 days (IQR 2.3 to 14) before the onset of cluster bout. The most frequent symptom in the pre-cluster symptoms was painful symptom (25.8%). Patients with pre-cluster symptoms had higher female proportion, prevalence of pre-attack symptom and seasonal rhythmicity, frequency of cluster headache attack per day, and total number of cluster bouts than patients without pre-cluster symptoms. In univariable and multivariable logistic regression analysis, being female was associated with the predictability of pre-cluster symptoms (OR=2.026, p= 0.039).

Conclusions: Pre-cluster symptoms were predictable in about twofifth of patients with cluster headache, which may allow earlier preventive treatment and help understanding pathophysiology. Background and objective: No data regarding treatment status and response of cluster headache have been reported from Asian population. Methods: In this multicenter study, patients with cluster headache were recruited between September 2016 and January 2019 from 16 hospitals in Korea. At baseline visit, we surveyed the patients about previous experience of CH treatment, and acute and/or preventive treatments were prescribed by the physician"s discretion. Treatment response was prospectively evaluated using a structured case report form.

Results: Among 295 patients recruited, 262 within the active bout was included in this analysis. An experience of disease-specific treatments was reported by only one third of patients. At the baseline visit, oral triptans (73.4%), verapamil, (68.3%), and systemic steroids (55.6%) were the top three most common treatments prescribed by the investigators. For the acute treatment, oral triptans and oxygen were effective in 90.1% and 86.8%, respectively. For the preventive treatment, verapamil, lithium, systemic steroids, and suboccipital steroid injection were effective in 85.5%, 75.0%, 91.8%, and 80.6%, respectively. Conclusions: Our data provide the first prospective analysis of treatment response in Asian population. Patients well responded to treatments despite of a limited availability of treatment options. Most patients were undertreated previously, suggesting a need of raising awareness of CH among primary physicians.

Objective: Migraine is often complicated by GI conditions such as gastroparesis, functional dyspepsia -both associated with delayed gastric emptying, and cyclic vomiting syndrome. For example, GI comorbidity was reported in 38.4% of 354 subjects enrolled in STOP 301, with 20.3% reporting GERD. Here we review the current state of scientific evidence that exists linking migraine and gastric stasis. Methods: Key words, gastric stasis, migraine, autonomic dysfunction were used to obtain relevant studies in a literature search of EMBASE and PubMED. Results: Delayed aspirin absorption was reported in 19 out of 42 patients during a spontaneous attack, but not interictally. However, scintigraphy studies showed that gastric emptying after an induced migraine attack was delayed 78% ictally, and 80% interictally. Delayed emptying during spontaneous migraine attacks was reported as well but others have reported contradictory results. Compared to migraine patients, subjects with functional dyspepsia had more delayed emptying and others reported delayed ictal, but not interictal, emptying in patients compared to controls. An NIH Gastroparesis consortium survey reported migraine as the most common extra-GI comorbidity (36.6%) and was associated with more severe gastroparesis symptoms. Conclusion: The association between gastroparesis and migraine may be important if patients have GI symptoms and do not experience migraine relief with oral abortive treatment.

Sleep assessment in patients with Cluster headacheself reported vs observed data C. Ran 1 , C. Objective: Cluster Headache (CH) is a primary headache disorder often characterized by a circadian timing of headache attacks. The hypothalamus is reported to be activated during attacks, and several genes involved in the regulation of the molecular clock have been linked to CH. To investigate this further, we analyzed sleep patterns in CH patients compared to controls and in relation to active period and remission. Methods: 92 individuals were recruited for sleep assessment, 42 controls and 50 patients. Sleep was recorded during a two-week period using MotionWatch 8 actigraphs (CamNTech) containing an accelerometer recording physical movement. Study participants were instructed to wear the unit during rest and sleep and to fill out a short version of the Karolinska Sleep Diary in order to compare recorded sleep data with perceived sleep.

Results: 77 individuals have completed the study, two individuals discontinued the study because of technical difficulties, and six because of personal reasons or health problems. Preliminary results from the sleep diary suggests that CH patients take significantly longer time to fall asleep compared to controls, 30 min. vs 15 min., and CH patients remain in bed for a longer time in the morning compared to controls, 40 min. vs 20 min. Conclusion: Our preliminary data suggest that sleep is affected in CH patients, manifesting in prolonged sleep latency and increased time in bed. These data will be verified using actigraphy.

Prevalence of pre-cluster symptoms in episodic cluster headache: Is it possible to predict an upcoming bout? A. S. Pedersen 1 Background: Early symptoms prior to a cluster headache bout have been reported to occur days or weeks before the actual beginning of the cluster headache bouts. This study aimed to describe the prevalence of pre-cluster (premonitory) symptoms and examine the predictability of an upcoming cluster headache bout. Methods: 100 patients with episodic cluster headache were included in this retrospective cross-sectional study. All patients underwent a semi-structured interview including 25 questions concerning precluster symptoms.

Results: Pre-cluster symptoms were reported by 86% of patients with a mean of 6.8 days (interquartile range [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] preceding the bout. An ability to predict an upcoming bout was reported by 57% with a mean 4.6 days (interquartile range 2-7) before the bout. Occurrence of shadow attacks was associated with increased predictability (odds ratio: 3.06, confidence interval: 1.19-7.88, p-value=0.020 ). In remission periods, 58% of patients reported mild cluster headache symptoms and 53% reported occurrence of single shadow attacks. Conclusions: The majority of episodic cluster headache patients experienced pre-cluster symptoms, and more than half could predict an upcoming bout, suggesting a significant potential of early intervention. Furthermore, the experience of mild cluster headache symptoms and infrequent shadow attacks in remission periods is common and suggest an underlying pathophysiology extending beyond the cluster headache bouts. Objective: To use data from a mobile phone application to study realworld burden of self-diagnosed headache and describe its impact on daily life in headache sufferers not routinely seek medical advice. Methods: This retrospective, non-interventional, cross-sectional study analysed self-reported data from the "Migraine Buddy" app. Selfreported characteristics of headache and migraine, such as triggers, duration, frequency; treatment patterns and impact on daily activity in headache sufferers from Australia, Brazil, France, Germany, Japan were described. Demographics, self-diagnosed episode type: headache/migraine, duration, potential triggers, and impact on daily activity are reported. All analyses were exploratory and performed per country. Results: Self-reported data were collected from 60,474 users between August 2016-August 2018. Of users~90% were females; >60% was aged 24-45 years. Over one-third of users reported having 2-5 episodes of headache or migraine per month; impact included impaired concentration, being slower and missing work or social activities. Variation across countries were observed; within countries, episode characteristics were very similar for self-diagnosed headache vs migraine. Conclusions: Headache disorders present a range of important issues for patients that deserve more study and reinforce the need for better approaches to management. Big data can provide directions and potential insights to help improve headache management broadly.

Add on treatment with galacanezumab improved refractory cluster headache in 5 out of 6 tested cases Objective: To observe whether galcanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP), improves cluster headache (CH) as add-on treatment in a real-world setting. Methods: We prospectively collected data from 6 refractory CH patients (3 with episodic CH and 3 with chronic CH) at weeks 1 through 4, following the first dose of galcanezumab (120mg, sc). Results: The average number of previous treatments with limited or no response was 3.6 (range 2-5). At baseline the average number of attacks per week was 22.7. After adding galcanezumab the frequency of attacks decreased by 17.1 across weeks 1 through 4. One patient became headache free; in 2 patients a more than 75% and in other 2 a more than 50% reduction of attacks was recorded. One patient with episodic CH did not report changes in headache frequency. A significant reduction in days of acute medication use was noted in all cases (vs. baseline). Reduction in attack frequency started at week 1 and was consistent throughout the observation period. No adverse effect was noted. Conclusion: Galcanezumab was effective and safe in 5 out of our 6 CH patients, supporting individual off-label treatment attempts with anti-CGRP/R antibodies in refractory and disabled CH patients with poor outcomes.

Cluster Headache Impact Questionnaire (CHIQ) -A tool for assessing disability in cluster headache patients Objective: Cluster headache (CH) is a severe, highly disabling primary headache disorder. The aim of this study was to develop a CHspecific, short questionnaire to assess disability due to CH. Methods: Based on a literature review and semi-structured interviews with CH patients and headache experts, the 8-item Cluster Headache Impact Questionnaire (CHIQ) was developed and pretested. Subsequently, the CHIQ was administered online or on paper to CH patients visiting our headache center or via a German patient group. Reliability and validity were evaluated. Results: Active episodic (n = 85) and chronic (n = 111) CH patients (65.3% male, 47.21 ± 11.64 years) were included. The CHIQ showed good internal consistency (Cronbach"s α = 0.88) and factor analysis identified a single factor. Test-retest reliability was adequate (ICC 0.82, n = 38) . Convergent validity was shown by significant correlations with the Headache Impact Test™ (HIT-6™, r = 0.62, p < 0.01), subscales of the depression, anxiety and stress scales (DASS, r = 0.46 -0.59; p < 0.01) and with CH attack frequency (r = 0.39; p < 0.01). Conclusion: The CHIQ is a short, CH-specific questionnaire for the assessment of the impact of CH. The questionnaire is reliable, valid, and easy to administer which makes it a useful tool for clinical use and research.

Telencephalic cortical thickness in chronic cluster headache L. Giani Objective: Previous studies on brain morphologiy in chronic cluster headache (CCH) revealed inconsistent findings, maybe due to limitations of VBM. We investigated telencephalic cortical thickness in CCH patients employing a highly robust state-of-the-art approach for thickness estimation (Freesurfer). Methods: CCH patients (n=28; 23 males; age 45±11.7) and sex-and age-matched healthy individuals were scanned with a 3T-MRI for 3D-T1 images. No other pain, vascular or psychiatric comorbidities were admitted. We used Freesurfer 6 to obtain surface-based individual telencephalic cortical thickness estimates. CCH and controls were compared with a vertex-wise between-group analysis. Results were considered significant with a vertex-wise threshold of p<0.001 and a cluster-wise threshold of 50 mm2. Results: CCH patients showed significant cortical thinning in the right midcingulate cortex (MCC), the left posterior insula (postIC), the left superior temporal sulcus (STS) and the left collateral/lingual sulcus (CLS) (p<0.001 for all). Conclusions: CCH patients show abnormalities in regions belonging to the spino-thalamo-cortical tract, involved in sensory-motivational aspects of nociception (MCC, postIC), and in areas involved in social cognition (STS, CLS), a possible expression of behavioral/psychological vulnerability of CCH patients.

Objective: Diencephalic-mesencephalic structures have been implicated in the pathogenesis of cluster headache (CH). Among them, the ventral tegmental area (VTA) is part of the mesocorticolimbic dopaminergic system, which is involved in rewarding, avoidance, chronic pain. We hypothesized structural abnormalities in elements of the mesocorticolimbic system in patients with chronic CH (CCH Background: Neuroimaging studies have been carried out to analyze whether there are microstructural alterations in white matter and gray substance in patients with migraine. Methods: This is a single-center case-control study based on structural magnetic resonance image (MRI) description in migraine to compare the thickness and volume of brain gray matter and the diffusivity and anisotropy of brain white matter regions involved in the pathophysiology of migraine in patients and controls. Images were collected using 1.5T MRI. Post-processing of the cortical morphometry images (Statistical Parametric Mapping-12 and Freesurfer) and microstructural analysis in white matter (diffusion tensor image) of regions of interest (somatosensory cortex, visual areas (V3, MT+), hypothalamus, caudal portion of the sensory nucleus of the trigeminal nerve and dorsolateral pons) were extracted. Results: 128 patients with migraine (69 without aura, 46 with aura) and 48 controls were included. The statistically significant differences (p< 0.05) found were a volume and thickness increase in the gray matter of somatosensory cortex that is influenced by disease duration, a reduction in gray matter volume in the caudal portion of the sensitive nucleus of trigeminal nerve, as well as a reduction in the fractional anisotropy of the dorso-lateral pons in patients with migraine. Conclusions: Patients with migraine present micro-structural changes in regions of interest related to the pathophysiology of migraine. Our results suggests an altered anatomical substrate may correlate with the transmission, modulation, and perception of pain. Headache intensity was significantly higher in patients with more severe lung damage (p=0.033), probably due to hypoxia. Conclusions: Most of the neurological manifestations were comparable in frequency to those reported in the literature. The incidence of headache in our population was higher than reported, possibly due to the higher rate of primary headache history in our sample of patients. Methods: Exploratory case-control study. High-resolution brain diffusion Magnetic Resonance Imaging data were acquired in patients with persistent headache after COVID-19 infection and healthy controls (HC). Tract-Based Spatial Statistics was used to compare fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD) and the return-to-axial (RTAP), return-to-origin (RTOP) and return-toplane probability (RTPP) between the groups. RTAP, RTOP and RTPP were obtained with a new approach called AMURA (https://www.lpi.tel.uva.es/AMURA). Significant results were considered with p < 0.05 (Family-Wise Error corrected) and region size larger than 30 mm 3 . Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 ± 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 53.1 ± 7.0 years; nine women) were included in the study. Significant higher AD and lower RTPP values were found in patients with persistent headache compared to HC in five regions from the corona radiata, and the external and internal capsule. In the patients, significant lower RTPP values were identified in six additional areas from the same tracts and the superior longitudinal fasciculus. Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 ± 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 51.9 ± 6.6 years; nine women) were included in the study. Statistically significant higher functional connectivity was observed in the patients with persistent headache compared to HC in 10 connections. These connections were composed of an occipital region and another region that included the isthmus cingulate gyrus, a frontal or a parietal area. In the patients, significant lower functional connectivity was found in 12 connections between the cingulate and hippocampal gyri, parietal, temporal and frontal regions. Conclusions: Patients with persistent headache after COVID-19 infection present strengthened functional connectivity with occipital regions and weakened functional connectivity between frontal, temporal and parietal regions.

Facemask headache: a new nosographic entity among healthcare professionals in COVID-19 era L. Rapisarda Conclusions: Our data showed the appearance of de novo associated facemask headache in previous headache-free subjects and an exacerbation of pre-existing primary headache disorders, mostly experienced by people with migraine disease.

Clinical predictors of persistent post-COVID-19 headache D. Objective: Headache is within the most frequent symptoms of coronavirus disease 2019 . We aim to evaluate the long-term duration of headache attributed to COVID-19 in six cohorts that studied patients with headache during the first wave of the pandemic. Methods: We conducted an observational prospective study, including patients from six different centers that were studied during the first wave of the pandemic and completed at least 9 months of follow-up since headache onset. All six cohorts have already published data regarding the acute phase of the headache. We harmonized the databases and analyzed all common data elements. We present the data as percentage or median and inter-quartile range [IQR] . migraine Aura. However, recent reports raised doubt against the concept that CSD could account for all presentations of migraine aura.

Here, we show a series of atypical paediatric aura hardly explainable by the CSD, suggesting partly different pathophysiological mechanisms. Methods: We selected retrospectively our patients who had atypical aura on the basis of the following criteria:

1) the spreading wave appears to be not related to the CSD model 2) the chronological sequence and homunculus are not respected by the sequence and characters of aura symptoms 3) time intervals between symptoms onset not justified by CSD theory 4) atypical clinical symptoms not accountable by CSD 5) atypical correlation with pain onset and pain side Results: We collected 15 cases (5 M/10 F, range age 9-16 ys). All subjects underwent EEG and Brain MRI. They were divided according to the criteria described above: 4 subjects met criterion 1, 5 the second, 5 the third, 5 the fourth, 1 the fifth, some children met multiple criteria. Conclusion: Our cases show that the current CSD theory cannot fully explain the modalities of the aura presentation in some subjects. Therefore, some aspects need further investigation and reassessment on the basis of clinical practice. Moreover, we underline how accurate exploration of migraine aura can provide useful insight on pathophysiological aspects.

Recurrent headache in Internet-addicted Central Siberia urban adolescents: a school-based study S. Tereshchenko 1 , L. Psychosomatic symptoms prevalence and types in Internet-addicted (IA) adolescents are not studied well. We aimed to investigate IA comorbidity with recurrent headache in Central Siberia urban adolescents. Methods: 2950 urban Siberian (Krasnoyarsk) school-based adolescents (aged 12-18; boys/girl ratio 1348/1602) were tested with Chen Internet Addiction Scale (CIAS). Based on the CIAS, score Internet users were categorized into three groups: adaptive Internet users (AIU-1) (scoring 27-42); maladaptive Internet users (MIU) (scoring 43-64); and pathological Internet users (PIU) (scoring ≥65). Adolescents were also asked about headache presence/frequency and according to answer were divided into three groups: (1) No headache group, (2) frequent episodic headache with episodes frequency 1-15 per month, and (3) chronic headache with episodes frequency >15 per month. A Chi-square test was used. Results: The prevalence of AIU, MIU, and PIU were 50.4%, 42.8%, and 6.8%, respectively. Significant positive associations were detected between CIAS scores and headache, especially for the chronic headache group (р1-2=0,0047, р1-3<0,0001, р2-3=0,0008, where 1-AIU, 2-MIU, 3-PIU; Fig. 1 ). Conclusion: The Internet addiction group have significantly higher headache frequency that may be explained by the presence of common risk factors such as emotional stress, depression, and anxiety. The reported study was funded by RFBR according to the research project № 18-29-22032.

Dairy intake and odds of peadiatric migraine: A case control study S. Ariyanfar 1, 2 Objective: Migraine is recognized as a disease with various pathophysiologic pathways, which are not fully understood. This study was designed following the relation between dairy intake and various chronic conditions in children and also the paucity of data on the probable role of dairy intake on pediatrics" odds of migraine. Methods: The present study was a population based casecontrol design and included 290 children. Definite diagnosis of migraine was performed by a neurologist, with respect to the 2018 international classification of headache disorder 3(ICHD3) criteria. The usual dietary intake of participants was evaluated, using a validated semiquantitative food frequency questionnaire (FFQ). Result: In the second regression model, odds of migraine were 48% (OR:0.52;95%CI:0.27-1.00) diminished in the second tertile, and 53%(OR:0.47;95%CI:0.24-0.92) in the third tertile of low-fat dairy intake (P-trend:0.03). In fully adjusted model, the migraine ORs were 0.48 (95% CI:0.240.95) in the second tertile and 0.46(95%CI:0.21-0.96) in the third tertile (P-trend:0.04), respectively. Children with more high-fat dairy intake, also consumed higher amounts of energy, pastries, simple sugar, and hydrogenated oil(P<0.05). Conclusion: Greater amount of low-fat dairy intake may attenuates the odds of having migraine attacks in pediatrics, who might be at risk of headache. It can be attributed to the micronutrient and bioactive content of these dietary components.

Background: Molecular mechanisms of pain are complex and difficult to entangle, but important to understand to treat pain disorders. The cold pressor test (CPT) is used as pain provocation test in pain research. We hypothesize, that performing multi-omic analyses during CPT gives the opportunity to home in on molecular mechanisms involved. Methods: Twenty-two females diagnosed with migraine were phenotypically assessed before and after a CPT, and blood samples were taken interictal. RNA-Sequencing, steroid profiling and untargeted metabolomics were performed. Each "omic level was analyzed separately at both single-feature and systems-level (e.g. principal component and partial least squares regression analysis) and all "omic levels were combined using an integrative multi-omics approach, all using the paired-sample design. Results: We showed that unsupervised methods were not able to discriminate time points, while supervised clustering did significantly distinguish time points using metabolomics and/or transcriptomic data, but not using conventional physiological measures. Transcriptomic and metabolomic data revealed at feature-, systems-and integrative-level biologically relevant processes involved during CPT, e.g. lipid metabolism and stress response. Conclusion: Multi-omics strategies should be exploited in pain research to gain knowledge on the biological mechanisms involved in pain.

Combined Oral Contraceptive was associated to protection for severe allodynia A. Vitali da Silva 1 Objective: To assess the effect of combined hormonal contraceptive (CHC) use on the prevalence of severe allodynia in women with migraine. Methods: study composed by women with migraine with or without aura, who were not pregnant, lactating or in menopause. The research was developed through a digital platform. Clinical features and contraceptive method were registered. In sequence, the participants answered to the validated self-applicable questionnaires: Migraine Disability Assessment, Allodynia Symptom Checklist, Generalized Anxiety Disorder and Beck Depression Inventory. To determine variables associated with severe allodynia, 2 binary logistic regression models were used, the first which included all forms of exposure to estrogen and the second included oral CHC. Results: 440 women were included at the study. An amount of 176 women were taking estrogen by taking CHC, and 164 of these were taking it by oral pills. Severe allodynia was identified in 126 participants (29.2%). In multivariate analysis, severe allodynia was independently associated with the presence of aura (OR=2.57 IC95%1.43-4.61; p=0.002), depression (OR= 1.67 IC95%0.97-2.86; p=0.062), migraine-related disability (OR=3.08 IC95%11.82-5.2; p<0.001), and estrogen in the form of oral CHC (OR=0.56 IC95%0,33-0.95; p=0.030). Age, BMI, smoking, menstrual migraine, and anxiety were not related to the presence of severe allodynia. Conclusion: the oral CHC was shown to be a protective factor to severe allodynia. During the last 20 years, our group clinically characterized more than thousand individuals with migraine (with/without aura -MA/MO) or cluster headache (CH). We found several genetic variants involved in vascular component, trigeminal nociceptive plasticity, neurogenic inflammation and in neurotransmitters release. Despite all advances, genetic basis of primary headaches remains unknown. Whole-exome sequencing (WES) is a powerful approach to explore coding regions, particularly low-frequency variants. Objective: Calcitonin gene-related peptide receptor (CGRP-R) antagonists and monoclonal antibodies (mAB) against CGRP or its receptor have few side effects but erenumab in contrast to ligand binding mAB causes constipation in 40% of cases. CGRP activates both the CGRP-R and the structurally related amylin-1 receptor (AMY 1 -R) which have opposing effects on the GI tract. It is unknown if different affinity to these receptors may be the cause of constipation. Methods: Xenopus laevis oocytes expressing human CGRP-R, human AMY 1 -R or their subunits was examined by two-electrode voltage clamp.

Results: CGRP induced a concentration-dependent increase in current in receptor expressing oocytes with the order of potency CGRP-R>>AMY 1 -R>calcitonin receptor (CTR). There was no effect on single components of the CGRP-R. Amylin was only effective on AMY 1 -R and CTR. Inhibition potencies (pIC 50 ) for erenumab on CGRP-induced currents were 10.86 and 9.31 for CGRP-R and AMY 1 -R, respectively. Fig. 1 (abstract P051) . See text for description Rimegepant inhibited CGRP-induced currents with pIC 50 values of 11.30 and 9.91 for CGRP-R and AMY 1 -R, respectively. Conclusions: Our results show that erenumab and rimegepant are potent inhibitors of CGRP-R and AMY 1 -R with 35-and 25-times preference for the CGRP-R over the AMY 1 -R. Clinically, the unopposed anti-peristaltic AMY 1 -R in the absence of the balancing CGRP-R may explain constipation by erenumab while ligand binding mAB keep the balance and cause no constipation. Objective: To investigate how patients and healthcare workers perceive stock images of migraine attacks. Methods: We conducted an anonymous web-based survey among the following two groups: 1) Patients with migraine treated at the Charité Headache Center in 2020 (migraine group); 2) Charité employees and students (healthcare group). We presented ten selected stock pictures (Adobe Stock©) of migraine attacks to all participants. Participants rated on a scale from 0-100% how much each picture corresponds to a realistic migraine attack (realism score). We analysed the mean realism score for all pictures and in the following categories: male/female actors, younger/older actors, unilateral/bilateral pain pose. Results: The survey was completed by 367 patients with migraine and 331 employees and students. In both groups, the mean realism score was <50% (47.8% ±18.3 in the migraine group and 46.0% ±16.2 in the healthcare group). Both patients and healthcare workers considered pictures with male actors more realistic than pictures with females (p<0.001) and pictures with older actors more realistic than those with younger actors (p<0.001). Only in the healthcare group, a bilateral pain posture was considered more realistic than a unilateral pain posture (p<0.001). Conclusion: Standard images of migraine attacks are perceived as not realistic by patients and healthcare workers. A better representation in the media could help raise awareness for migraine and reduce the associated stigma. Objective: Assess pressure pain threshold (PPT) in trigeminal, cervical, and extra trigeminal/cervical pain-free areas in episodic migraine (EM) patients in all the 4 phases of the migraine cycle Methods: Multicenter, cross-sectional, observational study. EM patients and healthy controls (HC) (age 18 -65) were included. Temporal summation of pain (10 consecutive stimuli, 50 g von Frey, 1 Hz frequency) in the trigeminal area and PPT over temporalis muscle, neck region, and dominant hand were assessed. A linear regression model using the variable group to predict the results was performed. Age and sex matched healthy controls were used as the reference group Results: 48 Control, 38 interictal EM, 42 Preictal EM, 30 Ictal EM, and 26 postictal EM were included. Temporal summation was facilitated in Ictal EM compared to HC (p=0.003), with no other difference (p>0.092). In all phases, EM patients had lower PPT in the temporal and cervical area compared to HC (p<0.024; p<0.008). PPT over the dominant hand was reduced only in Preictal EM compared to HC (p= 0.009), with no other differences (p>0.108) Conclusion: EM patients in all phases of the migraine cycle have increased pressure pain sensitization of the trigeminocervical complex, with patients in the ictal phase have further enhanced sensitization. Signs of widespread sensitization are present only in preictal EM patients, and this may reflect an enhanced activation of cortical and subcortical areas in this phase. Methods: Male Sprague-Dawley rats received nitroglycerin (NTG) or vehicle, followed by a NAAA inhibitor (ARN726) or vehicle. Four hours after NTG administration, the expected time of maximal expression of NTG-induced hyperalgesia, we evaluated in the open field the locomotor ability by calculating total distance and anxiety-related behavior by time spent in the central area for 10 minutes, then exposed them to the orofacial formalin test. Rats were then sacrificed to assess gene expression of IL-10 and IL-1beta in the meninges, trigeminal ganglion and medulla pons were collected to assess. CGRP serum levels were analyzed by ELISA kit. Results: ARN726 significantly reversed NTG-induced trigeminal hyperalgesia, but it did not affect the inactivity induced by NTG injection. ARN726 also reduced IL-1beta mRNA levels in meninges and medulla-pons, as well as CGRP serum levels, while it increased IL-10 mRNA levels in meninges and trigeminal ganglion. Conclusions: Our data show that NAAA inhibition has an antiinflammatory effect in the NTG animal model of migraine, where it also prevents NTG-induced hyperalgesia. NAAA inhibition thus represents a potential drug target for migraine treatment. Objective: KATP channel agonist levcromakalim was shown to induce migraine attacks in migraineurs by a high incidence. To investigate the role of KATP channels in migraine, we first tested efficacy of KATP channel inhibition in two distinct rodent models of migraine. Secondly, using levcromakalim as provoking substance, we tested the inhibitory effect of a CGRP monoclonal antibody. Methods: Hind paw and periorbital sensitivity to tactile stimulation were used as surrogate markers of migraine pain in three different rodent models: (i) the GTN mouse model of migraine, (ii) the STA (spontaneous trigeminal allodynia) rat model and (iii) a mouse model of levcromakalim induced migraine. Results: The KATP channel antagonist glibenclamide inhibited the effect of GTN in mice and in STA rats the allodynia was alleviated. Mice injected repeatedly with levcromakalim (1 mg/kg, i.p.) developed a progressive hyperalgesia similar, but milder than that mediated by GTN (10 mg/kg, i.p.). The effect was completely inhibited by glibenclamide, but surprisingly also by a CGRP monoclonal antibody. Conclusion: Reversal of tactile hypersensitivity in two distinct animal models indicates that KATP channel blockers could be effective drugs in the treatment of migraine. Despite KATP channel opening being a downstream event from CGRP binding to its receptor, we find a secondary release of CGRP in vivo after administration of levcromakalim as proven by the efficacy of the CGRP monoclonal antibody.

Profiling PACAP-responsive receptor pharmacology and agonistdependent antagonism Z. Tasma Objective: Calcitonin gene-related peptide (CGRP) is an important neuropeptide in the pathophysiology of migraine and a target for novel anti-migraine medication. While its signaling is assumed to be mediated via increases in cAMP, we focused on actually elucidating intracellular signaling pathways involved in CGRP-induced relaxation of human isolated coronary arteries (HCA). Methods: Concentration-response curves to CGRP (10 pM-1 μM) were constructed in HCA segments obtained from 11 male and 5 female donors (age 49±4 years), incubated with or without the PKA inhibitor Rp-8-Br-cAMPs (100 μM), the adenylate cyclase (AC) inhibitors SQ22536 (100 μM) and 2′,3′-dideoxyadenosine (DDA, 10 μM), or the guanylate cyclase (GC) inhibitor ODQ (10 μM). Results: The AC inhibitors SQ22536 and DDA, and the PKA inhibitor Rp-8-Br-cAMPs, did not inhibit the CGRP-induced relaxation of HCA, nor did the GC inhibitor ODQ. Conclusion: While CGRP signaling is generally assumed to act via cAMP, the CGRP-induced vasodilation in HCA could not be inhibited by targeting this intracellular signaling pathway at different levels. As inhibition of GC also did not affect relaxations to CGRP, it is important to further identify the intracellular signaling cascade after binding of CGRP to its receptor in human arteries. This would ultimately allow novel anti-migraine medication to target specific parts of the intracellular signaling pathway that reduces migraine, while limiting (cardiovascular) side effects.

The impact of glucose on mitochondrial function in a brain slice model of cortical spreading depression O. Grech 1 , D. Objective: A fundamental mechanism of migraine is cortical spreading depression (CSD), a wave of depolarisation across the cortex.

Fasting is noted to trigger and aggravate migraine attacks. Using a mouse brain slice model, we investigated the impact of hypoglycaemia and CSD on mitochondrial function. Methods: CSD was induced with 1ul 2M KCl (KCl+ vs. KCl-) to cortical regions of acute brain slices (C57BL/6J). 10 minutes after KCl, mitochondrial oxidative respiration was assessed using Oroboros O2k oxygraphy, in the presence or absence of glucose (10mM vs 0mM). CSD was measured with Fluo-4-AM, a fluorescent calcium indicator. Results: Fluo-4-AM induced a wave of calcium following KCl. In KCland KCl+ slices basal respiration is unchanged, however, in the absence of glucose we observed increased oxidative capacity from complex I and II (12.54 vs. 17.94 pmol O2/mg-1/s-1 p = 0.002) and maximal rates of uncoupled respiration (13.60 vs. 19.93 pmol O2/mg-1/s-1, p<0.001, n = 6). This was rescued with glucose (n=6). Conclusions: In the absence of glucose, CSD increased the oxidative capacity of complex I and II and maximal rates of uncoupled respiration, which was rescued by glucose (10mM). Energetic deficits due to glucose deficiency may trigger upregulated oxidative respiration following CSD, in order to compensate. Adequate glucose appeared to ameliorate CSD disturbances in energy metabolism. This may be relevant to observations that migraine attacks are aggravated by fasting. Objective: To assess the frequency of opioid use for acute headache treatment in the Emergency Department (ED) of a private Hospital in Brazil. Methods: Cross-sectional study which included all patients admitted to the ED of the Sao Paulo Samaritano Hospital in 2018, who were diagnosed with International Classification of Diseases codes R51, G43 or G44. The subjects treated with opioids were compared to those who were not for demographical characteristics, ED visit duration and healthcare-related costs. Results: We identified 3,943 ED visits due to headache, and opioids were used in 11.3% of these. The types of administered opioids were: tramadol (92.4%), morphine (3.9%), tramadol and acetaminophen combination (3.3%) and nalbuphine (0.2%). Subjects who received opioids had greater probability to return to the ED in the same studied year (OR 1.61, 95%CI 1, 99) . They also stayed 45.5% longer in the ED than those who did not receive opioids. Average cost per visit among opioid-treated subjects was 51.1% greater (95%CI 21.4-42.3%). Subjects who received opioids were more frequently: female (p=0.018) and admitted in the period from 0:00 a.m. to 6:00 a.m (p< 0.001). Conclusion: We found a high frequency of opioid use for acute headache treatment in the ED, however lower than those previously reported by north-american studies. Opioid use was associated with higher healthcare-related costs per visit. These data were previously presented at the 33 th Brazilian Headache Congress. Objective: Excessive daytime sleepiness (EDS) is one of the most common sleep disorders in adolescents associated with social behaviors patterns and school performance. We aimed to investigate EDS comorbidity with recurrent headache in Central Siberia urban adolescents. Materials and Methods: 4680 urban Siberian (Krasnoyarsk, Abakan, Kysyl) school-based adolescents (aged 12-18; boys/girl ratio 2190/ 2490) were tested with Pediatric Daytime Sleepiness Scale (PDSS); cutoffs for EDS were PDSS 95% percentiles for each age group. Adolescents were also asked about headache presence/frequency and pain intensity according to 6-points Visual Analogue Scale (VAS). Clinically relevant recurrent headache was diagnosed at headache frequency ≥ 2 per month and VAS score ≥ 4 points. Chi-square and Mann-Whitney tests were used. Results: The recurrent headache group exhibited a higher prevalence of EDS in comparison with the non-headache group (1.50% and 4.81%, respectively, p<0.001). PDSS score was higher in headachers (headache group -14 (10-18), non-headache group 10 (7-14), p< 0.001). Also, we found a positive correlation between PDSS and VAS scores (Spearman's r=0.366, p<0.05) Conclusion: EDS is strongly associated with recurrent headache in Siberian adolescents. The possible explanations of this relation may be night sleep disturbances in headachers and the presence of common pathogenic factors, such as personality characteristics, depression, anxiety.

Interactions of the neuropeptide galanin with cortical spreading depolarization and cortical neuronal excitability F. Galanin modulates in hippocampal neurons the release of neurotransmitters, and thereby it influences neuronal excitability. To test its actions on neurons in cerebral cortex, we recorded ongoing brain activity and induced cortical spreading depolarization (CSD) before and after application of galanin. In spontaneously breathing anesthetized adult rats (sodium thiopentone, 100 mg/kg, i.p.) the electrocorticogram was recorded with arrays of glass microelectrodes in two areas (treated with galanin and untreated) and different depths. CSD was induced by KCl microinjection. CSD-related potential shifts, changes in extracellular potassium concentration and in regional cerebral blood flow were continuously monitored. Galanin at concentrations of 10 -6 , 10 -7 , 10 -8 , 10 -9 , and 10 -10 M was applied for 3 h and then washed away with artificial cerebrospinal fluid. Galanin at concentrations of 10 -6 , 10 -7 , and 10 -8 M increased the threshold for elicitation of CSD, reduced amplitudes of CSD and significantly slowed propagation velocity of CSD. In some rats, during galanin, the CSD propagated only in the untreated area. Lower concentrations of galanin had no significant effects. In the washout phase after these three concentrations of galanin ictal discharging or repetitive seizure activity were observed in nearly 50 % of rats. We conclude that galanin has the potential to control cortical neuronal activity. This could be a target for brain diseases that involve cortical hyperexcitablity. Objective: To estimate headache disability and explore its association with lifestyle factors, health perception, and mental disorders symptoms in a national health survey in Brazil. Methods: In a cross-sectional analysis of the PNS 2013 Survey, logistic regression models computed the associations between headacherelated disability (days lost from work, school, or household chores in the past 2 weeks) and lifestyle factors, health perception, and mental disorders symptoms compared to other disease-related disabilities or no day lost group. The adjusted models controlled for the effects of age, sex, income, and educational levels. Results: In the sample aged ≥ 18 years (n = 145,580), 10,728 (7.4 %) participants reported any disease-related disability in the past 2 weeks [median interquartile range (IQR) for age = 47 (33-59) years, 62 % women], with the median (IQR) days lost = 5 (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) . Headache disability represented 5.3 % (572/10,728) of all diseases, constituting the 2nd as most prevalent disability (13%) in young people, Headache disability associated with physical inactivity, poorer health perception and mental disorders symptoms. Conclusion: Headache disability represents a leading cause of disease-related disability in Brazil, and associates with unhealthy lifestyle factors, poorer health perception, and mental disorders symptoms. Objective: Headache patients in the emergency room (ER) present multiple challenges, like excluding secondary headache (SH), providing efficient pain relieve for primary headache (PH) patients, provide recommendations for treatment. Research in this field could improve execution of these tasks. Methods: This prospective research involves quantitative analysis of 50 ER patients with primary complaint of headache over 4-month period. The data of patient questioning, examination are documented in a specially designed questionnaire. Results: Out of 50 patients, aged 22 to 77 years, 48% were PH patients, whereas 36% were SH, 16% unspecified headache patients. Most common headache types in this research are listed in Table 1 . Although 68% of the patients had previously suffered a headache, 14% had sought medical attention, but only 10% are diagnosed with a headache disorder. 54% described their headache at 4 out of 5 points, with 62% experiencing accompanying symptoms, such as nausea (41%), photophobia (24%). Almost all participants (90%) presented with at least one "red flag" symptom for SH, such as unfamiliar headache (26%), meningeal signs (13%). Only 28% needed to be hospitalized. Conclusion: Majority of headache patients in the ER consist of PH patients, who can be treated on outpatient basis. More patients need to seek medical care to be diagnosed and receive treatment. Better education and detailed recommendations are necessary for all patients, to reduce unnecessary ER visits. Migraine patients are interested in lifestyle influences on their attacks and 25% have stopped consuming or never consumed alcohol because of presumed trigger effects (Onderwater et al. Eur J Neurol. 2019; 26:588-95) . However, it is unknown if they apply restrictions on potential triggers compared to healthy controls and the general Dutch population. In this cross sectional study in migraine patients and controls from the Leiden LUMINA cohort, we collected data for alcohol, tobacco and illicit drug consumption. Data from the general population (GP) were extracted from the annual health survey (Statistics Netherlands). From the LUMINA-cohort, n=6228 subjects were included (migraine n=5689, controls n=539). In the migraine group, 5487 subjects provided data to distinguish between episodic (EM) and chronic migraine (CM). From the general population 14,542 subjects were included. Migraine patients used less illicit drugs, tobacco and alcohol compared to GP (p<0.01). For our control group; controls had higher consumption of alcohol and packyears (both p<0.01) compared to migraineurs, but showed reduced illicit drug use compared to GP (p<0.01). CM had lower consumption and less consumers of alcohol (p<0.01) compared to EM, more smokers and packyears (p< 0.01), but no difference in illicit drug use. Migraine patients avoid illicit drugs, tobacco and alcohol compared to the GP. CM report less alcohol use, more smoking, but similar low illicit drug use compared to EM. Background: CGRP plays a key role in the pathogenesis of migraine. Objective: To assess saliva as a substrate to measure CGRP by comparing interictal levels in episodic migraine (EM) and controls (HC); and to evaluate its temporal profile during migraine attacks. Methods: This is a prospective observational pilot study in which we monitored salivary CGRP during 30 consecutive days and during migraine attacks. We considered 6 timepoints:interictal (72h headache free), preictal(PRE-24h before), ictal (headache onset, after 2h and 8h), postictal (POST-24h after). Results: 44 women (22 EM, 22 HC) 3, 160 .0) pg/ml;p<0.001). Patients were classified as having CGRP-dependent (79.6%) and non-CGRP dependent migraine attacks (20.4%) according to the magnitude of change between preictal and ictal. Photophobia and phonophobia were significantly associated to first group. Conclusions: Salivary CGRP levels, which interictally are elevated in episodic migraine, usually increase during a migraine attack in the majority of patients. However, not every attack is CGRP-dependent.

Micro-array analysis of the hypothalamus in an animal migraine model R. Abuukar Abdullahi 1,2 , T. Takahashi Objective: Migraines can be defined as a cyclical disorder with 4 phases, the premonitory phase reflects the initiation of the migraine and hypothalamic dysfunction has been implicated in it. Infusion of GTN has been shown to trigger migraines and premonitory symptoms similar to those seen in spontaneous attacks. This study aims to investigate early transcriptional responses to GTN-infusion in the mouse hypothalamus in order to elucidate the mechanisms involved in the initiation of migraine attacks. Methods: Mice were anaesthetized and infused with GTN or vehicle for 30 minutes. Thereafter, the hypothalamus was collected for microarray analysis. Expression patterns of selected genes were confirmed by qPCR. Pathways analysis was carried out using DAVID Bioinformatics Resource. Results: Differences in gene expression were detected in 45037 genes between treatments, and of those 864 were significantly different (P <0.05). The DAVID analysis demonstrated enrichment of pathways suggesting an increase in circadian rhythm, signal transduction and immune responses. Conclusion: Several of the pathways known to be involved at later phases in migraine, such as dysregulation of neurotransmission, seem to be initiated in the hypothalamus. Additionally, we found unexpected enrichment in pathways, such as inflammation which previously have not been reported in the premonitory phase of migraine. Further studies are needed to assess their role in the initiation of a migraine attack.

The influence of calcitonin gene-related peptide on cerebral hemodynamics and calcitonin gene-related peptide-induced headache in migraine with aura M. Zaletel 1 , D. Background: Exogenous calcitonin gene-related peptide (eCGRP) can induce CGRP induced headache (CGRP-IH). In patients with migraine with aura (MA), eCGRP may induce aura attacks. This implies a common pathophysiological mechanism of trigeminovascular sensitization (TVS). We predicted that cerebral hemodynamic detected by TCD and induced by eCGRP differ between migraine without aura (MwA) and MA using TCD. Background: Calcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (KATP) channels.

Here, we investigated the effect of the KATP channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers. Methods: In a randomized, double-blind, placebo-controlled, crossover study, 20 healthy volunteers were randomly allocated to receive an intravenous infusion of 1.5 μg/min CGRP after oral pretreatment with glibenclamide or placebo. The primary endpoints were the difference in incidence of headache and the difference in AUC for headache intensity scores between glibenclamide and placebo. The secondary endpoints were the difference in AUC for VMCA, STA and RA diameter, facial flushing, HR and MAP between glibenclamide and placebo. Results: We found no significant difference in the incidence of headache between glibenclamide-CGRP day and placebo-CGRP day (P= 0.06). The AUC for headache intensity, VMCA, STA, RA, facial skin blood flow, HR and MAP did not differ between glibenclamide-CGRP day compared to placebo-CGRP day (P > 0.05). Conclusion: Pretreatment with a non-selective KATP channel inhibitor glibenclamide did not attenuate CGRP-induced headache and hemodynamic changes in healthy volunteers. We suggest that CGRPinduced responses could be mediated via activation of specific isoforms of sulfonylurea receptor subunits of KATP channel. Objective: We examined the diffusion tensor imaging (DTI) parameters and neurite orientation and dispersion imaging (NODDI) in patients with migraine and healthy control. Materials and Methods: Twenty-six patients with migraines and 24 healthy controls were recruited. All patients underwent DTI and NODDI using 3.0 T MRI. The fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, orientation dispersion index (ODI), the fraction of intracellular volume (ficv), and the fraction of isodiffusion (fiso) values in the whole brain were analyzed using tractbased spatial statistics. Results: Twenty-six migraine patients (43.4±13.8 years old) and 23 healthy control (44.9±12.7 years old) were included for the analysis. The mean disease duration of migraine was 21.3±15.9 years. Migraine frequency was episodic for 16 patients, and chronic for 10 patients. Medication overuse headache was associated in 4 migraine patients.

There were no significant differences between migraine patients and healthy control in the DTI and NODDI parameters. The ficv of chronic migraine patients showed slightly lower at right temporal than those of episodic migraine patients. Conclusion: Our study demonstrated neurite damage in chronic migraine patients. NODDI may be useful to understand the pathophysiology of migraines.

Effect of adrenomedullin on migraine-like attacks in patients with migraine: A randomized crossover study H. Ghanizada Danish Headache Center, Neurology, Taastrup Objective: To determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients. Methods: Twenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline). The primary outcome of the study was predefined as a difference in migraine incidence (0-12 h) and the secondary outcome were the headache intensity score"s area under curve (AUC0-12 h). Results: Eleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo (P= 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion (P= 0.035). AUC0-90 min for HR and, flushing (P < 0.05) were significant and MAP (P = 0.502) remain unchanged. Common adverse events reported were facial flushing, heat sensation and palpitation (P <0.001) Conclusion: Our data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hypothesized that levcromakalim, an ATP-sensitive potassium channel opener, would trigger migraine attacks with aura in migraine with aura patients. In a randomized, double-blind, placebo-controlled, crossover study, 17 patients aged 21-59 years and diagnosed with migraine with aura exclusively were randomly allocated to receive an infusion of 0.05 mg/minute levcromakalim or placebo (isotonic saline) on two different days (ClinicalTrials.gov, ID: NCT04012047). The primary endpoints were the difference in incidence of migraine attacks with or without aura, headache and the difference in the area under the curve for headache intensity scores (0-12h). Seventeen patients completed the study. Fourteen of 17 (82%) patients developed migraine attacks with and without aura after levcromakalim compared with 1 of 17 (6%) after placebo (P<0.001). Ten patients (59%) developed migraine with aura after levcromakalim compared with none after placebo (P=0.002). One additional patient reported "possible" aura, only partially fulfilling the criteria. is likely a novel migraine aura-inducing substance in humans. These findings highlight the ATP-sensitive potassium channel as a shared target in migraine aura and migraine headache. Likely, ATP-sensitive potassium channel opening leads to triggering of aura and headache, respectively, via distinct mechanisms. Background and Objective: Preventive treatment is crucial for patients with chronic migraine (CM). Present study aimed to associate 3-month preventive treatment outcomes of flunarizine with restingstate cortical oscillations at baseline. Methods: Treatment naïve CM patients and healthy controls (HC) were recruited. Resting-state EEG data was recorded under eyeclosed condition and analyzed over the bilateral primary somatosensory (S1) and visual (V1) cortex. According to the changes of the monthly headache days (MHDs) (3-month vs. baseline), CM patients were arranged into responders (≥50% decrease) and non-responders. The oscillatory powers were compared between groups (CM and HC; responders and non-responders). Results: The demographic, clinical and resting-state EEG data from 72 CM and 50 HC were analyzed. No significant difference was observed in the demographic data; however, elevated level of anxiety, depression, and stress were noted in CM. Resting-state theta power in bilateral S1 and alpha and gamma power in the right S1 were increased for CM. Regarding the treatment outcome, augmented alpha powers in bilateral V1 were noted in non-responders. The alpha powers exhibited significant correlations with the change of MHDs. Conclusion: Resting-state occipital alpha activities at baseline determine the 3-month treatment outcome. This EEG measurement might be one of the signatures for conceivable treatment plan towards personalizing migraine medicine. Objective: To verify the presence of abnormalities of the morphology of gyrification and cortical thickness (CT) in pediatric patients with migraine without aura Reading View. Premere ALT+MAIUSC+A per visualizzare la Guida per l'accessibilità.and to identify the clinicalradiological correlations. Materials and Methods: Estimation of CT and gyrification morphology was performed on the 3D T1 MPRAGE sequence without contrast medium of 73 patients and 49 controls (CTR). Permutational statistical analysis for linear models was carried out to evaluate the significance of the results obtained. Results: Statistically significant data (p<0.05) are related to the reduction of CT in migraine patients <12 years of age compared to CTR, in particular areas involved are the convolutions: superior frontal, middle frontal, pre-central, post-central of the right hemisphere; superior frontal, post-central, superior parietal lobule, precuneus of the left hemisphere. Regarding the gyrification index, statistically significant differences (p<0.05) were found in migraine patients who presented <5 monthly attacks compared to CTR, in particular altered areas are the lateral and medial orbitofrontal cortex of the left hemisphere. Conclusion: The areas involved are in the networks of nociception, pain processing and of executive functions, and it"s interesting to note that this result is present only in youngest patients who therefore have a more recent history of disease, suggesting that these alterations may be a true biomarker of migraine.

Neural signatures associated with treatment response in chronic migraine H. Y. Liu 1,2 , K. H. Chou 3, 4 , P. L. Lee 3, 4 , Y. F. Wang 1,2 , S. P. Chen 1, 2, 4, 5 Objective: To identify the neural signatures associated with treatment response in patients with chronic migraine. Methods: We enrolled 20-60 years old newly diagnosed CM patients. All patients were asked to record the headache diary. Clinical data and a brain MRI were obtained at first visit. Based on diary, headache frequency in the 1st month without treatment was baseline frequency. We gave flunarizine as first line treatment, and topiramate as the second line treatment, and longitudinally followed up the patients for another 3 months. Good response was defined as ≥50% reduction at the 4th month headache frequency compared to the baseline frequency. The others were considered as poor response. Gray matter volume of each brain region was obtained using Freesurfer and Desikan-Killany atlas. Analysis of covariance test was used to compare volumes between patients with different responses. Results: A total of 78 patients with CM were included in the study. Among them, 41 had good response and 37 had poor response to treatments. Patients with good and poor responses were comparable in age, sex, and scores of hospital anxiety and depression scale and migraine disability assessment. Compared to those with good response, patients with poor response had higher baseline headache frequency, and had smaller volumes of the bilateral medial and lateral orbitofrontal, inferior frontal, and temporal pole, right hippocampus, and left post-central gyrus. Conclusion: Reduced cortical and subcortical volumes are associated with poor response to treatments in patients with CM.

Investigation of cortical thickness and volume during spontaneous attacks of migraine without aura: a 3-Tesla MRI study Aim and hypothesis: The aim of the present study was to investigate transient changes in cortical thickness during spontaneous migraine attacks. We hypothesized that pain-related cortical area would be affected during the attack compared to an inter-ictal phase. Methods: 25 patients with migraine without aura underwent 3D T1w imaging on a 3T MRI scanner during spontaneous and untreated migraine attacks. Subsequently, 20 patients were scanned in the interictal phase, while 5 patients did not show up for the inter-ictal scan. Four patients were excluded from the analysis because of bilateral migraine pain and another one patient was excluded due to technical error in the imaging. Imaging analysis was done using FreeSurger. ANOVA was used for statistical analysis and he level of significance was set at p=0.025. Results: Cortical thickness of prefrontal (p=0.023), pericalcarine (p= 0.024), and temporal pole (p=0.017) cortices during attack compared to the inter-ictal phase. Cortical volume was reduced in prefrontal (p=0.018) and pericalcarine (p=0.017) cortices as well as the hippocampus (p=0.007). No correlations between these findings and clinical parameters were found. Conclusion: Spontaneous migraine attacks are accompanied by transient reduced cortical thickness and volume in pain-related areas. The findings constitute a fingerprint of acute pain in migraine patients, which can be used as a biomarker to predict antimigraine treatment (e.g. TMS) effect in future studies. Background and objective: Occipital nerve stimulation (ONS) is a surgical treatment proposed for redractory chronic cluster headache (rCCH). Long-term series assessing its efficacy are scarce. Our objective is to share the outcome of rCCH treated with ONS in our unit. Methods: We designed a retrospective observational study with consecutive sampling, evaluating the follow-up of 22 rCCH patients who underwent ONS. Our endpoint was the weekly attacks reduction. We also evaluated the pain intensity scored by the Visual Analogue Scale (VAS), patient overall perceived improvement and decrease in oral medication intake. .002]. 23.5% had an overall perceived improvement of ≥70% at 3 months, 41.2% at 1 year and 27.8% at the end of follow-up. Reducing prophylactic oral medication was possible in 59.1% and it was stopped in 13.6%. Triptan use decreased in all the responder patients and 13.6% stopped its intake. 40.9% presented mild adverse events. Conclusions: Our long-term experience shows that ONS is a beneficial treatment which does not entail serious harm and should be offered as the first option for rCCH management. Human models of migraine have been used for the past 30 years to test putative "trigger" molecules and ascertain whether they induce migraine attacks in humans. However, nocebo effects using this model have never been systematically explored. Objective: To assess the nocebo response rate in randomised clinical trials conducted at the Danish Headache Center. Methods: Studies of human models of migraine with a randomised, double-blind, placebo-controlled, two-way crossover design that included data on the incidence of migraine attacks or headache after infusion of placebo. A total of 943 articles were screened. Of these, 27 studies met the inclusion criteria (1994 and 2020) and were included in the qualitative and quantitative analysis. Results: 12 studies reported data for adults with migraine (n=182) whereas 16 studies reported data for healthy volunteers (n=210). For adults with migraine, the pooled incidence of migraine attacks after placebo was 8.1% (95% CI = 2.5-15.5%, I2=50.8%). The pooled incidence of delayed headache was 25.9% (95% CI = 18.5-34.1%, I2= 18.9%). For healthy volunteers, the pooled incidence of migraine attacks after placebo was 0.5% (95% CI = 0.0-3.6%, I2=0.0%) while the pooled incidence of delayed headache was 10.5% (95% CI = 4.8%-17.6%, I2=45.2%). Conclusion: The nocebo response in randomised, placebo-controlled two-way crossover trials with intravenous infusions of placebo in migraine is negligible. Objective: To evaluate a patient-identified most bothersome symptom (PI-MBS) measure from PROMISE-2 as a patient-reported outcome measure (PROM) for the preventive treatment in chronic migraine. Methods: Rather than selecting from a predefined list, the PROMISE-2 PI-MBS was captured at screening by querying patients using an open-ended question; responses were recorded and then categorized by investigators. Correlations between PI-MBS, monthly migraine days (MMDs), and PROMs at week 12 were calculated. Linear regression models were used to calculate unique effects of PI-MBS controlling for MMD changes. Results: Patients (N=1072) reported 23 unique PI-MBS, grouped into 3 classes: pain-related (n=462), cardinal non-pain (n=440), and other (n=170). The 3 classes did not significantly differ in week 12 improvement (P>0.05), nor in associations among week 12 PROMs (P>0.05), supporting pooling over symptom classes for subsequent analyses. PI-MBS significantly correlated with MMDs and all PROMs (all P<0.01); PI-MBS correlated highly with Patient Global Impression of Change (r=0.84) and more strongly with headache-related PROMs (r~0.5) vs general PROMs (r=0.21-0.34). Controlling for MMD changes, PI-MBS improvement provided unique effects on PROMs (all P<0.01). Conclusion: These exploratory analyses suggest that the PROMISE-2 PI-MBS may be a unique measure for assessing patient-centered aspects of burden of disease and benefits of treatment. Objective: To assess the relationship of acute treatment optimization to lost productive time (LPT) and variation in this relationship by number of monthly headache days (MHDs). Methods: This analysis included CaMEO survey respondents who met modified migraine criteria consistent with International Classification of Headache Disorders-3; were current users of acute prescription medications for migraine; and were employed full-time. LPT was defined as the sum of absenteeism and presenteeism days in the prior 3 months. Acute treatment optimization scores based on the Migraine Treatment Optimization Questionnaire (mTOQ-5) (dichotomous scoring) ranged from optimal (5 positive responses) to very poor (0 positive responses). Headache frequency groups included 0-3, 4-7, 8-14, or ≥15 MHDs. Results: Of 16,789 respondents with migraine, 2455 (14.6%) met inclusion criteria. Positive responses on the mTOQ-5 were associated with less LPT. This relationship was statistically significant in all MHD groups (linear trend test: P≤0.001) except 8-14 MHDs. For example, in the ≥15 MHD group, mean 3-month LPT was 30.4 days in the poor/very poor groups (≤1 positive response), but 7.1 days in the optimal group (5 positive responses). Results were similar after controlling for sociodemographic and headache characteristics. Conclusion: In people with migraine, suboptimal acute treatment optimization was associated with greater LPT. Optimizing acute treatment may mitigate LPT and reduce indirect costs. To assess the safety and tolerability of atogepant, an oral, calcitonin gene-related peptide (CGRP) receptor antagonist in development for migraine preventive treatment, once daily over 1 year. Multicenter, open-label trial (NCT03700320). Adults with migraine were randomized 5:2 to atogepant (ato) or oral standard-of-care (SOC) migraine prevention. 744 randomized participants (pts; n=546 atogepant), 739 safety population pts (n=543 ato). Adverse events (AEs) were reported by 67.0% of ato pts; 18.0% of pts had AEs considered related to ato by the investigator. Most commonly reported AEs (≥5% of pts) following ato treatment were upper respiratory tract infection (10.3%), constipation (7.2%), nausea (6.3%), and urinary tract infection (5.2%). 4.4% of ato pts reported serious AEs and included a broad variety of common medical conditions; no event was seen in ≥1 pt and none were ato-related. Two deaths were reported in pts treated with ato (victim of homicide; group A beta-hemolytic streptococcal sepsis [toxic shock syndrome]); both were considered not related. 5.7% of ato pts discontinued due to AEs. Alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels ≥3Xs the upper limit of normal were reported for 2.4% of ato pts (n=13/531) and 3.2% for SOC pts (n=6/ 190). No cases of potential Hy"s Law were reported. Long-term, once-daily use of atogepant for the preventive treatment of migraine over 1 year was safe and well-tolerated with no safety concerns identified. Objective: To investigate the predictors of neck disability in migraine and determine if scores from the Neck Disability Index (NDI) versions (NDI-physical, NDI-mental, NDI-8, NDI-5) are associated with cervical musculoskeletal dysfunction.

Methods: Migraineurs with neck pain (n=104) were assessed on migraine and neck pain features, the Neck Disability Index (NDI), Headache Impact Test (HIT6), Allodynia Symptom Checklist (ASC12) and pressure pain thresholds (PPTs). Cervical dysfunction was previously identified in 45 but not in 59 of these individuals. NDI score was regressed on migraine features, HIT-6, total PPT, ASC12, while accounting for neck pain features and the presence or not of cervical dysfunction. Presence of cervical dysfunction was regressed on the scores of NDI versions. Results: Neck pain intensity (B=2.26, p<0.001) and frequency (B=5.08, p<0.001), the ASC12 (B=0.71, p=0.018) and HIT6 scores (B=0.42, p= 0.049) were significantly predictive of NDI score. Presence of cervical dysfunction and other variables were not predictive of NDI score. No version of NDI was associated with cervical dysfunction (NDI-physical: Χ 2 =0.038, df=1, p=0.85, NDI-mental: Χ 2 =0.246, df=1, p=0.62, NDI-8: Χ 2 =0.010, df=1, p=0.92, NDI-5: Χ 2 =0.274, df=1, p=0.60). Conclusion: The NDI is a complex measure of neck disability in migraine that is related to headache disability and allodynia, but not necessarily indicative of cervical dysfunction. Objective: Periaqueductal gray (PAG) plays an important role in the modulation of descending pain control. Previous MRI studies showed that increased PAG iron levels in both episodic and chronic migraine patients correlated with disease duration. Transcranial sonography (TCS) is an imaging technique that allows visualization of heavy metals in the brain parenchyma as an area of hyperecogenicity. Our aim was to investigate hyperechogenicity of PAG in migraine patients. Methods: We investigated with TCS 13 patients with episodic migraine (EM), 15 with chronic migraine and medication overuse headache (CM+MOH) and 10 Healthy Controls (HCs). The area of PAG hypercogenicity visualized through the transtemporal window was measured semiautomatically on each side and then calculated as a mean value. Results: PAG hyperechogenicity was visualized in 100% of the CM+MOH patients, 69% of EM patients and 44% of HCs (p <0.001). No significant difference was found in the hyperechogenic PAG area among the three groups (p=0.295). However PAG hyperecogenicity area correlated with disease duration (p<0.023), pain intensity (p< 0.031) and scores of the HIT-6 scale (p<0.043). Conclusion: These preliminary data suggest that repeated migraine attacks may lead over time to increased oxidative stress and free radicals release, contributing to secondary damage, contextual hyperaemia, and iron deposit in the PAG. Introduction: White matter hyperintensities (WMH) are frequently detected in migraine patients, however, their significance remains uncertain. Objective: To evaluate the WMH pattern of different migraine subtypes Methods: A brain MRI (Siemens, Germany, 3T) was performed in 92 otherwise healthy migraine patients with no vascular risk factors (73 females, mean age 34.6±8.9; 61 episodic migraine, 31 chronic migraine, 36 migraine with aura, 56 migraine without aura). Results: The prevalence of WMH in different types of migraine was similar and ranged from 38.7% to 44.4%. The distribution of focal WMH decreased from the frontal to the parietal and to the temporal lobe. In most cases, WMH were located in the juxtacortical and/or deep white matter; only 2 patients had periventricular WMH. WMH appeared as round or slightly elongated foci with a median size of 2.5 mm [1.5; 3] . Total number, size and prevalence of WMH by lobes and white matter regions were similar between groups, and no interaction with age or sex was found. Conclusion: Patients with different subtypes of migraine and without vascular risk factors have a similar pattern of WMH and no subclinical infarctions and microbleedings, which indicates the low prognostic value of WMH in identifying a specific migraine subtype or vascular complications of migraine. WMH pattern may be used to differentiate migraine as a primary disorder and other disorders with migraine-like headache and WMH. Objective: to verify if a craniocervical exercises protocol was able to reduce the disability caused by migraine. Methods: thirty-three women with a diagnosis of migraine with a mean age of 32.5 (SD=8.5) years and a frequency of 9.8 (SD=7.6) days/month were included. All volunteers signed an informed consent form and answered the Migraine Disability Assessment (MIDAS) questionnaire. The craniocervical exercise protocol started after the initial data collection and lasted for 8 weeks. The protocol consisted of active exercises for the deep and superficial flexor and extensor muscles of the cervical spine. The volunteers had once weekly sessions with the physiotherapist to progress the exercises. At the end of the treatment, the MIDAS questionnaire was applied again. For the comparison between pre and post treatment, a paired Student"s t test was used. SPSS version 20.0 software was used and a significance level of 0.05 was adopted. The study was approved by the local ethics committee (6146/2016). Results: we observed a significant reduction of 14.6 (SD=29.5; 95% CI=4.2 -25.1; p=0.008) points in the total score of the MIDAS questionnaire after the 8-week treatment. A reduction of 5 points in MIDAS questionnaire is considered a clinically important change and 21 (63.6%) volunteers showed a reduction of ≥5 points in questionnaire. Conclusion: a craniocervical exercises protocol lasting 8 weeks had a positive effect in reducing the disability in patients with migraine.

Pharmacological characterisation of mouse calcitonin and calcitonin receptor-like receptors reveals differences compared to human receptors M. Garelja 1 , C. Walker 2,3 , D. Hay 1, 3 gene-related peptide (CGRP) and amylin. CGRP has been successfully targeted for the treatment of migraine but mechanistic understanding of exactly how CGRP contributes to migraine is still poorly resolved. Mouse models are commonly used to probe CGRP and related peptide biology. However, the pharmacology of mouse calcitonin family receptors is poorly characterised, creating challenges for data interpretation and translation of pre-clinical findings to humans. We therefore investigated the pharmacology of mouse calcitonin family receptors. Methods: Plasmids encoding mouse receptors were transfected into Cos7 cells. Cells were stimulated with agonists with and without antagonists and cAMP production measured. Results: The pharmacology of these receptors differed between humans and mice, with mouse receptors generally displaying less discrimination between peptides. This was most apparent for receptors that included the calcitonin receptor. Overall, CGRP had nanomolar potency at four mouse receptors. Conclusion: Our findings are a framework for interpreting pre-clinical findings. The data reveal challenges in interpreting which receptor may underlie an effect in pre-clinical models, and thus translation of findings from mice to humans. The work also highlights the need for more selective ligands that can differentiate between these receptors. Objective: Compare maternal, fetal and infant outcomes among pregnant women with migraine exposed to galcanezumab to those exposed or not exposed to other migraine medications. There is a need to study utilization and safety of these medications before/during pregnancy since data on outcomes of pregnancies exposed to galcanezumab is limited. Methods: This multidrug pregnancy registry will enroll women with migraine exposed to galcanezumab up to 5 half-lives before/during pregnancy. Pregnant women with migraine (exposed or not exposed to other migraine medications) will be enrolled into comparator groups. Eligible women may enroll or be enrolled by their Health Care Provider by calling the phone number/visiting the website listed in the US Package Insert. Information on mother and fetus/infant (eg, demographics/medical history/exposures/outcomes) will be collected at multiple time points during pregnancy and to 1 year post delivery. Results: The primary outcome assessed in this pregnancy registry is major congenital malformations. Additional maternal, fetal and infant outcomes (to 1 year of age) will be evaluated. Conclusions: Real-world studies are needed to evaluate utilization and safety of new migraine medication exposures in pregnancy. This registry is part of a larger effort towards this goal. Sufficient enrollment of pregnant women will enable execution of two comparative safety studies using this registry. Objective: Determine if mindfulness-based stress reduction (MBSR) improves migraine outcomes compared to Headache (HA) Education. Methods: Randomized clinical trial in adults with 4-20 migraine days/ month comparing MBSR vs. HA Education (n=89), both delivered in eight weekly classes. Participants were blinded to active vs. comparator group assignments, and PI/data analysts to group assignments. Results: Participants in both groups had fewer migraine days at 12 weeks (MBSR: -1.6 migraine days/month; 95% CI: [-0.7, -2.5]; HA Education -2.0; [-1.1, -2.9]), without group differences (p=0.51). MBSR participants, compared to HA Education, had improvements from baseline at all follow-up time points on measures of disability (5.92 (95% CI 2.8, 9.0) p<0.001); quality of life (5.1 (1.2, 8.9 ) p=0.01); selfefficacy (8.2 (0.3, 16.1, p=0 .04); pain catastrophizing (5.8 (2.9, 8.8) , p< 0.001); depression scores (1.6 (0.4, 2.7) p=0.008), and decreased experimentally induced pain intensity and unpleasantness (p= 0.004 and 0.005, respectively, at 36 weeks). One reported adverse event was deemed unrelated to study protocol. Conclusion: Both MBSR and HA Education improved migraine frequency. MBSR also had clinically meaningful improvements in disability, quality of life, self-efficacy, pain-catastrophizing, and depression out to 36 weeks, with decreased experimentally induced pain suggesting a potential shift in pain appraisal. MBSR may safely help treat total migraine burden. Objective: Comparing switching patterns in patients with migraine initiating CGRP mAbs vs non-CGRP mAbs. Methods: This retrospective observational cohort study used administrative claims databases. Adults with ≥1 claim (first claim=index) for CGRP mAb (galcanezumab/ erenumab/fremanezumab) or non-CGRP mAb treatment (antidepressants/beta-blockers//neurotoxin) May 2018-June 2019 with continuous enrollment in medical and pharmacy benefits for 12 and 6 months pre-/post-index were included. Chi-square and Student"s t-tests were conducted on study measures. Results: 12681 CGRP mAb (mean (SD) age 44.3(11.6); 87% female) and 21474 non-CGRP mAb patients (mean (SD) age 41(12.5); 85% female) met criteria. Top 2 prescriber specialties were neurologists (CGRP mAbs: 30%; non-CGRP mAbs: 25.8%) and primary care providers (CGRP mAbs: 25.5%; non-CGRP mAbs: 43%) (p<0.001). Over 6 months (post-index), 31.5% CGRP mAb and 60.2% non-CGRP mAb initiators discontinued therapy(p<0.001). Of those who discontinued, 40.7% CGRP mAb and 17.9% non-CGRP-mAb initiators switched to another therapy(p<0.001). For those who switched, average mean (SD) time to switch after index drug initiation was 104.2 (39.9) and, 97.2 (42.4) days for CGRP mAb and non-CGRP-mAb patients(p< 0.001). Conclusion: Over 6-month post-index period, compared to non-CGRP mAb initiators, CGRP mAb initiators were less likely to discontinue therapy; those who discontinued were more likely to switch; took longer time to switch.

Objective: Evaluate the real-world safety and efficacy of adding a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) to onabotulinumtoxinA (onabotA) for chronic migraine (CM). Methods: Retrospective, longitudinal chart review from adults (≥18 years) with CM treated with ≥2 consecutive cycles of onabotA before ≥1 month of onabotA + mAb combination therapy. Safety and efficacy (monthly headache days [MHD] ) were recorded at first mAb prescription (index) and up to 4 onabotA visits~3, 6, 9, and 12 months post-index. Results: Charts were collected for 192 patients; 149 met eligibility criteria. 57% of patients were prescribed erenumab, 42.3% fremanezumab, and 0.7% galcanezumab. Mean (SD) MHD were 20.3 (6.6) prior to onabotA and 14.0 (6.9) prior to the addition of a mAb. There were significant reductions in MHD at the first visit (~3 month) and at all subsequent visits ( Figure 1 ). OnabotA was discontinued by 42 (28.2%) patients and a mAb by 50 (33.6%) patients. Most common reasons for discontinuing either treatment were lack of reimbursement (40%) and lack of effect (34%); 14% discontinued a mAb and none onabotA due to safety/tolerability. Adverse events (AEs) were reported by 18 patients (12.1%); no serious AEs were reported. Conclusions: In this real-world study, onabotA was effective at reducing MHD and the addition of a CGRP mAb was well tolerated and associated with incremental reductions in MHD for those on the combination. No new safety signals were identified. Introduction: Occipital nerve stimulation (ONS) is a specific form of peripheral neuromodulation used in the treatment of chronic pain disorders. A particular field of application is in the therapy of treatment-refractory headaches, especially of chronic migraine. The precise mode of action is unknown. It is presumed that central and peripheral sensitization are reduced in patients with chronic headache. The aim of this study was to examine the effect of ONS on pain-modulatory mechanisms in the trigeminocervical area in patients with chronic migraine.

Methods: In a balanced repeated measurements design in eight patients with chronic migraine with and without active ONS, we analyzed which effects ONS had on the orbicularis oculi reflex dynamically elicited by corneal air flow. Results: The orbicularis oculi reflex in active ONS (7.38 ± 20.14 eyelid closures/minute) compared to inactive ONS (18.73 ± 14.30 eyelid closures/minute) is significantly reduced (p = 0.021). Conclusions: The results show that under active ONS compared to inactive ONS in patients with chronic migraine, the orbicularis oculi reflex, dynamically triggered by a standardized air flow, is significantly reduced. This suggests that ONS is able to directly counteract the trigeminally mediated central sensitization in chronic migraine and protectively reduce the effects of aversive peripheral stimulation. Resting-state fMRI studies allow to objectify the effect of treatment. We aimed to determine the differences between large-scale networks functional connectivity (FC) in migraine patients due to repetitive transcranial magnetic stimulation (rTMS) course and their correlation with clinical features. 19 patients with migraine without aura (39.8±11.1 years; 3 men) underwent a 5-day course of rTMS with a 10 Hz frequency of the projection of the ventrolateral prefrontal cortex and trigeminal nerve branches bilaterally. Before and after the course of TMS, each patient was offered a test battery (Numerical Pain Rating Scale, Migraine Disability Assessment Questionnaire, Hospital Anxiety and Depression Scale, Leeds Addiction Questionnaire) and underwent fMRI. FC changes was carried out with paired t-test based on the 10-factors group independent component analysis (ICA) results with the pFDRcorrection. We founded increased FC in Default Mode Network (DMN), decreased FC in SensoriMotor Network, and both decreased and increased FC in Salience Network ( Fig. 1 ). Responders (15) differed from nonresponders in that the higher the reduction of the severity of headache, the increased the strength within DMN connectivity. The reduction of drug dependence was correlated with increased FC between DMN and Visual Network (Fig. 2 ). Considering the results of previous neuroimaging studies based on the ICA, our data may indicate a partial restoration of FC alterations as a result of TMS therapy. Background: Merging of sensory information is an important process for all species. Co-application of bi-modal stimulations results in greater neural activation than the sum of each unimodal stimuli delivered independently. Here, we have tested how the multisensory integration take place in episodic migraine patients (MO), by evaluating the potential ability of bi-modal stimulations to affect the mechanisms of habituation. Methods: We recorded somatosensory evoked potentials (SSEPs) in 20 healthy volunteers (HVs) and in 21 patients with MO before, during, and after simultaneous visual stimulation. 600 sweeps were acquired for each condition and partitioned in 2 blocks of 100 sweeps for the calculation of habituation as the slope of the regression line between the 1st and the 2nd block of averaged N20-P25 SSEP amplitude response. Results: In both groups the visuo-somesthetic stimulation changed the SSEP N20-P25 habituation seen at baseline, but in opposite way. In HVs the concurrent stimulation provoked a significant loss of habituation. In patients with MO, who had a deficient habituation at baseline, the simultaneous stimulation produced a significant amplitude decrement. Conclusion: There is ample scientific evidence which sustain that MO patients have an atypical way of processing unimodal information.

Our result suggests that also the multisensory integration is affected, and this process, by modifying cortical responsivity, could influence the migraine cycle.

The association of cortical thickness at MRI with clinical presentation of migraine aura: a whole brain surface-based morphometry study C. Abagnale 1 Background: We were aimed to study intracerebral white matter fiber bundles, using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI), and grey matter cortical thickness from structural magnetic resonance imaging data in migraine patients with pure visual auras (MA), and in patients with complex neurological auras (MA+), i.e. with the addition of at least one of sensory and language symptoms. Methods: 3T MRI data from 20 patients with MA and 15 with MA+ were collected and compared with data from 19 healthy controls (HCs). For everyone, we performed DTI to calculate diffusivity metrics and we obtained cortical thickness maps from structural MRI.

Results: TBSS showed no significant differences in the diffusivity maps between both patients" groups and HCs. As compared to HCs, both patients with MA and MA+ significantly showed tinner temporal cortices, frontal areas, insula, post-central area, and primary and associative visual areas. In the MA group, the high-level visualinformation-processing areas, including lingual gyrus, were thicker, in contrast to the MA+ group where they were thinner than in HCs. Discussion: These findings suggest that clinical heterogeneity of migraine with aura is associated with common cortical surface morphological features as well as with an opposite morphological involvement of the high-level visual-information-processing areas.

Erenumab effects at the level of the caudal trigeminal nucleus and on the somatosensory cortex Background: Erenumab is a monoclonal antibody against CGRP receptor approved as a prophylactic treatment of migraine. It is not yet clear if its neurophysiological effects are confined to the peripheral trigeminal system or also occur at the cortical level. This study assessed the neurophysiological effects of the drug in migrainous patients unresponsive to ≥2 prophylactic treatments. Methods: We prospectively enrolled 20 patients. For each patient we recorded the blink reflex (nBR), after stimulation of the right supraorbital nerve with a nociception specific concentric electrode, and the non-noxious somatosensory evoked potentials (SSEPs) after repetitive electrical stimulation of the median nerve. We measured nBR R2 area-under-the-curve (AUC) and habituation, and SSEP N20-P25 amplitude and habituation. Neurophysiological measurements were recorded before and at month-1 (T1) and month-2 (T2) before each monthly erenumab injection. Results: At T2, erenumab reduced the severity of headache, the mean monthly headache days and tablet intake (all p=<0.001). Compared to baseline, the nBR AUC was significantly reduced at T1. An increase in SSEP habituation, was noted at T1 and, more so, at T2 compared to the baseline (slope baseline =+0.103, T1 =-0.167, T2 =-0.229, p< 0.05). Conclusion: The results of our study show that the clinical improvement induced by Erenumab can be attributed to neurophysiological changes occurring at both the brainstem and cortical levels. Objective: Since monoclonal antibodies anti-CGRP or its receptor (a-CGRP mAbs) are available, we have been using them in our Headache Unit. Using a second a-CGRP mAbs after the failure of the first one could be interesting. Methods: We have carried out a real-life study collecting the patients with refractory migraine with a-CGRP mAbs since January 2020. We initiated 220 patients. 52 patients switch the a-CGRP mAb: 37 patients after 3 months with the first one, 8 after 6 months and 7 after 9 months. We present the data (migraine days (MD), headache days (HD)) and scales (HIT-6, MIDAS, MSQ, pain catastrophizing scale (PCS)) and willing of continue with the treatment, collected before and 3 months after the switch. Results: Collected data from 52 patients. They had failure an average of 6 preventive treatment. Before the switch: 24,2 HD, 22 MD, 98,7 points in MIDAS. 3 months after the switch with a second a-CGRP mAb, 46,15% wanted to continue with the treatment. These patients (n=24) reduced MD from 22 to 16,6 days, use of symptomatic treatment was reduced from 20 days per month to 14,6. The results of the scales are: MIDAS was reduced from 105,4 points to 83,4 points (39,37%), HIT-6 was reduced 4,33 points, and MSQ increased an average of 9,5 points. The 25% responder rate was 36%. 2 patients reduced more than 75% of MD.

It could be interesting to switch the a-CHGRP mAb after a failure because a percentage of patients improve their rate of MD and quality of life. Objective: To evaluate the efficacy and safety of eptinezumab for migraine prevention in patients with self-reported aura. Methods: Patients with episodic migraine (EM; PROMISE-1) or chronic migraine (CM; PROMISE-2) and self-reported migraine with aura at screening were included. Symptoms constituting aura were discussed with/explained by investigators to patients to improve accuracy of future symptom capture. In both studies, the primary efficacy outcome was the reduction in monthly migraine days (MMDs) over weeks 1-12.

Results: Of patients with EM,~75% reported a history of experiencing aura at screening (eptinezumab 100mg, 167/221; eptinezumab 300mg, 173/222; placebo, 167/222); of patients with CM,~35% reported a history of aura (100mg, 115/356; 300mg, 173/350; placebo, 167/366). In EM patients with aura, mean changes from baseline in MMDs were -4.0 (100mg) and -4.2 (300mg) vs -3.1 (placebo). In CM patients with aura, mean changes were -7.1 (100mg) and -7.6 (300mg) vs -6.0 (placebo). These changes were comparable to the total PROMISE-1 and PROMISE-2 populations. A similar percentage of patients experienced adverse events across treatment groups (100mg, 56.0%; 300mg, 57.4%; placebo, 55.4%).

Conclusion: This subgroup analysis showed efficacy and safety with eptinezumab vs placebo in patients with self-reported migraine with aura, consistent with the full populations, demonstrating the clinical utility of eptinezumab treatment in this subpopulation of patients with migraine. Background and objective: We aimed to provide the first real-world data of anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody in Asians. Methods: We prospectively recruited patients with migraine who received galcanezumab treatment in a single university hospital from June 2020 and Dec 2020. Treatment response was assessed after 3 consecutive monthly injections. A 50% responder rate was defined as ≥50% o reduction in moderate-to-severe headache days.

Results: A total of 54 patients were eligible for the analysis. Patients were mostly female (81.5%) with a mean age was 41.8± 12.0 (range 17-71), had chronic migraine in 42 and medication overuse in 27, and previously failed ≥3 classes of preventive medication in 45 (83.3%). After 3 months of treatment, mean changes of monthly headache days, moderate to severe headache days, crystal clear days, and days of acute medication use were -7.4 ± 8.61, -5.0 ± 11.18, +7.4 ± 8.61, and -4.0 ± 9.40, respectively. The 50% responder rate was 77%, 56%, and 44% in patients who previously failed ≤3, 4, and 5 preventive medication classes. Total 68% patients reported any improvement and satisfaction from the treatment. Conclusion: In our cohort, efficacy and safety of galcanezumab were comparable to those reported from clinical trials and even better in patients who failed multiple preventive drug classes. Our study provides the first real-world evidence of benefits of galcanezumab treatment in Asian patients with migraine. Haematohidrosis is an extremely rare clinical condition in which the patient experiences sweat mixed with blood. Till date only a few cases of haematohidrosis have been reported in national and international medical journals. Pathogenesis of the condition is not yet established but rupture of the blood vessels of sweat glands due to activation of sympathetic nervous system from stress, anxiety or any other reason have been proposed as the cause of bleeding.

It was aimed to present the case who presented with episodes of sweat mixed with blood from different sites of her body. A case of haematohidrosis who experiences bloody sweat which comes with episodes of headache, was studied during in Bangabandhu Sheikh Mujib Medical University, Dhaka. Interestingly, it was to be found that a child of the patient, who is a 4 year old boy and a nephew of her, are suffering from the same condition. No family history was found in any of the previous cases. All other history and the investigations were 6-months, 81.3% at 12-months ( Figure: 1a) and 88.7% at 24-months post-index date. Of the 28.1% (n=2773) who initiated a second OMPM class 67.3% discontinued it and of the 6.4% (n=631) who initiated a third OMPM class and 57.2% discontinued it, within 12 months of index OMPM initiation ( Figure:1b) . Similar patterns were observed at 6-and 24-months post-index as well as among the patients with EM. Conclusions: Discontinuation rate among migraine patients initiating OMPMs are high and increase with follow-up. Switching or adding another OMPM class is not very common and the discontinuation rates with subsequent therapies are also high. Background: This project seeks to identify classes of medications most likely to cause drug-induced headaches in the FDA Event Reporting System (FAERS). Methods: We extracted case ID, adverse events, and attributed medications for entries in the FAERS database from July 2018 to March 2020. Each entry occupied a line in our data. We removed duplicate words in each line. We separated entries into two files based on whether each contained the word "headache(s)". We counted the occurrences for unique words in each file. Using this result, we calculated the reporting odds ratios (ROR) and 95% confidence interval for unique words in the "headache(s)" database. We then excluded all English words from the list and ranked the resultant list of drug names by ROR. Objective: There is a paucity of research about telemedicine in the treatment of migraine, and that which does exist involves telemedicine as a follow-up strategy after an initial in-office visit. The purpose of this study was to determine if clinically meaningful improvement in migraine can be achieved with the use of synchronous telemedicine visits only. Methods: In a retrospective chart review we assessed Headache Impact Test -6 (HIT-6) scores for new patients at the initial visit, which was conducted via synchronous telemedicine. HIT-6 scores were also assessed at follow-up visits. Patient visits from 3 March 2020 -18 March 2021 were included. Patients who had an in-office initial or follow-up visit or did not complete HIT-6 test were excluded from the study. Results: At follow up 80% of patients who met screening criteria (n= 73) had an improvement in HIT-6 score, and 60% of those patients with improvement had a reduction of > 6 points, which is a threshold previously identified as clinically meaningful in patients with chronic migraine. Mean improvement in HIT-6 scores at > 1 month follow-up was 5 points, and mean improvement in HIT-6 scores at follow-up visits > 3 months was > 6 points. Data was analyzed with SPSS version 27. Conclusions: Clinically meaningful improvement in migraine can be achieved with the exclusive use of telemedicine visits for migraine care. Further research is needed to compare this improvement with that which is seen using in-office visits.

How much weight loss is required to reduce intracranial pressure in idiopathic intracranial hypertension? S. Background: The amount of weight loss required in idiopathic intracranial hypertension to reduce intracranial pressure (ICP) has not been established. Methods: Using the IIH:weight trial data from 66 active patients randomised to bariatric surgery or community weight management intervention (CWI) (1:1). The expected ICP values are predicted by a linear hierarchical regression model fit to the trial outcomes, adjusted for time, treatment arm and weight. Results: Modelling the trial outcomes demonstrated that greater reduction in ICP was predicted with greater weight loss, with 24% weight loss resulting in normalisation of ICP in this population. The effect on ICP further improves between 12 to 24 months as the participants continue to lose weight. For expected ICP values to cross the threshold for normal, at 25cmCSF within 2 years, it is generally required that the patient would be allocated to the bariatric surgery arm and achieve a weight of 110kg. Those with a higher starting weight needed to lose more weight to meaningfully reduce ICP. This model also demonstrated that in the CWI arm if no or little weight loss was achieved in those with a high baseline weight an increase in ICP would be expected.

Conclusions: There should be care when exposing women with IIH and BMI≥35kg/m2 to repeated cycles of lifestyle interventions that fail to achieve adequate weight loss, as this approach is unlikely to achieve sustained remission of disease. Fig. 1 (abstract P0117) . See text for description Objective: The aim was to characterise headache and investigate the association with intracranial pressure (ICP) in Idiopathic Intracranial Hypertension (IIH).

Methods: IIH:WT was a randomised controlled trial investigating weight management methods in IIH. Active IIH participants (evidenced by papilloedema) and a body mass index (BMI) ≥35kg/m 2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measures were performed. Results: Sixty-six women were included (mean age 32.0 years (SD ± 7.8)), and mean body mass index of 43.9 ± 7.0 kg/m 2 . The headache phenotype was migraine-like in 86%. Headache severity correlated with ICP) at baseline (r=0.285; p=0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r=0.454, p=0.001 and r=0.419, p=0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r= 0.479, p<0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36). Conclusions: We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported. Those with the greatest reduction in ICP had the greatest reduction in headache frequency and severity. Background: Patients with cavernous malformations (CM) and a primary headache disorder are often limited in medication options due to concern for bleeding risk. Methods: From a prospective cohort of patients at Mayo Clinic with CM between 2015 and February 2021, demographics, clinical presentation, and radiographic lesion location data were collected. Medical record reviews and written surveys were used for patient follow-ups. We studied medications used from the time of diagnosis of the CM to a censor date of first prospective symptomatic hemorrhage, complete surgical excision of sporadic form CM, or death. Using logistic regression, the influence of non-aspirin NSAID (NA-NSAID), triptan, or OnabotulinumtoxinA on prospective hemorrhage risk was assessed.

Results: 329 patients with spinal or cerebral CM (58% female; 20.1% familial; 42.2% presentation to medical attention from hemorrhage; 27.4% brainstem) were included. During a follow-up of 1799.9 patient-years, 92 prospective hemorrhages occurred. The use of NA-NSAIDs, triptans, and OnabotulinumtoxinA after the diagnosis of CM was not associated with an increased risk of prospective hemorrhage. NSAID and triptan users were more commonly women and less commonly had a history of hemorrhage at diagnosis. Conclusions: The use of triptans and NA-NSAIDs in patients with CM studied, does not precipitate hemorrhage. Similarly, we did not find that OnabotulinumtoxinA (≤200 units per session) precipitated CM hemorrhage. Objective: Thunderclap headache is frequently associated with intracranial vascular disorders and is a frequent cause for emergency department admission. A correlation of thunderclap headache with autoimmune disorders, such as steroid responsive encephalopathy with autoimmune thyroiditis (SREAT), is highly unusual. Method: A 79-year-old female presented with a sudden onset of high-intensity bifrontal headache without other neurological manifestations. CSF analysis revealed moderate lymphocytic pleocytosis without evidence of infectious, neoplastic or metabolic causes. Brain MRI showed diffuse white matter signal abnormality and hyperperfusion of leptomeningeal arteries. Result: The medical history revealed an episode of aseptic meningoencephalitis which responded to steroids. On further analysis increased levels of serum anti-TPO antibodies were identified and against the background of a previous steroid responsive aseptic meningoencephalitis, diagnosis of SREAT was considered highly probable. Steroid therapy was initiated, which resulted in a full recovery. Conclusion: In particular because SREAT responds well to steroids, our case underlines the importance of considering SREAT during assessment of a sudden high-intensity headache associated with mild to moderate neuropsychiatric symptoms. Introduction: Telemetric intracranial pressure (ICP) monitoring is increasingly utilised to manage complex cerebrospinal fluid disorders. Changes in ICP waveforms are poorly understood. We aimed to evaluate the changes in ICP waveforms due to alterations in posture. Methods: Telemetric ICP monitors (RauMedic p-Tel, Hembrechts, Germany) were inserted in patients with active IIH (papilloedema, ICP > 25cmCSF) at least one week prior to baseline assessment. ICP was recorded over 60 minutes in supine and standing positions. For each ICP recording average peak pressure, trough pressure and waveform amplitude were determined using LabChart 7 peak analysis software. Results: ICP waveforms were recorded in 16 females (one withdrew and one had recording error). At enrolment ICP was 24.8 (SD 4.1) mmHg (equivalent to 33.7cmCSF), mean age 28±9 yrs and body mass index 38.1±6.2 kg/m2. In supine position mean ICP was 24.0± 4.8 mmHg and fell to 12.9±3.4 mmHg in standing position (change mean -11.1±4.7 mmHg, p<0.0001). Changing from supine to standing lead to a significant fall in peak pressure (-11.1± 6.6 mmHg, p< 0.0001), and trough pressure (-11.9±4.3 mmHg, p<0.0001), and significant rise in amplitude (+2.0±0.9 mmHg, p<0.0001). Conclusions: Moving from supine to standing decreased ICP by 50% and altered the waveform parameters. Extending ICP analysis to interpreting waveforms is likely to lead to greater understanding of cerebral compliance and perturbations by disease. Objective: Obesity is a risk factor for idiopathic intracranial hypertension (IIH) and obstructive sleep apnoea (OSA). The aim was to determine the prevalence of OSA in IIH, and the association between OSA and papilloedema. Methods: The IIH:WT was a multicentre, randomised controlled trial that evaluated bariatric surgery vs. community weight management intervention (CWI) on intracranial pressure (ICP). In this planned substudy, OSA was measured (two consecutive nights) using home polygraphy measuring the apnoea-hypopnoea index (AHI) at baseline and 12 months. Results: Analysis included 40 women with active IIH. OSA prevalence was 47% (n=25) (American Academy of Sleep Medicine criteria). Questionnaire screening for OSA had greatest sensitivity with STOP-BANG (84%) compared to Berlin (68%) and the Epworth Sleepiness Scale (69%). Bariatric surgery improved OSA severity compared to CWI (median[95%CI] AHI reduction of -2.8 [-11.9 , 0.7], p=0.017). The reduction in the AHI over 12 months correlated with reduction in papilloedema (optic nerve head volume) (r=0.543, p=0.045), which remained significant after adjustment for changes in body mass index (BMI) (R2=0.522, p=0.017). Conclusion: OSA is common in IIH, STOP-BANG was the most sensitive screening tool and bariatric surgery improved OSA in IIH. Importantly, improvement in OSA was associated with reduction in papilloedema independent of changes in BMI. Treating OSA in IIH may improve papilloedema and needs further investigation. Background: Glial tumors make up the majority of primary tumors of the CNS in adults and include a whole range of tumors with different levels of cellular differentiation and malignancy. Headaches are one of the most common complaints of patients with low-grade gliomas (LGG). Materials and methods: A clinical study of 80 patients with LGG was conducted. The analysis of the pain and quality of life was carried out before the operation, as well as for 5 years after the surgery. Age of the patients: from 18 to 72 years (median 47,5 years). To assess intensity of pain and the quality of life we selected VAS and special questionnaire EORTC QLQ-C30. Results and discussion: In the early postoperative period, patients report an increase in the severity of pain(VAS 8), but 3-6 months after surgery-a decrease in pain to VAS 4. In the first year of the study marked a significant improvement in the quality of life in patients with LGG for the functional scales, cognitive functioning, pain syndrome (p<0,05). Statistically significant influence on the period of transformation LGG to HGG, physical, social, emotional functioning, pain intensity, factors such as patient age, the size of the formation, morphological variation of the LGG, the presence of mutations IDH, BRAF, TERT, Vim (p<0,05). Conclusion: Surgical treatment has a positive effect in the pain syndrome and on the quality of life of LGG patients in the late postoperative syndrome.

Methods: Between 4-2019 and 12-2020 we included all consecutive patients with SIH undergoing surgery for a spinal CSF-leak. CSF leaks were diagnosed by dynamic myelography. Surgery was performed under general anesthesia in the prone position via a 2.5 cm dorsal midline incision using 20 mm tubular retractors. Primary outcome was the minimal invasive closure of the CSF leak, secondary outcome was the occurrence of complications. Results: We included 58 patients, median age 46 (IQR 36-55), 38 female (65.5%) with the diagnosis of SIH. We performed 62 surgical procedures. We diagnosed 38 ventral leaks (65.5%), 17 lateral leaks (29.3%) and 2 CSF-venous fistulas (3.4%) . In all but one patient (98%) the leak could be approached, identified and closed via the tubular retractor. 1 patient had two surgeries due to wrong level. Immediately after surgery in 76% of patients symptoms of SIH subsided completely or even transformed to high pressure headache. Overall revision rate was 8.6% due to seroma, suture insufficiency and 2 recurrent leaks. There was 1 patient with a mild permanent weakness of the thumb ( Background: The International Classification of Headache Disorders (ICHD) diagnostic criteria for acute headache attributed to ischemic stroke are based primarily on the opinion of experts. The aim of this study was to field test, for the first time, the diagnostic criteria for these headaches of the ICHD-3. Methods: The study population consisted of 550 patients (mean age 63,1, 54% males) with first-ever ischemic stroke, and 192 control patients (mean age 58.7, 36% males) admitted to the emergency room without any acute neurological deficits or serious disorders. All data were collected prospectively, using a standardized case-report form during face-to-face interviews by neurologists.

Results: Headache at onset of ischemic stroke was present in 82 (14.9%) of 550 patients with stroke. A new type of headache occurred in 46 (56%) of patients with stroke and in no controls, a previous headache with altered characteristics was found in 30 of the 82 patients with stroke (36%) and two control patients (p<0.009). Six patients had a usual headache. Only 30% of the headaches at stroke onset fulfilled the diagnostic criteria of ICHD-3. We propose new criteria fulfilled by 85% of the headaches. Specificity remained excellent as only two controls had a headache fulfilling the proposed criteria. Conclusions: Existing diagnostic criteria for acute headache attributed to stroke of the ICHD-3 are too insensitive. We suggest new criteria with high sensitivity and preserved specificity.

Sex Differences in Spontaneous Intracranial Hypotension S. J. Wang 1,2,3 , P. T. Lin 1,2 , Y. F. Wang 1,2,3 , J. W. Wu 2, 4 , J. F. Lirng 2,3,5 , S. S. Hseu 6 , S. P. Chen 1, 2, 3 Objectives: To determine sex differences in clinical profiles and treatment outcomes following epidural blood patch (EBP) in patients with spontaneous intracranial hypotension (SIH). Methods: We retrospectively reviewed the medical records of patients with SIH at a tertiary medical center. Demographics, histories, and imaging were collected and compared between sexes. The primary outcome measure was the treatment response to the first EBP. Background and objective: Congenital anomalies are infrequent causes of symptomatic headache. These include Chiari malformation type 1 (CM1), which usually presents as cough headache but may also mimic other primary headache disorders such as migraine. Previous literature on semiology of headache associated with CM1 is sparse. The aim is to describe headache patterns and to identify factors that influence the course of headache. Methods: 89 patients diagnosed with CM1 from 2010 until 2021 will be analysed retro -and prospectively. Age, sex, comorbidities, semiology according to ICHD-3 as well as radiological and neurosurgical data will be assessed. Specifically, individual aspects such as side of tonsillectomy, if present, and tonsillar descent are analysed. In the case of syrinx, longitudinal extent is analysed. All of the above data will be evaluated pre -and postoperatively. Background and objective: Some evidence suggests that heart rate variability biofeedback-based training (HRV-BBT) might be an effective way to treat headaches and psychological symptoms. The aim to examine the effect of HRV-BBT on anxiety and depression in adolescents with tension-type headache (TTH). Methods: 118 adolescents were examined. We formed four groups of adolescents with episodic (ETTH) and chronic TTH (CTTH) who received only drug therapy and only HRV-BBT and 5th groupadolescents with CTTH who received a combination of drug and HRV-BBT. The intensity of the pain (VAS); the level of reactive and personal anxiety (self-esteem scale Spielberger-Hanin); the level of depression (scale V.A. Zhmurova) were performed. Results: We observed a decrease in the level of anxiety in adolescents with TTH after HRV-BBT. However, only the reduction in reactive anxiety was significant (ETTH: before and after treatment -42,6± 7,5 and 33,5±5,4, р<0,05; CTTH: 37,7±6, 8 and 29,2±6,8, р<0,05) . The level of depression was significantly reduced after HRV-BBT in adolescents of all groups (ETTH: before and after treatment -20,2±4,7 and 14,4±3,9, р<0,05; CTTH: 24,9±5, 3 and 9,4±3,8, р<0,05) , and the use of pharmacotherapy had a positive effect only in the group with CTTH who more often received amitriptyline. Conclusions: Our findings support the beneficial impact of HRV-BBT on anxiety and depression for adolescents with TTH with higher effectiveness in adolescents with episodic forms.

Psychological predictors of real-life experience with Erenumab in chronic migraine with or without medication overuse: data from a 1-year follow-up S. Bottiroli Objective: Efficacy of a newly developed migraine-specific cognitive behavioral therapy (CBT) program combining several approaches (education and counselling, coping with fear of attacks, trigger management) was evaluated. Methods: N=121 adults with migraine were randomized to either CBT, or relaxation training (RLX), or a waiting-list control-group (WLC). The outpatient group therapy (CBT or RLX) comprised seven sessions each 90 minutes. Participants who completed the WLCgroup were subsequently randomized to CBT or RLX. Baseline was compared to post-treatment, and followed by assessments 4-and 12-months post-treatment. Main outcomes are headache days, disability by the Headache Disability Inventory (HDI), and self-efficacy by the Headache Management Self-Efficacy Scale (HMSE-G-SF).

Results: N=97 participants completed the pre-post assessment. The pre-post analyses showed higher self-efficacy (HMSE-G-SF) in both treatments (CBT: p=0.021; RLX: p=0.006) compared to the WLC. The follow-up analyses yielded reductions from pre after 12-months (N= 77 completer) in headache days (-1.84 days, p<0.001) and disability by HDI (-11.70 points, p<0.001) for the completer (CBT and RLX), whereas there was no significant difference between both treatment groups. Conclusion: Migraine-specific CBT and RLX have similar, moderate long-term effects in migraine-prophylaxis. Thus, CBT may be a promising alternative for patients who are demanding for a more tailored behavioral intervention. Background and Objective: Visual snow is a syndrome of unremitting positive visual phenomena that involve the entire visual field. It is often co-morbid with headache, depression, and anxiety. Visual quality of life has not been evaluated in this population. Methods: An electronic survey was created with questions about visual snow symptoms and previously validated questionnaires including the Headache Impact Test (HIT-6), Visual Function Questionnaire-25 (VFQ-25), and Utah Photophobia Symptom Impact Scale-12 (UPSIS-12). Patients were identified via electronic health record starting from July 2015. Inclusion criteria included age >18. Exclusion criteria included concurrent ophthalmic disease other than refractive error or dry eye. Results: Response rate was 65% (32/49 of invited subjects). 72% were female; mean age was 35. 69% of patients carried a prior headache diagnosis, while 75% reported having tinnitus. Median composite VFQ-25 scores were lower than published population-based values (Hirneiss et al. 2010) , and were inversely correlated with HIT-6 (r=-0.44, p=0.012) and UPSIS-12 (r=-0.67, p<0.001) scores. Correlations with VFQ-25 and PHQ-9 and GAD-7 were not statistically significant. Conclusions: Visual snow is associated with reduced visual quality of life. Tinnitus and headache are co-morbid conditions prevalent in patients with visual snow. Visual quality of life worsened with increased headache and light sensitivity; there was no correlation with affective symptoms. Despite the significant headache morbidity in Idiopathic intracranial hypertension (IIH), there is no evidence-based treatment for longterm headache management. We report a case in which a patient with HII persisted with daily headache, even ocular remission (resolved papilledema), and presented a good response to galcanezumab. 44 years old, female, with episodic migraine, presents a change in headache pattern, with an important increase in intensity and poor response to simple analgesics. Concomitant to the new headache pattern, there was deterioration of visual acuity. After conducting an investigation for secondary headache, she was diagnosed with idiopathic intracranial hypertension. After pharmacological treatment with Topiramate and acetazolamide, there was an important improvement in visual acuity, but no improvement in headache. Headache persisted, with daily frequency, even after optimization of drug Results: All participants were male; mean age was 48.2±8 in the control group and 50.2±10.9 in the patient group. Patients had had an attack free period of at least 1 month (mean attack free period 9.5± 12.9 months). We found no differences in RMET (p=0.152), HADS Anxiety score (p=0.107) nor HADS Depression score (p=0.530). We found differences in Hinting task (p=0.006) and SDMT (p=0.001). Conclusion: Our results suggest that ECH patients can perceive other people"s or one"s own feelings (affective ToM) but have difficulties at recognizing beliefs (cognitive ToM). These deficits are not apparently attributable to depression or anxiety states yet are in accordance with worst cognitive performance.

Psychosocial variables and healthcare resources in patients with cluster headache and in patients with migraine E. Calandre 1 , J. Garcia-Leiva 1 , J. Ordoñez-Carrasco 2 , L. In contrast with non-comorbid CH, female sex predominated in comorbid CH. Medical comorbidities were significantly more frequent among CH+FM, and CH+M+FM than in non-comorbid CH. Depression and suicidal ideation were frequent in all groups without differences among them. Insomnia, also common to all groups, was significantly higher in CH+M+FM group. EQ-5D-5L and EQ-5D-5L VAS scores were low in all groups but significantly lower in CH+M+FM. Medical analyses were more frequent in CH+FM and CH+M+FM. Introduction: CGRP is released after trigeminal-autonomic reflex activation during a cluster headache attack. Galcanezumab has shown positive results in episodic cluster headache. Erenumab has also been described as effective in cluster headache and comorbid migraine.

We present a case of off-label use of Erenumab for chronic cluster headache treatment, refractory to all treatments, except corticosteroids.

Case: A 63-year-old male developed in 2015 a chronic cluster headache: he presented daily headache, ranging from one attack per night in the first year, to several nocturnal and diurnal attacks in the following two years. He was medicated with verapamil, melatonin, lithium, topiramate and occipital nerve block, without success. He then started oral corticosteroids with efficacy but become dependent of this medication. Valproate and botulinum toxin were also tried. In 2020 he started Erenumab 140mg, after informed consent. After oneweek, complete resolution of the attacks occurred, and it lasted 10 weeks, when he was able to stop corticosteroids. After 9 months of treatment, he shows a significant reduction in frequency and intensity of the attacks. Conclusion: In this case, Erenumab allowed control of refractory cluster headache and suspension of corticosteroids. We emphasize that, because CGRP is involved in the pathophysiology of the disease, anti-CGRP therapies may improve its treatment.

Absence Patients who showed tumors presented atypical features (facial hypoesthesia on examination and episodes of prolonged duration that progressed to continuous refractory pain without specific pattern, respectively) and they did not fulfill, retrospectively, IHS CH criteria. Conclusions: Brain MRI in patients who meet the IHS CH criteria, with no atypical features, does not show any correlatable findings, suggesting that these criteria are highly predictive of its primary origin. Background and objective: Cluster headache is the most frequent trigeminal autonomic headache syndromes, with high morbidity due to its pain severity. Chronic cluster headache, comprised of 10-20% patients, can be more difficult to control, mandates for efficient prophylactic therapy for the patient. We present a woman with chronic cluster headache with successful verapamil prophylactic treatment.

Case report: A 53 years old woman, admitted in neurology outpatient clinic, complained of 2 years severe left periorbital pain in temporal region with Numeric Pain Rating Scale (NPRS) 10, accompanied by Fig. 1 (abstract P0152) . See text for description Background and objective: Greater occipital nerve blockade (GONB) can be used for transitional treatment in cluster headache (CH). A wide range of GONB protocols are described, and it is uncertain which leads to better results. In this observational prospectivestudy we aim to evaluate the effectiveness and safety of GONB with methylprednisolone (MP) and lidocaine in CH. Methods: We consecutively recruited patients accessed to our Headache Centre for episodic (ECH) or chronic CH (CCH). Patients underwent to GONB with slow-release MP 80 mg and Lidocaine 40 mg. Primary outcome was the absence of CH attacks at one month. Secondary outcome was the reduction of at least 50% of daily attacks.

Results: A total of 32 patients were recruited: 23 with ECH and 9 with ECH. Ten patients (31%) were attacks free at one month, while a total amount of 19 patients (59%) show a reduction of at least 50% of daily attacks. In non-attack-free patients, daily frequency of attacks decreased from a median of 2 (IQR:1-3) to 0.5 (IQR:0.4-0.6) (p<0.05) and the intensity of pain decreased from a median of 8 (IQR: 7-9.5) to 6.3 (IQR:3.9-7.5) (p<0.05). Eleven patients needed further therapies and were considered non-responders.No serious adverse events were reported. Conclusion: At one month after GONB, 31% of patients were attacks free and 59% showed a reduction of at least 50% of daily attacks. Our findings confirm that GONB with MP and lidocaine may have an important role as transitional CH management.

Phenotype of Cluster Headache: clinical variability, persisting pain between attacks, and comorbidities -a observational cohort study in 825 patients C. Göbel Background and objective: Cluster headaches can occur with considerable clinical variability. The aim of the study was to analyze the severity and extent of the clinical symptoms of episodic and chronic cluster headaches with regard to their variability and to compare them with the requirements of the ICHD-3 diagnostic criteria. Methods: The study was carried out as a cross-sectional analysis of 825 patients who had been diagnosed with cluster headaches by their physician. Using an online questionnaire, standardized questions on sociodemographic variables, clinical features of the cluster headache according to ICHD-3 and accompanying clinical symptoms were recorded. Results: The majority of patients with cluster headaches have clinical features that are mapped by the diagnostic criteria of ICHD-3. However there is a significant proportion of clinical phenotypes that are not captured by the ICHD-3 criteria for cluster headaches. In addition, sequential change in the side of the pain, pain location as well as persisting pain between the attacks is not addressed in the ICHD-3 criteria. Conclusion: The variability of the phenotype of cluster headaches can preclude some patients from receiving an appropriate diagnosis and effective therapy if the diagnostic criteria applied are too strict.

The occurrence of persisting pain between attacks should also be diagnostically evaluated due to its high prevalence and severity as well as psychological strain. Background: A prefilled syringe of a dose of 300 mg of galcanezumab has not been available in most countries including Korea. We investigated the role of two doses of 120 mg of galcanezumab for episodic cluster headache in clinical practices. Methods: Among 33 patients with episodic cluster headache who received at least one dose of 240 mg of galcanezumab since February 2020 to January 2021. Global impression of improvement and adverse drug responses were collected based on the headache diary or history taking or telephone interviews. Results: Twenty-eight men and 5 women were enrolled, mean age was 38.4 ± 8.9 years, mean body weight was 72.3 ± 10.8 kg, and 9 patients had comorbid migraine. Twenty-five patients received concomitant preventive medications and 8 patients received only 240 mg of galcanezumab as their preventives. Global impressions of improvement were marked in 17 (51.5%), moderated in 8 (24.2%), mild improvement in 6 (18.1%), and no changed in 2 (6.1%). Among 8 patients treated with galcanezumab only, global impressions of improvement were marked in 5 (62.5%), moderated in 2 (25%), mild improvement in 1 (12.5%), and no changed in 1 (12.5%). There were no serious adverse events. Conclusion: A dose of 240 mg of galcanezumab can be administered for patients with episodic cluster headache with favorable impression of improvement from patients in daily practices.

Association between migraine-related disability and negative thought content, metacognition and emotional distress in adult patients with migraine B. Results: Ninety out of 493 patients (20.5%) completed the telephone interview. Baseline data of participants and dropouts showed no statistically significant differences. At follow-up dependent-like behavior (i.e. an SDS score >5) was found in 64.8% of the patients and one third experienced primary treatment failure or relapse into MOH. In these non-responders, SDS scores were higher than in patients with sustained absence of MOH (8.5±4.3 vs. 5.7±3.9, p=0.003). Univariate ANOVA showed that improvement was shortest in the group with highest SDS scores, (p= 0.027). SDS, BDI-II, and BAI scores were statistically significantly correlated (r=0.4, p<0.001). Non-responders were significantly more common among dependent patients with than without psychiatric co-morbidity (p=0.05). Conclusion: After an average of 9.1 years after inpatient detoxification for MOH, dependent-like behavior is present in almost two thirds of the patients. Poor outcome is associated with higher SDS scores and prognosis is worse in patients with dependent-like behavior and comorbid affective disorders. Background: Typically, women with migraine improve during pregnancy. This may not apply to chronic migraine and medication overuse headache (MOH) patients. We wanted to identify if women whose migraine headaches remained severe or worsened during pregnancy were more likely to have psychiatric comorbidity. Design/Methods: All patients referred to our headache clinic complete a detailed questionnaire prior to their first visit, including questions regarding current pregnancy, headache characteristics, depression and anxiety symptoms and perceived stress. This is analyzed along with headache diagnosis. Results: 38 patients were pregnant and 37 patients had migraine. Of those, 29 had chronic migraine, and 22 were identified with medication overuse headache. Of these, 17 (44%) had anxiety and 14 (36%) patients had depression, 4 patients had post-traumatic stress disorder and 2 had bipolar disorder. In 31(81%), the patients" headache impaired their work. Conclusions: Our results show high incidence of psychiatric comorbidities in pregnant women presenting to the headache clinic. ormonal fluctuations in connection with pregnancy can influence attack frequency. Previous studies, including analyses of patient data at our headache clinic, suggest that psychiatric comorbidities are more common in chronic migraine. These patients warrant a greater degree of attention in headache clinic, as they may have more severe health issues while having limited treatment options due to pregnancy.

Assessment of the condition neck muscles proprioreception as predictor of migraine chronization M. Mozheiko Conclusions: Constipation overall and by subtypes was more common in patients with migraine than in headache controls, which could be influenced by responder bias. Additional work will explore constipation management and comorbidities.

Napping and headache outcomes in adults with episodic migraine: a six-week prospective cohort study in Boston, Massachusetts, USA Objective: To prospectively examine and quantify the associations of napping with headache frequency, duration, and pain intensity. Methods: 98 adults with physician-confirmed ICHD-3 episodic migraine reported on headaches and sleep behaviors on twice-daily electronic diaries and wore wrist actigraphs for six weeks. Naps were identified by self-report and confirmed by actigraphy. We used linear regression to examine whether napping was associated with headache outcomes. Results: Over 4,406 study days, participants reported 1,081 headache days. Over 80% of the sample napped at least once during the study, with naps on 117/1,081 (10.8%) of headache days and 285/3,325 (8.5%) of non-headache days. In age/sex-adjusted models, napping during the study was associated with an additional 1.2 (95%CI -1.1, 3.5) headache days/month. There was no association between napping and average maximum headache pain (1-10 scale) (-0.6 95%CI -7. 1, 8.4) or headache duration (0.4 95%CI -5.1, 5.9 hours). Effect estimates were similar after additional adjustment for employment, alcohol and caffeine intake, medication use, disability (HIT-6 score), and sleep quality. Conclusions: In a primarily employed cohort of patients with episodic migraine in the US, napping was prospectively recorded with a modestly higher prevalence on headache (10.8%) than non-headache days (8.5%). Napping at least once during the study was associated with 1.2 more headache days per month, though estimates were imprecise. Objectives: to assess the prevalence of headache and migraine, headache related disability, and symptomatic migraine treatment in women attending a menopause clinic. Methods: Women attending the weekly menopause outpatient clinic from October 2019 were asked to complete a simple questionnaire regarding headache and disability. The questionnaire included validated questionnaires to diagnose migraine (ID-migraine to diagnose migraine without aura, and the Visual Rating Scale (VARS) to diagnose migraine aura. HIT-6 was used to assess headache related disability. Patients were also asked to record drugs used for acute treatment.

Results: Data collection was terminated at the end of February 2020 due to the pandemic. Of 117 women completing the questionnaire, 68 reported headache (58%) of which 48 were diagnosed with migraine (41%) and 20 (17%) had non-migraine headache. Of women with migraine, 35/48 had attacks only of migraine without aura and 13/48 had attacks of migraine with aura. Headache associated disability was very severe (HIT-6 60+) or substantial (HIT-6 ≥56≤59) in 51/68 of all women with headache and in 23/48 women with migraine. Of women with migraine, 11/48 treated attacks with triptans, 6/48 took codeine containing medication, and 31/48 used paracetamol only. Conclusion: Disabling headache affected a substantial number of women and inappropriate treatment was common. There is an unmet need for effective diagnosis and management of migraine in menopause. Results: Nineteen articles with cross-selectional studies, cohort and case report were summarized in Table 1 . The main neurological symptoms reported were: headache (8 to 74.6%), dizziness (13%), anosmia and ageusia (33,9 to 68%). Headache was the symptom most observed in the patients in the studies, varying from 8 to 74,6% of the cases. It was reported as pain of moderate to severe intensity, holocranial location, with a focus on the frontal and temporal areas bilaterally, lasting more than 72 hours, predominance in males, associated with anosmia and ageusia. Conclusion: From this, it is concluded that headache is obtained as the most common neurological manifestation, and may or may not be associated with other symptoms. Keywords: "headache"; "COVID-19"; "neurological disorders".

Evaluation of Amitriptyline as a potential treatment for COVID-19 persistent headache A. Objective: Headache is a frequent symptom of COVID-19. Two distinct headache phenotypes have been described in relation with SARS-CoV-2 infection, one associating migraine symptoms and another including tension-type headache (TTH) symptoms. Amitriptyline is a preventive treatment widely employed for both migraine and TTH. We aim to describe COVID-19 persistent headache response to amitriptyline in a series of patients with COVID-19 persistent headache. Methods: We performed a retrospective cohort study including patients prospectively collected with COVID-19 persistent headache followed-up at two Headache Units and were treated with amitriptyline between March 2020 and October 2020. We gathered the demographic characteristics, COVID-19 headache phenotype as well as amitriptyline response (reduction of 50% in the number of days with headache). Results: We included 11 patients with COVID-19 persistent headache, 72% (9/11) females, median age 43 (IQR:21) years old. 27% (3/11) had prior diagnosis of migraine and 18% (2/11) had prior history of TTH. TTH COVID-19 phenotype was found in 82% (9/ 11). Median time follow up was 12 (IQR:6) months. We found that 63% (7/11) improved in either intensity or headache days, all of which presented a TTH COVID-19 phenotype, while none of migraine phenotype did. Conclusion: Amitriptyline may be an effective preventive treatment for COVID-19 persistent TTH phenotype but not for migraine phenotype, although further larger studies are necessary. Objective: The SARS-CoV-2 Pandemic resulted since March 2020 in massive restrictions of everyday life. The study investigates quality of life, symptoms of depression, anxiety and stress, headache impact and frequency in patients with migraine in the pandemic. Methods: In a prospective study, 76 patients with episodic or chronic migraine with and without aura were analysed using patient reported questionnaires: headache diary, HIT-6 for headache impact on daily life, DASS for depression, anxiety and stress and MSQ v2.1 for migraine-specific quality of life. First data collection was carried out in March 2020 (T0). 3(T1), 6(T2), 9(T3) and 12(T4) months later data was collected again. Results: We report first results of our ongoing data collection. Overall, headache impact on daily life remained relatively stable over time (HIT-6 median T0:62,T1:61,T2:61,T3: 62). The median DASS score started in March 2020 with 17,5, reduced in June and September to 15 and 13,5 and increased in December to 20 points. Most relevant changes were seen in the depression scale, starting with median 5, decreasing to 4 and 3 in the summer months and increasing in December to 7. The median MSQ was 59.29 at the first survey in March 2020. It increased to 65 after 6 months and 63.57 after 9 months. T4 is actually collected. Conclusion: Our data show a dynamic development in migraine specific quality of life and self reported symptoms of depression in patients with migraine between March and December 2020. Objective: Previous studies have demonstrated that migraine can worsen due to stress, changes in lifestyle habits or infections. We hypothesize that changes during coronavirus disease 2019 (COVID-19) lockdown might have worsened the clinical course of migraine. Methods: Retrospective survey study collecting demographic data, clinical variables related to headache (frequency), migraine (subjective worsening, frequency, and intensity), lockdown, and symptoms of post-traumatic stress from migraine patients followed-up at three Headache Units between June-July 2020. Results: 222 subjects were included. Among them, 201/222 (90.5%) were women, aged 42.5 ± 12.0 (mean±SD). Subjective improvement of migraine was reported in 31/222 participants (14.0%), while worsening in 105/222 (47.3%) and was associated with changes in migraine triggers such as stress related to going outdoors and intake of specific foods/drinks. Intensity of attacks increased in 67/222 patients (30.2%), and it was associated with the subjective worsening, female sex, recent insomnia, and use of acute medication during a headache. An increase in monthly days with any headache was observed in 105/222 patients (47.3%) and was related to symptoms of posttraumatic stress, older age and living with five or more people. Conclusion: Approximately half the migraine patients reported worsening of their usual pain during the lockdown; worsening was related to changes in triggers and the emotional impact of the lockdown. Objective: COVID-19 lockdown modified lifestyle, behaviours, physical activity (PA) and working habits. Aim of the study is to assess the impact of lockdown on migraine according to behavioural changes. Methods: Migraineurs who attended the Headache Centre in 2019 were interviewed. All were prophylaxis free or with the same prophylaxis from at least 3 months. Demographics, working routine, lifestyle, migraine characteristics and disability (HIT-6) were compared between the first month of the lockdown and January 2020. Results: Thirty-seven patients were analysed as migraine without aura Objective: Due to the COVID-19 pandemic Spanish government imposed a nationwide lockdown with strict confinement measures from March 15 to May 10, 2020. During this period, there was a decrease in the number of patients who attended the Emergency Department (ED). Our aim is to evaluate the number of patients with primary headaches who visited the ED during lockdown and their management in the ED. Methods: We retrospectively reviewed patients who visited the ED with diagnosis at discharge of primary headache from 15th March to 10th May 2020 and during the same period of 2019. Demographics, number of admissions, headache duration prior to ED visit, and length of stay in the ED were compared between the two periods. Results: We found a significant decrease in the number of patients who visited the ED for neurological reasons (396 vs 168) during lockdown in 2020, especially for primary headaches (42 vs 8; p = 0.028) as well as in the length of stay in the ED during the lockdown (198 min vs 444 min; p = 0.002). In addition, headache duration prior to ED visit was longer during the lockdown (245 h vs 119 h), however this difference was not statistically significant (p = 0.114). There were no differences regarding sex, hospital admissions and previous assistance by the Primary Care Physician. Conclusion: There was a significant decrease in the number of patients attending the ED for primary headache and in the length of stay in the ED during the COVID-19 lockdown. Objective: We aimed to investigate the impact of COVID-19 pandemic on migraine characteristics. Methods: 400 migraine patients were enrolled in the current crosssectional study. We administered a self-reported survey that included demographic, migraine-related and lifestyle factors in regard to the period before and after the pandemic of Covid-19. Results: The frequency, duration and the severity of attacks were found to be significantly higher after the pandemic of Covid-19 than before (10.7 ± 9.9 vs. 9.6 ± 10.4 P= 0.005; 14.3 ± 17.5 vs. 13 ± 15.6 P= 0.001; 7.1 ± 2.1 vs 6.7 ± 2.2 P= 0.001, respectively). After classifying the participants based on the trends of migraine frequency into three groups (decrease, stable and increase) it was found that in the group that the frequency of headache attacks increased, the percentage of patients who using N-95 and N-99 masks was significantly higher than the other two groups. Decreased sleep hours, fast food intake, irregular diet, caffeinated beverage consumption, decreased neck exercise and physical activity and working hours with electronic devices were significantly more reported by patients whose number of headache attacks increased during the pandemic period. Conclusion: These findings suggest that COVID-19 pandemic had an overall negative impact on migraineurs. Practical strategies should be implemented for patients with migraine, with emphasis on appropriate lifestyle modifications. Background: Headache, loss of smell and taste are among the initial symptoms of Covid-19, and hyposmia often persists even after infection is resolved. We investigate the clinical course of patients with pre-existing migraine after Covid-19 and in particular the response of hyposmia to a structured 3month olfactory training. Methods: 3patients with pre-existing chronic migraine (cM) and episodic migraine without aura (eM) reported anosmia after infection with SARS-Cov19. We present data on headache frequency and intensity, headache days, days of work disability and headache-related impairment of daily life, as well as olfactory threshold, discrimination and identification, and trigeminal sensitivity. Clinical and history data, headache diary, Midas and the Sniffin Stick Test are collected. Results: Covid-19 lead to a change in headache type and headache frequency in the patients shown here Case report: We report the case of a 45-year-old male patient COVID-19 positive one month ago, without any other comorbidities, who presents in the Emergency Room in a stuporous state and bilateral midriasis after a tonic bilateral epileptic seizure. Two hours later he was lucid and oriented, without any focal neurological deficit but bilateral midriasis persisted. The patient complained severe, holocranial throbbing headache with dizziness, nausea and significant visual blurring. Ophthalmological examination reveals bilateral optic disc oedema, peripapillary hemorrhagic petechiae and venous tortuosity. Brain MRI , Angio-MRI and EEG resulted normal. The patient is treated with a high-dose of corticosteroids for three days and acetazolamide. After treatment he has no other complaints and the headache is less severe. We scheduled a follow-up with fundoscopy, after being treated with acetazolamide for 10 days. Discussion: Headache is one of the frequent neurological symptoms associated with COVID-19. In the absence of evidence of infectious or vascular disease, pseudotumor cerebri should be considered. Background: Covid-19 pandemia affected significantly global economy, health care systems and individuals worldwide. Primary headache disorders clinical course may be affected by the social circunstances and the infection itself. Individuals without history of primary headaches may develop headache as symptom of covid-19 infection. Limited information is available regarding the impact of the new coronavirus in Brazil. Objective. We aimed in this study to access the impact of covid-19 pandemia and infection in primary headaches in the general population. Methods. A sample representative of the general population according to the last Brazilian Census through a panel of 1000 respondents was studied. Lifetime prevalence and 1-year prevalence were ascertained. Headache course during pandemia, as covid-19 diagnosis and symptoms were asked. Results. 3.6% of the total population reported they never had a headache before and started to have headaches after the pandemia, 17.7% reported their headache worsened during the pandemia, 74.7% had no change, 2.3% reported headache improvement; 12.5% had confirmed covid-19 diagnosis (5.3% had new headaches), 22% had symptoms without confirmed diagnosis (4.5%). Covid diagnosis or symptoms increased 2.5 times the likelyhood of worsening primary headaches during pandemia (34.8% vs 13.9%). Conclusion. Covid-19 infection and pandemia affected significantly primary headaches patients as increased new headaches in the Brazilian general population. Objective: Primary trigeminal neuralgia (TN) is a neuropathic pain disorder with shock-like touch-evoked pain paroxysms in the trigeminal territory. Microvascular decompression (MVD) is first choice surgical treatment. This is the first high-quality prospective study using independent assessors of outcome and complications of MVD. Methods: We recorded clinical characteristics, outcome and complications in consecutive patients with TN who underwent MVD. Patients were assessed by a neurologist before and 3, 6, 12 and 24 months after MVD. Neurovascular contact (NVC) was evaluated by 3.0 Tesla MRI with the radiologist blinded to symptomatic side. Results: We included 115 patients. Ninety-nine (86%) patients had a clinically significant effect, whereof eighty (70%) patients had an excellent outcome. There was a significant association between an excellent surgical outcome and the male sex (4.9 (CI 1.9-12.8), p = 0.001) and NVC with morphological changes (2.5 (CI 1.1 -6.0), p = 0.036), respectively. Thirty-three (29%) patients had major and 64 (56%) had minor complications. At 24-months follow-up 81 (70%) patients did not have any complications. The most frequent major complication was permanent hearing impairment (10%). The most frequent minor complication was transient hearing impairment (15%). Conclusions: MVD is effective for TN with a high chance of longlasting effect. Surgical complications are relatively frequent warranting thorough patient information preoperatively.

Effects of two programs with aerobic exercise in headache attributed to temporomandibular disorder P. Objective: Assess the effects of two 8-week aerobic exercise programs on frequency, intensity, and impact of headaches attributed to temporomandibular disorder (TMD). Methods: Thirty patients diagnosed with headache attributed to TMD were divided into two groups of 15 participants: an aerobic and therapeutic exercise program (G1, mean age:26.0±4.4 years), and an aerobic exercise program (G2, mean age:24.9±3.4 years). Headache frequency and intensity were evaluated using a headache diary, intensity was reported using a numerical pain rating scale (NRS), and headache impact was evaluated using a Headache Impact Test (HIT-6). These parameters were evaluated twice at baseline (A01/A02), at the end of the 8-week intervention period (A1), and 8-12 weeks after the end of the intervention (A2 Conclusion: G1 program had the best results with total relieve of frequency of headache and score decrease of HIT-6 at A1, which remained unchanged at A2. Interventions to reduce headache attributed to TMD should be multimodal.

Painful ophthalmoplegia due to involvement of cavernous sinus region by malignant neoplasm: report of three cases G. Barros Objective: Previous studies have pointed to sex differences in primary trigeminal neuralgia (TN) in various sub-analyses. This is the first study aiming to evaluate sex differences in TN aetiology, demographics, clinical characteristics and medical treatment response. Methods: We systematically and prospectively collected data in consecutive patients diagnosed with TN by experts in headache and facial pain using semi-structured questionnaires and patient-directed questionnaires. Patients were scanned using 3.0 Tesla MRI. A blinded neuroradiologist evaluated the presence and degree of neurovascular contact. Results: We included 516 patients with TN out of whom 333 (65%) were women and 183 (35%) were men (p < 0.001). The age at disease onset was 4 years younger in women compared to men (52.9 vs. 57.7 years, p < 0.001). There were no differences in pain characteristics except concomitant persistent pain was more prevalent in women (193 (56%) vs. 87 (48%), p = 0.023). Response to medical treatment and medication dosages at 2-year follow-up was equal. The association (OR) between a neurovascular contact with morphological changes of the trigeminal nerve and the symptomatic side was higher in men (18.5 (6.9-69.7) p < 0.001) compared to women (6.9 (3.5-13.9), p < 0.001).

Conclusions: Based on a unique, large and prospective dataset, we demonstrate that there are significant sex differences in TN pointing to sex-specific distinct TN aetiologies. Results: The visual analogue scale scores reduced significantly as early as week 1, and sustained until week 8 throughout the study. Evaluation of the Patient Global Impression of Change demonstrated that 71.6% of the patients reported that their pain symptoms were "much improved" or "very much improved". All adverse reactions were graded as mild or moderate. Conclusions: BTX-A injection in TN is safe and efficient. It is a useful treatment for refractory TN. Introduction: Idiopathic intracranial hypertension (IIH) usually presents with generalized headache, visual obscurations and papilledema. To our knowledge, this is the first case reported of unilateral trigeminal symptoms related to IIH in a patient with a skull base abnormality. Case report: A 44-year-old overweight woman presented with intermittent shock like pains and paresthesia on the right side of her face in the distribution of V1-V3. Neurological exam was normal including fundoscopy and facial sensation. A contrast enhanced brain MRI showed a hypoplastic Meckel's cave on the right (figure 1), and a small area of hyperintensity and enhancement along the adjacent dura. MRI was repeated twice and the finding was determined to be venous plexus and not a region of inflammation or a space occupying lesion. A CT of the brain done to further investigate bony structures of the skull base showed hypoplasia of the right skull base (figure 2), and a partially empty sella -suggestive of raised intracranial pressure. LP was performed and opening pressure was slightly elevated at 21 cm H2O, there was no pleocytosis or elevated protein. She had relief of her pain after drainage of CSF which was sustained by treatment with acetazolamide. Conclusion: We hypothesize that the hypoplastic Meckel"s cave increased the trigeminal nerve susceptibility to irritation from the small elevation in intracranial pressure. Therefore, our patient presented solely with trigeminal pain.

Migraine premonitory phase prospective study (ProdromaBot study). Preliminary data K. Skorobogatykh 1 , J. Premonitory phase of migraine attack is hard to study as the symptoms are very unspecific and hard to recall after the attack. The objective of our study was to evaluate the symptoms of the premonitory phase prospectively and to find predictors of the migraine attack. Here we report results of the first part of the study. Methods: We used Migrebot headache diary database to select subjects with migrainosus features and headache frequency 3-8 days per month. After that selected subjects proceeded to complete a specially designed version of the diary (ProdromaBot) to assess the interictal symptoms and migraine attacks for at least 30 days. Participants were required to complete three time points (TP) daily (9am,15pm,21pm). At each TP, participants answered 51 questions about well being, potential triggers, premonitory symptoms, as well as the presence of a headache and its characteristics.

Results: 98 subjects entered the study. 71 subjects completed a 30 days period with at least 80% compliance. 59 subjects visited the headache clinic to confirm migraine. From these 59 subjects we collected for further analysis: diary days-3602; total # of TPs-10644; total # of answers-542844; TPs with headache (new or ongoing)-1783; TPs with episodes of new headache-960. Results: The design of ProdromaBot diary has proved its reliability for data collection over 30 consecutive days with three time points a day with 51 questions at each TP. Most subjects were at least 80% diary compliant.

The Objectives: To determine the prevalence and clinical correlates of NOTCH3 p.R544C variant, which is associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, in migraine patients. Methods: Migraine patients were prospectively enrolled, with the diagnosis made according to the ICHD criteria by headache specialists. DNA samples of 3,502 population controls free of stroke, dementia, and headache were obtained from the Taiwan Biobank. Genotyping of p.R544C was carried out by TaqMan genotyping assay or Axiom Genome-Wide TWB 2.0 Array. Results: The study recruited 2,884 migraine patients (2,279F/605M, mean age 38.8±11.7 years), including 324 (11.2%) with migraine with aura (MA). 32 patients (1.1%) harbored the p.R544C variant, and the percentage was comparable to that in population controls (36/3,502; 1.0%) (p=0.846). Overall, migraine patients with and without p.R544C had similar headache profiles. However, those carrying the p.R544C variant had less pulsatile headache (50.0% vs. 68.2%, p=0.028), and a trend toward a higher percentage of moderate to severe white matter hyperintensities in the anterior temporal lobe (9.1% vs. 0%, p=0.091). (410) we were unable to reach a specific diagnosis. Patients diagnosed with TTH reported having more emotional difficulties (p = 0.001). No significant differences were found in headache characteristics, frequency or intensity between the younger children and the adolescents within either group, TTH or migraine. Conclusions: Retrospective application of International Headache Society Criteria in a large cohort of children with headaches failed to diagnose a specific type of headache in 41.5% of children. Migraine and TTH were equally prevalent, and both constituted a major burden on our patients' everyday lives. We found no major differences in frequency, intensity, and characteristics of pain between younger children and adolescents.

Systematic review and meta-analysis on physical differences between migraine, cervicogenic headache and healthy controls E. Objective: Identification of physical differences between patients with migraine and cervicogenic headache (CGH). Methods: A systematic search of electronic databases published until January 2020 was performed. Down"s and Black Scale was used to assess the risk of bias and the agreement was calculated with Cohen"s Kappa. Data extraction was performed by one reviewer and checked by a second. A narrative synthesis was conducted, data was combined and a meta-analysis with random effect models was performed, when possible. All steps were performed by two independent reviewers, followed the recommendations of the Cochrane Handbook and were reported according to PRISMA. The review was registered at PROSPERO and a study-protocol was published. Results: Seven publications were eligible and six of them were included in the meta-analysis. The results showed decreased range of motion (ROM) on the flexion-rotation test (FRT) (17.67, 95%CI 13.69 to 21.65) and reduced neck flexion strength (23.81 95%CI 8.78 to 38.85) in patients with CGH compared to those with migraine. Further studies, not included in the meta-analysis, suggested an increased percentage of cervical dysfunction, poorer performance on the cranio-cervical flexion test, reduced pressure pain thresholds and increased mechano-sensitivity of neural tissue in patients with CGH compared to migraine patients. Fig. 1 (abstract P0201) . See text for description When adding the additional criterion F ("the symptoms may not be better explained by another medical or mental disorder"), specificity significantly increased to 98%. Conclusions: The data show that the EDCT in its modified version are a highly useful tool for clinicians. They display a high sensitivity and specificity to accurately diagnose TIAs in patients referred to the emergency department with a suspected TIA. Objective: Data on the possibile association between anxiety, depression, eating disorders and migraine severity in pediatric migraine are sparse. We aimed to analyze: 1) the prevalence of eating disorders symptoms in adolescents with migraine; 2) the possible relationship between anxiety, depression, eating disorders symptoms and migraine frequency. Methods: We studied 35 adolescent girls with migraine (m.a. 13.9± 1.5 years). Due to their low frequencies, we excluded male patients from our analysis. According to the frequency of migraine, patients were classified in "high" and "low" frequency. Anxiety, depression and eating disorders symptoms were assessed by SAFA battery.

Results: Among our patients, 71.5% reported symptoms of anorexic (42.9%) and bulimic (28.6%) behaviour. We found significant higher scores in "School related anxiety" (p= 0.03) and "Perfectionism" (p= 0.01) subscales in patients with high frequency of attacks. In the "high frequency" patients, bulimic symptoms showed a positive and significant correlation with school anxiety (p= 0.03), depressed mood (p= 0.00) and sense of desperation (p= 0.00). Conclusions: Symptoms of eating disorders may be common among adolescent girls with migraine. Our data suggest that anxiety and depression may mediate the association between bulimic behaviour and migraine frequency. We suppose that school anxiety and depressive symptoms may lead to bulimic behaviour; these symptoms may, in turn, influence the frequency of migraine. Fig. 1 (abstract P0212) . See text for description Backgound: Migraine and tension-type headache (TTH) are common among children and adolescents, yet their long-term prognosis is not well understood. Objective: To evaluate the long-term outcomes of pediatric migraine and TTH. Methods: Pediatric patients who visited the pediatric neurology clinic due to diagnoses of migraine or TTH were contacted by phone 8-10 years after their initial diagnosis and interviewed about their outcomes. Results: Of 120 patients, 59 were seen initially due to migraine and 61 due to TTH. For the migraine patients, headaches improved in 48 and worsened in 4. Regarding diagnosis at follow-up, 59% still had migraine, 17% had TTH, and 23% were headache-free. Aura and photophobia were significantly associated with persistence of a migraine diagnosis. For the TTH patients, headaches improved in 49 and worsened in 9. Regarding diagnosis at follow-up, 36.7% still had TTH, 18.3% had migraine, and 45% were headache-free. TTH patients became headache-free at twice the rate of migraine patients. 36.7% of the patients with TTH retained their initial diagnosis compared to 59.3% among the migraine patients. Conclusions: Most pediatric patients presenting with migraine or TTH will experience a favorable outcome over 10 years, with TTH patients having twice the chance of complete resolution.

Odours that trigger migraine attacks and differences in the frequency of migraine attacks induced by odour according to clinical characteristics N. Imai 1 , A. Objectives: Our objective was to specifically determine the odours that trigger migraine attacks and the frequency of migraine attacks induced by odour according to clinical characteristics. Methods: In total, 101 patients were included in our study. A questionnaire was used to determine the types of odour that triggered migraine attacks and the differences in the frequency of migraine attacks induced by specific odours according to their clinical characteristics. Results: Odours that triggered migraine attacks included the following: perfume (56%), tobacco (48%), fabric softener (33%), body odour (33%), kitchen refuse (25%), hairdressing and hairdresser-related odours (23%), and automobile-related odours (23%). Patients whose migraine attacks were triggered by tobacco, soap or hairdressing and hairdresser-related odours were significantly younger than those whose migraine attacks were not triggered by these odours. Male migraineurs were significantly triggered by moth repellent than female migraineurs. Migraine attacks in patients with chronic migraine were significantly more frequently triggered by excrement, animals, socks, sweat, fabric softener, coffee, soap, kitchen refuse, cheese and vomit than in patients with episodic migraine. Conclusion: We found that migraine attacks were more frequently triggered by odours among younger patients and patients with chronic migraine, and the triggering odours differed between each group. Background: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were first FDA approved in 2018 for prevention of migraine in adults. Here, adherence and persistence to CGRP mAb versus other preventive migraine treatments (non-CGRP mAb) are compared over 12 months (mo). Methods: This retrospective, observational study was conducted using MarketScan® Databases. Adults with ≥1 claim (first claim= index) for CGRP mAb (erenumab, fremanezumab, or galcanezumab) or non-CGRP mAb (e.g., antidepressants, anticonvulsants) from 01 May 2018 to 30 Jun 2019 with continuous enrollment for ≥12mo pre-and post-index (follow-up) were included. Adherence was assessed as proportion of days covered (PDC) during 12-mo followup. Persistence was defined as days of continuous therapy (gap ≤60 days) from index date to end of follow-up. Descriptive, chi-square (categorical variables), and t-test (continuous variables) analyses were conducted. Results: Overall, 4528 patients (pts) on CGRP mAb and 10,897 pts on non-CGRP mAb were included (Table 1) . Mean 12-mo PDC was higher for CGRP mAb versus non-CGRP mAb (55.2% vs 37.8%, P<.001). More pts on CGRP mAb were adherent (PDC ≥80%) versus pts on non-CGRP mAb (P<.001) at 12mo. At end of follow-up, mean persistence was greater for CGRP mAb versus non-CGRP mAb (212.8 vs 142.9 days, P<.001). Conclusion: At 12-mo follow-up, pts on CGRP mAb had higher medication adherence and persistence compared with pts on non-CGRP mAb. Sponsor: Eli Lilly and Company. (Figure) . Those seeing headache specialists were most satisfied. Predictors of low satisfaction were higher monthly headache days, more pharmacological treatments tried, and lower levels of education and income. Those employed full time were more satisfied and those "occupationally disabled" less satisfied (Table) . Monthly headache days was inversely correlated with satisfaction (r s = -0.34, p < 0.001).

Conclusions: Despite widespread treatment use in this sample with high frequency migraine, satisfaction was low and varied by respondent characteristics; particularly those with more severe and impactful disease. Background: Migraine could be episodic or chronic over a one person lifetime. Migrebot is an interactive chat-based headache diary. Aim: In this study we analyzed the evolution of migraine frequency among the Migrebot users. Methods: From more than 20000 Migrebot users we selected those who have had at least one day with migraine. Migraine day was defined as: day with headache with photo-AND phonophobia AND/ OR nausea AND/OR any triptan was taken. From these users we selected those, who completed the diary for more than 6 months. We analysed the 1st and the 6th month in these cohorts. We excluded those subjects who completed the diary less than 25 days per month in these months. Results. We got 1161 subjects and divided them into 4 groups based on the number of headache days during the 1st month. Group A:1-4 days (20,6%); group B:5-8 days (34,1%); group C:9-14 days (29,9%); group D:15-30 days (15,4%). After 6 month: in group A 76,2% users remained in group A, 19,2% moved to group B, 4,2% moved to groupC, 0,4% moved to group D; in group D 28,5% users remained in group D, 13,4% moved to group A, 24,6% moved to group B, 33,5% moved to group C. Conclusion: Over 6 month: most of the users with infrequent episodic migraine tend to stay in this group; the majority of users with chronic migraine (71,5%) have improved. Background: Education level effects migraine, lower education correlates with risk of migraine chronification. This study aims to quantify the level of education in patients referred to our headache clinic, evaluate whether lassociated with an increased risk of chronification, and relates to other common migraine comorbidities. Method: New patients referred to our headache clinic complete a patient intake questionnaire that asks about the highest level of education completed, as well as about headache characteristics, sleep, depression, anxiety, and stress. Data was analyzed with patients' diagnoses. Results: In our analysis, 4408 unique patients were diagnosed with migraine, 75% with chronic migraine. 5.72% had a doctorate or higher, 16.88% had a masters, 39.58% completed at least college, 34.32% completed at least high school. 63% of patients seen in the clinic have college or higher education. Statistical analysis shows that having a higher education correlates with less chronification. This effect is robust when correcting for gender and age. Conclusions: It is notable that most patients seen in our headache clinic have college or higher education and yet suffer from chronic migraine. However, we show that patients with college or higher education have less headache days per month and less severe headaches compared to patients with less than college education. Educational attainment may be protective due to greater functional brain reserve. Background: The efficacy of triptans as the main acute treatment strategy for migraine headache at the population wide level needs to be understood to inform clinical decision-making. We summarize key trends in triptan use using more than 25 years of Danish nationwide data. Methods: We conduct a nationwide register-based cohort study based on all Danish residents with access to public healthcare between Jan 1st, 1994 and Oct. 31st, 2019 and summarize informative trends of all purchases of triptans in Denmark in the same period. Results: Over a 25-year period, triptan use almost tripled and the yearly prevalence of triptan use increased from 5.17 to 14.57 per 1,000 inhabitants. Between 2014 and 2019, 12.3% of the Danish migraine population purchased a triptan. After an initial purchase, 43% of patients had not repurchased triptans within 5 years. At most 10% of patients indicating triptan discontinuation tried more than one triptan. The prevalence of triptan overuse increased in parallel with the prevalence of triptan use, prevalent in 56 of every 1,000 triptan users every year between 2014 and 2019. Conclusion: In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance.

The -100, 75-84, 55-74, 40-54, and <40) . At Month 3 the greatest proportions of patients that self-rated on the PGI-S as "Normal, not at all ill," or "Borderline ill" (51.0%) fell into the 85-100 category, "Mildly impaired" (36.9%) in the 75-84 category, "Moderately ill" (42.3%) in the 55-74 category, "Markedly ill" (39.9%) in the 40-54 category, and "Severely ill," and "Extremely ill" (46.1%) in the <40 category. Conclusions: The proposed MSQ RFR score categories provide cutoffs to define disease severity and functional impairment, aiding score interpretation.

Timely diagnosis of migraine -A prospective observational study assessing the potential to prevent unnecessary emergency department visits for headache H. Drangova Objectives: I-GRAINE-NEW aims to follow a large representative sample of patients with migraine with the following principal specific objectives:

1. provide information on migraine natural history and its evolution over time; 2. provide epidemiological, social and sanitary resource use data 3. identify the impact of patient management on prognosis Methods: Data will be acquired through an observational, prospective study including 41 headache centers. I-GRAINE-NEW will enroll a representative sample of 10% of adult patients with episodic or chronic migraine and will last at least 5 years. Patients will be evaluated by face-to-face interviews using a detailed semi-structured questionnaire. A subgroup of 6000 patients referred for a first outpatient visit, will be considered for a retrospective-prospective sub-study that will collect more in-depth information using the clinical interview, a daily headache diary and a series of PROMs. Data will be stored in the electronic case report forms. All procedures will by compliant with GDPR 2016/697. Results and conclusions: The I-GRAINE registry is expected to shed light on migraine unmet needs, define the endophenotypes, and improve clinical management, resulting in increased disease awareness, better healthcare resource allocation, and reduced economic burden. Objective: Assess respondents' ability to return to their usual activities and level of impairment of those activities after migraine acute treatment with lasmiditan. Methods: A 15-min web-based survey was conducted on adult respondents who had enrolled in the US patient support program, redeemed a savings card, and treated at least 1 migraine attack with lasmiditan within the prior month. Symptoms/outcomes/ability to engage in various activities after recent lasmiditan-treated migraine attack were assessed using descriptive statistics. Results: 78 respondents completed the survey (mean age 48 years/ 93.6% female/16.9 mean headache days/month). Untreated/ unsuccessfully treated migraine attacks prior to ever taking lasmiditan resulted in inability/ severely impaired ability to perform various activities (Table) . At the time of lasmiditan dosing (most recent attack), 49% had severe and 45% had moderate pain. By 2hours post-dose, 94% respondents had some/complete pain improvement. After lasmiditan treatment, 45-75% respondents returned to their current/planned activities, except for planned activities outside home (22%). Extent of ability to perform current/planned activities varied by activity (Table) . 77% respondents were satisfied with lasmiditan; 62% were satisfied with its ability to return them to their usual activities. Conclusion: With lasmiditan, majority respondents were satisfied and able to return to their usual activities with no/some degree of impairment.

The route of patients to the diagnosis of hemiplegic migraine and the peculiarities of this migraine type M. Bozhenko 1 , N. Objective: Hemiplegic migraine(HM) is considered a rare type of migraine with an aura. Due to the brightness of neurological manifestations and lack of awareness about this form of migraine, these patients are often misdiagnosed. Methods: A review and analysis of HM clinical cases and their route to diagnosis among outpatients of Lviv regional clinical hospital during 2019-2020. Results: During 2019-2020 years 6 patients with HM were identified. 4-female, 2-male. With the age range from 16 to 32 years old. None of them previously had been diagnosed with HM. Only one had a familial form. The onset of a migraine was in the age 14-17 years. Time from attacks onset to diagnosis of HM was from 2 to 16 years. These attacks were previously diagnosed as panic attacks, TIA, and epilepsy. Misdiagnosing led to a lack of adequate migraine treatment. In the case of a female with 16 years of hemiplegic migraine attacks history, it led to migrainous infarction after the last attack. In 2 more patients foci of gliosis on MRI were described. Also, we found typical weakness spreading from the distal parts to the proximal. Conclusion: Lack of awareness among general practitioners and pediatricians leads to the fact that hemiplegic migraine attacks are often perceived by doctors as other paroxysmal conditions, which leads to a lack of adequate treatment of these patients, which significantly affects their quality of life and can sometimes lead to complications such as migrainous infarction.

Neck symptoms as a risk factor for headache: a scoping systematic review (1.42-3.63) . Conclusions: Neck symptoms are a significant risk factor for Unspecified Headaches and Migraine but the relationship with Tension-Type Headache and Chronic Tension-Type Headache is different for adults and paediatric groups. If neck symptoms are a risk factor for disabling headache then a risk-factor reduction approach may simplify headache treatment and eliminate controversy surrounding cervicogenic headache.

Impact of Headache on Quality of Life in United States Veterans: a Qualitative Study I. Gosnell 1, 2 , T. Damush 3, 4, 2 , H. Lindsey 2,5 , R. Goldman 2,6,7 , A. Grinberg 1,2 , S. Riley 4 , L. Burrone 2 , S. Baird 4 , B. Fenton 2,5 , J. J. Sico 2,5 , E. K. Seng 1, 8, 2, 9 1 Objective: Headache is a common, chronic and disabling disease with episodic exacerbations that impact quality of life. We evaluated health-related quality of life (HRQoL) in veterans living with headache and receiving care in the Veterans Health Administration (VHA) Headache Center of Excellence program.

Methods: We conducted semi-structured qualitative interviews with a purposeful sample of 20 veterans across VHA. Patients were asked about headache characteristics, management, and healthcare. We qualitatively coded all NVivo files using an apriori/emergent codebook. We conducted a comparative case analysis to identify emergent domains of HRQoL. Results: The 20 participants (16 men, 4 women) had a mean age of 54 years (SD=13.77) and headache diagnosis of migraine (n=15), other (n=7), tension-type (n=3), cluster (n=1), medication overuse (n= 1), and/or post-traumatic headache (n=1). Participants were white (n=15), Black (n=4), Asian (n=1), and Hispanic (n=1). Headache impacted patients" HRQoL via: 1) hopelessness around lack of control; 2) frustration that pain occurred at random; 3) regardless of treatment, relief did not last; 4) headache attacks led to social withdrawal; and 5) headache attacks prevented participation in life activities. Conclusions: Chronic headache pain and unpredictable symptom occurrence contribute to reduction in HRQoL in people living with headache. Further research is needed into how to maintain or improve quality of life in veterans with headache. Background: Although headache is a noticeable symptom and can follow stroke manifestation, it is often underestimated in the acute period of stroke in Kyrgyzstan. Aim: We aimed to analyze the prevalence of the headache as the symptom in the acute stroke patients in Bishkek. Methods: In an observational study we studied logistics, onset symptoms and behavior of 477 acute stroke patients, examined by the emergency medical team and hospitalized in stroke units in a period from November, 2019 till March, 2020. Results: Headache was presented as a reason for call to emergency services in 22% of cases of all strokes, while 32% of patients mentioned headache in the stroke onset in the interview with the emergency team. 69% of patients had acute headache and in 48% it followed with the weakness in limbs and speech disturbances. Headache was expressed in high hypertension with systolic blood pressure higher than 180 (OR=4, 95% CI, p = 0.001;) was described as bilateral, dull, continuous and localised in temples and occipital part (78%) and was more associated with a lacunar stroke. Patients used hypotensive medications (captopril), paracetamol+aspirin to abort the headache and green tea as a remedy. Conclusion: Headache was a frequent symptom in a stroke onset and is associated with the sudden rise of a blood pressure in a stroke onset. Patients encouraged medical personnel to include headache as a symptom in stroke recognition algorithms which exist in Kyrgyzstan. Background and Objectives: Primary headaches are remarkably prevalent worldwide. We examined the prevalence of primary headache disorders among students of higher education institutions. Methods: We conducted study that included 1381 students of higher education institutions in the 2019/2020 academic year. Prevalence and attributable burden of headaches, definite and probable migraines, definite and probable tension-type headaches, chronic headaches, and medication-overuse headaches were assessed using the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire. Results: Of 1381 questionnaires that were distributed, 1,101 students completed the questionnaire. The study population consisted of 36% man and 64%woman with a mean age of 18,5±1.1 years. The 1-year prevalence of primary headache disorders was 41.5%, with more middle secondary-year than thirst-year students (51.7 vs. 29,8%; p< 0.02). When stratified according to diagnostic criteria, migraine headaches were the most frequently reported (22,3%) , followed by tension type headaches (19,1%), chronic headaches (2,8%), and probable medication-overuse headaches (2,4%) . Conclusions: Primary headaches are remarkably common in Ukrainian students, with migraine headaches being the most frequently reported type. These findings necessitate the direction of health services such as lifestyle modification training to prevent primary headache in this population. Background: Migraine among medical students further compounds the demanding nature of medical training. Objective: This study aimed to determine migraine prevalence, associated absenteeism and headache-related health-seeking roles among undergraduate medical students of the University of Calabar, Nigeria. Methods: In this cross-sectional descriptive study, we used a structured questionnaire incorporating the International Headache Society criteria for migraine to identify migraine among the aforementioned students, besides obtaining data on headache-related absenteeism and health-seeking behavior. Two hundred and twenty participants, comprising 62.3% males and 37.7% females, completed the study. Results: Overall, 5.9% of them had migraine headaches, with genderspecific prevalence values of 4.4% and 8.4% for males and females, respectively. 53.8% of the affected persons had migraine with aura. The age at migraine onset ranged from 11 to 16 years, with a mean (standard deviation) and median ages of 13.6 (1.92) years and 13.5 years, respectively. All the students diagnosed with migraine reported being absent from scheduled activity because of headaches. More than half of those with migraine relied on self-medication; whereas, only a quarter had consulted a physician for their migraine attacks. Conclusion: Migraine was common among this set of medical students, with frequent headache-induced absenteeism. There was poor utilization of available healthcare resources, for migraine treatment, even among the medical students with access to tertiary health care. Background and objective: Fasting is adopted by many individuals worldwide either for health optimization or for religious reasons. Fasting, however, exacerbate migraine. This work aimed at studying factors that may contribute to migraine exacerbation during long fasting among Egyptian migraineurs who fast for religious reasons 16 hours daily for one full month (Ramadan). Methods: This was a cross-sectional study conducted on 30 migraine patients. Patients filled a diary about dietary consumption, fluid intake, and sleep habits during Ramadan. A comparative analysis was made between days with and days without migraine. Results: Of 222 days recorded, 48 days were with migraine and 74 days were without. On regression analysis, initial insomnia (OR 5.1, CI 2.3-10.9, p<0.001), fried food (OR 2.9, CI 1.19-6.79, p=0.018), coffee (OR 2.3, p=0 .015), citrus fruits (OR 2.3, CI 0.97-19.5, p= 0.037), watermelon (OR 12.7, p=0 .002), dairy products (OR 2.14, CI 1.17-3.91, p=0.012) were found to increase the odds of migraine occurrence. Factors associated with low odds of migraine occurrence were fluid intake (OR 0.88, CI 0.77-0.88, p=0.034), frequent meals (OR 0.44, p=0.004) , and dessert consumption (OR 0.49, p=0.025) . Conclusion: Sleep habits, fluid intake, coffee consumption and dietary habits contribute to migraine occurrence during long fasting states and should be considered for adequate control of the disease during fasting. Introduction: ClinicalTrials.gov is a centralized venue for monitoring clinical research and allows access to information on publicly and privately funded studies. Objective: To identify major organizations conducting clinical migraine trials and the frequency of different study designs. Methods: Utilizing ClinicalTrials.gov application programming interface, we extracted studies including individuals with migraine from February 29, 2000 to July 28, 2020 for the following: (1) host organization; (2) study type; (3) primary purpose; (4) intervention model; (5) allocation. The top 32 (3%) organizations each produced ≥5 entries totaling 40.0% of entries. Approximately 86% were interventional studies; 13.6% were observational studies. Randomized design allocation is the most frequent. The most frequent primary purpose is treatment (62.4%) followed by prevention (13.0%). There were 56.9% parallel assignment, 15.2% single group assignment, and 12.4% crossover assignment models. Discussion: A minority of organizations contribute to a significant number of registrations of clinical migraine trials. The most common study is interventional, randomized, with parallel assignment for treatment purpose. Organizations should aim to improve preregistrations to increase transparency and to reduce introduction of bias in clinical studies. Objective: Oral ingestion of MSG results in reports of headache and craniofacial tenderness in healthy humans. We examined whether systemic administration of MSG could produce evidence of headache in rats. Methods: The behavior of Sprague Dawley rats (6 male, 6 female) was video recorded before and after intraperitoneal injections of either MSG (1-1000 mg/kg), nitroglycerin (GTN, 10 mg/kg) or normal saline in a randomized order by a blinded experimenter. Behaviors (grimace score, head shakes, rearing, head scratches, facial grooming, temporalis muscle mechanical withdrawal threshold (MT)) were evaluated from the recordings by two blinded assessors. Plasma glutamate and a-CGRP concentrations after administration of 1000 mg/kg MSG were measured in anesthetized rats as a terminal experiment. Significant differences were assessed with two-way repeated measures ANOVA. Results: Compared with GTN and saline, MSG (500-1000 mg/kg) significantly increased grimace scores and headshakes, and significantly decreased rearing, head scratches, and facial grooming for 20-30 minutes post administration. MT was unchanged. Plasma glutamate and a-CGRP concentrations increased from 30 to 3800 mM and 2 to 10 pg/ml, respectively, 30 min post injection. Conclusion: MSG induces headache-like behaviors in a dose-related manner associated with increased plasma glutamate and CGRP concentrations. These findings suggest that, like humans, systemic administration of MSG in rodents may induce headache.

Evidence that monosodium glutamate (MSG) administration induces nausea-like behavior in rats Objective: Oral ingestion of MSG results in reports of headache and nausea in healthy humans. We examined whether systemic administration of MSG could evoke a nausea-like state in rats.

Methods: The behavior of Sprague Dawley rats (6 male, 6 female) was video recorded before and after intraperitoneal injections of either MSG (500-1000 mg/kg), nitroglycerin (GTN, 10 mg/kg) or normal saline. Treatments were given in a randomized order by a blinded experimenter. The duration of lying-on-belly (LOB) nausea-like behavior was evaluated by two blinded assessors. Cutaneous temperature of the nose was measured before and every 10 minutes after intraperitoneal injections via infrared thermography. Significant differences were assessed with two-way repeated measures ANOVA. Correlation between LOB and facial cutaneous temperature was determined with Pearson"s correlation analysis. Results: Compared with GTN and saline, MSG (1000 mg/kg) significantly increased LOB behavior between 20 and 30 minutes post administration. Nose cutaneous temperature was significantly decreased compared to GTN and saline from 10-30 minutes post MSG (1000 mg/kg) administration. A significant inverse correlation between LOB behavior duration and nose cutaneous temperature was found. Conclusion: MSG induces nausea-like behavior in rats that consists of increased LOB duration and facial cutaneous hypothermia. This data suggests that, like humans, systemic administration of MSG to rats may induce nausea. Objective: Assess if patients with episodic migraine (EM) have increase musculoskeletal impairments of the cervical spine compared to healthy controls independently by the phases of the migraine cycle and the presence of neck pain Methods: In this multicenter cross-sectional, observational study, EM patients and healthy controls (age 18-65) were included. Cervical active range of movement (AROM), craniocervical flexion test (CCFT), flexion rotation test (FRT), and pressure pain threshold (PPT) over the neck were assessed. A linear regression model using the variable group to predict the results was performed. Healthy controls were used as reference groups adjusting the model for age, sex, and disability due to neck pain Results: 42 Control, 32 interictal EM, 34 Preictal EM, 25 Ictal EM, and 23 postictal EM were included. The AROM was lower only in Ictal EM compared to healthy controls (p=0.033), with no other differences (p>0.111). Healthy controls had higher CCFT (p<0.001), lower FRT (p< 0.001) compared to EM patients in all phases with no differences in neck PPT (p>0.096) Conclusion: EM patients in all phases of the migraine cycle have reduced functionality of deep cervical flexors muscles and restricted passive range of motion of the upper cervical spine. No neck hyperalgesia was observed in any of the phases. The active range of motion was impaired only in the ictal phase, suggesting that acute headache could cause a reduction in functionality of the neck movement. Objectives: Headache is a predominant co-morbidity in raised intracranial pressure (ICP) disorders. Obesity is associated with an increased risk of idiopathic intracranial hypertension and migraine. We assessed the effect of diet-induced obesity (DIO) on cephalic sensitivity in a non-traumatic raised ICP model. Methods: Female Sprague-Dawley rats received high fat diet (60% fat) or matched control diet. Blinded periorbital and hind paw pain thresholds were measured throughout the diet by a von frey anaesthesiometer. Prior to implantation with an ICP telemetric device, body composition was assessed via dual energy x-ray absorptiometry (DEXA). Expression of headache relevant genes was studied in the trigeminal ganglia (TG). Results: Over the course of a 15-17 week diet DIO rats demonstrated cyclical periorbital allodynia (P=0.003) but normal hind paw thresholds. On the day of DEXA, DIO rats were 17.5% heavier (P<0.0001) with a higher abdominal (Abd) fat percentage (P<0.0001) with raised ICP (P=0.005). DIO rats had periorbital allodynia (P<0.0001) with an inverse correlation with Abd fat percentage (r=-0.65, P=0.0005). Hind paw thresholds were normal. In support, DIO TG had increased expression of Trpv1 (P<0.01) and Cgrpa (CGRPα) (P<0.01). Proinflammatory gene expression was unaltered.

Conclusion: DIO rats demonstrated cephalic cutaneous allodynia likely involving the CGRP pathway, in the context of raised ICP. Further investigation into the mechanisms could lead to novel therapeutics.

Background and objective: Several members of kynurenine pathway (KP) are able to influence the glutamatergic neurotransmission, subsequently the pathomechanism of migraine. Our aim was to reveal the complete peripheral tryptophan (Trp) catabolism, which comprises the KP in episodic migraineurs and its relationship with clinical characteristics of patients. Methods: Female migraineurs (n=50) and healthy subjects (n=34) aged between 25-50 years were enrolled. Peripheral blood samples were collected from subjects (during both the interictal/ictal periods in patients). 12 metabolites were determined by neurochemical measurements. Results: Significantly decreased plasma concentrations of Trp (p< 0.025), L-kynurenine (p<0.001), kynurenic acid (KYNA) (p<0.016), anthranilic acid (ANA) (p<0.007), picolinic acid (PICA) (p<0.03), 5hydroxy-indoleaceticacid (5-HIAA) (p<0.025) and melatonin (MELA) (p<0.023) were detected in the interictal period of migraine without aura patients compared to controls, while elevated ANA, 5-HIAA and MELA levels were found during attacks. Correlations were identified between the followings: xanthurenic acid, MELA-attack frequency, KYNA-menstruation cycle-related headache, PICA-last attack before ictal sampling. Conclusions: Metabolic imbalance is assumed during the attack free period, which can manifest in depressed peripheral KP contributing glutamate excess, neurotoxicity and generalised hyperexcitability. KP may have clinical relevance in migraine. menstrual cycle, the VAS was 7.14±2.32 points, the blood serotonin level was 194.64±34.8 ng/ml, and with an unstable one, it is 9.05± 4.63 points and 132.8±53.4 ng/ml, respectively (p=0.041). In patients with a stable cycle, depression is not observed, and when the cycle is disrupted, is determined severe depression (13.9±9.1 points, p= 0.000810). The correlation analysis revealed a relationship between the indicators of headache intensity and personal anxiety (РА) (r= 0.3552; p=0.0050), depression and blood serotonin levels (r=-0.4218; p=0.0013).

Conclusions: In women with gynecological pathology, TH is more common than M. Women with an unstable cycle are more likely to suffer with depression and have low serum serotonin levels.

The Introduction: HPT (Hyperventilation provocation tests) is useful for the study of electroencephalography (EEG). The research aimed classified pathological EEG responses to HPT according to different parameters:time of manifestation and age of patients with neurological disorder headaches, fatigue etc. Methods: The outpatient applied to the Beritashvili Centre of experimental Biomedicine. The control group consisted of 1201 participants whose EEG response to hyperventilation was within normal range. The three types of pathological EEG responses to hyperventilation (PERH) were detected in 985 outpatients PERHI corresponds to disorganization of basic rhythm. PERHII-paroxysmal discharges without epileptic elements. PERHIII-epileptic activity. The patients were divided by PERH into the following age groups: 3-6, 7-12, 13-18, 19-30, 31-50, 51higher . Results: In all age revealed disorganization of basic EEG rhythm in the first, second and third minutes of HPT. In the first minute of HPT the three types of PERH were revealed in all age, which was not observed in the second and third minutes. Conclusion: 3 main types of PERH detected in all age-groups of patients might be informative for correct diagnosis, monitoring treatment plans and functional outcomes. The EEG reaction to hyperventilation undergoes permanent changes during brain maturation and development. Point out that children, adults, and elderly have different individual sensitivity to hypocapnia developed during hyperventilation. CGRP is a key component of migraine pathophysiology at peripheral and, probably, also at central sites.

Objective: To evaluate the effect of CGRP blockade in peripheral and central areas of the nervous system in two animal models of migraine.

Methods: Male Sprague-Dawley rats were exposed to nitroglycerin (NTG) or vehicle and treated with the CGRP antagonist olcegepant or vehicle 1h before undergoing the orofacial formalin test. In another group of rats we applied the inflammatory soup (IS) on the dura mater to induce neurogenic inflammation model and 10 min later treated them with olcegepant or vehicle. All animals were sacrificed at the end of the experimental session and gene expression of CGRP and pro-inflammatory cytokines were evaluated in the trigeminal ganglion, meninges and medulla-pons. Results: Olcegepant significantly attenuated NTG-induced trigeminal hyperalgesia in the orofacial formalin test, while decreasing proinflammatory cytokines and CGRP mRNA levels in all areas. Similar effects were also observed in the neurogenic inflammation model. Conclusions: The findings show that the antagonism of CGRP receptor induces changes in molecules that are relevant for migraine pathophysiology in both peripheral and central nervous system areas. This observation may be clinically relevant, as migraine patients not responding to monoclonal antibodies targeting CGRP, whose effect is mostly peripheral, may still benefit from the treatment with a CGRP antagonist. Objective: Spontaneous Intracranial Hypotension due to spinal CSF leak is a secondary cause of headache with potentially devastating consequences for patients who suffer from it. Diagnosis is complicated by the lack of a reasonable, minimally invasive screening test. This results in many patients going undiagnosed for years after headache onset. Current testing approaches are either overly invasive, such as CSF infusion protocols, or both invasive and insensitive, such as lumbar puncture with opening pressure or CT myelogram as it is commonly used-both require access to the thecal space and lack sensitivity. CT Myelogram will not see a leak if it is intermittent, or very slow, and in the setting of spinal CSF leak, opening pressure on LP may be high, low, or normal. A potential remedy for this state is T2 Space Protocol spinal MR Myelogram. Methods: Chart review of patients who have had T2 space MRI and Myelogram to assess if findings are consistent between the study types. Results: We have few patients who have had both studies at our facility; we did find 2 who had, and these show clear indications of CSF leak on both myelogram and T2 space protocol MRI. Conclusions: The presence of CSF leak-evidence on T2 space MRI corroborated by Myelogram demonstrates the potential value of this protocol as a screening tool. It is highly sensitive for spinal pathology and minimally invasive, making it an excellent choice for screening patients suspected of spinal CSF leak. Objectives: Cortical spreading depression (CSD) induces activation of the meninges and associated vasculature (MAV), a key process leading to trigeminal nerve activation and migraine pain. However, how CSD mediates these phenomena in migraine is poorly understood. The aim of this study is to examine CSD-mediated transcriptomic profile of the MAV. Methods: CSD was recorded using electrophysiology in rats. RNA-seq analysis and qPCR were applied for gene expression analysis. Results: RNA-seq analysis showed that multiple CSD rapidly induced profound changes in gene expression profile in the ipsilateral MAV of rats. CSD induced a total of 1126 genes with altered expression levels, of which 953 CSD-induced DEGs were upregulated and 173 CSD-induced DEGs were downregulated in the rat ipsilateral MAV. All these genes were, for the first time, identified to be altered by CSD in the MAV. These transcriptomic changes accounts to 4.8 % of genes identified in the MAV of rats. Furthermore, these changes of transcriptomic profile were largely associated with altered pathways in synaptic transmission, ion transport and neuroinflamma-tion. Conclusions: These data implied that MAV activation may be attributed to changes in its transcriptomic profile which are markedly induced by CSD. The authors declare that there is no conflict of interests. Background and objective: TRPA1 is a promising therapeutic target in migraine by responding to migraine triggers and regulating migraine pathogenesis. However, TRPA1-invovled signaling events in migraine are poorly understood. In this study, we explored the potential role of Src family kinases (SFK) in TRPA1-mediated migraine pathophysiology in trigeminal ganglion (TG), the key anatomical region for migraine pain transmission from periphery to brain. Methods: A mouse trigeminal ganglia (TG) tissue culture model was applied. The level of SFK activation was detected using Western Blot; calcitonin gene-related peptide (CGRP) release was detected using ELSIA and IL-1β gene expression was detected using qPCR. Results: The results showed that activation of TRPA1 by umbellulone increased the level of phosphorylated SFK at Y416 in TG, which was reduced by inhibition of protein kinase A by PKI (14-22) amide.

Moreover, inhibition of SFK activity by saracatinib reduced umbellulone-enhanced CGRP release and IL-1β gene expression in TG. Conclusions: These findings suggest that SFK participate in TRPA1 signaling in TG to mediate neuropeptide release and neuroinflammation, leading to peripheral sensitization and the development of migraine.

Is there a link between pain chronification, and allodynia and vitamin D deficiency in headache? C. Baiata 1,2 , V. Rebecchi 2 , L. Princiotta Cariddi 2,3 , D. Gallo 4, 5 Objective: The vitamin D deficit has been associated to pain chronification, and chronic migraine is frequently associated with allodynia. The aim of this study was to assess the potential role of VitD in pain chronification and its relation to the occurrence of allodynia. Methods: We recruited 76 consecutive patients: 32 belonged to the episodic migraine (EM), 34 to the chronic migraine and medication overuse (CM-MOH) groups and 10 to the tension-type headache (TTH) group. All patients underwent neurological and physical examination and anamnestic data collection including allodynia and serum calcifediol (25(OH)D) assessment. Results: The occurrence of patients with vit D deficit was significantly higher in the CM-MOH (46%), than in the EM groups (25.7%) and in the TTH group (11.4%). The Vit D deficit was not significantly associated with any of the other variables. Allodynia also was more frequent in CM-MOH (66.7%) than in the EM (29.2%) and TTH groups (6.7%). On the contrary the occurrence of allodynia was independent from the vit D deficit (allodynia occurred in 42.4% of patients with and 57.6% without vit D deficit) Conclusion: Prevalence of VitD deficiency and allodynia were significantly higher in patients suffering from CM-MOH, however the co-occurrence of allodynia and VitD deficiency were not correlated, thus suggesting that chronification and allodynia do not stem from the same pathophysiological mechanism.

COmbining UbRogepAnt and preventives for miGrainE (COURAGE) study using the Migraine Buddy application: A novel, entirely remote design for collecting real-world evidence To describe COURAGE, a novel, mobile (Migraine Buddy) app-based, study evaluating the real-world effectiveness of ubrogepant for the acute treatment of migraine when used with an approved preventive. Eligible adults (≥3 ubrogepant-treated attacks, ≥3 migraine attacks in last 30 days) used ubrogepant with onabotulinumtoxinA (ub+obA), or with anti-CGRP monoclonal antibody (ub+mAb), or with both medication (ub+both). Over 30 days, participants reported treatment outcomes at <1, 1-2, 2-4, or >4 hrs post-ubrogepant. Interim marginal odds of achieving meaningful pain relief (MPR) for the 1st ubrogepant-treated attack by 2 and 4 hrs post dose were modeled via logistic regression. Covariates were age, MIDAS, ubrogepant dose. As of 01/2021, 492 respondents consented, with 461 screened and then 354 enrolled; users with baseline treated ≥1 attack with ubrogepant) were ub+obtA, n=88 (83); ub+mAb, n=206 (175); ub+both, n=60 (51). 237 completed the study and 177 logged ≥3 ubrogepant-treated attacks. Interim data suggests many patients achieving MPR by 2 hrs post-treatment with a larger majority achieving MPR at 4 hrs. Adjusted odds were significant (p<0.001) for ub+obA and ub+mAb. COURAGE has successfully assessed treatment value and usage patterns remotely to keep patients and HCP safe during the COVID-19 pandemic. Interim findings suggest that ubrogepant is effective when used with approved migraine preventives; final data may inform clinicians how best to optimize treatment. Objective: To assess the real-world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center. Method: This was a cohort study conducted at Mayo Clinic Arizona. All patients prescribed ubrogepant were tracked and contacted 1-3 months after the prescription to answer a list of standardized questions. Results: We obtained eligible responses from 106 patients; 86.8% had chronic migraine. Complete headache freedom, and headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant was achieved in 19.0% and 47.6% patients, respectively. 31.1% patients were being "very satisfied" with ubrogepant. Adverse events were reported in 39.6% patients, including fatigue 27.4%, dry mouth 7.5%, nausea 6.6%, constipation 4.7%, dizziness 2.8%, and others 6.6%. Predictive factors for being a "good responder" to ubrogepant included migraine with aura, episodic migraine, <5 prior unsuccessful preventive or acute treatments, successful responses to a CGRP monoclonal antibody and onabotulinumtoxinA. For the 62 (58.5%) patients concurrently using a CGRP monoclonal antibody, there was no difference in the "good responder" rate or adverse event rate compared to those who were not on a CGRP monoclonal antibody, though the rate of moderate adverse events was higher. Conclusion: Our study confirms and extends the efficacy profile and tolerability of ubrogepant in a real-world tertiary headache clinic and identifies factors that may predict efficacy. Objective: Our aim was to analyze if addition of sodium bicarbonate (SB) to bupivacaine for occipital nerve block (ONB) relieves injection related pain. reported less injection related pain in both sides (4.4±2.7 vs 6.5士1.3, p=0.005), in symptomatic side (4.2±2.9 vs 6.5±1.5, p=0.013) and in non-symptomatic side (3.3±2.4 vs 6.0±1.8, p=0.002). Tenderness to palpation was related to less painful injections only in right side. MMD, days from last attack and the presence of allodynia did not correlate with injection pain scores. We found no differences in patient reported improvement or number of headache days 1 week after injection between site1 and site 2.

Conclusion: The addition of SB to bupivacaine resulted in less painful injections in ONB. Well-designed studies are needed to confirm this finding. Objective: To examine the relationship between monthly headache days (MHDs) at cross-section and 3 months earlier on current Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) scores. Methods: CaMEO is a web-based, longitudinal study that identified US individuals who met migraine criteria consistent with the International Classification of Headache Disorders-3. Groups defined by MHD frequency at 3 and 6 months were established and mean MSQ Role Function-Restrictive (MSQ-RFR) scores calculated. MSQ-RFR scores at 6 months were modeled as the outcome in nested linear regression models examining 6-and 3-month MHDs.

Results: Among 16,789 migraine respondents, 6509 (38.8%) had valid MHD and MSQ-RFR data. At 6 months, 4640 (71.3%) respondents reported 0-3 MHDs, 896 (13.8%) reported 4-7 MHDs, 510 (7.8%) reported 8-14 MHDs, and 463 (7.1%) reported ≥15 MHDs. Across 6month MHD categories, mean MSQ-RFR scores were 82.5, 61.5, 56.8, and 47.5 among those reporting 0-3, 4-7, 8-14, and ≥15 MHDs, respectively. Within each 6-month MHD group, mean 6-month MSQ-RFR showed a trend towards lower MSQ-RFR with higher 3-month (prior) MHD category. Linear regression showed that MSQ-RFR at 6 months was significantly associated with MHD frequency at 6 and 3 months (P=0.001 for each). Conclusion: Our results demonstrate an inverse relationship between MSQ-RFR score at 6 months and MHD frequency at both 6 months and 3 months. Improvements in MSQ-RFR scores may lag behind improvements in MHDs. Objective: To evaluate an alternative method of characterizing success in clinical trials for the acute treatment of migraine. Methods: Pooled data for placebo and ubrogepant 50 mg (ACHIEVE I and ACHIEVE II trials) and data for ubrogepant 100 mg (ACHIEVE I) were used for this analysis. To define treatment success, we used confirmatory latent class modeling (LCM) that included inputs at baseline and 2 hours for pain severity and functional disability, and binary measures of nausea, photophobia, and phonophobia. Treatment success rates and predictive validity (using satisfaction with study medications [SWSM] 24 hours post-dose) with LCM were compared with 2-hour pain freedom (2hPF). Results: LCM-based treatment success rates were 53.2% for ubrogepant 50 mg, 54.9% for ubrogepant 100 mg, and 39.0% for placebo, yielding a placebo-corrected difference of 14.2% (P<0.001) for the 50 mg dose and 15.9% (P<0.001) for the 100 mg dose. The LCM approach estimated higher rates of treatment success and larger placebo-corrected differences than with 2hPF. Using SWSM as the gold standard, sensitivity (0.72 vs 0.31) and Youden"s index (0.44 vs 0.28) were higher with LCM than for 2hPF. Conclusion: The LCM approach more sensitively predicted treatment satisfaction at 24 hours and better aligned with our clinical understanding of migraine as a symptom complex. In contrast, 2hPF failed to capture a substantial proportion of patients satisfied with treatment. Objective: To evaluate an alternative method of characterizing early treatment success (1-hour post-dose) in clinical trials for the acute treatment of migraine. Methods: Pooled data for placebo and ubrogepant 50mg (ACHIEVE I and ACHIEVE II trials) and data for ubrogepant 100mg (ACHIEVE I) were used for this analysis. To define treatment success, we used confirmatory latent class modeling (LCM) that included inputs at baseline and 1 hour for pain severity and functional disability, and binary measures of nausea, photophobia, and phonophobia. Treatment success rates and predictive validity (using satisfaction with study medications [SWSM] 24 hours post-dose) with LCM were compared with 1-hour pain freedom (1hPF).

Results: Treatment success rates based on LCM were 34.3% for ubrogepant 50mg, 34.2% for ubrogepant 100mg, and 25.9% for placebo, yielding a placebo-corrected difference of 8.4% (P<0.001) for the 50mg dose and 8.3% (P<0.001) for the 100mg dose. In comparison, the 1hPF endpoint estimated very low rates with no differences between active treatment and placebo. Using SWSM as the gold standard, sensitivity (0.46 vs 0.07) and Youden"s index (0.26 vs 0.06) were higher for LCM than for 1hPF. Conclusion: The LCM approach was a more sensitive predictor of treatment satisfaction at 24 hours and better aligned with our clinical understanding of migraine as a symptom complex. Compared with LCM, 1hPF failed to capture a substantial proportion of people satisfied with treatment. Objectives: Migraine is a complex neurological disorder, however, therapeutics have focused on targeting a relatively narrow set of receptors i.e. 5HT1B/1D/F or CGRP. Comparative receptor pharmacology of various acute therapies for migraine were examined. Methods: Following a literature review, additional, functional receptor activity of DHE was screened against 170 G-protein coupled receptors. Results: DHE mesylate (10 μM) exhibited agonist activity at: Adrenoceptor α2B, CXCR7, Dopamine D2, D5, 5HT1A/1B/2A/2C/5A, binding with high affinity to the 5HT1B, Adrenoreceptor α2B, Dopamine D2receptors and exhibited antagonist activity at: Adrenoceptor a1B, a2A, a2C, CALCR-RAMP2, Dopamine D1, D3, D4, D5 and 5HT1F. Further work showed DHE did not bind to the 5HT3 receptor and did so in a limited capacity to the 5HT4E receptor, at concentrations up to 300 nM. Comparative receptor binding of migraine specific therapies is presented in tabular format. A model was created to show where in migraine progression each acute migraine specific therapeutic acts to address migraine symptoms. Conclusion: DHE interacts with several different receptor subtypes. Unlike other migraine therapeutics, it may exert a wider influence over the pathophysiology of the migraine. Moreover, the slow dissociation of DHE from target receptors is thought to sustain its anti-migraine effects, extending duration of benefit, reducing headache recurrence rates and, perhaps, medication overuse headache. were organized into subgroups by number of baseline CV risk factors (0, 1, ≥2) and Framingham 10-year risk of developing a CV condition (low = <10%, moderate to high = ≥10%). Results: Of the 1800 rimegepant-treated subjects, 735 (40.8%) had CV risk factors (518 [28.8%] had 1 and 217 [12.1%] had ≥2]) and 126 (7.0%) had a moderate to high risk 10-year CV risk. The most common adverse events (AEs) regardless of relationship to treatment were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%), and the proportion of subjects reporting ≥1 AE was similar across all subgroups (Table 1) . No serious AEs were considered by the investigator to be related to rimegepant. Only 1 subject out of 1800, a 53 year-old male with a history of CV disease (angina pectoris), experienced an ischemic Cardiac Disorder SOC AE (angina pectoris) deemed by the investigator to be not related to rimegepant. Conclusion: Rimegepant dosed up to once daily for up to 1 year showed favorable safety and tolerability in adults with migraine with CV risk factors, including adults with moderate to high CV risk. Objective: Evaluate the efficacy, safety, and tolerability of intranasal zavegepanta third-generation, high-affinity, selective and structurally unique, small molecule CGRP receptor antagonistin the acute treatment of migraine. Methods: In this randomized, dose-ranging, placebo-controlled, Phase 2/3 trial (NCT03872453), adults with migraine treated 1 attack of moderate to severe pain intensity with intranasal zavegepant 5, 10, 20 mg, or placebo. Coprimary efficacy endpoints were pain freedom and freedom from the most bothersome symptom (MBS; ie, photophobia, phonophobia, or nausea) at 2 hours postdose. Endpoints were tested hierarchically at an alpha level of 0.0167. Results: In total 1581 subjects (median age 40 years, 85.5% female, 14% taking preventive migraine medication) were in the modified intention-to-treat population [zavegepant 5 mg (n=387), 10 mg (n= 391), 20 mg (n=402), placebo (n=401)]. On the coprimary endpoints (Table 1) , zavegepant 10 mg and 20 mg were superior to placebo. Figure 1 shows pain relief rates through 2 hours postdose for all zavegepant dose strengths. The most common (>5%) adverse events (AEs) with zavegepant were dysgeusia (13.5%-16.1% vs 3.5% with placebo) and nasal discomfort (1.3%-5.2% vs 0.2% with placebo). The majority of AEs were mild or moderate. There was no signal of hepatoxicity. Conclusion: Intranasal zavegepant 10 mg and 20 mg were effective for the acute treatment of migraine, with a favorable safety profile. Objective: Assess the efficacy of rimegepantan oral small molecule calcitonin gene-related peptide receptor antagonistfor the acute treatment of migraine in subjects with and without a history of triptan treatment failure. Methods: Three double-blind, placebo-controlled trials of similar design randomized adults with migraine to rimegepant 75 mg tablet (NCT03235479, NCT03237845) or ODT (NCT03461757) or placebo to treat 1 migraine attack of moderate to severe pain intensity. Subgroups with a history of treatment failure with 1 or ≥2 triptans and those without a history of triptan failure, including triptan-naïve and current triptan users, were analyzed. Triptan treatment failure was defined as self-reporting a history of discontinuing ≥1 triptan due to inadequate efficacy and/or poor tolerability. The coprimary endpoints were 2-hour freedom from pain and the most bothersome symptom (MBS). Results: In the pooled population (N=3507: rimegepant n=1749, placebo n=1758), 2272 (64.8%) subjects had no history of triptan treatment failure and 1235 (35.2%) had a history of treatment failure with ≥1 triptan. Results for the coprimary endpoints in each triptan subgroup are shown in Figure 1 . No differences in coprimary endpoints were found in pairwise comparisons of triptan subgroups in rimegepant-treated subjects (Table 1) . Conclusions: Rimegepant was effective for the acute treatment of migraine in subjects with and without a history of triptan treatment failure. (EOD+PRN). The Migraine Disability Assessment (MIDAS) was given at baseline and Weeks 12, 24, 36, and 52; disability was scored as 0-5 (little or no), 6-10 (mild), 11-20 (moderate), and ≥21 (severe). Subgroups with no history of triptan failure (including triptan naive and current triptan users) and a history of failure with 1 or ≥2 triptans were assessed. Triptan failure was defined as having a history of discontinuing ≥1 triptan due to inadequate efficacy and/or poor tolerability. Results: Of the 1800 subjects, 546 (30.3%) had 1 triptan failure, and 246 (13.7%) had ≥2 triptan failures. Baseline mean (SD) MIDAS total scores showed severe disability: 0 triptan failures 32.8 (33.1); 1 triptan failure 34.5 (31.8); and ≥2 triptan failures 36.9 (32.0). Changes from baseline in MIDAS total scores exceeded the clinically important difference threshold at all time points for all 3 subgroups (Figure 1 ). Conclusions: Rimegepant 75 mg reduced migraine-related disability versus baseline regardless of prior history of triptan treatment failure. Table 1 .

The percentage of subjects with a 100% reduction in select analgesic and antiemetic use consistently increased during Weeks 1-4, Weeks 5-8, and Weeks 9-12 of rimegepant PRN and QOD+PRN treatment ( Figure 1 ). During Weeks 49-52 of PRN treatment, 61.3% (95% CI: 57.8, 64.6) of subjects had a 100% reduction in select analgesic and antiemetic use. The migraine-specific quality of life questionnaire (MSQv2) was administered at baseline and weeks 12, 24, 36, and 52; domains include Role-Restrictive (RR), Role Preventative (RP), and Emotional Function (EF). Raw total scores were rescaled from 0-100; higher scores indicate better quality of life. This post-hoc analysis assessed MSQv2 in subgroups with a history of discontinuing 1 or ≥2 triptans due to inadequate efficacy or poor tolerability (i.e., treatment failure). Results: Respective mean baseline MSQv2 scores for RR, RP, and EF were 53.6, 69.4, and 62.5 among subjects with a history of 1 triptan treatment failure (n=546) and 51.5, 66.7, and 56.2 among subjects with ≥2 triptan treatment failures (n=246). Both subgroups showed positive mean (95% CI) changes from baseline on all MSQv2 domains beginning at week 12 and continuing through week 52 (Figure 1 ). The effect of selective attrition cannot be assessed. Conclusions: Long-term treatment with rimegepant was associated with improved MSQoL among adults with migraine and a history of triptan treatment failure, regardless of the number of triptans previously tried and failed. Objectives: Assess preference of medication, satisfaction with medication, and Clinical Global Impression of Change (CGI-C) in participants using oral rimegepant, a small molecule CGRP receptor antagonist with demonstrated efficacy in the acute and preventive treatment of migraine. Methods: Multicenter, long-term, open-label safety study (NCT03266588) enrolled adults with a history of 2-14 monthly migraine attacks of moderate to severe pain intensity. Subjects used rimegepant 75 mg as needed up to once daily to treat attacks of any pain intensity for up to 52 weeks. Preference of medication compared with previous acute treatments for migraine and satisfaction with medication were recorded by subjects via electronic diary; CGI-C was administered by clinicians. Results: Overall, 1514 participants began the 52-week treatment period. At Week 24, 78.7% of subjects preferred rimegepant over their previous migraine medications, 89.4% of subjects were satisfied with rimegepant, and 88.8% of subjects were considered improved since study entry on the CGI-C scale. The percentages (95% CIs) of subjects at Week 52 who preferred rimegepant, were satisfied with rimegepant, and were considered improved since study entry are shown in Figure 1 . Among individuals using rimegepant as an acute treatment for 1 year, 4 in 5 preferred rimegepant to their previous migraine medications, 7 in 10 were satisfied withrimegepant, and 9 in 10 experienced clinical improvement relative to baseline. Objective: Assess long-term safety and clinical improvement with rimegepantan oral small molecule CGRP receptor antagonist with demonstrated efficacy in acute and preventive treatment of migraine in adults with frequent migraine attacks. Methods: Open-label safety study of adults with 2-14 monthly migraine attacks of moderate-severe intensity. Subjects with chronic migraine were allowed; there were no limitations on the number of monthly migraine or non-migraine headache days. A 30-day observation period (OP) was followed by long-term treatment with rimegepant 75 mg orally up to once daily for up to 52 weeks. Migraine days were captured via electronic diary. This post-hoc analysis assessed safety and clinical global impression of change (CGI-C) in subjects experiencing ≥15 migraine days per 30 days in the OP. Results: In total, 13.7% (246/1800) of subjects had ≥15 migraine days per 30 days in the OP. In this subgroup, the most common adverse events (AEs) were nasopharyngitis (8.5%), sinusitis (6.1%), and upper respiratory tract infection (5.3%); 4.9% of subjects discontinued due to an AE; and 3.7% had a serious AE, none of which were related to rimegepant. Percentages (95% CI) of subjects who were improved since study entry on the CGI-C scale, were 89. 2% (83.3, 93.2) and 87.5% (80.0, 92.5) at week 24 (n=157) and week 52 (n=112), respectively ( Figure 1 ). Conclusion: Rimegepant was well-tolerated and associated with clinical improvement in adults with frequent migraine. Background: Choosing migraine prevention medications often involves trial and error. Operations research (OR) allow us to derive a mathematically optimum way to conduct such trial and error processes.

Objective: Given probability of success and adverse events as a function of time, we seek to develop and solve an OR model, applicable to any arbitrary patient, minimizing time until discovery of an effective migraine prevention medication. We then seek to apply our model to real life data for chronic migraine prevention.

Design: An OR model is developed and then solved for the optimum solution, taking into account the likelihood of reaching 50% headache day reduction as a function of time. We then estimate key variables using FORWARD study as well as erenumab data published by Barbanti et al. at IHC 2019. Results: The solution for our model is to order the medications in decreasing order by probability of efficacy per unit time. This result can be generalized through calculation of Gittins index. In chronic migraine the optimum sequence of prevention medication trial is erenumab for 12 weeks, followed Botox for 32 weeks, followed by topiramate for 32 weeks. Conclusions: We propose an optimal sequence for preventive medication trial for patients with chronic migraine. Since our model makes limited assumptions on the characteristics of disease, our model can be applied to other scenarios so long as probability of success/adverse event as a function of time can be estimated. Objective: Collect real-world data and improve our understanding of the potential benefits of adding a CGRP mAb to onabotulinumtoxinA (onabotA) in CM. Methods: This chart review included adults with CM treated at 1 clinic (10/2018-11/2019) with ≥2 consecutive onabotA injections before ≥1 month of onabotA plus erenumab, fremanezumab, or galcanezumab. Charts at time of first CGRP mAb prescription (baseline) and up to 4 visits over ≤12 months were reviewed for adverse events (AEs), discontinuations, monthly headache days (MHDs), and migraine-related disability (MIDAS). Outcomes were also evaluated in patients who completed~12 months of onabotA treatment (4 visits) after starting CGRP mAb. Results: Of 300 charts reviewed, 257 met criteria for the primary cohort; 103 (40%) were completers. The CGRP mAbs were erenumab (primary: 78%; completers: 84%), galcanezumab (16%; 11%), and fremanezumab (6%; 5%). Patients discontinued CGRP mAb more than onabotA (23% vs 3%). The most common AE was constipation (9%). Mean MHDs were 21.5 (primary) and 22.4 (completers) before initiating onabotA, and 12.1 before adding CGRP mAb in both cohorts. Following the initiation of combination treatment, mean MHDs significantly decreased at all visits (month 12: 4.0 [95% CI: Objective: To evaluate the course of migraine after discontinuation of migraine preventive treatment with CGRP-(receptor) monoclonal antibodies (mAb) following EHF guidelines.

Methods: This longitudinal cohort study included patients with migraine who received a CGRP-(receptor) mAb for ≥8 months before treatment discontinuation. We collected headache data during the four weeks prior to mAb treatment initiation (baseline), in the month before the last treatment injection, in weeks 1-4 and weeks 9-12 after treatment completion (i.e. weeks 5-8 and 13-16 after the last injection). Primary outcome of the study was the number of monthly migraine days (MMD) at baseline and at every study intervall. Secondary outcomes were the number of monthly headache days (MHD) and monthly days with acute medication use (AMD). Results: We included n=62 patients in the study, n=31 treated with erenumab and n=31 treated with galcanezumab or fremanezumab. Patients reported 13.27 ±6.40 MMD at baseline, which decreased to 8.24 ±6.59 in the last active treatement period (p<0.001). In the first month of the drug holiday, MMD increased to 10.32 ±6.85 but remained significantly lower than baseline (p=0.033). In the third month, MMD returned to baseline levels (12.47 ±6.64, p>0.999) . MHD and AMD also showed a gradual worsening starting with the first month after interruption. Conclusion: The discontinuation of migraine prevention with CGRP-(receptor) mAbs led to a progressive worsening of migraine over time. Introduction: There is a lack of data to help us know when and how to switch from one ineffective monoclonal antibody to another in migraine patients. Methods: We describe how the switch from an ineffective monoclonal antibody to another has been made, the result and the safety of the change. We considered ineffective treatment when the patient experienced less than 50% reduction in migraine days per month after 12 weeks of treatment. We chose the antibody to make the switch based on the target of the previous antibody (erenumab acts against the receptor of the peptide related to the calcitonin gene, while galcanezumab and fremanezumab act by blocking the ligand). The switch was made directly, without waiting longer than the half-life of the previous antibody. Results: We included 19 patients with chronic migraine that had not responded to the first monoclonal antibody. 89,4% were women and the average age was 47,7 years old. A total of 21 changes were made, 5 changes from erenumab to galcanezumab, 10 changes from erenumab to fremanezumab, 4 changes from galcanezumab to erenumab, and 2 patients, as a last chance, from galcanezumab to fremanezumab.. 33.3% of patients got to be responders after switching from one antibody to another. No patient had adverse effects in the context of switching from one to the other Conclusion: If a first monoclonal antibody is ineffective as a preventive treatment for migraine, it may be a good option to change to another with a different target because a third of the patients will be able to achieve improvement. The direct switch from one monoclonal antibody to another is safe. Objective: To investigate real-world erenumab efficacy in converting highly-refractory chronic migraine (CM) to episodic migraine (EM). Methods: 21 chronic migraineurs refractory to OnabotulinumtoxinA and ≥4 oral preventatives were treated with erenumab in a prospective case series in a United Kingdom secondary care headache clinic. Each patient failed a mean of 5.5 oral preventatives and 6.0 cycles of Onabo-tulinumtoxinA. We measured monthly headache days (MHD), migraine days (MMD) and headache-free days (HFD To present the patient-reported outcomes (PROs) following 52-weeks of once-daily oral atogepant (ato) 60 mg, a CGRP antagonist being developed for migraine prevention.

This multicenter, open-label trial (NCT03700320) enrolled and randomized adults (4-10 migraine days/month) 5:2 to ato or oral standard of care migraine prevention (SOC). Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) and Physical Impairment (PI) domains, Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ v2.1) Role Function-Restrictive (RFR) domain, and HIT-6 total scores were analyzed on the modified intent-to-treat population (mITT; only ato pts). 744 participants were randomized and 521 comprised the mITT (mean age: 42.5 years, 88.3% were female, 76.8% were White). AIM-D PDA and PI domain score changes for first and last timepoints (Fig. 1) . MSQv2.1 RFR least squares (LS) mean (standard error [SE]) at baseline was 48.1 (20.26) and score changes (Fig. 2) . HIT-6 scores followed a similar trend to AIM-D and MSQv2.1 scores. As indicated by confidence intervals not including 0, significant improvements were observed for all PROs at the earliest timepoint assessed and appeared to increase with treatment duration. At Week 52, 80.1% of participants were HIT-6 responders (≥5 points decrease from baseline). Long-term ato use was associated with reduced impairment due to migraine, improvements in migraine-specific quality of life, and reductions in the impact of headache. Objective: Evaluating one-year effectiveness of galcanezumab in patients with chronic migraine (CM) with and without medication overuse headache. Methods: We analyzed 26 patients (F22, M4, mean age: 53yrs, migraine history: 38yrs) who failed at least 3 preventive therapies. Galcanezumab was administered monthly for 12 treatments (T1 through T12) with a loading dose of 240 mg and maintenance dose of 120mg. Two patients interrupted treatment for inefficacy at T7 and T9. We collected clinical data on headache features (diary), disability and allodynia (standardized questionnaires) at baseline and quarterly. Results: Patients with a pattern reversal from chronic to episodic migraine (i. e.>50% responders) were 42% at T1, rising to 62% at T12. Super-responders (i. e.>75% responders) were 8% at T1, 21% at T12. A significant improvement in headache was detected already at T1 and persisted over one-year treatment- Fig. 1 . An improvement in MIDAS and HIT-6 scores was detected from T3(p<0.001), while allodynia intensity decreased significantly from T12 (p=0.03)- Fig. 2 . Mild side effects were reported by 33% of patients (constipation, cutaneous reaction and fatigue). Conclusion: Galcanezumab is related to high percentage of pattern reversal in difficult-to-treat patients and to improvement in clinical features already during the 1st month of treatment and in headacherelated disability after a few months. Efficacy is maintained over the long-term showing a positive tolerability profile. Multicenter, open-label trial (NCT03700320) randomized adults with migraine 5:2 to atogepant 60 mg QD (ato) or oral standard of care (SOC) migraine preventive. Efficacy measures (not collected for the SOC arm) were analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population (mITT). 744 participants (pts) were randomized (ato, n=546); 521 ato pts were in the mITT population (mean age of 42.5 years, 88.3% were female, and 76.8% were White). Baseline mean (SE) monthly migraine days (MMDs) were 7.30 (2.62); least-squares (LS) mean change from baseline at weeks (wks) 1-4 and 49-52 was -3.84 and -5.19 . Baseline mean (SE) monthly acute medication use days were 6.63 (3.26) ; LS mean change at wks 1-4 and 49-52 was -4.04 and -4.93 . All 95% confidence intervals were non-zero. The proportions of responders based on reductions in MMDs are shown in the Figure; proportions of responders increased throughout the trial. Atogepant 60 mg once-daily reduced MMDs, acute medication use days, and improved response; response was observed early, sustained over 1 year, and appeared to increase with treatment duration. Results support the use of atogepant as a long-term, preventive treatment of migraine. Backgound&Objective: Local regulations require a 3-month interruption of CRGP antibodies treatment in migraine after a 12-month course. Limited data are available on the persistence of their effect after interruption. We report migraine pattern during suspension period in chronic migraine patients (CM) Methods: We analyzed 65CM patients: F45, M20, mean age: 49.2+9.3, treated with erenumab for over a year (mean duration 17± 5.6months) before the mandatory suspension. We evaluated changes in monthly headache days (MHD), related disability (MIDAS), monthly medication doses (MMD) and days of drug intake (DDI) at baseline (T 0 ), end of treatment (T end ) and during suspension. Results: MHD significantly improved at T end compared to baseline (T 0 23.6+5.5, T end 10.1+7), as did MDD (T 0 30.1+25.3, T end 8.2+5.8) and DDI (T 0 19.7+7.7, T end 7.1+4.3), p<0.001. All parameters significantly worsened already in the 1 st month of suspension when compared to T end , p<0.01 (Fig. 1) and maintained a worsening pattern over the subsequent 2months. Though significantly worse, the clinical condition observed in the last month of suspension was still better than T 0 values. MIDAS worsened accordingly, p<0.001 ( Fig. 2 ; T end 18.9+26.1, after stop 45.3+37.2) Conclusions: Erenumab suspension was associated with an early and progressive worsening of headache-related parameters and disability. Regulators should consider the possibility to allow prolonged treatment in migraine subjects resistant to other preventive therapies. We found that a lower intake of sweets, processed meat, refined grains, and condiments, as well as a higher intake of vegetables, fruits, whole grains, and low-fat dairy products, might be associated with better clinical symptoms of migraine headache.

Effect of synbiotic supplementation on migraine characteristics, gut permeability and inflammatory biomarker in women with migraine: Results of a randomised controlled trial Background: Previous studies have shown a role of gut-brain axis in migraine headaches pathogenesis. We aimed to examine the effect of synbiotic supplementation on the characteristics of migraine attacks, gut permeability and inflammation in women with migraine. Methods: Sixty-nine migraine patients who completed this randomized double-blind controlled trial received two capsules of synbiotic or placebo. The migraine severity, frequency and duration of attacks, gastrointestinal problems, serum Hs-CRP and zonulin levels were measured at baseline and the end of the intervention. Results: After a 12-week intervention, among participants the mean frequency of migraine attacks significantly reduced in the synbiotic group (mean change: -1.02 per month, P=0.011). Also, a nonsignificant reduction was also evident in the migraine severity (mean decrease: -0.17; P=0.168) and duration (mean decrease: -3.97 hours; P= 0.327) in the synbiotic group. Patients who received the synbiotic also showed significant reduction of gastrointestinal problems (P= 0.032). In contrast to the placebo, synbiotic supplementation significantly decreased the zonulin levels as gut permeability (mean change: -4.12 vs 0.85 respectively, P=0.034) and Hs-CRP levels as inflammation (mean change: -0.43 vs -0.09 respectively, P=0.022) in migraine patients. Conclusion: The results of this study showed that the synbiotic supplementation could be an effective supplement to improve migraine headache. Background: Abrupt onset of unremitting daily headache is generally refractory to conventional migraine prophylactic treatments. CGRP monoclonal antibodies have been shown to be effective in clinical trials in migraine but we are not aware of any real-world data involving the CGRP treatment in this patient group. Objective: To prospectively assess the benefit of Erenumab on Quality of Life (QOL) in a group of patients with abrupt onset daily persistent headache who have failed multiple preventative migraine therapies. Methods: 52 patients who received either 70mg or 140mg Erenumab every 28 days by subcutaneous injection. Patients were asked to complete migraine specific QOL questionnaires before starting treatment, and at 3-6 months intervals, up to two years after starting treatment. The migraine specific QOL questionnaires included: the Headache Impact Test-6 (HIT-6), Migraine Associated Disability Assessment (MIDAS) test and Migraine-Specific Quality-of-Life Questionnaire (MSQ Erenumab, a CGRP receptor antagonist, was the first monoclonal antibody approved for preventive migraine treatment. The SPECTRE study (characteriSation of Prescription patterns in Episodic and Chronic migraine patients starting Treatment in a Reallife setting with Erenumab in Germany) aims to better understand patient profiles and treatment patterns for erenumab in Germany based on migraine characteristics and comorbidities. This non-interventional study is conducted at 139 centers in Germany and enrolled 572 adult migraine patients. Apart from a daily headache diary, the patient-reported-outcome (PRO) questionnaires HIT-6 and TSQM are documented at 3-month intervals. Previous baseline analysis of a small proportion of patients showed that the majority of erenumab patients in this subgroup were women with chronic migraine, with a high proportion of psychiatric comorbidities. Here we expand this analysis to about 400 erenumab patients. Baseline characteristics, including monthly migraine days, prophylactic pretreatments and comorbidities, and 6-month followup data, including information from an app-based migraine diary and PRO data, will be presented. SPECTRE will provide valuable insights into the use of erenumab in clinical practice in Germany, help characterize prescription patterns, patient profiles and analyse the respective therapy response. This will possibly allow for development of individual treatment strategies for each patient.

Wearing-off effect of onabotulinumtoxinA: A prospective realworld study M. P. Navarro-Pérez 1,2 , R. Objective: To understand Indian neurologist"s knowledge, awareness and perception regarding the challenges with oral prophylactic agents; the role of CGRP in migraine pathophysiology and possible role of anti-CGRP mAbs in migraine prophylaxis Methodology: A nationwide cross-sectional questionnaire-based online survey was conducted among registered Indian Neurologists. The questionnaire was validated by a group of neurologists participating in the advisory board and was rolled out to a random sample of 140 neurologists and their response was anonymized. Aggregate data was summarized by percentage graphs. Results: 47 neurologists voluntarily participated. Participating neurologists believe that most patients (61%) have ≤3months adherence to current oral prophylactics citing adverse events (33%) as common cause. Most participants believe that adverse events (76.3%), limited efficacy (73.7%) and lack of target specificity (55.3%) are the most common challenges with oral prophylactics. Most participants were aware on the role of CGRP in migraine pathophysiology (94%) and most participants perceived antagonizing CGRP would be a promising option for migraine prophylaxis (97%) Conclusion: Results highlight that there is an unmet need with currently used oral prophylactics among neurologists who believe targeting CGRP may be a promising option. Hence anti-CGRP mAbs could be an attractive option if they can address unmet needs with current oral prophylactics. This was a pilot survey with a small sample size. Further research on clinical utility in terms of ideal patient profile, duration of therapy, etc with anti-CGRP drugs is warranted.

MIDAS score reduction in the decision-making process of erenmab treatment: pearls and pitfalls R. De Icco 1 Objective: To evaluate patients with episodic (EM) or chronic migraine (CM) achieving a ≥75% migraine responder rate (MRR) over weeks [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] with eptinezumab vs placebo (pbo), the consistency of that response, and its impact on patient-reported outcomes (PROs). Methods: Patients with EM (PROMISE-1) or CM (PROMISE-2) treated with eptinezumab 100mg, 300mg, or pbo and experiencing ≥75% MRR over Wk1-12 were included. PROs (from PROMISE-2) included 6item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC). At Month 3, a statistically significant reduction from baseline in mean MMD ( Figure) was observed with erenumab compared with PBO; similarly, a higher proportion of patients achieved ≥50% reduction in MMD and greater reductions in MSMD and HIT-6™ score were reported with erenumab versus PBO (Table) . The safety profile of erenumab was in line with that of the global population with no newlyemergent safety signals. Objective: Therapeutic options for preventive treatment of migraine during pregnancy are very limited. Although not specifically assessed in pregnancy, a safe alternative is anesthetic blockade of the great occipital nerve (GON). We present a small series of pregnant women who have underwent anesthetic blockade of GON for the treatment of migraine. Methods: Retrospective analysis of a series of pregnant women with migraine treated with anesthetic blockade of both GON with 2% lidocaine. The assessment was based on the headache calendar, the opinion of the patients and the result of impact scales. Results: 4 pregnant women were included, all treated in the second and third trimester. Only one had chronic migraine and analgesic abuse and the rest had episodic migraine.

There was an excellent response in 3 patients (in one with complete response after the first treatment and in the others with a significant improvement in the frequency and intensity); only one patients had no response to the first treatment and lost follow-up. In all, the procedure was well tolerated and without side effects. The blockade was effective a few days after the injection, lasting from 2 weeks to several months. Conclusion: The blockage of the GON was safe, technically easy and efficacious in this small series. It seemed to have an effect not only as an acute treatment but also as a preventive. It should therefore be offered to all women whose migraine needs treatment during pregnancy. Objective: Not all patients respond to a CGRP monoclonal antibody (mAb). Non-responders to one CGRP mAb class (receptor/ligand) may benefit from a switch to the other class, but there are no efficacy data so far. We aimed to assess treatment response to a CGRP-mAb in patients that have previously failed the CGRP-receptor-mAb in a real-world analysis. Methods: We performed a retrospective cohort study from November 2018 to May 2020 in patients who switched from erenumab to either galcanezumab or fremanezumab. Only nonresponders (<30% reduction of monthly headache days (MHD) after 3 treatment cycles) were included in the analysis. MHD and acute medication days (AMD) were extracted from patient headache diaries. Endpoints were the ≥30% and ≥50% reduction of MHD, and the reduction of MHD and AMD in month 3 compared to baseline after switch. The Friedman test for repeated measures with the Dunn"s post-hoc test and Bonferroni correction were used to evaluate treatment effects. Objective: A preventive migraine drug is usually considered successful if it reduces migraine days by at least 50%. Here, we aimed to develop a multidimensional composite score that combines measures that are clinically relevant to establish migraine patients" response to erenumab. Methods: The primary outcome of the study was erenumab efficacy, established following standard clinical evaluation. A composite treatment response score was calculated as a linear combination of response criteria evaluating significant changes in migraine frequency, headache frequency, severity of the migraine attack and migraine-related disability. Logistic regression models were run to assess the association of the composite response score, as well as different response criteria, with the primary efficacy outcome. The Brier Score and receiver-operating characteristic (ROC) analyses were performed to assess model discriminative ability. Results: Fifty-three percent, 68% and 73% of patients achieved the primary efficacy outcome after 3, 6 and 12 months of erenumab. The composite response score achieved the lowest Brier scores at each time point, suggesting a higher predictive accuracy. Compared to the other response criteria, the composite response score had the highest AUC values at each time point. Conclusion: Here, we proposed a simple and exhaustive multidimensional score that may facilitate patients" management in clinical practice and may expand patients" access to effective therapies.

Objective: During the COVID-19 pandemic face-to-face procedures have been postponed. We aim to evaluate the impact of onabotuli-numtoxinA follow-up delay in migraine during COVID-19 pandemic. Methods: Subjective worsening, intensity of migraine attacks and frequency of headache and migraine were retrospectively compared between patients with unmodified and interrupted onabotulinumtoxinA follow-up in Headache Units. Results: We included 67 patients with chronic migraine or highfrequency episodic migraine under onabotulinumtoxinA treatment, 65 (97.0%) female, 44.5±12.1 years old. Treatment administration was voluntarily delayed in 14 (20.9%) patients and nine (13.4%) were unable to continue follow-up. Patients with uninterrupted follow-up during lockdown presented 8.4 and 8.1 less monthly days with headache (adjusted p=0.011) and migraine attacks (adjusted p=0.009) compared to patients whose follow-up was interrupted, respectively. Conclusion: Involuntary delay of onabotulinumtoxinA follow-up in patients with migraine due to COVID-19 pandemic was associated with a higher frequency of headache and migraine attacks. Safe administration of onabotulinumtoxinA during lockdown should be promoted. Objective: Our aim was to assess the adverse events (AE) reported by patients with migraine treated with monoclonal antibodies against CGRP or its receptor (anti-CGRP mAbs) in daily clinical practice. Methods: Data were prospectively collected after three months of treatment with galcanezumab, erenumab and fremanezumab at the Headache Clinic of a tertiary University Hospital, between January 2020 and January 2021. The variables included were: sex, age, presence and type of , concomitant preventive therapies for migraine and migraine characteristics. Results: A total of 134 patients were included. AE were reported in 69 patients (51.5%). Constipation was the most frequent AE, reported by 45 patients (33.6%). Less frequent AE were dizziness (6 patients, 4.5%), myalgia (5 patients, 3.7%) and asthenia (5 patients, 3.7%). No severe AE occurred, however, constipation led to treatment discontinuation in one patient (<0.7%). We found no association between any AE (including constipation) and the anti-CGRP mAb used, epidemiological variables, concomitant treatment or migraine characteristics. Conclusions: In patients with migraine anti-CGRP mAbs were well tolerated. Approximately half of patients suffered from AE in our series, but most of them were mild. The most frequent AE was constipation. Objective: To evaluate psychometric properties of the Migraine Symptom and Impact Questionnaire (Mi-SAIQ), a novel, patientreported outcome (PRO) tool designed to fully assess migraine impact across all 4 phases of a migraine attack and interictal phase between attacks. Methods: Psychometric properties of Mi-SAIQ, including key elements of validity and reliability, were evaluated using data from a prospective, longitudinal, noninterventional study in adult migraine patients (n=126). Item-level analyses investigated behavior of Mi-SAIQ items and questionnaire structure to optimize scoring rules; subsequent composite-level analyses examined reliability, validity, and responsiveness of candidate Mi-SAIQ composite scores. Results: Item-level frequency distributions supported the appropriateness of Mi-SAIQ response options. Confirmatory factor model fit indices were acceptable for 1-and 4-factor models, supporting the Mi-SAIQ composite scoring. For candidate composite scores, Cronbach's alphas (≥0.80) and test-retest intraclass correlation coefficients (≥0.75) were satisfactory. Correlations with validated PRO scores supported Mi-SAIQ composite score construct validity and known-group analyses supported their discriminating ability. Conclusions: Overall findings support Mi-SAIQ as a useful tool for clinical practice/trial settings to describe the full migraine experience. Results suggest a short-form version could be useful, providing a potential avenue for future study.

Which patient related outcome best reflects the willing of a patient to continue with an anti-CGRP monoclonal preventive treatment? A sub-analysis of a prospective study Objetive: Refractory migraine is one of the most disabling pathologies. We present this study to analyze which indicator is the best correlation with the continuation of galcanezumab and erenumab. Methods: We have carried out a real-life study collecting the patients with refractory migraine with treatment with galcanezumab or erenumab since January 2020. We present a sub-analysis of the data (migraine days, headache days) and scales (HIT-6, MIDAS, MSQ, pain catastrophizing scale (PCS)) and correlate them with the continuation of treatment at 3 months. Results: Collected data from 220 patients, 81,55% women, 111 with erenumab and 109 with galcanezumab. 158 patients (71,82%) are satisfied with the treatment and continue after three months. The migraine frequency was reduced from 20,57 days to 16,78 (18,42%), use of triptans was reduced from 17,13 days per month to 10,26 (40,11%) . The results of the scales are: EVA was reduced from 8,65 points of average to 6,85 points (20,81%), MIDAS was reduced from 93 points to 56,38 points (39,37%), HIT-6 was reduced from 68,86 points to 60,74 (24,71%), PCS changed from 32,74 to 22,28 (31,95%) and MSQ was increased from 29,2 of average to 47,51 (62,71%). Conclusion: Quality of life measured with the MSQ scale correlates with the percentage of patients in a better way than migraine days. PROs which have in account the patient"s perception could be a good way to evaluate the willing of the patient to continue with a treatment. Objective: Digitalisation offers new treatment approaches for people with migraine. Smartphone applications (apps) for migraine patients include a wide variety of functions, ranging from digital headache calendars to app-based treatments. Further possibilities arise by using electronic communication tools. However, there is currently insufficient evidence on the benefits of digital tools for patients. SMARTGEM aims to fill in this research gap. Methods: SMARTGEM is a randomised controlled trial assessing whether the provision of a new digital form of care leads to a reduction in migraine frequency, improves quality of life, reduces medical costs and work absenteeism in people with migraine. It consists of M-sense (a medical app) and a communication platform with online consultations and a patient forum moderated by headache specialists (DRKSID: DRKS00016328). Results: Adult patients with ≥ 5 migraine days/month at baseline were recruited from outpatient headache centres over 23 months and are being followed up for a year. Patients" baseline characteristics will be presented. First results are expected in 2022. Conclusion: SMARTGEM constitutes a new integrated approach for migraine treatment. Its protocol offers an example of how to evaluate therapies using digital tools. Results will provide insightful information on the efficacy of electronic health tools in improving the quality of life of patients suffering from migraine while reducing healthcare resource consumption. Background: CGRP monoclonal antibodies have been shown to be effective in patients with chronic migraine. Erenumab is a fullyhuman anti-CGRP monoclonal antibody which targets the CGRP receptor. Quality of Life (QOL) questionnaires are one of the only tools that we have to measure response to treatment in episodic and chronic migraine. Objective: To prospectively determine the efficacy of Erenumab on QOL in chronic migraine patients who have been refractory to at least 4-5 prior preventative migraine therapies. Methods: 148 consecutive chronic migraine patients were given either 70mg or 140mg Erenumab every 28 days by subcutaneous injection. Patients completed migraine specific QOL questionnaires before starting treatment with Erenumab, and at 3-6 months intervals, continuing for up to two years after starting treatment. The migraine specific QOL questionnaires were: the Headache Impact Test-6 (HIT-6), Migraine Associated Disability Assessment (MIDAS) test and Migraine-Specific Quality-of-Life Questionnaire (MSQ). Results: 148 chronic patients started Erenumab between December 2018 and October 2019. Approximately 45% of these patients stopped treatment during the first year due to lack of efficacy and/or side effects. Up to 55% of patients had clinically significant improvement after treatment for 6-12 months, and wished to stay on treatment. Conclusion: Clinically significant improvements in QOL were experienced by approximately 55% of treatment refractory chronic migraine patients treated with Erenumab over a 1-2 year period. Objective: The objective was to evaluate the relative efficacy of rimegepant, atogepant, and monoclonal antibodies (mAbs) for migraine prevention. Methods: A comprehensive systematic literature review (SLR) was conducted. Efficacy was compared via network meta-analyses (NMAs). Evidence consisted of placebo-controlled trials of: rimegepant 75mg, atogepant 10mg, 30mg, 60mg, erenumab 70mg, 140mg, galcanezumab 120mg, 240mg, eptinezumab 30mg, 100mg, 300mg, and fremanezumab 225mg, 675mg. The rimegepant study included episodic migraine (77%) and chronic migraine (23%) patients; others had 100% episodic migraine patients. Efficacy outcomes included change from baseline in monthly migraine days (MMDs) and number achieving a 50% reduction in MMDs. Results: Significantly favourable differences for change in MMDs and number achieving a 50% reduction in MMDs were seen with active treatments versus (vs.) placebo ( Figure 1 ). Change in MMDs vs. placebo ranged from eptinezumab 100mg (mean difference -0.70 MMDs [95% credible interval (Crl) -1.26, -0.14]) to galcanezumab 240mg (-1.76 [-2.21, -1.31 Objective: The objective was to review guidelines for modeling migraine prevention therapies and features of novel therapies to identify further recommendations. Methods: A targeted literature review was undertaken for recent/ emerging migraine prevention therapies and economic modeling considerations, focusing on therapy features anticipated to impact modeling. Results: Monoclonal antibodies (mAbs) and gepants were identified as migraine prevention therapies of interest. Rimegepant bears consideration for modeling because of its efficacy as both an acute and preventive therapy. Migraine prevention models focusing on monthly migraine days (MMDs) should encompass interactions between acute and preventive therapies, and potential variation in acute therapy efficacy. The mAbs are administered via periodic injections and may have health-related quality of life (HRQoL) implications beyond those associated with MMDs and/or toxicity, such as patient treatment preferences, waning of effectiveness throughout an injection cycle, and cyclical patterns of migraine. Thus, economic evaluations of rimegepant should encompass both acute and preventive treatment with respect to MMDs, while economic evaluations of mAbs should include comprehensive HRQoL impacts. Conclusion: Migraine prevention models should account for features of gepants and mAbs, including interactions between acute and preventive therapy and implications beyond MMD reduction. Background and objectives: CGRP monoclonal antibodies (mAbs) were approved for migraine prevention in Russia in August 2020. They are not covered by insurance but available for purchase in pharmacies. We want to present the characteristics of patients who were prescribed CGRP mAbs in our headache clinic. Methods: We evaluated all patients, with whom CGRP mAbs were used as the medication of choice. To assess migraine's severity, we used Migraine Disability Assessment Test (MIDAS) and Work Productivity and Activity Impairment Questionnaire (WPAI). We also used Hospital Anxiety and Depression Scale (HADS). Results: From October 2020 till March 2021, 70 patients started monthly injections of CGRP mAbs. 65 women, 10 men, mean age 37,2±6,3. From them,27 patients had episodic migraine,43-chronic. Prior preventive therapy experience ranged from 0 in 13 patients, to 3 or more medication groups.13 patients had clinically significant anxiety (mean 5,8±4 points),9depression (mean 3,7±3,5). The mean MIDAS score was 47,6. Out of 44 patients working for pay, 14 reported missing their work due to their migraine attack. 38 people (86%) said that migraine interferes with their work productivity intensity with 5 or more out of 10. Conclusions: Patients who prefer CGRP mAbs therapy usually have severe disabling migraine, sometimes resistant or refractory. However, patients with episodic migraine with no previous preventive treatment also choose monthly injections instead of daily intake of pills. Fig. 1 (abstract P0339) . See text for description P0342 Crowdsourcing post-marketing safety surveillance for migraine preventives: Self-reported adverse events associated with calcitonin gene-related peptide (CGRP) therapeutics on a social media forum P. Zhang Objectives: Real-world observational data, such as those contained within social media platforms, can summarize diverse patient experiences and detect drug-related safety signals. We characterized adverse events related to calcitonin gene-related peptide therapeutics on Reddit, an anonymous online discussion forum. Methods: We examined differences in word frequencies from posts extracted from Reddit subforum r/Migraine from 2010 to 2020 using computational linguistics. In the validation phase, we compared propranolol versus topiramate, as well as propranolol and topiramate each against randomly selected posts. In the application phase, we examined posts discussing the CGRP therapeutics erenumab and fremanezumab to determine frequently discussed side effects. Results: From 22,467 Reddit r/Migraine posts, we extracted 402 propranolol posts, 1423 topiramate posts, 468 erenumab posts, and 73 fremanezumab posts. Comparing topiramate against propranolol identified a number of expected side effects. Erenumab compared against a random selection of terms identified "constipation" as a recurring key word. Erenumab against fremanezumab identified "constipation," "depression," "vomiting," and "muscle." No adverse events were identified for fremanezumab. Conclusions: Computational linguistics applied to social media can identify potential adverse events of interest for migraine preventives. Further studies are needed to explore side effects and safety of the novel CGRP medications.

The real-life early and continuative response to Galcanezumab in chronic migraine: 3-month analysis of the multicenter prospective cohort GARLIT study C. Altamura 1 , N. Brunelli 1 Conclusions: Unilateral pain, good response to triptans and normal weight may be associated with a positive sustained response in the first three months of therapy with Galcanezumab in chronic migraine.

The efficacy of re-using medicines for preventive treatment of Objective: to determine the duration of the therapeutic effect of preventive treatment in therapeutic groups and the effectiveness of their reuse. Material and methods: The study included 76 persons who had a 50% or more reduction in migraine attacks after three-month treatment with a combination of amitriptyline (average daily dose of amitriptyline was 37.0±2.4 mg and propranolol 80.0±4.7 mg) -29, lamotrigine (111.1±7.2 mg) -23, gabapentin (864.0±46.9 mg) -24 patients. The duration of the therapeutic effect was estimated after 6 months. Results:

The return of attacks is less than 50% Objective: Combined occipital and trigeminal nerve stimulation (COT-NS) has shown marked results in the abortive treatment of migraines. Until recently, COT-NS was only available with implanted systems. A new noninvasive COT-NS system (Relivion®) was recently approved by the FDA for acute migraine, following successful results of a pivotal clinical trial. The current retrospective study was designed to collect real-world data regarding the safety and efficacy of the COT-NS system in the preventive treatment of migraines. Methods: Seventeen patients with high-frequency episodic migraine or chronic migraine self-administered daily 20-minute treatments with the COT-NS system and electronically reported migraine characteristics for a duration of 3-6 months. The primary efficacy measure was change (%) in monthly migraine days in the final treatment month compared to baseline. Responder-rate (patients with ≥50% reduction in monthly migraine days) was additionally measured. A physician remotely monitored treatment progress. Reports of adverse events were collected as well. Results: Average migraine days frequency decreased by 63%, from 14.6 days per month at baseline to 5.4 days at the final treatment month (p<0.0001). Patient responder rate was 76%. No serious adverse events were reported. Conclusions: These initial results indicate for the first time that COT-NS may serve as a highly effective preventive treatment to reduce headache frequency in episodic and chronic migraine patients. Objectives: Migraine is a disabling disease but with the development of calcitonin gene-related peptide receptor antagonists there is a new therapeutic option for migraine prophylaxis. We intended to evaluate the therapeutic response with Erenumab in patients who have previously failed treatments with Onabotulinum toxin A (BoNT-A). Methodology: Prospective analysis of patients with refractory migraine who failed previous treatment with BoNT-A (January 2016 to January 2021) and that started Erenumab. Demographic data, frequency and intensity of crises and side effects were analyzed. Results: Twelve patients (11 women and 1 man) with an average age of 45.7 years (23-70) were included. Six patients were diagnosed with frequent episodic migraine and the remaining chronic migraine. Most patients discontinued BoNT-A treatment because of therapeutic inefficiency (n=10) or adverse reaction (n=1). Overall, there was an improvement in both the intensity and frequency of headache with an average reduction of 4.8 days per month with headache and an average reduction of 4.2 days per month with moderate or severe headache. Four patients with chronic migraine interrupted treatments due to lack of effectiveness (n=3) or pregnancy plans (n=1). Conclusion: There was an improvement in patients treated with Erenumab previously submitted to treatments with BoNT-A with an excellent safety profile. For patients refractory to Erenumab and BoNT-A, alternatives will be needed.

Satisfaction with galcanezumab as a medication: a cross sectional study in migraine patients A. Background and objective: Treatment satisfaction is of utmost importance for ensuring adherence. Galcanezumab is a new therapy for the treatment of migraine. The objective was to evaluate treatment satisfaction with galcanezumab and to identify factors that may influence patients" satisfaction. Methods: Patient perspectives on satisfaction were evaluated with the Spanish versin of the Treatment Satisfaction Questionnaire for Medication version 1.4(TSQM 1.4). The TSQM 1.4 domain scores range from 0 to 100. Results: Study participants consisted of thirty migraine patients, of which 76.67% had chronic migraine and 80% were women. TSQM scores at 12 weeks were as follows: graded effectiveness 80.6%, graded side effects 100%, graded convenience 83.3% and global satisfaction (GS) 78.6%. At 24 weeks: effectiveness 66.7%, side effects 100%, convenience 83.3% and GS 85.7%. Compared to previous preventive treatment, higher median scores were observed in the dimensions"side effects", "convenience" and "effectiveness"(93.5 ± 14.8 Vs 73.1 ± 21.0 and 64.8 ± 20.6, respectively). Regression analysis showed that the change in monthly migraine days(MMDs), Headache Impact Test scores(HIT) and Migraine Disability Assessment(MIDAS) scores were significantly associated with global satisfaction at 12 weeks. Conclusion: The results of this study revealed that the majority of migraine patients were highly satisfied with galcanezumab in terms of efficacy, safety, convenience, and global satisfaction. Background and Objective: Only sparse data on treatments for vestibular migraine (VM) are published. Greater occipital nerve blocks (GONBs) are widely used for the prevention of primary and secondary headache disorders. However no data evaluating the effectiveness in VM is available. We present a retrospective analysis on the effect of GONBs in adults with VM coming from a single specialist Headache clinic. Methods: Consecutive patients with VM diagnosed between 2019-2020 who underwent at least one GONB were included. Responders were defined as patients that obtained at least 50% reduction in headache days. Results: Twenty adults were identified. After the first GONB, 15 patients (75%) were considered responders: six obtained a 100% improvement in headache symptoms and nine obtained at least a 50% headache improvement. Four patients did not respond. One patient experienced a transient worsening. The mean duration of improvement in responders was 68 days (SD ±78.6, range 21-304 days). 13/15 responders to the first GONB had a second treatment three months later. Nine of them (69%) continued to respond. Of these, seven patients (78%) reported a sustained response to the third GONB. There were no adverse events. Conclusion: GONBs are a safe, possibly effective with sustained benefit overt time for the headache symptoms of VM. Larger studies with an accurate evaluation of the effect of GONBs on the vestibular component of VM would clarify the role of this treatment for VM.

Objective: To evaluate the efficacy and safety of noninvasive auricular vagus nerve stimulation (aVNS) in the prevention of episodic migraine. Methods: This study enrolled participants 18-65 years of age, with a >1-year history of migraine and 4-14 migraine headache days/month. Following a 1-month baseline period, eligible participants received purpose-designed earbuds that transcutaneously deliver electrical stimulation to the auricular vagus nerve. Treatment was administered daily for 6 months. The primary outcome was the overall mean change from baseline in the number migraine days/month. Secondary measures included the proportion of subjects with ≥50%, ≥75%, and 100% reduction in migraine days/month and the incidence of treatment-emergent adverse events. Results: Forty-five subjects were enrolled; 35 were included in the modified ITT population. The mean (SD) number of migraine days/ month decreased from 8.3 (2.6) at baseline by an average of -4.04 (3.42) (p<0.05) at Months 4 to 6. At Months 4 to 6, 45%, 27%, and 17% of subjects had a ≥50%, ≥75%, or 100% decrease, respectively, in the number of migraine days/month. Sixteen device-related events were reported; all were mild or moderate and were resolved without intervention or further sequalae. Conclusions: This mode of aVNS, used for 6 months, provided clinical benefits to participants with episodic migraine with minimal side effects. Further evaluation in larger, well-controlled studies is needed.

Effect of transcranial direct current stimulation compared to sham in episodic migraine: systematic review and meta-analysis of randomized controlled trials F. Haghdoost Objective: To do a meta-analysis to evaluate the effect of transcranial direct current stimulation (tDCS) on episodic migraine. Methods: MEDLINE and EMBASE were searched until October 2020. Randomized clinical trials that compared the effect of tDCS to sham in adults with episodic migraine and reported migraine frequency per month were included. Two researchers, independently in duplicate, screened the studies, and collected data from included studies. Meta-analysis for mean difference in headache frequency per month was conducted using random effects model by Comprehensive Meta-Analysis (CMA) software. Results: Overall, five studies (185 participants) were included. Studies were grouped based on the lead placement. Figure 1 illustrates the results. Headache frequency per month reduced significantly in studies with active anodal stimulation (excitatory) over occipital cortex [mean difference=1.8 (95% CI: 0.4, 3.1)] and motor cortex [mean difference=1 (95% CI: 0.4, 1.6)] but not in studies with cathodal stimulation (inhibitory) over occipital area [mean difference=0.2 (95% CI: -0.5, 0.8)] compared to sham. Among trials with benefits, there was evidence that these benefits continued after the tDCS treatment period. Conclusion: This meta-analysis indicates that at least for two montages in tDCS there is encouraging evidence of benefit in episodic migraine patients compare to sham. However, there is ongoing uncertainty on the size of benefits, optimal placement and duration of therapy. Background: treating migraine, using a non-invasive, multifunctional, and alternate monotherapy, is an interesting challenge regarding many patients with migraine, the complicated pathophysiology of migraine, the unknown or varied mechanisms of action of migrainerelated, available monotherapies or add-on therapies, and their varied adverse effect profile. Objectives and methods: a five-group, single-blind, and randomized design with pre-post-test and 6-month assessments was used to test the effectiveness of tDCS in the patients with chronic migraine. Using ICHD-3, patients were randomly assigned to one of the study groups to receive 11 consecutive weeks (i.e., 24 sessions; each session = two montages; each montage = 20min /2mA) of tDCS with four protocols and eight bipolar montages: Objective: Cervicogenic headache (CH), which is caused by cervical spinal diseases, is reportedly resistant to pharmacological treatment. The objective was to describe a case of CH in an elderly patient with polypharmacy. Methods: A case report. Results: A 90-year-old man had experienced dull, continuous, left occipital pain and neck pain with restriction of range of motion 4 years earlier. Although he was diagnosed with occipital neuralgia and tension-type headache and treated with acetaminophen, celecoxib, tizanidine, etizolam, pregabalin, lomerizine and tofisopam, these were ineffective. He was diagnosed with cervical spondylosis and radiculopathy (left C2) by a spine surgeon and was referred to our outpatient pain clinic. We diagnosed him with CH according to ICHD3 and performed a great occipital nerve (GON) block. He had complete headache relief without adverse effects. 2 years later, he had a chronic daily headache and visited our clinic again. Lightheadedness and hypotension were also observed. As adverse effects of polypharmacy were thought, we discontinued all his medications except pregabalin. After the symptoms had resolved, we performed a GON block and achieved complete pain relief. He was subjected to GON block on a weekly basis for 3 weeks, and his headache improved significantly. Conclusion: CH has a risk of polypharmacy because of its resistance to pharmacological therapy. GON block could be a safe and effective alternative therapy for elderly patients with CH. Headache is a common complaint but intracranial hypotension (IH) is a rare cause often misdiagnosed. We present a case of low CSF pressure headache resulting from a CSF leak. A middle-aged woman with a 2-week history of persistent frontotemporal headache associated with photophonophobia, nausea, vertigo, bilateral tinnitus, following an episode of neck trauma. A head CT revealed blood at Sylvian fissure and SAH was suspected. She had a normal neurologic examination on admission. CTA showed a left subdural hematoma (SDH) without vassal abnormality. She had a minor head trauma 2 months ago on the left parietal side and untreated hypertension. She left the hospital in good condition. The patient was readmitted to hospital 8 days later with intensive headache persisting in the lying position and enhanced after the slightest changes of head position. A control head CT showed bilateral SDH. Laboratory and blood coagulation workup was unremarkable. Brain MRI revealed signs of intracranial hypotension and cervico-thoracal MRI show extradural liquor collection at the C1-C2 level. We concluded that SDH was a complication of IH due to CSF leakage. As the conservative treatment was not effective, she underwent blood patch therapy with excellent outcomes. Reviewing the literature, we emphasize that IH should be highly suspected in all patients presenting with bilateral or recurrent SDH, as well as in middle-aged patients with new-onset, daily persistent headaches. There are no studies about steroids response in MCN in Mexican population, so we want to establish if headache as initial manifestation of MCN has a good steroids response. Methods: We carried out an observational, case series, analytical, and retrospective study in Neurology service at Centro Medico Nacional Siglo XXI, in Mexico City. Information was collected from medical records of patients with MCN from January 2015 to December 2020, obtaining the proportion of patients with headache and steroids response, performing Fisher exact method. Results: 25 patients were included (Table 1) . 11 (44%) had headache as initial manifestation, with remission of headache in 10 (90.9%) after steroids; in the other 14 (56%), only 7 (50%) had. OR 10, 95%CI 0.99-100.4 (p 0.04). Conclusions: Headache as initial manifestation of MCN has a better response than headache after other symptoms in Mexican population, which could lead to a treatment algorithm in this pathology. Further studies with a larger sample are required in order to prove these results. Objective: Although idiopathic intracranial hypertension (IIH) and iron deficiency anemia (IDA) are both common conditions in women of childbearing age, there is growing evidence suggesting more than an incidental association. Methods: We present a case of severe IDA presenting as IIH.

Results: A 44-year-old female presented with recent onset headache, bilateral blurred vision and pulsatile tinnitus. She complained about a daily headache of moderate intensity that awaken her from sleep and improved immediately when standing up. Past medical history was remarkable for obesity and chronic menorrhagia. Ophthalmologic examination revealed bilateral decreased visual acuity and papilledema while rest neurological examination was unremarkable. Brain magnetic resonance imaging indicated an empty sella, prominent subarachnoid space around optic nerves and vertical tortuosity of them. Venous sinuses were normal. Cerebrospinal fluid analysis was normal with an opening pressure of 25cmH 2 O. Blood tests revealed iron deficiency anemia with hemoglobin 6.8 g/dl and hematocrit 22.8%. She received a single unit of blood transfusion, intravenous iron supplementation and acetazolamide. Within 1 month disk edema had completely resolved. Acetazolamide was discontinued 4 months later that patient"s body mass index returned within normal limits. Conclusion: Physicians must be aware of the rare association of IDA with IIH, as the rapid correction of anemia may be vision-saving, preventing disease recurrence.

Chiari 1 For elevated frequency and increased of cerebrospinal fluid in optic nerve he was undergoing surgery, but headache was reappearing. Results: treatment of CM1-related headaches is difficult because pain in occipital region or coughing headache suggests symptomatic CM1, but children may suffer migraine or tension-type headache. In our cases age of onset, clinical characteristic and triggers of headache are principal factors that could be considerate to perform neuroimaging. Conclusions: onset of headache at an early age, occipital localization during cough and absence of familial history lead to suppose secondary causes, as CM1.This can be treated surgically, although not in all cases headache resolves after surgery

Neurological presentation of spontaneous skull base defects: Retrospective study Y. Orlova 1 , G. Kalamangalam 1 , S. Chen 2 , J. Poynter 2 , J. Justice 2 , B. Lobo 2 examination was normal. Brain MRI revealed indirect signs of spontaneous intracranial hypotensionbrain sagging, pituitary enlargement, and hyperemia, flattening of the anterior pons, venous sinus dilatation, and enhancement of the pachymeninges. A blind L1-L2 blood patch was performed with a transient improvement followed by worsening. Dynamic CT myelography was conducted and showed contrast in a paravertebral vein at T09-T10 level. Digital subtraction myelography (DSM) confirmed the CSF venous fistula. During surgery, a network of engorged epidural veins was treated with bipolar coagulation and clipping. Another intraoperative finding was a dural tear surrounding the T9 nerve root, which was obliterated with a muscle patch and fibrin glue. The patient became symptom-free one week after the procedure. Conclusions: CSF-venous fistula is a treatable cause of Spontaneous Intracranial Hypotension with increasing recognition with invasive neuroimaging technique improvements. To our knowledge, we describe the first case of a dual mechanism of CSF loss (CSF venous fistula plus dural tear).

Headache related to endovascular thrombectomy: a prospective study D. Gallo Objective: To study headache in thrombectomy. Method: We prospectively evaluated clinical features of headache after endovascular thrombectomy using an ad hoc questionnaire in consecutive patients who underwent endovascular thrombectomy during one year. Results: 117 thrombectomies were performed (mean age 68 years; 55% female). Most patients had anterior circulation strokes (105; 89,74%). Mean NIHSS score pre and post-procedure was 13 and 6, respectively. 93 patients (79,5%) received general anaesthesia (average 45.6 minutes) and 62.4% required stent or aspiration thrombectomy. 33 (28,2%) had headache related to the procedure. There was a higher prevalence of previous primary headache (24,3% vs 7,1%), female sex (60% vs 40%) and posterior circulation strokes in the headache group. No differences were observed in the ASPECTS and NIHSS scores or in the procedure complexity. Headache locations concurred with the affected artery territory and were usually ipsilateral, although headache was bilateral in 34% of cases, mostly oppressive, with a mean duration of 2-3 days and moderate-severe intensity. Conclusions: One-third of patients who underwent endovascular thrombectomy had procedural headache. Female sex, history of primary headache and posterior circulation stroke were associated with headache occurrence. Procedural complexity was not associated with headache. Headache after endovascular thrombectomy meets the ICHD-3 criteria for headache caused by endovascular procedures. Objective: Headache is one of the most common complaints among patients with MS. But the relationship between headache and MS still not clearly understood. It is very difficult to determine whether this headache is primary or secondary to MS. CT-perfusion of patients with headache showed reduced flow through structurally normal brain region remote from cAVM. These changes were accompanied by cognitive impairment. Conclusions: The pathogenesis of headache in cAVM patients may involve several mechanisms, including steel-fenomen, cortical spread depression, increased intracranial pressure and demonstrate general lesion of the brain vessels caused by arteriovenous shunting. Introduction: Headache in ischemic stroke (IS) has an incidence of 8-34%. The clinical description varies between series. It is generally accepted that IS in the posterior circulation present with headaches more frequently and the characteristics are more similar to a tensiontype headache. As far as we know, no series of IS in Mexico has studied, ad hoc, headaches. The aim is to report the clinical characteristics of headaches as part of IS in a Mexican population. Methods: iReNe (i-Registro Neurovascular) is a database that gathers information on IS in our institution. In September 2018 we began to collect information on headaches, as well as to perform a paraclinical neurovascular evaluation. Results: Of 282 patients, 45(16%) had a headache. Headache as the initial manifestation occurred in 21(47%). The pain was oppressive and stabbing in 13 cases each (28%). Immediate zenith occurred in 16(35%) and 6 minutes-4 hours in 9(20%). Bilateral location in 29(64%). Presence of accompanying symptoms in 32(71%), with nausea in 21(46%). Anterior topography was in 33 and posterior in 12. There was no correlation between headache and IS topography. Conclusion: This is the first series of its kind in Mexico. Most of the headaches started with the other manifestations. No characteristic clinical profile or topographic correlation with IS was found. We conclude that headache is not unusual but, in our series, it does not add localization value. Tuberculous meningitis (TBM) represents the most serious form of tuberculosis with significant morbidity and mortality. Hydrocephalus, a known complication, can occur either early or late in the clinical course. It has been reported in 87%-90% of children with TBM, whereas it is seen in about 12% of adults. Hydrocephalus could be either of the communicating type or the obstructive type with the former being more frequently seen.

We present an interesting case of patient with worsening headache due to late onset hydrocephalus. A 21-year-old man complains of holocephalic headache that worsened over the period of several weeks and was followed with dizziness, memory and concentration disturbance. According to his medical history he was diagnosed and treated of TBM in the age 14. A cranial CT revealed internal hydrocephalus. Thoracic X-rays taken in the supine position were normal. The cranial MRI displayed restricted third ventricle with widening of the ventral horns of the lateral ventricles as a sign of aqueductal stenosis. Patient was transferred to neurosurgical department where he underwent shunt surgery. In our case, the patient developed late onset hydrocephalus, thus, it can be hypothesized that subclinical relapse of the disease was cause of it. Our case proves that in the case of a secondary headache unusual causes, but according to the patient's medical history possible headache causes deserve to be taken into consideration.

Perceived stress and pain severity in individuals with chronic migraine: A longitudinal cohort study using daily prospective diary data M. Background: To describe patterns of peak pain severity from day-today, and in relation to perceived stress, in individuals with chronic migraine (CM).

Methods: This was a prospective longitudinal cohort study among adults with CM. Daily data about headache, symptoms, and lifestyle factors were collected using the N1-Headache™ digital health platform for 90 days. Days were classified as "migraine days" according to ICHD criteria. Perceived stress was measured on a 0-10 rating scale. On "migraine days", peak pain severity was recorded on a 4-point categorical scale. A logit ordinal model with random effects for intercept and slope was used to assess the relationship between peak severity and stress, adjusting for gender, age, continuous headache, menstrual bleeding, day of the week, and disability. Findings: Data on 136 participants with 8,216 migraine days were analyzed. Sixty-nine percent of participants (94/136) reported the same peak severity on the majority (>50%) of their migraine days. For every unit increase in stress, the odds of reporting a higher peak severity were 10% higher (OR[95%CI]=1.10[1.07-1.14]). The inclusion of random effects for the intercept and slope improved the model and showed that there were large differences in individuals' reporting of peak severity and in its relationship to stress. Interpretation: While overall higher perceived stress was associated with higher peak severity, there is a substantial amount of variation between individuals. Background: Most people worldwide consume at least some caffeine. Caffeine can be both a headache trigger and a pain reliever. We examined whether caffeine consumption has a clearly defined relationship to migraine symptoms and comorbidity in our patient population, in a region famous for coffee consumption. Methods: All new patients referred to the Headache Clinic at the University of Washington complete a detailed patient intake questionnaire that includes questions regarding caffeine use, headache characteristics, sleep, depression, anxiety, and stress. These were analyzed along with headache diagnosis. Results: Of 5677 unique patients with migraine, 74 % of these had chronic migraine. Caffeine use was identified in 82% of patients. 70% consumed one one or less serving of caffeine per day, while 4% consumed three or more. In chronic migraine, higher caffeine use correlates with increased number of headache days per month. We found no correlation of caffeine use and any migraine comorbidities such as difficulty with sleep, perception of stress and depression measures. Conclusions: Most of our patients with migraine consume caffeine. We found a correlation with headache days in chronic, but not episodic migraine patients, and no correlation with comorbidities in any patients, which was surprising. These findings may mean that caffeine consumption is not a significant migraine trigger, or else that patients limit their caffeine consumption to avoid this.

Alexithymia and psychological distress in chronic migraine and fibromyalgia: A comparative study S. Bottiroli 1,2 , A. Ghiggia 3, 4 , F. Galli 5 , L. Castelli 3, 4 -20) , and the Hospital Anxiety and Depression Scale (HADS). A HC group (n=280; age: 51.8±9.0) was also enrolled and assessed by TAS-20 and HADS. Results: FM had significantly higher levels of alexithymia (p < .001) and psychological distress (p < .001) than CM and HC. CM patients reported higher levels compared to HC group in the total score (p < .001) and in the Difficulty Identifying Feeling subscale of the TAS-20 (p < .001). A moderation analysis was performed to examine the moderation effect of the group (CM vs. FM) on the relationship between alexithymia and psychological distress. Besides a strong relationship between alexithymia and distress, the group variable was not a significant moderator. Conclusions: These findings suggest a common psychological dysregulation in patients suffering from CM and FM, which manifests into a different expression of the physical symptom.

Associations between physical activity, quality of life and headache in people with Idiopathic Intracranial Hypertension A. Background and objective: Physical activity is reduced in people with headache conditions such as migraine, this has not been explored in people with Idiopathic Intracranial Hypertension (pwIIH). This survey aimed to quantify physical activity and explore relationships between physical activity, health related quality of life (HRQoL), headache impact and other clinical characteristics in pwIIH. Methods: An online questionnaire via IIH UK. Primary measures were physical activity (PASIPD) and HRQoL(SF-36®) with secondary outcome measures of headache impact (HIT-6™), Body Mass Index (BMI) and age. Results: 164 pwIIH completed the questionnaire. PASIPD measures showed that pwIIH have low levels of physical activity (10.38 (IQR ± 17.6) MET hr/day) and a low level of engagement with exercise and muscle strengthening programmes, similar to people with physical disabilities and other headache disorders. Significant moderate correlations were found between PASIPD total score, headache impact (HIT-6™) and HRQoL (Physical component score and subcategories of SF-36® physical functioning, physical role, general health, vitality and social role) (p<0.05) however there were no significant correlations between PASIPD and Mental component score, age or current BMI(p>0.05). Conclusion: The results suggest that future research should explore the barriers to physical activity and exercise in pwIIH and find ways of increasing physical activity and engagement with exercise. Objective: To assess neurological and psychological disorders in children with sickle celldisease (SCD) using multimodal approach through clinical, laboratory, neuroimaging and neurophysiological studies in a trial to detect etiological risk factors. Method: This study was conducted on 50 children (27 male and 23 female; age range 2-18years) with SCD and 25 healthy children matched age and sex in Department of Pediatric (Hematology Unit) and Department of Neurology, Tanta University Hospital Egypt, between April 2016 and April 2018. All subjects were subjected to fullhistory taking, neurologic examination using pediatric neurological sheet, laboratory investigations,neuroimaging including: CT and /or MRI, MRA and/or CT angiography, also MRV, TCCD, EEG and Stanford-Binet Intelligence scales-Fifth Edition.

Results: Most of patients presented with headache 66%, cognitive decline 48%, seizures 28%, and visual affection 24%. Less common presentations were, ischemic and hemorrhagic stroke 6%and 4% respectively. SCD children showed many abnormalities on neurological examination andon different modalities of MR imaging on the brain with positive correlation (X2=7.641, p-value<0.001*, r= 0.248) with many risk factors. Prophylactic blood transfusion in SCD patients with abnormal TCD had a role in reducing the incidence of stroke. Conclusion: Children with SCD were presented with variable neuropsychological disturbances that correlated with the brain imaging. The average age of pregnancy has increased from 24.6 to 27.2 in the past 30 years, increasing pregnancy-associated complications. As neurological diseases contribute to approximately 20% of maternal deaths, it is important to identify these at risk population. Cerebrovascular complications are classified into ischemic infarctions, subarachnoid hemorrhage, eclamptic encephalopathy, postpartum cerebral angiopathy, and cerebral venous thrombosis. Some are easily recognized by obstetricians and are managed without significant neurological input unless seizures develop. Others are relatively benign, but should be recognized by neurohospitalists as they are often reasons for consults. Some diseases initially present with nonspecific symptoms such as headache. However, headache is a common complaint in pregnant women and distinguishing the benign headache from one that is a sign of serious disease is often not considered until serious neurological complications develop. A CT study should be avoided due to a significant increase of the Xray exposure and to the necessity of administering intravenous contrast unless the information is critical to guide therapy. There is no evidence of adverse fetal effects in humans to the magnetic field exposure for magnetic resonance imaging (MRI). This review highlight on pearls in neuroimaging findings of main cerebrovascular events in peripartum period.

Spontaneous intracranial hypotension, findings, misdiagnosis: a systematic review S. Shaafi, E. Sadeghi Tabriz University of medical science, Neurology, Tabriz, Iran Correspondence: S. Shaafi The Journal of Headache and Pain 2021, 22(Suppl 1):P0377

Background: Spontaneous intracranial hypotension (SIH) is a pathology characterized by orthostatic headaches, diffuse pachymeningeal enhancement on magnetic resonance imaging (MRI), and low to normal cerebrospinal fluid pressures. SIH results from a CSF leak secondary to structural weakness in the dura, either at the cervicothoracic junction or the thoracic spine. Patients may develop subdural hematomas or hygromas. Misdiagnosis may delay appropriate treatment and expose the patient to risks of therapeutic interventions for headache mimics. The pathognomonic findings on contrasted MRI brain are diffuse, smooth, pachymeningeal gadolinium enhancement, and brain sagging. Methods: We have reviewed current literature including published original, review articles, and case reports or case series in PubMed/ MEDLINE and other databases using the keywords; Spontaneous, intracranial hypotension, findings, misdiagnosis. Results: In most of reports emphasis is on that spontaneous intracranial hypotension is an important cause of "new daily persistent headaches". Patients with spontaneous intracranial hypotension are commonly misdiagnosed, causing a significant delay in the initiation of effective treatments. Conclusion: Many radiologic and clinical findings may mimic these classic findings, and conversely, secondary changes from SIH can give rise to symptoms that imitate other conditions. Because SIH is a curable condition, it is important for physicians to recognize its nonclassic presentations and be familiar with the differential diagnoses of its radiologic and clinical findings.

events with LTN were dizziness, asthenia, muscular weakness, and somnolence. Conclusions: In Chinese population, LTN was significantly better than PBO for both primary endpoints with an acceptable safety profile. These findings were generally consistent with that observed in CENTURION primary cohort population.

Disability and psychosocial features in patients with acute whiplash associated disorders with and without headache: a casecontrol study E. Anarte-Lazo 1 , C. Bernal-Utrera 1 , D. Falla 2 , C. Conclusion: Our findings showed that psychosocial features and disability were greater in patients with headache following a whiplash injury when compared to those patients with acute WAD who did not develop headache. These findings should be considered and integrated within the management of these patients. Headache is a sequel of traumatic head and neck injuries. It has a prevalence of 33-92%, mostly occurring during the first week postinjury, and improves within 3-6 months. It mostly resembles primary headaches including migraine, tension-type headache, trigeminal autonomic cephalgias, and cervicogenic headaches. Several risk factors and underlying mechanisms have been addressed for this type of headache. Comprehensive patient evaluation and exclusion of serious underlying causes and associated disorders is needed for its management. Red flags, including altered mental status, focal neurological deficit, progressively worsening headache, intractable headache, and headaches caused by Valsalva maneuver or changing position indicate serious underlying causes, requiring appropriate work-up. When a diagnosis was made, a multidisciplinary therapeutic approach should be performed. Management of comorbidities and proper patient education is also required. In case of headache persistence for 3-6 months after proper therapeutic plans, patients should be referred to a tertiary headache clinic for further evaluations. Objective: Efficacy of ubrogepant in treating migraine with moderate/severe pain was demonstrated in 2 phase-3 trials. Clinical guidance recommends treatment when pain is mild, a strategy examined here in participants treating ≥1 attack with mild pain and ≥1 attack with moderate/severe pain. Methods: Phase-3, 52-week trial (NCT02873221). Adults randomized 1:1:1 to usual care, or ubrogepant 50mg or 100mg, treated ≤8 migraine attacks every 4 weeks. Efficacy measures were collected only for ubrogepant. Results: 459 of 808 participants treated ≥1 attack with mild pain and ≥1 attack with moderate/severe pain and were eligible for this analysis. A higher proportion of attacks with mild pain vs moderate/ severe achieved 2-hr pain freedom (50mg: 57.1% vs 30.9%; 100mg: 51.1% vs 27.2%); absence of nausea, photophobia and phonophobia and restoration of normal function all occurred in significantly higher proportions for attacks treated with mild pain (P Conclusions: Among persons treating both mild and moderate/ severe attacks, outcomes were better for attacks treated when pain is mild. Findings in this subgroup extend prior results and further support the recommendation to treat early when pain is mild. Introduction: Headache is one of the most common disorders of the nervous system. Headache means pain in the head. The (WHO) reports that almost half of the adults worldwide will experience headache in any time at any given year. Objectives: To determine the prevalence rate and clinical characteristics of headache among medical students in Alzaiem Alazhari university in Khartoum state, Sudan in 2020 Methodology: A descriptive cross-sectional study using a 41 items questionnaire was introduced to 71 medical students from Alzaeim Alazhari university in the period from January 1st to 15th of February.

Results: Out of the 71 respondents 35 (49.3%) were Male and 36 (50.7%) were female while most of them were in the (21-24) age group by (69.01%). Most of the participants responded that they headaches (74.65%) with (32.31%) of them having continuous and (67.69%) of them with no continuous headache. 32 (45.07%) of them had headaches, half of them lasted for 1-2 hours and the other half lasted more than 10 hours per day. The most common location for the headache was both sides (23.02%) followed by the fore head (22.22%) . The most common characteristic of headache was pulsating (48.48%) followed by pressure like (37.88%). Conclusion: There is a high prevalence rate of headache among medical students with migraine as the most common cause of headache

Migrainous infraction: a case report of a rare and overlooked phenomenon P. Gklinos Background & objective: The objective of this study is to present a case of a patient with migrainous infraction during the course of a typical migraine attack with aura and discuss the clinical presentation, radiological findings, and differential diagnosis of this rare migraine complication. Methods: A 31-year-old, right-handed male patient with a history of migraine with aura and epilepsy of unknown etiology was admitted to our hospital due to an episode of right-sided numbness involving his right arm and face, as well as expressive aphasia, lasting for 30 minutes, followed by a typical migraine headache. Minutes after presentation at the emergency room (ER), the patient developed two additional transient episodes of Broca"s aphasia that completely resolved within 10 minutes. Results: Brain computerized tomography (CT) scan, electroencephalography (EEG), and blood tests were unremarkable while the MRI FLAIR sequence revealed a hyperintense signal in the left frontoparietal cortex. The diffusion-weighted image (DWI) sequence demonstrated high signal intensity in the same cortical region with corresponding low value on apparent diffusion coefficient mapping (ADC), which indicated restricted diffusion. The clinical diagnosis was migrainous infraction, and the patient was treated with antiplatelet therapy. Conclusion: Migrainous infraction is a rare complication of migraine. Prompt diagnosis may improve the outcome of patients and avoid inappropriate management of symptoms. Background and objective: The aims of our study were to describe the clinical features of the pediatric PSH and to investigate whether PSH is related to more common primary headaches. Methods: Nineteen patients with PSH were recruited (13 girls and 6 boys, aged from 4 to 16 years). Results: In our patients, pain had usually involved bilateral frontotemporal region. Four patients failed to identify a precise pain location. Stabs were usually lasting less than 1 minute. In one patient, each attack included several stabs and lasted around 20 minutes. Pain intensity was usually mild to moderate. Strong pain intensity was referred by 2 patients. Eight patients presented with associated symptoms, as photophobia (5), phonophobia (6), and nausea (3). Migraine was associated with PSH in 5 patients and tension-type headache (TTH) in one. Episodic syndromes which may be associated with migraine, as infantile colic, motion sickness, limb pain, recurrent abdominal pain, and vertigos, were referred by 13 patients. Discussion: In our pediatric case series, PSH clinical features were very similar to those described in adulthood. While in adults PSH is frequently associated with migraine and TTH, only 32% of our patients referred another primary headache. It is noteworthy that 70% of our PSH patients had a history of episodic syndromes. Conclusion: in pediatric age PSH could represent an age-related phenotype of the migrainous syndrome which will turn later into a more typical migraine. Background: Headache disorders a major cause of public ill-health, require trained resources for appropriate management and hence, an acute need to institute systematic initiatives and organise services. Objective: Levels of knowledge and practice regarding the management of Primary headache disorders among Health personnel in Government sector within a district were assessed. The readiness for headache services in the district with respect to planning, training, personnel and support services including availability of drugs was documented. Methodology: A mixed methodology strategy included eliciting response to Case vignettes along with Key informant Interviews. Results: 80% of medical officers had correct knowledge for provisional diagnosis in dealing cases of organic conditions; 60% had correctly given provisional diagnosis of Migraine. Non-medical health personnel did not have the desired knowledge and required expertise regarding correct treatment and referral for headache disorders. Discrepancies were observed related to management of individual headache disorders. Further, KIIs indicated that there have been no plans or discussions for introducing headache services. Headache services did not feature in the priority at the district or state level. Conclusion: Despite a proven burden, headache services at the district level is poorly organised. However, opportunities exist aplenty for making headache services at district and sub-district levels more systematic.

Results: Migraine was identified in n=33,549 patients, and dementia was identified in n=8,668 patients. N=149 patients had both migraine and dementia. 46% (n=69) of those with dementia and migraine also had anxiety (ICD10: F41.0-41.9) versus 20% (n=1740) of those with dementia alone. 36% (n=53) of patients with dementia and migraine were diagnosed with insomnia (ICD10: G47.00-G47.09) versus 14% (n=1242) in dementia alone. Hypertension (ICD10: I10) was noted in 72% (n=107) of those with dementia and migraine. Hypertension was present in 59% (n=5114) of those with dementia alone and 21% (n=7132) in migraine alone. Conclusion: Migraine is an infrequent concurrent diagnosis in those with dementia and represents 1.7% of patients in this cohort. Rates of anxiety, insomnia, and hypertension were higher in those with migraine and dementia over those with dementia alone. Clinical experience shows that we rarely see migraine concurrently diagnosed in dementia patients, and this is difficult to explain with current scientific understanding.

New master's degree program "Master of Migraine At the University of Kiel, Germany, a new academic master's course "Master of Migraine and Headache Medicine" (MMHM) of four academic semesters is planned to start in the winter term of 2021/ 2022. The concept was positively assessed by a national and international expert board. The Master's degree is divided into four terms, with the first three terms being allocated to teaching sessions, the fourth term being allocated to the master's thesis. In the first term (Foundation, Organization, Clinical pathways), the foundation of headache disorders and the clinical processes in a hospital specialized in the treatment of headache disorders are presented. The focus hereby lies on epidemiology, classification, pathophysiology of headache disorders, medical ethics and organization / leading of teams. Three days are reserved for clinical practice.

The second term (Diagnostic pathways and therapies) focuses on the methods and criteria for diagnosing different headache disorders. At the forefront lie interdisciplinary approaches using various evidencebased methods and clinical practice.

In the focus of the third term (Organization/Structure of headache treatment and prevention, perspectives for the coming decade) lies the concrete interdisciplinary teamwork in headache centres, which is presented as part of hospital days. Teaching will consist of a mixture of face-to-face teaching as well as clinical on-site training.

Why patients do not comply with headache diaries? C. Borbinha 1 , I. Pavão Martins 2 potency) as these items were previously shown to differentiate androgen deficiency symptoms from anxiety and depression. Results: The questionnaire was completed by n=534 men with migraine, n=437 with cluster headache and n=152 controls. Patients reported more severe symptoms of androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference±SE: migraine 5.44±0.90, p<0.001; CH 5.62±0.99, p<0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: -3.16±0.50, p<0.001; CH: -5.25±0.56, p<0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4%, 20.6%, 7.2%, p=0.001). Conclusion: Men with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than non-headache male controls. (Bruni O et al, 1996) . APBAH dosage was 15-20 mg/kg daily, A -20-30 mg daily per os. According to the criterion of a 50% or more reduction in the average number of headache attacks per month the improvement was achieved in group 1 (APBAH) in 56.7% of patients, group 2 (A)in 73.3%, the group 3 (BG)in 30%. According to a more strict criterion for headache attacks reduction by 75% or more per month, the response was observed in group 1 in 30%, group 2 -23.3%, group 3 -3.3% of patients. Significant differences with the group 3 for response to therapy were confirmed for groups 1 and 2. In groups 1 and 2, along with a significant decrease in the frequency, duration and intensity of TTH attacks, the significant improvement in daily activity with favorable effects on the fatigue, anxiety and sleep disorders manifestations was demonstrated. The preventive efficacy of BG was confirmed with the reduction of TTH frequency, duration, intensity and diminishing their negative impact on daily activity.

The role of NO system in tension-type headache and arterial hypertension phenotype development P. Background: Patients with tension-type headache (TTH) have an increased risk of developing arterial hypertension (AH), while hypertensive subjects do seem to have an increased risk of TTH. The aim is to study the role of SNVs of the NOS1, NOS2, and NOS3 genes in the comorbidity of AH and TTH. Methods: We searched for full-text English publications in databases over the past 15 years. In addition, earlier publications of historical interest were included in the review. Results: In our review, we summed up the single nucleotide variants (SNVs) of Nitric Oxide Synthases (NOSs) genes involved in the development of essential AH and TTH. The results of studies we discussed in this review are contradictory. This might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. Conclusions: The contribution of genetic and environmental factors remains understudied. This makes the issue interesting for researchers, as understanding these mechanisms can contribute to a search for new approaches to pathogenetic and disease-modifying treatment of the AH and TTH phenotype. New drugs against AH and TTH can be based on inhibition of nitric oxide (NO) production, blockade of steps in the NO-cGMP pathway, or NO scavenging. Indeed, selective neuronal NOS (n-NOS) and inducible NOS (i-NOS) inhibitors are already in early clinical development.

References: https://doi.org/10.3390/molecules26061556 

HIT-6) in a 12-Week, Double-blind, Randomized Phase 3 (ADVANCE) Trial for Preventive Treatment of Migraine R. B. Lipton 1 , P

Objective: To evaluate the effect of atogepant, an oral CGRP receptor antagonist for migraine prevention, on 2 patient-reported outcome measures: AIM-D and HIT-6. Methods: Phase 3, randomized, double-blind, placebo (PBO)-controlled trial (ADVANCE; NCT03777059). Participants with 4−14 migraine d/mo received oral atogepant 10, 30, or 60mg, or PBO once daily for 12 wks. The AIM-D, collected daily by e-diary, has 2 domains (0-100 scale; lowest-greatest impact): Performance of Daily Activities (PDA) and Physical Impairment (PI). Changes from baseline in mean monthly AIM-D PDA or PI scores across 12 wks were alpha-controlled secondary endpoints. HIT-6 (completed monthly) was exploratory. Results: Of 910 participants randomized, 902 were treated (mean age 42 y; 89% female), including 873 in modified intent-to-treat population (10mg n=214

Methods: Phase 3, randomized, double-blind, placebo (PBO)-controlled trial (ADVANCE; NCT03777059). Participants (4−14 migraine d/ mo) received oral atogepant 10, 30, 60mg, or PBO once daily for 12 wks. Change from baseline in MSQ Role Function-Restrictive (RFR) domain at wk 12 was an alpha-controlled secondary endpoint. Leastsquares mean differences (95% CI) vs PBO for change from baseline at wks 4, 8, and 12 in MSQ RFR

At wk 12, all atogepant groups had statistically significant improvements vs PBO in RFR (10mg, 9

All atogepant groups achieved within-group minimally important difference in each domain at wks 4, 8 and 12. Conclusion: Atogepant produced significant and clinically

) criteria, experiencing 4-14 migraine days/month, were randomized to receive oral atogepant 10, 30, or 60mg or placebo once daily. These analyses evaluated ≥25%, ≥50%, ≥75%, and 100% reductions in mean monthly migraine days (MMDs) across 12 weeks and each 4-week interval. Adverse events (AEs) in ≥5% of participants are reported. Results: The efficacy analysis population included 873 participants: placebo: n=214; atogepant: 10mg: n=214; 30mg: n=223; 60mg: n= 222. Atogepant-treated participants were more likely to experience a ≥50% reduction in the 3-month mean MMDs (56-61% vs 29% with placebo; P<0.0001). The proportion of participants experiencing ≥25%, ≥50%, ≥75%, and 100% reductions in mean MMDs significantly increased during each 4-week interval (≥50% reduction: 48-71% vs 27-47% with placebo). The most common AEs for atogepant were constipation

Daily Atogepant Provides a Rapid Onset and Sustained Benefit in the Preventive Treatment of Migraine T

Results: PROMISE-1 ≥75% MRRs over Wk1-12 were 22.2% (100mg, P= 0.1126), 29.7% (300mg, P=0.0007), and

Once ≥75% MRR over Wk1-12 was achieved, >70% of EM and >80% of CM patients maintained ≥75% MRR over subsequent doses across groups. In CM patients with ≥75% MRR over Wk1-12, mean change in Wk12 HIT-6 total score with eptinezumab (pooled) was -11.7, with 64.4% reporting little to no/some life impact and >80% reporting much/very much improved on PI-MBS and PGIC. Conclusion: More eptinezumab-treated patients achieved ≥75% MRR over Wk1-12 vs pbo across patients with migraine, with response primarily consistent across the 24-week treatment period. For CM patients achieving ≥75 MRR, PRO results indicated substantial improvements in headache-related impact and symptoms. P0313 Reductions in Migraine Frequency With Fremanezumab Treatment in Individuals With Chronic and Episodic Migraine S

Methods: In all 3 studies, pts with chronic or episodic migraine (CM/ EM) were randomized 1:1:1 to quarterly (QTY) fremanezumab, monthly (MLY) fremanezumab, or matched PBO. The percentages of pts with a shift of ≥1 category down during 12 weeks of treatment were evaluated by baseline (BL) frequency category (high-frequency CM

Conclusion: Both QTY and MLY fremanezumab resulted in favorable migraine frequency category shifts to a greater extent than PBO. P0314 Impact of Fremanezumab Treatment on Clinical Outcomes Among Migraine Patients With Comorbid Depression

Changes in mean antidepressant prescription (AD) and anxiolytic prescription (AX) use from the 6-month baseline period to 6 months after fremanezumab initiation were assessed by comorbidity. For the comorbid HTN subgroup, changes in systolic and diastolic blood pressure (SBP/DBP) were analyzed. Results: For the DEP (n=172) subgroup, proportion of pts with AD (−12.2%; P=0.003) and number of AD used (−0.2; P=0.008) were statistically significantly reduced with fremanezumab treatment. For the ANX subgroup (n=180), fremanezumab treatment resulted in significant reductions in proportion of pts with AX

Among pts with HTN, nonsignificant reductions in SBP and DBP were observed. P0318 Fremanezumab in the prevention of high-frequency episodic and chronic migraine: FRIEND (FRemanezumab In rEal world stuDy), the first Italian multicenter, prospective real-life study

Methods: This is a 24-week, multicenter (n=9), longitudinal, cohort, real life study performed from 28/01/020 to 15/03/2021. We considered all consecutive patients with HFEM or CM aged 18-65 years. Change in monthly migraine days (MMD) at weeks 21-24 compared to baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake and change in VAS, HIT-6 and MIDAS scores during the same time interval. Results: 47 patients received >1 fremanezumab dose (225 mg monthly, n=38; 625 mg quarterly, n=9). Thirty-one patients were treated for 24 weeks and considered for effectiveness analysis

Taipei Veterans General Hospital

Novartis Pharmaceuticals Corporation

Secondary endpoints assessed were achievement of ≥50% reduction in MMD, Objective: This posthoc analysis assessed headache-free days (HFD) and migraine-free days (MFD) gained in patients using fremanezumab from a 1-year (yr) extension study (HALO LTS). Methods: Patients continued or were randomized 1:1 to quarterly (QTY) or monthly (MLY) fremanezumab

FINESSE: Fremanezumab for Preventive

P0325 Objective: Effectiveness and side effects of fremanezumab, a monoclonal antibody that selectively binds calcitonin gene-related peptide (CGRP) and prevents its binding to the CGRP receptor, as preventive treatment of episodic and chronic migraine (EM, CM) during 6 months after first dose in a real-world setting. Methods: Prospective, non-interventional study in adults with EM or CM in routine clinical practice. Primary endpoint: Proportion of patients reaching ≥ 50% reduction in average MDM (Migraine Days per Month) during 6 months after first dose. Relevant secondary endpoints include changes from baseline in: (1) Monthly average number of migraine days; (2) Disability scores (Migraine Disability Assessment questionnaire/MIDAS; six-item Headache Impact Test/HIT-6); (3) Days of concomitant acute migraine medication

BoNT-A efficacy in high frequency migraine: an open label, single arm, exploratory study applying the PREEMPT paradigm D. Martinelli 1 , S. Arceri 2 , R. De Icco 1

Objective: Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) have been shown to improve disability among migraineur patients. Nevertheless, studies assessing patient-reported outcomes (PROs) in the more complex population of a real-world clinical setting are scarce. Our aim was to evaluate changes on headache-related disability in a series of patients with migraine treated with anti-CGRP mAbs. Methods: This was a single-center prospective cohort study that includes patients with chronic migraine (CM) or high frequency episodic migraine (HFEM) and multiple preventive treatment failures who received anti-CGRP mAbs (erenumab, galcanezumab or fremanezumab). Migraine Disability Assessment Test (MIDAS) and Headache Impact Test-6 (HIT-6) scores were collected at baseline, 3 months and 6 months. Results: 134 patients were prescribed anti-CGRP mAbs from

Fig. 1 (abstract P0330). See text for description The Journal of Headache and Pain

University Hospital of Rome "Tor Vergata

Background: Erenumab proved to be safe and well tolerated in a 5-year continuation of a 1-year double-blind, placebo-controlled study. Aim: to assess >48-week erenumab tolerability and safety in a realworld setting Methods: In this long term (>48-week), multicenter (n=15), longitudinal cohort real life study, we monitored all the adverse events emerged in consecutive adult patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) treated with monthly erenumab 70 mg or 140 mg from

Most common TEAE were constipation (n =66; 14.9 %), injection site erythema (n =15; 3.4%), and influenza (n =7; 1.6%). Serious adverse events (SAE) were reported by 8 patients (1.8%) and led to treatment discontinuation: severe constipation (n=3), abdominal pain (n=1), NSTEMI (n=3), Covid-19 infection (n=1). Only severe constipation was considered treatment-related SAE (0.45%). Conclusion: Erenumab is safe and well

See text for description The Journal of Headache and Pain

Noninvasive Vagus Nerve Stimulation for Prevention of Episodic Migraine: a Proof-of-Concept Study

United States; 3 Barrow Neurological Institute

Hernandez-Dominguez Instituto Mexicano del Seguro Social

Objective: To report a case of headache secondary to a cerebrospinal fluid (CSF) venous fistula with an associated dural tear. Methods: case description and presentation of neuroimaging findings. Results: A 47-years-old female presented with continuous orthostatic headache, bilateral, predominating in occipital, irradiating to vertex, photophobia, phonophobia, and nausea. The neurological P0378 Lasmiditan Over Four Migraine Attacks in Chinese Population: Findings from CENTURION Study L

Methods: Patients were randomized 1:1:1 to LTN 200 mg; LTN 100 mg; or a control group receiving PBO for 3 attacks and LTN 50 mg for either the 3 rd or 4 th attack (1:1). The primary endpoints were pain freedom at 2h (1 st attack) and pain freedom at 2h in ≥2/3 attacks. Results: 275 patients (mean age 37.6 years; 72.4% female; MIDAS mean score 36.6) were treated ≥1 migraine attack with study drug (control, n=92; LTN 100 mg, n=91, LTN 200 mg, n=92)

Methods: CENTURION randomized patients with migraine with/ without aura to lasmiditan (LTN) 200mg/LTN100 for 4 attacks or placebo and LTN50 for 3 and 1 attack. TIR were: subset with inconsistent response to their most recent triptan; taking triptan; had poor/very poor migraine Treatment Optimization Questionnaire(mTOQ-6) score; had discontinued their most recent triptan due to efficacy/ tolerability issues/contraindications. Gated secondary endpoint: pain freedom at 2hours (h). Results are for first attack through 2h postdose, sustained effects through 48h and response consistency, defined as reaching outcome at 2h in ≥2/3 attacks. Results: During first attack, both lasmiditan doses showed statistically significant benefit over placebo for pain freedom and relief starting at 1h and 0.5h(LTN200) or 1h (LTN100)(p<0.05) and consistency of effect across attacks for pain freedom and relief at 2h

Significant differences from placebo were evident for 1/both lasmiditan doses for migraine-related disability freedom at 2h, much/ very much better on Patient Global Impression of Change at 2h, most bothersome symptom freedom at 2h, rescue medication need and sustained pain freedom at 24 and 48h(p<0.05). Conclusions: Lasmiditan was beneficial across various clinical endpoints in TIR. P0388 Red ear syndrome and headache: a systematic reviw of literature

Objectives: establishing impact of vascular risk factors, particularly migraine on severity of Parkinson's disease. Methods: Analysis included 29 consecutive PD patients from Moldovan cohort (20.80009.8007.39), mean age 63.3±8.1 yo, mean disease duration 48.9±12.9 mo., mean disease onset age of 59.0±8.7 y. Motor assessment (UPDRS II scale, Tremor Score, Akinetic-rigid Score), quality of life impairment (PDQ39), cognitive performance (MoCA) were conducted. Presence of vascular risk factors (FRV), including migraine (Mg), QRISK3 scores and relative cardiovascular risk were determined. Results: Twenty-five (86.2%) of total PD patients had VRF. Migraine present in 41% of them. PD+VRF was associated with higher scores of disease severity: UPDRS II 46

25±20.16) and lower cognitive MoCA scores 21.75±4.07 (vs

09±3.90), no statistically significant difference. PD+Mg patients had significantly higher relative cardiovascular risk scores -2.80±6.84 (vs. 1.53±0.66, p = 0.02). Conclusions: Vascular risk factors, if present in PD patients, may predict a worse motor and cognitive performance. Migraine presence significantly increases the patients cardiovascular risk. P0403 Quality analysis of primary headaches diagnosis and treatment: online survey results from Russian Federation D

Maassen van den Brink, A

A. P049 Vives-Mestres, M

Acknowledgements: This work was supported by the Italian Ministry of Health (RF-2016-02364909) Acknowledgements: Supported by the Italian Ministry of Health (RF-2016-02364909).Acknowledgments: This work was funded by IINFACTS, CESPU and FEDER Regional funds (COMPETE 2020 -Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020) and through FCT -Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-029486 (PTDC/MEC-NEU/29486/2017). 

Objective: This post hoc analysis evaluated ≥50% reductions in days with nausea or vomiting (N/V) and photophobia and phonophobia (P/P) using data from HALO (chronic migraine [CM] , episodic migraine [EM] , and long-term safety [LTS] ) and FOCUS studies. Methods: Patients (pts) were randomized 1:1:1 to quarterly (QTY) fremanezumab, monthly (MLY) fremanezumab, or placebo (PBO) over 3 months (mo) in HALO CM, HALO EM, and FOCUS. Pts continued or were randomized 1:1 to QTY or MLY fremanezumab over 12 mo in HALO LTS. Proportions of pts with ≥50% reductions in monthly average days with N/V and P/P over 3 mo in HALO CM, EM, and FOCUS and at mo 12 in HALO LTS (≥50% N/V and P/P response) were evaluated. Results: In HALO CM (N=1,121), significantly higher proportions of pts achieved ≥50% N/V response with fremanezumab (QTY, 45%; MLY, 43%) versus PBO (27%; P<0.0001) and ≥50% P/P response (QTY, 34%; MLY, 35% vs PBO, 26%; P≤0.0143). With QTY and MLY fremanezumab, respectively, vs PBO, significantly higher proportions of pts achieved ≥50% N/V response (45% and 47% vs 32%; P< 0.0007) and ≥50% P/P response (43% and 41% vs 31%; P<0.0115) in HALO EM (N=865). Similar ≥50% N/V and P/P response rates were observed in FOCUS (N=837), and response rates increased over 12 mo of fremanezumab treatment in HALO LTS (N=1,103). Conclusions: With both fremanezumab regimens, many patients achieved clinically meaningful reductions in days with nausea/ vomiting and photophobia/phonophobia over up to 12 months. Erenumab is the first EMA and FDA approved monoclonal antibody targeting the CGRP-receptor specifically developed for preventive migraine treatment. Recently, 5-year data from an open-label treatment phase confirmed the long-term safety profile of erenumab in an international cohort. However, long-term data on safety and efficacy of erenumab is still limited for the German population. Further, the impact and relevance of a drug holiday in the erenumab treatment should be investigated. APOLLON is a 128-week open-label study of erenumab treatment, assessing long-term safety and tolerability in migraine patients in Germany who previously participated in a head-to-head trial of erenumab and topiramate (HER-MES, NCT03828539). The treating physician can change the erenumab dose according to the approved label or initiate a drug holiday. Thereby, impact of treatment discontinuation on monthly migraine days is assessed prior to, during and after the medication-free epoch. Detailed study design and results of the first interim analysis describing the baseline characteristics of the total study population of 701 enrolled patients will be presented. This analysis will provide insights into the patient population enrolled in the APOLLON study to assess long-term safety and tolerability of erenumab. Common treatment algorithms will be elucidated by this trial investigating the impact of drug holidays during preventive migraine treatment in the participating 80 headache centers.

BoNT-A efficacy in high frequency migraine: an exploratory study applying machine learning to predict therapy responsiveness D. Martinelli (Martinelli et al., submitted) . Objective: In this sub-analysis we sought to identify predicting elements of responsiveness to BoNT-A in HFEM.Methods: We enrolled 32 subjects with HFEM (8-14 migraine days/month) and thoroughly profiled them from a clinical/anamnestic perspective. After a 28-day baseline period, subjects underwent 4 BoNT-A treatments according to the PREEMPT paradigm, every 12 weeks. Subjects filled in a headache diary the number of monthly migraine days (MMD) was used to divide them into 2 groups according to the response to BoNT-A treatment in the last 12-weeks compared to baseline: responders (>50% migraine days reduction vs baseline). Collected data were used as input features to run a machine learning Random Forest (RF) algorithm. Results: RF discriminated responders from non responders with a high classification accuracy of 85.71% (AUC=90.91%) using 4 baseline features: migraine onset age, opioid use, hospital anxiety and depression score (HADS) and Migraine Disability Assessment (MIDAS) score. High responsiveness positively correlates with migraine onset age and HADS-A score, and negatively correlates with ongoing opioid use and MIDAS score. Conclusions: These findings identify a 4-feature panel of easy-toobtain parameters predictive of BoNT-A therapy responsiveness in HFEM.

Has onabotulinumtoxinA follow-up delay during COVID-19 lockdown affected the migraine course? A. Gonzalez-Martinez 1,2 , Á. Planchuelo-Gómez 3 , Á. L. Guerrero Peral 4,5,6 , D. García-Azorín 4,5 , S. Santos-Lasaosa 7 , M. P. Navarro-Pérez 7 , P. Odriozola-González 8 , M. J. Irurtia 8 , S. Quintas 1,2 , R. de Luis-García 3 , A. B. Gago Veiga 1, 2 There were no differences in AE between the different anti-CGRP mAbs.Conclusions: It"s necessary to study the optimal duration of preventive treatment and the choice of reuse of the drug should be individually given the probable reduction in their effectiveness.

Over 65 Objetive: People over 65 years old were excluded in randomized trials with Erenumab. We describe the efficacy of Erenumab with real-world evidence in people with or over 65 years-old. Methods: Retrospective study in the Headache Unit of a University Hospital. Charts of patients receiving Erenumab (70 /140mg) from December 2019 to March 2021 were reviewed. Demographic variables were collected and efficacy analysis included change from baseline in monthly headache days (MHD), and responses greater than 50% and 75% at 3 months. Results: We reviewed the charts of 240 patients. Twenty-one subjects older than 64 years and who had received at least three injections of Erenumab were included. The mean age was 69,62 (range 65-86). Nineteen patients (90.5%) had Chronic Migraine, and 2 (9,5%) had high frequency episodic migraine. As usual in Migraine, most of them were women 16 (76%). Mean baseline MHD was 19,4 (SD 7.4). After 3 months with Erenumab, mean MHD was 14,2 (SD 9.8). Mean improvement was -5,2 days per month (SD 6.1) with a 31,4% reduction of MHD. Seven patients (33%) had an improvement greater than 50% and 2 (9%) greater than 75%. No significant differences in terms of efficacy were found between the 70 and 140 milligram doses. Conclusion: Erenumab is effective in people older than 65 years old. We are looking to collect data at 6 months where we would probably find more 50% responses. More studies need to be done to confirm our suspect. Background/Objective: German regulatory guidelines demanded 5 (EM) or 6 (CM) failed/contraindicated first-line prophylactics before covering the costs of CGRP-mABs, Valproate meanwhile was omitted. Medical guidelines recommend a significant (50%) response as a prerequisite for sustained prescription. We aimed to describe results and implications of E. treatment in neurological practices under these conditions. Methods: The headache registry of NeuroTransData network of neurologists captures demographics, headache characteristics, comorbidities, symptom load and the use and effect of acute and preventive medication via standardized webbased data entry and smartphone app. Results: Currently (01.01.21) 5121 pts. fulfilled the ICHD-3-criteria for migraine. 435 (8,5 %) received E., 431 could be evaluated. 140 (32,5 %) had CM. 14 pts. (3,2 %) stopped therapy due to side effects, 76 (17,6 %) to lacking efficacy, 43 (9,9 %) to other reasons. The responder-rate (at least 50% reduction of migraine days) rose from 40 % after 3 up to 65% after 24 injections, 25 % of the patients had a less than 25 % response after 2 years. Conclusions: Treatment with Erenumab under the regulatory conditions in Germany was mostly well tolerated and effective. A considerable proportion of patients was treated for up to 2 years without reaching 50 % response. This indicates a good ratio between tolerability and effectiveness in the evaluated sample of therapy resistant migraine patients.Abstract Background: Headache is the most common pain disorder, affecting around 66% of the global population. This study aimed to investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating patients with primary chronic daily headaches (chronic tension-type headache and chronic migraine). Methods: Twenty-seven patients participated in the study, divided into 2 groups: a study group (16 patients) and a control group (11 patients). Treatment consisted of 12 high-frequency (5 Hz) real rTMS sessions, delivered over the left dorsolateral prefrontal cortex (DLPFC), whereas sham rTMS was used for the control group. Results: Patients of the study group, after real rTMS stimulation, showed a high statistically significant reduction of the measured headache parameters compared to the control group (P value < 0.001), and the percentage of improvement was 94.5%. No significant reduction of headache parameters, after sham rTMS stimulation, was observed in the control group (P value > 0.05) and the percentage of improvement was 7.9%. Conclusion: High-frequency rTMS is effective in reducing chronic tension headaches and chronic migraines. This finding runs with the approval of the suggested role of DLPFC in pain control. This might open opinions for new treatment strategies in tension-type headache and migraine prevention. Keywords: Repetitive trans-cranial magnetic stimulation, Chronic daily headache, Tension headache, MigraineObjective: The Red Ear Syndrome (RES) is an enigmatic disorder with approximately 100 published cases in literature. It is characterized by attacks of burning pain and erythema on the ear. RES is classified in idiopathic and secondary forms, often associated to primary headaches and upper cervical disorders respectively. The aim of this paper is to provide an overview of studies which reports this poorly understood condition. Methods: We review all previously described cases and 53 articles were selected following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. All the 94 patients collected from case reports were placed into idiopathic or secondary RES groups. Results: In both groups there are a female to male predilection ratio, unilateral attacks are more common, the duration of attacks can range seconds to hours and occur daily. In the idiopathic RES, 48,2% of patients the attacks were associated with primary headaches and 34,4% had isolated attacks, the most common trigger was tactile stimuli. On the other hand, in secondary RES the most common trigger was head movement. Furthermore, in 63,1% of the cases the pain extends to other regions beyond the ear mostly in secondary cases. Patients can also experience autonomic and vestibulocochlear symptoms. Conclusion: Our systematic review showed important clinical differences between primary and secondary RES. These results could shed light on the knowledge of this peculiar condition. contribution of neuropeptide release, and the CV risk in middle-aged women suffering from PCOS with and without migraine. Methods: Peripheral microvascular function was assessed crosssectionally using Local Thermal Hyperemia (LTH) of the forearm under control conditions, after inhibition of neuronal axon reflex by EMLA cream application, and inhibition of nitric oxide (NO) formation by L-NMMA. The dermal blood flow (DBF) response to LTH is characterized by a first peak mediated by neuropeptide release, followed by a plateau phase mainly involving NO. Results: We have included 49 women with PCOS, of which 23 suffered from migraine (mean age 50.8±2.9). Baseline characteristics of both groups were comparable, including their CV risk as traditionally determined by the Framingham Risk Score. EMLA cream application resulted in significantly lower inhibition of the total DBF response in migraine patientsexpressed as the Area Under the Curve (AUC)relative to control conditions (95% CI of the difference [4.04-33.47 ]; p=0.014). Also, EMLA cream caused a significantly lower inhibition in both the height and the AUC of the plateau phase relative to control conditions in migraine patients. Conclusions: Neuropeptide action was significantly decreased in migraine patients in the interictal period, which may contribute to the increased CV risk in migraine.

The Objective: Aim of the study was to evaluate specialist visits carried out in the patients discharged from emergency department (ED) with diagnosis of Not Otherwise Specified (NOS) headache in order to evidence discrepancies between specialist and ED diagnosis at discharge. Methods: All patients discharge from the ED of the tertiary-care University Hospital of Trieste with NOS headache as final diagnosis were retrospectively (1.6.2018-31.12.2018) analyzed. We included who underwent to one specialist examination at least. Demographic data, specialist and ED diagnosis were analyzed. Results: We analyzed 124 patients (93 F, 31 M, 44 y ±15). 71.8% of patients were examined only by a neurologist, 12.9% by nonneurologists, 15.3% by both neurologist and non-neurologist. Only 37% received a precise diagnosis, slightly more frequently by neurologist than the other consultants (40.5% vs 37.5%). Neurologists diagnosed primary headaches, headaches secondary to neurological diseases, and facial neuralgia; non-neurologists detected headaches secondary to non-neurological diseases. Primary headaches were diagnosed in 25.7% of cases, migraine being the most frequent. Physicians did not report any specialist diagnoses in the ED discharge sheet. Conclusions: Specialist consultants made specific diagnoses in onethird of patients that were not reported as final in the discharge records by the ED physician. This leads to a loss of diagnoses and to an overestimation of NOS headache. Adult oncohematologic patients who were referred to a neurologist in 2020 were included. Patients assessed by a neurologist in the early post-transplant period (100 days following hematopoietic stem cell transplant) or the intensive care unit were excluded. We recruited 268 patients with acute leukemia (68.6%), lymphoma (15.0%), chronic myeloproliferative disorders (8.2%), multiple myeloma (4.8%), or aplastic anemia (3.4%). Patients eligibility for ID Migraine was assessed with pretest criteria. After ID Migraine test, patients were assessed by a neurologist. Headache disorders were diagnosed with ICHD-3. Results: Headache was diagnosed in 58 patients (21.6%). Migraine without aura (11.6%) and Infrequent episodic tension-type headache (4.9%) were the most prevalent primary forms of headache. Postdural puncture headache (5.9%) was the most common secondary headache. Fourteen patients had two or more types of headache (24.1% of all headache patients). Thirty-nine patients (14.5%) met the pretest criteria of ID Migraine. ID migraine sensitivity and specificity was 91.3% (95% CI, 72.0% to 98.9%) and 62.5% (95% CI, 35.4% to 84.8%), respectively. Conclusion: In oncohematologic patients, ID migraine showed high sensitivity and low specificity.

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional study I. Verhagen 1 , R. Brandt 1 , C. Kruitbosch 1 , A. Maassen van den Brink 2 , R. Background and objectives: Despite the availability of the International Classification of Headache Disorders and clinical guidelines, patients with primary headaches still face misdiagnosis, prescription of non-informative investigations and ineffective therapy. We evaluated the quality of medical care for patients with primary headaches in Russian Federation. Methods: We created an online questionnaire for people with a diagnosed primary headache. The questionnaire consisted of 17 questions regarding diagnosis and treatment choices and patient satisfaction with the treatment results. Results: The study included 234 participants (227 women), mean age 36.5 ± 9.2. Among them, 174 patients had a migraine, 57 tensiontype headache and 3 cluster headache. Only 16% of patients received their diagnosis at the first doctor visit. In 80% of cases, doctors prescribed additional instrumental investigations ( fig. 1 ). The mean diagnostic delay was 4.7 ± 6.5 years. Fifty-six percent of the interviewees were prescribed ineffective medications for their headaches ( fig. 2 ). Forty-seven percent were dissatisfied with the treatment results and 58.5% wanted to find another specialist. Conclusions: Our findings emphasize the still existing challenges of diagnosing and treating primary headaches, as well as the need for improved specialized education for physicians in this area. Background and objectives: Outreach and health literacy are among the main objectives of professional associations and play an essential role for headache patients. With the modern Internet accessibility, web pages of medical societies and doctors in social networks increasingly attract patients and become a source of reliable information. We analyzed how medical information on the Internet affects headache patients. Methods: We created an online survey for Russian-speaking people with headaches. The questionnaire included 12 questions regarding the availability of medical information on the Internet and its impact on headache awareness. Results: The study included 307 participants (292 women) aged 36.6 ± 10.2. Information on the Internet helped 38.9% of respondents to ensure that the doctor diagnosed them correctly and be more susceptible to proper treatment. The medical information obtained on the Internet was helpful and valuable for 46% of interviewees. However, 51.1% were unaware of headache specialists, offices, and pain treatment centres. 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. Footnote Abstract authors were asked to disclose their Conflicts of Interest. The disclosures are available via this link. Index A Ardayfio, P. A. P0110 Foster, S. A. P097