Executive Functions, Anxiety, Social Participation and Quality of Life in Children with Migraine During COVID-19 (preprint)

Objective: To compare executive functions (EF), anxiety, social participation, and quality of life (QoL) between children with migraine and healthy controls during the COVID-19 pandemic, and to examine these parameters in children in each group who did vs. did not contract COVID-19. Background: Migraine is among the most prevalent headache disorders in children, especially in adolescents. Migraine is exacerbated by stress, and it holds potential to affect patients’ emotional and cognitive state and, by extension, their functioning and wellbeing – parameters that were also affected by the COVID-19 pandemic. Materials and Methods: A prospective cohort study. The patient group comprised children seen in our pediatric neurology clinic for migraine, and the control group was composed of aged-matched healthy children with no neurological findings or developmental disorders. Participants’ parents completed a health and demographic questionnaire, BRIEF (child/adolescent version), PedsQL, the State-Trait Anxiety Inventory for Children (STAIC) and CASP. Participants or their parents furnished information on whether the participant had contracted COVID-19. Results: 84 children and adolescents aged 6–17.5 participated in the study: 33 with migraine (17 boys, 16 girls); 51 healthy controls (28 boys, 23 girls). Children with migraine showed significantly lower EF due to reduced behavioral regulation, higher trait anxiety, and lower physical, emotional, and school related QoL. Reduced EFs correlated with intensity of migraine attacks, higher anxiety, reduced social participation, and reduced QoL. Lower social participation correlated with reduced QoL and predicted emotional and social QoL. The BRIEF metacognition scale predicted school-related QoL. Healthy children who contracted COVID-19 showed significantly lower EF than children with migraine in the inhibition (56.66±10.56 vs 45.71±7.12-, p=.013) and initiation (60.01±11.89 vs 46.01±6.54, p=.005) BRIEF scales, and in the general metacognition index (65.83±14.48 vs 46.75±9.19, p=.003). Healthy children who contracted COVID-19 had significantly worse initiation and working memory compared to those who did not contract COVID-19 (initiation: 60.01±11.89 vs 46.81±8.89, p=.007), working memory: 61.16±15.48 vs 47.21±11.06, p=.021). Conclusion: Migraine has a significant negative impact on executive functions in children and adolescents, even more than contracting COVID-19. Executive dysfunction influences their emotional state, participation in social activities, and quality of life. The COVID-19 pandemic had a less deleterious effect on migraine patients compared to the healthy control group. Further research on pediatric migraine is warranted.

SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models (preprint)

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.

Sarbecovirus disease susceptibility is conserved across viral and host models (preprint)

Coronaviruses have caused three severe epidemics since the start of the 21st century: SARS, MERS and COVID-19. The severity of the ongoing COVID-19 pandemic and increasing likelihood of future coronavirus outbreaks motivates greater understanding of factors leading to severe coronavirus disease. We screened ten strains from the Collaborative Cross mouse genetic reference panel and identified strains CC006/TauUnc (CC006) and CC044/Unc (CC044) as coronavirus-susceptible and resistant, respectively, as indicated by variable weight loss and lung congestion scores four days post-infection. We generated a genetic mapping population of 755 CC006xCC044 F2 mice and exposed the mice to one of three genetically distinct mouse-adapted coronaviruses: clade 1a SARS-CoV MA15 (n=391), clade 1b SARS-CoV-2 MA10 (n=274), and clade 2 HKU3-CoV MA (n=90). Quantitative trait loci (QTL) mapping in SARS-CoV- and SARS-CoV-2-infected F2 mice identified genetic loci associated with disease severity. Specifically, we identified seven loci associated with variation in outcome following infection with either virus, including one, HrS45, that is present in both groups. Three of these QTL, including HrS45, were also associated with HKU3-CoV MA outcome. HrS45 overlaps with a QTL previously reported by our lab that is associated with SARS-CoV outcome in CC011xCC074 F2 mice and is also syntenic with a human chromosomal region associated with severe COVID-19 outcomes in humans GWAS. The results reported here provide: (a) additional support for the involvement of this locus in SARS-CoV MA15 infection, (b) the first conclusive evidence that this locus is associated with susceptibility across the Sarbecovirus subgenus, and (c) demonstration of the relevance of mouse models in the study of coronavirus disease susceptibility in humans.

Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial.

BACKGROUND: No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. METHODS: This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. FINDINGS: 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. INTERPRETATION: Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. FUNDING: BioShin Limited. TRANSLATIONS: For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Advances in Management of the Stroke Etiology One-Percenters.

PURPOSE OF REVIEW: Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from "standard" care. RECENT FINDINGS: Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in "high-risk" patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of L-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance. Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.

Long-term treatment with lasmiditan in patients with migraine: Results from the open-label extension of the CENTURION randomized trial.

BACKGROUND: Following the CENTURION phase 3 randomized controlled trial's four-month double-blind phase, this 12-month open-label extension collected data for up to one year about dose optimization, patterns of use, migraine-related disability, and quality of life during lasmiditan treatment. METHODS: Migraine patients ≥18 years completing the double-blind phase and treating ≥3 migraine attacks could continue into the 12-month open-label extension. The initial oral lasmiditan dose was 100 mg; the dose could subsequently be adjusted to 50 mg or 200 mg at the investigator's discretion. RESULTS: 477 patients entered and 321 (72.1%) completed the extension; 445 (93.3%) treated ≥1 attack with lasmiditan. Of 11,327 attacks, 8654 (76.4%) were lasmiditan-treated (84.9% of these involved moderate or severe pain). By study end, 17.8%, 58.7%, and 23.4% of patients were taking lasmiditan 50, 100, and 200 mg, respectively. Mean improvements were observed in disability and quality of life. The most common treatment-emergent adverse event was dizziness (35.7% of patients, 9.5% of attacks). CONCLUSIONS: During this 12-month extension, lasmiditan was associated with a high rate of study completion, most attacks were treated with lasmiditan, and patients reported improvements in migraine-related disability and quality of life. No new safety findings were observed with longer exposure.Trial registration: ClinicalTrials.gov (NCT03670810); European Union Drug Regulating Authorities Clinical Trials Database (EUDRA CT: 2018-001661-17).

Vestibular migraine: a manifestation of long COVID syndrome in children.

Long COVID-19 syndrome has been reported among children and adolescents following COVID-19 recovery. Among them, notable symptoms include myalgia, insomnia, loss of smell and headache. Yet, novel manifestations are being discovered daily. Herein, we report two cases of vestibular migraine post-COVID-19 involving two children who presented with vestibular migraine symptoms following COVID-19 infection and their management. Children post-COVID-19 should be thoroughly evaluated for vestibular migraine symptoms so they can be managed promptly. This is the first article to report vestibular migraine as a manifestation of long COVID-19 syndrome.

The increasing role of electronic media in headache.

Most individuals with access to the internet use social media platforms. These platforms represent an excellent opportunity to disseminate knowledge about management and treatment to the benefit of patients. The International Headache Society, The European Headache Federation, and The American Headache Society have electronic media committees to promote and highlight the organizations' expertise and disseminate research findings. A growing mistrust in science has made dealing with infodemics (i.e., sudden access to excessive unvetted information) an increasing part of clinical management. An increasing role of these committees will be to address this challenge. As an example, recent studies have demonstrated that the most popular online content on migraine management is not evidence-based and is disseminated by for-profit organizations. As healthcare professionals and members of professional headache organizations, we are obliged to prioritize knowledge dissemination. A progressive social media strategy is associated not only with increased online visibility and outreach, but also with a higher scientific interest. To identify gaps and barriers, future research should assess the range of available information on headache disorders in electronic media, characterize direct and indirect consequences on clinical management, and recognize best practice and strategies to improve our communication on internet-based communication platforms. In turn, these efforts will reduce the burden of headache disorders by facilitating improved education of both patients and providers.

New Alzheimer Disease Drugs, Long COVID and the Central Nervous System, and a Nasal Spray for Migraines-Highlights From the 2023 American Academy of Neurology Conference.

This Medical News article discusses research presented at the recent American Academy of Neurology Conference.

Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic.

BACKGROUND: Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. OBJECTIVES: To review the impact of postponing BTX treatment on migraine control. METHODS: This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. RESULTS: The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). CONCLUSIONS: There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

ANTECEDENTES: Devido às medidas de resposta à pandemia de coronavirus disease 2019 (covid-19), a administração de toxina botulínica (TXB) foi adiada para muitos pacientes durante o primeiro confinamento em Portugal. OBJETIVOS: Avaliar o impacto do adiamento do tratamento com TXB no controle da enxaqueca. MéTODOS: Estudo retrospectivo unicêntrico. Foram incluídos pacientes com enxaqueca crônica com pelo menos três ciclos prévios de TXB e que tenham sido considerados respondedores. Os pacientes foram divididos em dois grupos, sendo um com atraso do tratamento (grupo P) e outro sem atraso (controles). O protocolo Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) foi utilizado. Dados clínicos relacionados com a enxaqueca foram obtidos na consulta inicial (T0) e nas três consultas subsequentes (T1­3). RESULTADOS: O presente estudo incluiu dois grupos, o grupo P (n = 30; 47,0 ± 14,5 anos; 27 mulheres, intervalo T0-1ª visita: 5,5 [4,1­5,8] meses) e o grupo controle (n = 6; 57,7 ± 13,2 anos; 6 mulheres; intervalo T0­1ª visita 3,0 [3,0­3,2] meses). Os grupos não apresentavam nenhuma diferença no início do estudo. Quando comparado à T0, o número de dias/mês com enxaqueca (5 [3­6,2] vs. 8 [6­15], p < 0,001), dias usando triptanos/mês (2,5 [0­6] vs. 3 [0­8], p = 0,027) e intensidade da dor (7 [5,8­10] vs. 9 [7­10], p = 0,012) foram maiores na primeira visita no grupo P, não apresentando os controles variação significativa. A piora dos indicadores relacionados com a enxaqueca diminuiu nas visitas seguintes; porém, mesmo na terceira visita, ainda não haviam retornado ao basal. As correlações foram significativas entre o atraso do tratamento e o aumento de dias/mês com enxaqueca na primeira consulta após o confinamento (r = 0,507; p = 0,004). CONCLUSãO: Houve piora clínica da enxaqueca após o adiamento do tratamento em correlação direta com a duração do atraso.

Long COVID and especially headache syndromes.

PURPOSE OF REVIEW: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache. RECENT FINDINGS: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine. Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms. SUMMARY: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.

Perceived Stress and Impact on Role Functioning in University Students with Migraine-Like Headaches during COVID-19.

Migraines, a chronic disease, can be debilitating in university students, affecting their academic performance, attendance, and social interactions. The purpose of this study was to identify the impact of COVID-19 on the role functioning and perceived stress levels of students suffering from migraine-like headaches. METHODS: Two identical cross-sectional surveys were sent to students in Fall 2019 and Spring 2021 at a mid-sized university in the U.S. The students were queried on the headache impact scale (HIT-6) and perceived stress scale (PSS-10). Associations between the migraine-like headaches, severity of the headaches, stress levels, and headache impacts on the individuals' role functioning were analyzed. RESULTS: The average age of the respondents (n = 721) was 20.81 ± 4.32 years in 2019 and (n = 520) 20.95 ± 3.19 years in 2021. A difference (p = 0.044) was found in the HIT-6 score <49 category. The other categories of the HIT-6 and the PSS-10 were not significant. CONCLUSIONS: During COVID-19, more students answered that their migraine-like headaches had lower impacts on their role functioning, thus suggesting that the students were having less severe migraines. A trend was seen for student's stress levels, indicating a decrease from 2019 to 2021. Furthermore, our results showed that the impact of headaches and stress levels slightly declined throughout the pandemic.

Reduced frequency of migraine attacks following coronavirus disease 2019: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 is a virus affecting different organs and causing a wide variety and severity of symptoms. Headache as well as loss of smell and taste are the most frequently reported neurological manifestations of coronavirus disease 2019 induced by severe acute respiratory syndrome coronavirus 2. Here we report on a patient with chronic migraine and medication overuse headache, who experienced remarkable mitigation of migraine following coronavirus disease 2019. CASE PRESENTATION: For many years prior to the severe acute respiratory syndrome coronavirus 2 infection, a 57-year-old Caucasian male suffered from very frequent migraine attacks and for control of headaches he had been taking triptans almost daily. In the 16-month period before the outbreak of coronavirus disease 2019, triptan was taken 98% of the days with only a 21-day prednisolone-supported triptan holiday, which, however, had no longer-lasting consequences on migraine frequency. Upon severe acute respiratory syndrome coronavirus 2 infection, the patient developed only mild symptoms including fever, fatigue, and headache. Directly following recovery from coronavirus disease 2019, the patient surprisingly experienced a period with largely reduced frequency and severity of migraine attacks. Indeed, during 80 days following coronavirus disease 2019, migraine as well as triptan usage were restricted to only 25% of the days, no longer fulfilling criteria of a chronic migraine and medication overuse headache. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection might be capable of triggering mitigation of migraine.

Cross-sectional, hospital-based analysis of headache types using ICHD-3 criteria in the Middle East, Asia, and Africa: the Head-MENAA study.

BACKGROUND: Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. METHODS: A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. RESULTS: Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients' mean age was 42.85 ± 14.89 (18-95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p < 0.001). CONCLUSIONS: The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions.

Serum alpha-CGRP levels are increased in COVID-19 patients with headache indicating an activation of the trigeminal system.

BACKGROUND: Headache is among the most frequent symptoms of acute COVID-19 infection. Its mechanisms remain obscure, but due to its migraine-like characteristics, the activation of the trigeminal system could account for its underlying pathophysiology. METHODS: Our aim was to compare the serum levels of CGRP, as a theoretical marker of trigemino-vascular activation, in 25 COVID-19 inpatients with lung involvement experiencing headache, against 15 COVID-19 inpatients without headache and with those of 25 matched healthy controls with no headache history. RESULTS: Morning serum alpha-CGRP levels, as measured by ELISA (Abbexa, UK), were increased in COVID-19 patients with headache (55.2±34.3 pg/mL) vs. controls (33.9±14.0 pg/mL) (p < 0.01). Alpha-CGRP levels in COVID-19 patients without headache were also significantly increased (43.3 ± 12.8 pg/mL; p = 0.05) versus healthy controls, but were numerically lower (-28.2%; p = 0.36) as compared to COVID-19 patients with headache. CONCLUSION: CGRP levels are increased in COVID-19 patients experiencing headache in the acute phase of this disease, which could explain why headache frequently occurs in COVID-19 and strongly supports a role for trigeminal activation in the pathophysiology of headache in this viral infection.

Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial.

BACKGROUND: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059). METHODS: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period. RESULTS: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard deviation) treatment duration of 233.6 (89.3) days. Treatment-emergent adverse events occurred in 62.5% of participants, with upper respiratory tract infection (5.5%), urinary tract infection (5.3%), nasopharyngitis (4.8%), sinusitis (3.6%), constipation (3.4%), and nausea (3.4%) occurring at ≥3%. Serious adverse events were observed in 3.4% of participants (none were treatment-related), and there were no deaths. Adverse events leading to discontinuation occurring at >0.1% were nausea (0.4%) and abdominal pain, vomiting, weight decrease, dizziness, and migraine (0.3% each). CONCLUSION: These results are consistent with atogepant's known safety profile and support long-term use of atogepant 60 mg once daily dosing as safe and well tolerated.ClinicalTrials.gov Registration Number: NCT03939312.

COVID-19 pandemic: Impact of quarantine on migraine and patients' care in Lithuania.

OBJECTIVE: there is a scarcity of data regarding the long-term (one year or more) impact of COVID-19 related quarantine on migraine burden. The aim of this cross-sectional study was to assess the impact of quarantine on migraine course, and the implications of a shift in migraine patients' care. METHODS: An anonymous online survey of 206 migraine patients in Lithuania was undertaken in April 2021. RESULTS: During quarantine, 42.2% of respondents reported migraine worsening, 17.0% - migraine improvement, and 40.8% reported no change. The most common causes of improvement specified by respondents were improved sleep, increased physical activity, and better eating habits. The most common reasons for migraine worsening were decreased physical activity, use of masks and respirators, and anxiety about own health. Logistic regression revealed that the changes in migraine course were associated not only with the migraine severity and educational level, but also with lifestyle alterations such as changes in sleep, the use of personal protective equipment, and increased home workload. A quarter of respondents were unable to consult a doctor. Patients who failed this started using more analgesics (65.0% and 55.0%, p = 0.004). Almost one-third of consultations were conducted over the telephone. Treatment changes were more common during face-to-face than remote consultations (63.6% and 18.2%, p = 0.009), however, the efficacy of treatment changes did not differ significantly (61.9% and 50.0%, p = 0.741). CONCLUSION: we found an overall rise in migraine burden because of lifestyle changes during the COVID-19 related quarantine. Inability to visit a doctor led to the emergence of remote consultations.

Triggers and clinical changes of childhood primary headache characteristics during COVID-19 pandemic lockdown.

OBJECTIVE: Children with primary headache are particularly vulnerable to the negative impacts of the pandemic due to factors like increased social isolation, disruption of sleep and impairment of healthy diet. We aimed to investigate the clinical changes and triggering factors for childhood primary headaches to demonstrate the impact of the pandemic lockdown. METHOD: Children aged between 60 months and 18 years with headache complaint attending the general outpatient clinic between December 2019 and December 2020 were included in the study. Patients were classified according to ICHD-3 regarding clinical and laboratory data. Primary headaches diagnosed before (December 2019-March 2020) and during the pandemic lockdown (April 2020-December 2020) were divided into two groups as migraine and tension-type headache (TTH). Clinical picture and triggering factors were compared between groups to illustrate the effect of the lockdown. RESULTS: The study included 612 subjects, with 463 patients (76%) classified in the primary headache group and 149 (24%) in the secondary headache group. Among the first group, 267 patients (58%) had migraine and 196 patients (42%) had TTH. Comparisons between before and during the pandemic lockdown showed significant increased frequency of TTH, but no difference in the frequency and duration of migraine. Both screen exposure and sleep pattern changes were found to be significantly increased in the TTH group during the pandemic lockdown. DISCUSSION: We found a significant increase in the attack frequency for TTH patients during the pandemic lockdown. Reduction in screen time is an important strategy in preventing primary headache attacks in children.