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BACKGROUND: Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) is a new avenue for treating migraine. The efficacy and safety of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention are unclear. METHODS: In a phase 2, double-blind, randomized, placebo-controlled trial, we enrolled adult participants (18 to 65 years of age) with migraine for whom two to four previous preventive treatments had failed to provide a benefit. The trial included a 4-week treatment period and an 8-week follow-up period. Participants were randomly assigned in a 2:1:2 ratio to receive a single-dose baseline infusion of 750 mg of Lu AG09222, 100 mg of Lu AG09222, or placebo. The primary end point was the mean change from baseline in the number of migraine days per month, during weeks 1 through 4, in the Lu AG09222 750-mg group as compared with the placebo group. RESULTS: Of 237 participants enrolled, 97 received 750 mg of Lu AG09222, 46 received 100 mg of Lu AG09222, and 94 received placebo. The mean number of baseline migraine days per month was 16.7 in the overall population, and the mean change from baseline over weeks 1 through 4 was -6.2 days in the Lu AG09222 750-mg group, as compared with -4.2 days in the placebo group (difference, -2.0 days; 95% confidence interval, -3.8 to -0.3; P = 0.02). Adverse events with a higher incidence in the Lu AG09222 750-mg group than in the placebo group during the 12-week observation period included coronavirus disease 2019 (7% vs. 3%), nasopharyngitis (7% vs. 4%), and fatigue (5% vs. 1%). CONCLUSIONS: In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 weeks. (Funded by H. Lundbeck; HOPE ClinicalTrials.gov number, NCT05133323.).

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Magnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3-8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches.

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BACKGROUND: Correctly diagnosing dizziness in children is essential for appropriate management; nevertheless, healthcare professionals face challenges due to children's limited ability to describe their symptoms and their cooperation during physical examination. The objective of this study is to describe the first 100 patients seen at a newly established pediatric vertigo center. METHODS: This is a retrospective review of a consecutive series of 100 patients seen at our pediatric vertigo clinic in a tertiary referral center from August 2019 until June 2022. Comprehensive clinical data were collected. The diagnoses were established by 2 pediatric otolaryngologists based on validated diagnostic criteria. Trends in diagnosis, investigation, and treatment of these patients were analyzed. RESULTS: A total of 100 children were included in the study. Vestibular migraine was the most common diagnosis (20%) followed by benign paroxysmal vertigo of childhood (14%). Eleven patients had combined pathologies. Fifteen out of 70 children (21%) had abnormal audiograms, 30 out of 48 children (62.5%) had abnormal vestibular testing, and 6 out of 31 (19%) patients had abnormal imaging. Fifty-one children received medical treatment, 23 received vestibular physiotherapy, and 9 patients had particle repositioning maneuvers; moreover, 17 of these patients received multimodal treatment. CONCLUSIONS: Our analysis suggests that imaging and audiology testing have relatively low yield in the assessment of pediatric vertigo. On the other hand, vestibular testing detected a high proportion of abnormalities, such as saccadic pursuit, vertical nystagmus, central positional nystagmus, and abnormal directional preponderance, particularly associated with vestibular migraine. Given the complexity of diagnosing vertigo in children, it is critical to establish multidisciplinary specialized centers capable of providing accurate diagnosis and treatment for these children.

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OBJECTIVE: Cortical spreading depolarization is one possible pathogenesis of migraine, of which slow neurophysiological change is barely recorded in conventional EEG settings. Using wide-band EEG conditions, we reappraised the features of EEG in migraineurs, including subdelta-band EEG changes. METHODS: This retrospective study included 144 patients with migraine. We delineated EEG of focal delta slow (FDS) (1-4 Hz) by time constant (TC) 0.3 s and focal subdelta slow (FSDS) (< 1 Hz) by TC 2 s. Relationships between clinical variables and EEG findings were evaluated. RESULTS: Of 144 patients, 39 had aura and 105 did not. FSDS and FDS were observed in 38 and 58 patients, respectively. No EEG was recorded during the aura. In multivariate analysis with the phase of migraine, family history, age, and percentage of sleep during EEG recording, the phase of migraine was related to the occurrence of FSDS (postdrome vs interictal, prodrome, and headache respectively (OR = 49.00 [95% CI = 3.89-616.66], 46.28 [2.99-715.78], 32.79 [2.23-481.96], p = 0.0026, 0.0061, 0.011). FDS was clinically unremarkable for differential evaluation. CONCLUSIONS: Wide-band EEG abnormality in migraineurs, i.e., FSDS, can be affected by migraine phase. SIGNIFICANCE: Wide-band EEG finding could be a biomarker related to clinical variables in migraines.

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OBJECTIVE: To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally. BACKGROUND: People in need of medical care for migraine should consult a health care professional knowledgeable in migraine management, obtain an accurate diagnosis, and receive an individualized treatment plan, which includes scientific society guideline-recommended treatments where appropriate. METHODS: The Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study was a cross-sectional, web-based survey conducted from July 2021 through March 2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States (US). Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria for migraine and had Migraine Disability Assessment Scale (MIDAS) scores of ≥ 6 (i.e., mild, moderate, or severe disability) were deemed to need medical care and were included in this analysis. Minimally effective treatment required that participants were currently consulting a health care professional for headache (barrier 1), reported an accurate diagnosis (barrier 2), and reported use of minimally appropriate pharmacologic treatment (barrier 3; based on American Headache Society 2021 Consensus Statement recommendations). Proportions of respondents who successfully traversed each barrier were calculated, and chi-square tests were used to assess overall difference among countries. RESULTS: Among 14,492 respondents with migraine, 8,330 had MIDAS scores of ≥ 6, were deemed in need of medical care, and were included in this analysis. Current headache consultation was reported by 35.1% (2926/8330) of respondents. Compared with the US, consultation rates and diagnosis rates were statistically significantly lower in all other countries except France where they were statistically significantly higher. Total appropriate treatment rates were also statistically significantly lower in all other countries compared with the US except France, which did not differ from the US. All 3 barriers were traversed by only 11.5% (955/8330) of respondents, with differences among countries (P < 0.001). CONCLUSIONS: Of people with migraine in need of medical care for migraine, less than 15% traverse all 3 barriers to care. Although rates of consultation, diagnosis, and treatment differed among countries, improvements are needed in all countries studied to reduce the global burden of migraine. TRIAL REGISTRATION: NA.

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Migraine is a chronic headache disorder. A prototype mobile app-based system was implemented to test data collection and improve data coverage for the Empatica E4 biometric sensor device. Results from the prototype testing are reported. Future iteration of the app will be tested with patients with migraine to predict events and potentially reduce event duration and therefore disease burden.

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Headache is the most common condition encountered in neurological practice. However, despite the burden to patients, migraine, a typical primary headache, is not life-threatening, and evaluation shows no abnormalities; therefore, it is often treated using analgesics. Moreover, patients often do not visit hospitals and clinics because over-the-counter analgesics, such as nonsteroidal anti-inflammatory drugs are easily available. However, many patients continue to experience headaches. Migraine therapy has progressed remarkably following the advent of calcitonin gene-related peptide antibody drugs in recent years. Many patients with migraine do not visit hospitals and clinics and do not receive appropriate treatment. Therefore, in the future, neurologists will need to play a key role in patient education and in training physicians to enable accurate diagnosis of headaches.

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BACKGROUND: Managing acute vertigo/dizziness for inpatients requires valid communication between the various healthcare professionals that triage such life-threatening presentations, yet there are no current scaling methods for managing such acute vertigo symptoms for inpatients. OBJECTIVE: To describe the development and validation of the Krems Acute Vertigo/Dizziness Scale (KAVEDIS), a new instrument for tracking subjective symptoms (vertigo, dizziness) and gait impairment across four unique vestibular diagnoses (Menière's disease, benign paroxysmal positional vertigo, peripheral vestibular hypofunction, and vestibular migraine) over a one-year period after inpatient hospital admission. METHODS: Retrospective data collection study from KAVEDIS scale and chart documentation. RESULTS: The KAVEDIS scale can significantly distinguish scores from admission to discharge in three of four vestibular diagnoses. The documented course of subjective vestibular symptoms and gait disturbances were correlated in all four groups. CONCLUSION: We suggest that KAVEDIS documentation among inpatients admitted with acute vertigo/dizziness may improve communication between the various intervening clinicians and help to raise concern in cases of symptomprogression.

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OBJECTIVE/BACKGROUND: Migraine is underdiagnosed. On average, medical students have approximately 3 h of exposure to headache education throughout medical school training. Moreover, some medical students have racially-based biases in pain. There is a paucity of underrepresented in medicine (UIM) headache practitioners. UIM practitioners are more likely to practice in underserved communities and provider-patient ethnic concordance may help eliminate healthcare disparities. The Student National Medical Association (SNMA) is an organization committed to supporting current and future UIM medical students and addressing the needs of underserved communities. The goal of this project was to develop and deliver a brief Migraine Diagnosis and Disparities Undergraduate Medical Education Program (MD2UMEP) to increase awareness of migraine diagnosis and disparities in UIM medical students in the SNMA. METHODS: For connecting/relationship-building with SNMA, the SNMA Region V website was reviewed. Calls were made to Wayne State University School of Medicine (WSUSOM) Office of Diversity, Equity, and Inclusion (ODEI) explaining the educational initiative with subsequent emails to the Director of WSUSOM's ODEI followed by a video-conference meeting (VCM). VCMs were conducted with two SNMA member leaders from WSUSOM. A local and regional presentation/delivery of the MD2UMEP was planned. Communication was maintained electronically. For development/delivery of the MD2UMEP, headache literature was reviewed for key concepts underpinning migraine diagnosis and migraine disparities with a focus on African Americans. Slides with talking points were developed with references. Pre- and posttest questions were drafted and made accessible via a QR code. The MD2UMEP was presented and students completed the questionnaires. Descriptive statistics were used to quantify responses. RESULTS: The MD2UMEP work began July 31, 2021, with program delivered in final form on October 1, 2022. A professional relationship was established with SNMA leadership. A MD2UMEP was developed then administered at the 2022 SNMA Region V Medical Education Conference. Headache medicine was introduced to UIM SNMA medical students. Anonymously, nine individuals responded to the MD2UMEP pretest questions. Eight individuals answered the posttest questions. At the program's conclusion, UIM student performance improved on seven of 10 test questions on migraine diagnosis and disparities and remained at 100% on one of 10 test questions. On two of the questions, the number correct remained the same (although percentage overall increased due to the smaller denominator). There was a higher proportion of correct responses on the posttest. CONCLUSIONS: There is great need for migraine diagnosis and disparities education among medical students. A new migraine diagnosis and disparities program was developed for medical students. SNMA members were receptive to the MD2UMEP and it strengthened their knowledge of migraine diagnosis and disparities. This program exposed UIM medical students to headache medicine.

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BACKGROUND: To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments. METHODS: Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0. RESULTS: Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies. CONCLUSIONS: This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.

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BACKGROUND: The Migraine Disability Assessment (MIDAS) is widely used. However, there are limited data on how much a reduction in the MIDAS score indicates a change that matters to the patient. METHODS: Data from the DMKG (i.e. German Migraine and Headache Society) Headache Registry were used to determine the minimal important difference (MID) of the MIDAS, using the Patient Global Impression of Change (PGIC) as anchor and applying average change and receiver operating characteristic curve methods. RESULTS: In total, 1218 adult migraine patients (85.6% female, 40.2 ± 12.8 years, baseline MIDAS 44.2 ± 47.4, follow-up MIDAS 36.5 ± 45.3) were included. For patients with baseline MIDAS >20 (MIDAS grade IV, n = 757), different methods using PGIC "somewhat improved" as anchor yielded percent change MIDs of the MIDAS between -29.4% and -33.2%. For baseline MIDAS between 6 and 20 (grades II and III, n = 334), using PGIC "much improved" as anchor, difference change MIDs were between -3.5 and -4.5 points. CONCLUSIONS: Based on the above results, we estimated the MID of the MIDAS at -30% for patients with a baseline MIDAS >20, and at -4 points for those with a baseline MIDAS of 6-20, for a tertiary headache care population. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

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BACKGROUND: Red Ear Syndrome is a burning sensation and erythema of the ear, associated with a various number of disorders including migraine, trigeminal neuralgia, autoimmune disorders etc. Theories for RES pathophysiology have developed from current understandings of comorbid conditions. Characterizing the underlying mechanism of RES is crucial for defining effective treatments. CASE PRESENTATION: Three caucasian patients, ages 15, 47, and 67 years, with migraine, one with erythromelalgia are reported in this manuscript. RES pathophysiology is not fully understood due to its variable clinical presentation and numerous comorbid conditions, making it difficult to identify effective treatments. CONCLUSION: RES seems to be largely treatment-resistant, and most options involve treating the associated disorders and minimizing pain. Further investigation of future cases should lead to a more comprehensive understanding of the fundamental cause of RES and, hopefully, successful treatments.

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Objective: To investigate the disease composition, clinical features, diagnosis, and treatment characteristics of vertigo in children. Methods: A total of 120 children with vertigo diagnosed and treated in the Department of Otorhinolaryngology, Children's Hospital, Capital Institute of Pediatrics in Beijing from February 2018 to February 2022 were retrospectively analyzed to explore the clinical characteristics of common peripheral vertigo in children and to summarize the experience of diagnosis and treatment. Results: The etiological composition of 120 cases of vertigo in children are as follows: 63 (52.5%) cases of vestibular migraine of childhood (VMC), 19 (15.8%) of recurrent vertigo of childhood (RVC), 11 (9.2%) of probable vestibular migraine of childhood (PVMC), 10 (8.3%) of secretory otitis media (SOM), 6 (5.0%) of persistent postural-perceptual dizziness (PPPD), 4 (3.3%) of benign paroxysmal positional vertigo (BPPV), 2 (1.7%) of vestibular neuritis (VN), 2 (1.7%) of Meniere's disease (MD), 2 (1.7%) of inner ear malformation (IEM), and 1 (0.8%) of vestibular paroxysmal syndrome (VP).The major cause of vertigo in children of different ages was different. SOM was the most important cause in preschool children, followed by RVC and VMC; VMC was the most important cause in school-age children, followed by RVC; and MD and BPPV were exclusive found in adolescents. The incidence rate of PPPD was higher in adolescents than in preschool and school-age children. Children with vertigo had good prognosis in general. Conclusions: VMC, RVC and SOM are the most common causes in vertigo in children, and their proportion was different in different aged children. Transforming abstract feelings into specific information is the skill required for collecting medical history of children with vertigo. Considering the age and cooperation of children, appropriate hearing and vestibular examination techniques are recommended. We should pay more attention to the mental health of children with vertigo and their parents.

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West Nile Virus (WNV) infection is a clinical picture that is transmitted from wild birds, its natural host, to humans through mosquitoes and generally shows an asymptomatic course. Influenza-like WNV fever is frequently seen in symptomatic individuals, and a neuroinvasive course is more rarely observed. Neuroinvasive WNV has a broad-spectrum profile of neurological signs and symptoms. WNV meningitis is one of the most common neuroinvasive forms of WNV, and it does not differ clinically and radiologically from other viral meningitis. Secondary headaches, which can mimic primary headaches, are an infectious factor that should be kept in mind in the etiology, especially in cases presenting in the summer months. In this study, a case of WNV meningitis presenting with a headache of migrainous character is presented.

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BACKGROUND: Pediatric headache is an increasing medical problem that has adverse effects on children's quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains. METHODS: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache. RESULTS: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache. CONCLUSIONS: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification. TRIAL REGISTRATION: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

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