Search

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.5% male) aged 5 to 16 on the Standardized Assessment of Concussion (SAC/SAC-Child), modified Balance Errors Scoring System (mBESS), Timed Tandem Gait (TTG), and the King-Devick Test (KDT) are provided. A total of 212 non-injured athletes repeated the measures post-season to assess test-retest reliability. Mean performance on the SAC-C, mBESS, TTG, and KDT tended to improve with age. KDT was the only measure that demonstrated good to excellent stability across age ranges (ICC = 0.758 to 0.941). Concentration was the only SAC/SAC-C subtest to demonstrate moderate test-retest stability (ICC = 0.503 to 0.706). TTG demonstrated moderate to good (ICC = 0.666 to 0.811) reliability. mBESS demonstrated poor to moderate reliability (ICC = -0.309 to 0.651). Commonly used measures of concussion vary regarding test-retest reliability in youth. The data support the use of at least annual sport concussion baseline assessments in the pediatric population to account for the evolution in performance as the child ages. Understanding the variation in the stability and the evolution of baseline performance will enable improved identification of possible injury.

Background: High-frequency headache/migraine (HFM) and overuse of acute medication (medication overuse [MO]) are associated with increased disability and impact. Experiencing both HFM and MO can potentially compound impacts, including stigma; however, evidence of this is limited. The objective of this report was to evaluate self-reported stigma, health-related quality of life (HRQoL), disability, and migraine symptomology in US adults with HFM + MO from the Harris Poll Migraine Report Card survey., Methods: US adults (≥ 18 yrs., no upper age limit) who screened positive for migraine per the ID Migraine™ screener completed an online survey. Participants were classified into "current HFM + MO" (≥ 8 days/month with headache/migraine and ≥ 10 days/month of acute medication use over last few months) or "previous HFM + MO" (previously experienced HFM + MO, headaches now occur ≤ 7 days/month with ≤ 9 days/month of acute medication use). Stigma, HRQoL, disability, and most bothersome symptom (MBS) were captured. The validated 8-item Stigma Scale for Chronic Illnesses (SSCI-8) assessed internal and external stigma (scores ≥ 60 are clinically significant). Raw data were weighted to the US adult population. Statistically significant differences were determined by a standard t-test of column proportions and means at the 90% (p < 0.1) and 95% (p < 0.05) confidence levels., Results: Participants (N = 550) were categorized as having current (n = 440; mean age 41.1 years; 54% female; 57% White, not Hispanic; 24% Hispanic; 11% Black, not Hispanic) or previous (n = 110; mean age 47.2 years; 49% female; 75% White, not Hispanic; 13% Hispanic; 4% Black, not Hispanic) HFM + MO. Compared to those with previous HFM + MO (21%), adults with current HFM + MO were more likely to experience clinically significant levels of stigma (47%). Men with current HFM + MO (52% compared to men with previous HFM + MO [25%] and women with current [41%] or previous [18%] HFM + MO), non-Hispanic Black (51% compared to White, not Hispanic [45%] and Hispanic [48%] current HFM + MO groups and White, not Hispanic previous HFM + MO [12%]), current HFM + MO aged 18-49 years (50% compared to those with current HFM + MO aged ≥ 50 years [33%] and those with previous HFM + MO aged 18-49 [34%] and ≥ 50 years [4%]), and employed respondents (53% current and 29% previous compared to those not employed [32% current and 12% previous]) reported higher rates of clinically significant stigma. Those with current HFM + MO were more likely to have worse HRQoL and disability due to headache/migraine. Respondents aged ≥ 50 years with current HFM + MO were more likely than respondents aged 18-49 years with current HFM + MO to indicate that their overall quality of life (66% vs. 52%) and their ability to participate in hobbies/activities they enjoy were negatively impacted by headache/migraine (61% vs. 49%). Pain-related symptoms were identified as the MBS., Conclusions: Together these data suggest that current and previous HFM + MO can be associated with undesirable outcomes, including stigma and reduced HRQoL, which were greatest among people with current HFM + MO, but still considerable for people with previous HFM + MO., (© 2024. The Author(s).)

Objective: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit., Background: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders., Methods: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation., Results: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338)., Conclusions: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice., (© 2024 American Headache Society.)

Objective: To investigate factors affecting the efficacy and tolerability of verapamil for migraine prevention using individual pharmacogenomic phenotypes., Background: Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual., Methods: This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the doses of verapamil for migraine prevention were assessed., Results: Our final analysis included 33 migraine patients (82% with aura). The mean minimum effective and maximum tolerable doses of verapamil were 178.2(20-320) mg and 227.9(20-480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status., Conclusions: We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Migraine is a disabling neurologic disease that can fluctuate over time in severity, frequency, and acute medication use. Harris Poll Migraine Report Card was a US population-based survey to ascertain quantifiable distinctions amongst individuals with current versus previous high-frequency headache/migraine and acute medication overuse (HFM+AMO). The objective of this report is to compare self-reported experiences in the migraine journey of adults with HFM+AMO to those who previously experienced HFM+AMO but currently have a sustained reduction in headache/migraine frequency and acute medication use., Methods: An online survey was available to a general population panel of adults (≥18 years) with migraine per the ID Migraine™ screener. Respondents were classified into "current HFM+AMO" (within the last few months had ≥8 headache days/month and ≥10 days/month of acute medication use; n=440) or "previous HFM+AMO" (previously had HFM+AMO, but within the last few months had ≤7 headache days/month and ≤9 days/month of acute medication use; n=110). Survey questions pertained to demographics, diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment., Results: Participants in the current HFM+AMO group had 15.2 monthly headache days and 17.4 days of monthly acute medication use in last few months compared to 4.2 and 4.1 days for the previous HFM+AMO group, respectively. Overall, current preventive pharmacologic treatment use was low (15-16%; P>0.1 for current vs previous) in both groups. Previous HFM+AMO respondents reported better current acute treatment optimization. More respondents with current (80%) than previous HFM+AMO (66%) expressed concern with their current health (P<0.05). More than one-third of both groups wished their HCP better understood their mental/emotional health (current 37%, previous 35%; P>0.1 for current vs previous) and 47% (current) to 54% (previous) of respondents worried about asking their HCP too many questions (P>0.1 for current vs previous)., Conclusion: Apart from optimization of acute medication, medical interventions did not significantly differentiate between the current and previous HFM+AMO groups. Use of preventive pharmacological medication was low in both groups. Adults with current HFM+AMO more often had health concerns, yet both groups expressed concerns of disease burden. Optimization of acute and preventive medication and addressing mental/emotional health concerns of patients are areas where migraine care may impact outcomes regardless of their disease burden., (© 2024. The Author(s).)

What Is This Summary About?: The Harris Poll Migraine Report Card was a survey about people's experiences and challenges with headaches and migraine. The survey was conducted from December 9, 2021, to January 10, 2022, in the United States. The people who took the survey had frequent headaches/migraine attacks (on 8 or more days per month) and used acute headache/migraine medication to relieve head pain and other symptoms (on 10 or more days per month). This summary focuses on the responses of adults with frequent headaches and frequent acute medication use at the time of the survey or within the few months (not specified) before the survey (and not those who previously had frequent headaches and frequent acute medication use at some point in their life prior to the survey). The group of people who took the survey will be called 'respondents'. The term 'headaches' can mean any type of headache including as part of a migraine attack, a tension type headache, or another unknown headache type. All respondents screened positive for having migraine, so many of the headaches they reported on may have been a migraine headache or part of a migraine attack., What Were the Results?: Over 50% of respondents said their headaches affected their overall quality of life. Many respondents wished their healthcare provider who was managing their headaches understood more about how headaches affect their mental well-being, how much pain their headaches cause, and why they get headaches. 80% of respondents had concerns about their overall health. Over 60% of respondents said they have experienced anxiety and/or depression. In this survey, although all respondents were eligible to receive a preventive headache/migraine medication because of their headache frequency, only 15% were taking one., What Do the Results of the Survey Mean?: The findings from this survey showed many ways that headaches/migraine care can improve, including talking about mental and emotional well-being, making sure the treatment plan works and does not have side effects that cannot be tolerated, and trying to prevent headaches/migraine from occurring.

The International Neuromodulation Society defines therapeutic neuromodulation as the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body. Neuromodulation for the treatment of migraine is an evolving field offering further insight into the pathophysiology of migraine as well as advanced therapeutics. Central and peripheral neuronal targets have been explored in the efforts to reduce the frequency and severity of attacks. Invasive and noninvasive techniques have been developed, targeting either the central or peripheral nervous system. Noninvasive central neuromodulation techniques have the benefit of a low side effect profile in addition to higher level of evidence for use thanks to sham-controlled trials; however, these modalities are less clinically available for use. Noninvasive transcutaneous neuromodulation techniques that target the peripheral nervous system have provided devices that are available over the counter or by prescription. Several of these devices are effective for abortive and preventive treatment of migraine. Invasive techniques such as cranial nerve stimulation with implanted stimulator devices or spinal cord stimulation may be used for more aggressive management in patients refractory to other treatments. Overall, neuromodulation techniques can be particularly beneficial for medically complex or refractory patients, those that prefer nonmedication options, and those that have experienced adverse effects from medications., (Copyright © 2024 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Eptinezumab demonstrated efficacy in adults with migraine and prior preventive treatment failures in the placebo-controlled phase of the DELIVER clinical trial; its long-term effectiveness in this population has not yet been reported. The objective of this study was to evaluate the long-term effectiveness of eptinezumab in a migraine patient population during the 48-week extension phase of DELIVER., Methods: DELIVER was conducted June 1, 2020 to September 15, 2022. 865 adults with migraine, with documented evidence of 2-4 prior preventive migraine treatment failures and with completion of the 24-week placebo-controlled period of DELIVER received eptinezumab (100 or 300 mg) during the dose-blinded extension, either continuing their randomized dose or, if originally receiving placebo, were randomized 1:1 to an eptinezumab dose (100 or 300 mg). A mixed model for repeated measures was used to evaluate changes from baseline in the number of monthly migraine days (MMDs)., Results: Of 865 patients entering the extension (eptinezumab 100 mg, n = 433; 300 mg, n = 432), 782 (90.4%) completed and 11 (1.3%) discontinued due to an adverse event. Eptinezumab was associated with early and sustained reductions in migraine frequency. Mean MMDs at baseline were approximately 14 days across groups. Mean (standard error) change from baseline in MMDs over the final dosing interval (weeks 61-72) was -6.4 (0.50) with placebo/eptinezumab 100 mg, -7.3 (0.49) with placebo/eptinezumab 300 mg, -7.1 (0.39) with eptinezumab 100 mg, and -7.0 (0.39) with eptinezumab 300 mg. During weeks 61-72, 63-70% of patients demonstrated ≥ 50% reduction in MMDs, and 36-45% demonstrated ≥ 75% reduction. Headache severity and acute medication use reductions, and patient-reported improvements in most bothersome symptom, disease status, quality of life, and work productivity, were observed. Adverse events were generally mild, transient, and similar in frequency/type to previous eptinezumab trials., Conclusions: The long-term effectiveness and safety/tolerability of eptinezumab in patients with migraine and 2-4 prior preventive treatment failures was demonstrated by high completion rates and migraine-preventive benefits sustained for up to 18 months, implying that eptinezumab is a viable long-term treatment option for patients still seeking successful migraine treatments., Trial Registration: ClinicalTrials.gov (Identifier: NCT04418765; URL: https://www., Clinicaltrials: gov/ct2/show/NCT04418765 ); EudraCT (Identifier: 2019-004497-25; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25 )., (© 2023. The Author(s).)

What Is This Summary About?: This is a summary of three articles describing preventive treatment of migraine in participants with a diagnosis of both chronic migraine and medication-overuse headache in a study called PROMISE-2 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy-2). People living with chronic migraine and medication-overuse headache have one of the most disabling, costly, and difficult-to-treat headache disorders., What Were the Results?: After preventive migraine treatment with eptinezumab (trade name Vyepti), participants with chronic migraine and medication-overuse headache experienced fewer migraine days, a reduced severity of migraine attacks, and a reduced use of acute medication. More participants receiving eptinezumab treatment no longer met the definition of either chronic migraine or medication-overuse headache throughout the study when compared with those receiving placebo., What Do the Results Mean?: Eptinezumab is beneficial for people who often use acute medication(s) due to frequent headache episodes or migraine attacks.

Migraine is a global neurologic disease that is highly prevalent, especially in women. Studies have observed a predisposition for the development of migraine in women, although the mechanisms involved have yet to be fully elucidated. This review aimed to summarize the recent evidence regarding the epidemiology, pathophysiology, and treatment of migraine and highlight key sex differences. We also identify gaps in care for both women and men living with migraine and discuss the presence of migraine-related stigma and how this may impact the efficacy of clinical care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Migraine is a highly prevalent, disabling neurological disorder that is also associated with gastrointestinal symptoms, autonomic dysfunction and allodynia. Despite the availability of multiple acute agents for migraine, an unmet need remains for effective, well-tolerated drugs that are nonoral and noninvasive. Here, we provide a drug evaluation of INP104, a novel drug-device combination product of dihydroergotamine (DHE) mesylate - a molecule with a long history of efficacy familiar to headache specialists - which is delivered to the difficult-to-reach upper nasal space where it is rapidly and consistently absorbed via Precision Olfactory Delivery (POD ® ). In clinical trials, INP104 exhibited favorable pharmacokinetics, a well-tolerated safety profile, and rapid symptom relief, highlighting its potential as a suitable acute therapy for migraine.

Background: The efficacy and safety of eptinezumab for preventive migraine treatment in adults have been demonstrated in multiple, large-scale clinical trials. This non-interventional, retrospective, observational chart review was conducted to examine patient response to eptinezumab 100 mg or 300 mg every 12 weeks for 6 months in the clinical setting., Methods: Eight headache specialists who reported early clinical experience with eptinezumab enrolled the first adults (1-6 adults per clinician; age ≥ 18 years) who met predefined selection criteria (including ≥ 12-month history of migraine, ≥ 4 migraine days/month prior to eptinezumab initiation, receipt of ≥ 2 consecutive eptinezumab doses, and ≥ 12-week follow-up period), and provided detailed patient, disease, treatment, and outcome information via SurveyMonkey and standardized case-report forms., Results: Charts from 31 adults (median age, 49 years) with migraine (93.6% chronic) who received eptinezumab for the preventive treatment of migraine were reviewed. Most patients (26/31 [83.9%]) were initiated at 100 mg. Eptinezumab reduced mean headache frequency (24.3 monthly headache days [MHDs] at baseline; 17.1 MHDs at Month 6); mean migraine frequency (17.3 monthly migraine days [MMDs] at baseline; 9.1 MMDs at Month 6); attack severity (17/31 [54.8%] patients); acute headache medication use (12.5 acute medication days at baseline; 7.4 at Month 6); and patient-reported disability (11/22 [50.0%] severe at baseline; 7/19 [36.8%] at Month 6). More than three-quarters of patients (24/31 [77.4%]) perceived improved disability/function and most (30/31 [96.8%]) perceived eptinezumab to be well tolerated after 6 months. Most of the headache specialists reported that eptinezumab was well tolerated by patients (30/31 [96.8%]) and that the intravenous infusion experience was not challenging., Conclusions: Patients with migraine who received 6 months of preventive treatment with eptinezumab experienced reductions in migraine and headache frequency, disability, and acute medication use during the course of treatment., (© 2023. The Author(s).)

Objective: The aim of this study was to compare the association between migraine and sleep quality in premenopausal versus perimenopausal women., Methods: A cross-sectional analysis from the Data Registry on the Experiences of Aging, Menopause and Sexuality was conducted using questionnaire data from premenopausal and perimenopausal women seen at women's health clinics at 3 geographic locations from 2015 to 2021. Sleep quality and duration were assessed with the Pittsburgh Sleep Quality Index. Associations between poor sleep quality (Pittsburgh Sleep Quality Index >5) and self-reported migraine history (Y/N) were evaluated using a multivariable logistic regression model, adjusting for body mass index, anxiety, depression, and vasomotor symptoms., Results: Of 2,067 women (mean age 43.2 years) included in the analysis, 594 (28.7%) reported a migraine history. Women were mostly white (92.2%), partnered (75.1%), and educated (86% with at least some college); 46.5% (n = 962) were premenopausal, 53.5% (n = 1,105) were perimenopausal, and 71.2% met the criteria for poor sleep. In univariate analysis, migraine history predicted poor sleep in both premenopausal and perimenopausal women ( P = 0.005 and P = 0.004, respectively). However, in multivariable analysis, migraine history remained associated with poor sleep in premenopausal women ( P = 0.044), but not in perimenopausal women ( P = 0.46)., Conclusions: A migraine history was associated with poor sleep in premenopausal women. The relationship in perimenopausal women seemed to be influenced by confounding factors that are more prevalent during the menopause transition and are known to affect the frequency of migraine and sleep disturbances, such as anxiety, depression, and vasomotor symptoms. These conditions may need to be the focus of management in migraineurs with sleep disturbances during the menopause transition., Competing Interests: Financial disclosure/conflicts of interest: J.M.K. has received past funding from Proctor and Gamble and Triangle Insights group. A.J.S. receives consulting fees from AbbVie, Allergan, Amgen, Axsome Therapeutics, Eli Lilly and Company, Everyday Health, Impel, Lundbeck, Med-IQ, Medscape, Neurolief, Novartis, Satsuma, Teva, and Theranica. E.K. has no conflicts of interest directly related to the subject of this manuscript. However, over the past 36 months, she has had the following conflicts of interest. She has been a consultant for Astellas and Mithra Pharmaceuticals, Scynexis, and Womaness. She receives grant support form Mithra Pharmaceuticals. She has received payment for development of educational content from Med Learning Group and Academy of Continued Healthcare Learning. She has received honoraria for CME activity from CogniMed, PriMed and OBG Management. E.K.'s times is partially supported by the NIA grant U54 AG044170. The other authors have nothing to disclose., (Copyright © 2023 by The North American Menopause Society.)

Objective: To evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH)., Background: MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect., Methods: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36)., Results: A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was "much" or "very much" improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores., Conclusions: This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes., (© 2023 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Patients with chronic migraine (CM) treated with eptinezumab in the PROMISE-2 trial achieved greater reductions in migraine and headache frequency, impact, and acute headache medication (AHM) use than did patients who received placebo. This post hoc analysis examines relationships between headache frequency reductions and changes in AHM use in patients in PROMISE-2., Methods: PROMISE-2 was a double-blind, placebo-controlled trial conducted in adults with CM. Patients were randomized to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously once every 12 weeks for up to two doses. Patients recorded headache/AHM information daily and for each event in an electronic diary; data from all days with daily reports were included. Shifts in headache frequency and AHM use were assessed in the three populations: total CM population, patients with CM and medication-overuse headache (MOH), and patients with CM and MOH who were ≥ 50% responders during treatment (response over weeks 1-24)., Results: A total of 1072 adults with CM received treatment (eptinezumab, n = 706; placebo, n = 366). Mean baseline headache frequency was 20.5 days; mean baseline AHM days was 13.4; 431 patients had MOH, of which 225 (52.2%) experienced ≥50% response over weeks 1-24. Relative to baseline, the proportion of days with both headache and AHM use decreased 25.1% (eptinezumab) versus 17.0% (placebo) in the total population (N = 1072), 29.2% versus 18.4% in the MOH subpopulation (n = 431), and 38.3% versus 31.5% in the CM with MOH population with ≥50% response subgroup (n = 225) during weeks 1-24. The proportion of days with headache and triptan use decreased 9.1% (eptinezumab) versus 5.8% (placebo), 11.8% versus 7.2%, and 14.5% versus 12.6%, respectively. Reductions in other AHM types were smaller., Conclusions: In this post hoc analysis, eptinezumab use in patients with CM was associated with greater decreases in days with headache with AHM overall and with triptans in particular. The magnitude of effect was greater in the subgroup of CM patients with MOH and ≥ 50% response., Trial Registration: ClinicalTrials.gov Identifier: NCT02974153 . Eptinezumab reduces headache frequency and acute medication use in patients with chronic migraine., (© 2022. The Author(s).)

Background:  Vestibular migraine (VM) is one of the common causes of episodic dizziness, but it is underdiagnosed and poorly understood. Previous research suggests that otolith reflex pathway performance is often impaired in this patient group, leading to altered perception of roll plane stimuli. Clinically, this perception can be measured with subjective visual vertical (SVV) testing., Purpose:  The aim of this study is to compare static SVV performance (absolute mean SVV tilt, variance) in a cohort of patients diagnosed with VM to results obtained from clinically derived normative data., Study Design:  Retrospective case review., Study Sample:  Ninety-four consecutive patients between 18 and 65 years of age diagnosed with VM were included in this comparison to clinically derived normative data., Data Collection and Analysis:  Retrospective chart review was completed. Demographic data, symptom report, and vestibular laboratory results were documented. SVV performance was documented in terms of absolute mean SVV tilt and response variance., Results:  Abnormal mean SVV tilt was described in 54% ( n  = 51) of patients with VM. Including abnormal response variance increased those identified with abnormal presentation to 67% ( n  = 63). Laboratory findings were insignificant for semicircular canal function, but of those with abnormal ocular vestibular myogenic potential results ( n  = 30), 77% ( n  = 23) demonstrated both abnormal SVV and utriculo-ocular reflex performance. There were no associations noted for SVV performance and demographic or other self-report variables., Conclusion:  Absolute mean SVV tilt and response variance are often abnormal in patients diagnosed with VM. These findings support theories suggesting atypical intralabyrinthine integration within the vestibular nuclei and cerebellar nodular pathways., Competing Interests: None declared., (American Academy of Audiology. This article is published by Thieme.)

Objective: The purpose of this study was to characterize cutaneous heat and light-induced pain thresholds in people with post-traumatic headache (PTH) compared with healthy controls (HCs)., Background: Photophobia and allodynia are common in PTH, and there is emerging evidence to support multimodal sensory dysfunction., Methods: In this age- and sex-matched cohort study, individuals with PTH (n = 20) and HCs (n = 20), aged 18-65 years, were recruited from an institutional database of research volunteers, from the concussion clinic, and via the use of approved flyers posted on the Mayo Clinic Campus in Scottsdale, Arizona. Participants were assessed using the Allodynia Symptom Checklist (ASC-12), Photosensitivity Assessment Questionnaire (PAQ), State Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). Quantitative sensory testing quantified heat pain thresholds. A light stimulation device quantified light-induced pain thresholds. Subsequently, heat pain thresholds were obtained immediately, 10, and 40 min after a bright light stressor., Results: The mean photophobia symptom severity score, based on the PAQ, was higher in participants with PTH compared with HCs, mean 0.62 (SD = 0.25) versus mean 0.24 (SD = 0.24), p < 0.001. Light-induced pain thresholds were lower in participants with PTH (median = 90.5 lux and quartiles = 17.8 to 378.5) compared with HCs (median = 863.5 lux and quartiles = 519.9 to 4906.5) and were independent from BDI and STAI (p < 0.001). Allodynia scores did not differ between participants with PTH and HCs after adjusting for BDI and STAI scores. Baseline forehead heat pain thresholds were not different, participants with PTH mean 41.9°C (SD = 0.89) versus HCs mean 44.3°C (SD = 0.89), p = 0.061; however, forearm heat pain thresholds were lower in participants with PTH compared with HCs, mean 40.8°C (SD = 0.80) versus mean 44.4°C (SD = 0.80), p = 0.002. The forehead heat pain threshold change from baseline post bright light stressor in participants with PTH versus HCs was different immediately (mean -1.2 (SD = 0.53), p = 0.025), 10 min (mean -1.8 (SD = 0.74), p = 0.015), and 40 min (mean -1.8 (SD = 0.88), p = 0.047). The forearm heat pain threshold change immediately post bright light stressor in participants with PTH versus HCs was different, mean -1.9°C (SD = 0.58), p = 0.001, however, not different at 10 and 40 min., Conclusions: Photophobia is higher and light-induced pain thresholds are lower in participants with PTH. Exposure to a light stressor reduced heat pain thresholds in participants with PTH immediately post bright light stressor, but not in HCs. This study provides evidence for multimodal sensory dysfunction in people with PTH., (© 2022 American Headache Society.)

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2-8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904 ., (© 2022. The Author(s).)

Objective: This post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE-2 study., Background: Eptinezumab, a monoclonal antibody that inhibits calcitonin gene-related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE-2 patients diagnosed with both CM and MOH., Methods: The phase 3, double-blind, placebo-controlled PROMISE-2 study (NCT02974153) randomized adults with CM to eptinezumab 100 mg, 300 mg, or placebo (administered intravenously every 12 weeks for up to two doses). MOH was prospectively diagnosed at screening by trained physicians based on 3 months of medication history and International Classification of Headache Disorders-3β criteria. This post hoc analysis evaluated changes in total and class-specific days of AHM usage, the percentage of patients using AHM at or above MOH diagnostic thresholds, and the percentage of patients experiencing monthly headache and migraine day frequency below diagnostic thresholds for MOH and/or CM., Results: In PROMISE-2, 431/1072 (40.2%) patients with CM were diagnosed with MOH (eptinezumab 100 mg, n = 139; 300 mg, n = 147; placebo, n = 145) and were included in this analysis. Total monthly AHM use decreased from 20.6 days/month at baseline to 10.6 days/month over 24 weeks of treatment (49% decrease) with eptinezumab 100 mg, from 20.7 to 10.5 days/month (49% decrease) with eptinezumab 300 mg, and from 19.8 to 14.0 days/month (29% decrease) with placebo. Numerically greater decreases from baseline with eptinezumab were also observed for individual drug classes. In each study month, the percentages of patients who were below MOH thresholds were numerically higher for both eptinezumab doses compared with placebo, as were the percentages of patients experiencing headache and migraine frequency below CM thresholds. Of patients with available data across the entire treatment period, 29.0% (58/200) of patients treated with eptinezumab stopped meeting and remained below diagnostic thresholds for both CM and MOH during Weeks 1-24, as well as 6.3% (6/96) of patients who received placebo., Conclusions: Across 24 weeks of treatment, eptinezumab reduced AHM use in patients diagnosed with CM and MOH. More than one-fourth (29%) of patients treated with eptinezumab did not meet the diagnostic thresholds for either CM or MOH for the entire treatment period., (© 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: To assess the real-world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center., Background: The efficacy and safety of ubrogepant for the acute treatment of migraine were established in phase 3 randomized controlled trials. However, there is no real-world data of patient experience with ubrogepant in a population in which the majority of patients have chronic migraine, multiple prior unsuccessful treatments, complex medical comorbidities, and concurrent use of other migraine-specific medications., Method: This was a post-market 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. Demographic information and additional headache history were obtained from chart review., Results: We obtained eligible questionnaire responses from 106 patients. Chronic migraine accounted for 92/106 (86.8%) of the population. Complete headache freedom (from mild/moderate/severe to no pain) and headache relief (from moderate/severe to mild/no pain or mild to no pain) for ≥75% of all treated attacks at 2 hours after taking ubrogepant were achieved in 20/105 (19.0%) and 50/105 (47.6%) patients, respectively. A total of 33/106 (31.1%) patients reported being "very satisfied" with ubrogepant. Adverse events were reported in 42/106 (39.6%) patients, including fatigue in 29/106 (27.4%), dry mouth in 8/106 (7.5%), nausea/vomiting in 7/106 (6.6%), constipation in 5/106 (4.7%), dizziness in 3/106 (2.8%), and other adverse events in 7/106 (6.6%). Predictive factors for being a "good responder" to ubrogepant, defined as headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant, included migraine with aura, episodic migraine, <5 prior unsuccessful preventive or acute treatment trials. Additionally, prior treatment responses to a CGRP monoclonal antibody and onabotulinumtoxinA injections are predictive of treatment responses and patient satisfaction to ubrogepant. For the 62/106 (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, as opposed to mild adverse events was higher, 11/62 (47.8%) versus 3/44 (17.6%), p = 0.048. Additionally, 16 patients had a history of significant cardiovascular or cerebrovascular diseases. No severe adverse events were reported in any patient., 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. Adverse event rates were higher than reported in clinical trials. Further studies are needed to confirm these findings and to evaluate the long-term efficacy and safety of ubrogepant., (© 2021 American Headache Society.)

The discovery of calcitonin gene-related peptide (CGRP) and its role in migraine has promoted a new era in migraine treatment: CGRP antagonism. Two classes of medications are currently available: small molecules targeting the CGRP receptor and monoclonal antibodies targeting the CGRP receptor or CGRP ligand. The revolution of these medications is represented by blurring the borders between acute and preventive treatments, episodic and chronic migraine, naïve and refractory patients and even between migraine and other headache disorders., Competing Interests: Disclosure E. Caronna has nothing to disclose. A.J. Starling has received consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, eNeura, Eli Lilly & Company, Impel, Lundbeck, Med-IQ, Medscape, Novartis, Teva, and Theranica; research funding from Migraine Research Foundation and Mayo Clinic; and honoraria from Migraine World Summit., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy, tolerability, and safety of eptinezumab 100 and 300 mg compared with placebo in patients with the dual diagnosis of chronic migraine (CM) and medication-overuse headache (MOH)., Background: Eptinezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, may be effective for treating patients with a dual diagnosis of CM and MOH., Methods: PROMISE-2 (NCT02974153) was a double-blind, randomized, placebo-controlled, phase 3 study that comprised a screening visit, a 28-day pretreatment period, and a 32-week study duration. Patients in this exploratory analysis of a prespecified subgroup had confirmed diagnoses of both CM and MOH at screening. Patients were randomly assigned to receive intravenous eptinezumab 100, 300 mg, or placebo every 12 weeks. Efficacy outcomes included mean changes from baseline in monthly migraine days (MMDs) during weeks 1-12, migraine responder rates at week 12, and percentages of patients below International Classification of Headache Disorders thresholds for CM and MOH over weeks 1-24., Results: There were 431 patients who were diagnosed with CM and MOH as specified in the protocol and received eptinezumab 100 mg (n = 139), 300 mg (n = 147), or placebo (n = 145). During the baseline period, these patients experienced an average of 16.7 migraine days across treatment arms. Over weeks 1-12, eptinezumab-treated patients experienced greater reductions from baseline in MMDs than placebo patients (100 mg, change from baseline = -8.4, difference from placebo [95% confidence interval (CI)] = -3.0 [-4.56, -1.52], p < 0.0001 vs. placebo; 300 mg, change from baseline = -8.6, difference from placebo [95% CI] = -3.2 [-4.66, -1.78], p < 0.0001 vs. placebo; placebo, -5.4). Compared with placebo, more eptinezumab-treated patients were ≥50% migraine responders (100 mg, 84/139 [60.4%]; 300 mg, 91/147 [61.9%]; placebo, 50/145 [34.5%]) or ≥75% responders (100 mg, 38/139 [27.3%]; 300 mg, 44/147 [29.9%]; placebo, 21/145 [14.5%]) over weeks 1-12. Therapeutic benefits with eptinezumab were observed from day 1 after dosing, and improvements were sustained with an additional dose. For the full 24-week treatment period, 71/139 (51.1%), 80/147 (54.4%), and 47/145 (32.4%) of 100, 300 mg, and placebo-treated patients, respectively, were below CM thresholds, and of the patients who provided sufficient acute medication data, 47/93 (50.5%), 53/107 (49.5%), and 26/96 (27.1%), respectively, were below medication-overuse thresholds., Conclusions: In patients diagnosed with both CM and MOH, eptinezumab treatment resulted in greater reductions in MMDs, higher responder rates, and fewer patients meeting CM and MOH criteria, thus demonstrating the efficacy and clinical utility of eptinezumab in this patient population., (© 2020 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Purpose of Review: The past two decades has seen an influx of noninvasive neuromodulation devices aimed at treatment of various primary headache disorders, including cluster headache and migraine. This narrative review is to summarize the current options in noninvasive neuromodulation in migraine., Recent Findings: A variety of noninvasive neuromodulation devices have been FDA cleared and marketed for use in migraine, including single-pulse transcranial magnetic stimulation (sTMS), noninvasive vagal nerve stimulators (nVNS), and external trigeminal nerve stimulators (eTNS). Newer devices include peripheral electrical stimulation devices (PES), caloric stimulation, and others. Each has varying levels of evidence supporting its use in migraine, tolerability profiles, and access issues. Noninvasive neuromodulation devices can be beneficial when used in patients with migraine, with minimal side effects. As more devices are developed, approved, and marketed in the future, rigorous research on efficacy and safety remain a top priority.

Introduction: Access to headache consultations by a headache specialist is limited. E-consultations are an efficient approach shown to reduce costs and improve continuity of care with the primary care provider. Indications, suitability, and uptake in the headache population are not well studied., Methods: This quality improvement pilot aims to explore the appropriateness of e-consultations for patients referred to a headache specialist. E-consultation feasibility was explored through (1) retrospective review of completed face-to-face consultations; (2) prospective survey of providers to identify face-to-face consultations appropriate for e-consultation; (3) cross-sectional review of the current waiting list to assess theoretical triaging to face-to-face vs e-consultation; and (4) prospective review of all e-consultations requested from an academic headache clinic to improve the understanding of e-consultation feasibility and referral triage., Results: The retrospective review included 75 face-to-face consultations with a mean (SD) wait time of 33 (39.4) days for consultations, of which 28/75 (37.3%) were deemed to be feasible e-consultations. The prospective survey of providers identified 10 face-to-face consultations that were felt to be theoretically appropriate for e-consultation. The cross-sectional review identified 20 patients on the clinic waiting list, of whom 5/20 (25%) were theoretically triaged to e-consultation. Finally, the prospective review found 12 requested e-consultations, of which 6/12 (50%) were for migraine prophylaxis recommendations. Chart data often lacked details for complete assessments, with 5/12 (41.7%) converted to face-to-face consultations and only 4/12 (33.3%) deemed appropriate for e-consultation., Conclusion: E-consultation in headache medicine could be considered if appropriately triaged. Pathways are needed to reach patients earlier in their disease course to ensure headache care meets guideline recommendations, and e-consultation is 1 option. However, better communication with primary care is required for system optimization., (© 2020 American Headache Society.)

Objective: This post hoc study investigated the relationship between patient response in terms of migraine headache day reduction and patient-reported outcomes of health-related quality of life (HRQoL) and disability categories., Background: Migraine causes considerable disease-related disability and negatively impacts HRQoL of patients. Calcitonin gene-related peptide inhibitors improve these outcomes and may eliminate disability due to migraine in some patients., Methods: Analyses used data from 3 double-blind, placebo (PBO)-controlled, phase 3 studies in adults with episodic migraine (EM) (EVOLVE-1: N = 858 and EVOLVE-2: N = 915) or chronic migraine (CM) (REGAIN: N = 1113). Patients were randomized 2:1:1 to subcutaneous injection of PBO, galcanezumab (GMB) 120 mg, or GMB 240 mg once monthly for 6 months in EVOLVE-1 and -2 and for 3 months in REGAIN. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Patients were divided into 4 response-level groups based on percent change from baseline (<30%, ≥30% to <50%, ≥50% to <75%, ≥75%). Patient-reported outcomes included the 14-item Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) and Migraine Disability Assessment (MIDAS) questionnaire., Results: Among patients with migraine, mean improvements from baseline in MSQ domain scores increased with each successive level of migraine headache day response. On a 100-pt scale, increases in Role Function-Restrictive score in EM were 16.8 and 36.0 at the <30% and ≥75% response levels, respectively, and for CM were 10.7 and 46.5. Similar patterns in scores were observed for the Role Function-Preventive and Emotional Function domains. Examination of improvement in MSQ item score by treatment group showed that, in patients with EM, approximately 10 to 20% more GMB-treated patients (N = 796 for GMB 120 mg and GMB 240 mg) had improvements in all 14 MSQ items compared with PBO-treated patients (N = 773) (all P < .001). In patients with CM, 3 to 16% more GMB-treated patients (N = 507) had improvements in the 14 MSQ items compared with PBO (N = 494), though differences were statistically significant in only 19 of 28 comparisons. At baseline, mean MIDAS scores (EM, 33.1; CM, 67.2) indicated severe mean disability for patients with EM and very severe disability for patients with CM. Among patients with EM, 215 of 425 (50.6%) of those treated with GMB 120 mg and 212 of 413 (51.3%) treated with 240 mg had little/no disability due to migraine after 6 months (PBO: 277 of 832 (33.3%), P < .001 for both). Among patients with CM, 50 of 254 (19.7%) of those treated with GMB 120 mg and 54 of 258 (20.9%) treated with 240 mg reached the level of little/no disability after 3 months of treatment (PBO: 70 of 504 (13.9%), P = .045 for 120 mg, P = .017 for 240 mg)., Conclusions: Because migraine greatly impairs an individual's ability to participate in activities of daily living, measurements of HRQoL are essential in clinical research. This study showed that function in daily life, as measured by MSQ score, improved as migraine headache days were reduced and that GMB-treated patients were more likely to see improvement in MSQ item scores compared with PBO-treated patients. Elimination of migraine-related disability was also more frequent in GMB-treated patients compared with placebo-treated patients., (© 2020 Eli Lilly and Company. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC, on behalf of American Headache Society.)

Background: Erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post-market observations are available to validate these findings in a real-world tertiary headache clinic population with complex comorbidities and refractory migraine., Objective: The goal of this study is to demonstrate the real-world performance of erenumab among patients in a tertiary care headache clinic by describing patient selection, experience, and clinical characteristics after 6 months of erenumab therapy., Methods: A retrospective, exploratory, observational study was conducted on patients receiving at least 1 erenumab injection (70 or 140 mg). Baseline data obtained by chart review and telephone calls were compared to 6-month follow-up telephone calls. The primary outcome was the reduction in self-reported headache days per month at baseline compared to 6 months for those with complete 6-month data. The significance level was set at P < .05. Secondary analyses explored the distribution of headache severity, responder rates, Migraine Disability Assessment scores, adverse effects, ineffective preventives, comorbidities, wearing-off, and discontinuation., Results: Of the 101 patients who consented to participate, 89.1% (90/101) were women, and the mean age of all patients was 49 years (range, 19-80 years). At baseline, 94.1% (95/101) of patients had chronic migraine, 5.0% (5/101) had episodic migraine, and 18.8% (19/101) had medication overuse headache. The mean (SD) number of baseline headache and migraine days per month for the entire cohort were 24.3 (8.2) and 18.2 (9.3) days, respectively. Participants had numerous comorbidities and had tried a mean of 11.2 unique oral medications and 4.8 unique medication categories before receiving erenumab, including 83.2% (84/101) who had also received onabotulinumtoxinA. Six-month post-erenumab follow-up data were available for 42.6% (43/101) of participants. For these 43 participants, the number of headache days per month decreased significantly by 6.5 days from a baseline mean (SD) of 24.8 (6.47) days to 18.3 (12) days at 6-month follow-up (P < .001); similarly, the monthly migraine days decreased significantly by 8.4 days from a baseline mean of 19.1 (9.3) days to 10.7 days at 6-month follow-up (P < .001). The 50% responder rate was 34.9% (15/43) for monthly headache days and 54.8% (23/43) for monthly migraine days. Of all 101 participants, 28 (27.7%) discontinued erenumab, primarily because it was ineffective (39.3%, 11/28) or because of adverse effects (42.9%, 12/28)., Conclusion: This post-market observational study of patient experience describes response to erenumab in a real-world tertiary headache clinic with a complex patient population. Overall, these complex patients had a significant positive clinical response to erenumab, but with high rates of discontinuation. This study also noted a 1-week wearing-off response and high rates of constipation. Further post-market studies are needed to better characterize patient selection and real-world response to erenumab., (© 2020 American Headache Society.)

Purpose of Review: We describe the pervasiveness of headache diseases across the globe and the need for healthcare advocacy, define healthcare advocacy, and identify how providers can incorporate healthcare advocacy into clinical practice and beyond., Recent Findings: Nearly 3 billion people across the globe experience migraine or tension-type headache, yet headache diseases receive a fraction of the funding that is allocated to other diseases. Despite its prevalence, those with headache diseases, especially migraine, experience external and internal stigma. As physicians, our job extends past the direct needs of the patient and must also focus on the systemic problems affecting our patients such as accessibility to healthcare providers and treatment options, as well as addressing stigma. We can empower our patients with education, community, and supportive, non-stigmatizing language used to describe headache diseases. Headache diseases are prevalent throughout the world and contribute to a substantial amount of disability. Disability is further compounded by stigma. Advocacy starts with empowering patients and peers with knowledge. It extends into the workplace to create accommodations and in the community to raise awareness and lobby for access to specialists, treatment options, and research funding.

Objective: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine., Background: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic., Methods: A detailed search of the scientific and popular literature was performed., Results: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome., Conclusion: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions., (© 2020 American Headache Society.)

Background: Noninvasive neuromodulation devices have been used for a variety of headache disorders, including cluster and migraine, since recently being cleared by the Federal Drug Administration. Although these devices have been touted as low-risk options for improved headache control, the data behind actual efficacy endpoints remain unclear., Objective: To critically assess current evidence regarding the efficacy of the noninvasive vagus nerve stimulator (nVNS) device for acute migraine management., Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions.Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of headache., Results: A randomized, double-blind, sham-controlled clinical trial was selected for critical appraisal. In this trial, the primary endpoint (pain freedom at 120 min after use of nVNS for first acute migraine attack) was not met when compared with sham device (30.4% for nVNS vs. 19.7% for sham; P=0.067). However, there were statistically significant differences found for various secondary endpoints favoring nVNS, such as pain freedom rates at 30 and 60 minutes, pain relief at 120 minutes, and mean percentage pain score reduction rates at 60 and 120 minutes., Conclusions: When comparing nVNS with sham, no statistically significant differences were found with regards to the primary endpoint of pain freedom at 120 minutes, although differences were found with various secondary endpoints and post hoc analysis. nVNS is likely a safe alternative to medications.

Objective: We surveyed the American Headache Society (AHS) New Investigators and Trainees Section (NITS), and International Headache Academy (IHA) attendees to better understand what they perceive as the most pressing issues for themselves as new investigators and trainees in the field of headache medicine., Background: The NITS and IHA are intended as platforms for mentorship, leadership training, and professional development in the field of headache medicine. Identifying and addressing pressing issues among new investigators and trainees based on their perceived needs is critical to encouraging their development and success as headache medicine clinicians and researchers., Methods: Paper surveys were administered at the NITS meeting at the November 2018 Scottsdale Headache Symposium and the January 2019 IHA. Additionally an online version was sent to the NIT listserv in November of 2018. The survey queried demographic information (gender, race, age, profession, training status, and years in practice) and asked participants to identify their top 3 most pressing issues/questions among a list of options., Results: Fifty-three responses were submitted (53/255; total response rate 20.7%). Among the surveys, 18 in-person responses were from the NITS meeting (18/20; response rate 90.0%), 23 in-person responses were from the IHA (23/45; response rate 51.1%), and 12 responses were from the online survey (12/190; response rate 6.3%). No duplicate responses were submitted based on comparison of demographics. One respondent identified as a researcher exclusively and was excluded from further analyses; the rest identified as clinicians at various levels of medical training. Fifteen respondents were not members of the NITS (28.8%); the most common reason for nonmembership was lack of awareness of the section (92.8%). Overall the most pressing issues/questions included (% of respondents who ranked issue/question among top 3): Career planning (51.9%), Logistics of running a headache clinic (40.4%), and Opportunities for involvement (38.5%). Most pressing issues/questions differed depending on level of training. Working with industry was the most pressing issue/question identified by early career physicians (55.0%). Career planning was the most pressing issue/question among fellows (72.2%) and residents (64.3%)., Conclusion: Many of the most pressing issues identified by respondents are topics that are not formally addressed in medical and research training., (© 2020 American Headache Society.)

Background: The King-Devick test is a timed rapid number naming task that involves complex cerebral functions. The objective of this pilot exploratory study is to determine whether there is a difference in the King-Devick test during a migraine attack compared to the interictal phase., Methods: We evaluated 29 adult subjects with migraine with aura or migraine without aura. For each participant, we performed King-Devick tests during migraine attacks and interictal phases. Subjects served as their own controls., Results: The King-Devick test was slower during the migraine attack compared to the interictal baseline (median 4.6 sec slower, p  < 0.001). The slowing of the King-Devick test during migraine attack was more prominent in those with migraine with aura compared to subjects with migraine without aura (median 7.5 vs. 2.8 sec, p  = 0.028)., Conclusions: This exploratory, observational study shows changes in the King-Devick test during migraine compared to the interictal phase. Future studies are required to determine if the King-Devick test may be used as a rapid and simple tool to objectively characterize migraine-associated disability.

Background: Concussion affects almost 4 million individuals annually. There are many sideline screening tools available to assist in the detection of sports-related concussion. The King-Devick (K-D) test in association with Mayo Clinic utilizes rapid number naming to test saccadic eye movements in order to screen for concussion. An ideal screening tool for concussion would correctly identify all athletes with active concussion. The accuracy of K-D testing compared with other sideline screening tools is undetermined., Objective: To critically assess current evidence regarding the utility of K-D testing as a sideline screening tool for acute concussion and compare K-D testing to other sideline concussion assessments., Methods: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of concussion neurology and neuro-ophthalmology., Results: A recent meta-analysis was selected for critical appraisal. Cohorts analyzing athletes with sports-related concussion were selected, and utilized K-D testing as the main baseline and sideline assessment of concussion. K-D testing was found to have a high sensitivity and specificity for detecting concussion when there was worsening from baseline., Conclusion: K-D testing has high sensitivity and specificity for detecting sideline concussion. Compared with other sideline screening tools that do not include vision testing, it has greater accuracy. Screening for concussion is optimized when multiple testing modalities are used in conjunction.

The coronavirus responsible for the COVID-19 pandemic, SARS-2-CoV, most commonly involves the respiratory tract; however, more severe cases have been found to have multi-organ involvement, including the central nervous system. Headache has been documented as a presenting symptom of COVID-19, which may prompt neurology consultation. To date, few cases of COVID-19 meningitis have been confirmed, but it must remain in the differential diagnosis for patients with headache and fever. A 58-year-old female with multiple sclerosis on fingolimod, chronic migraine well-controlled on fremanezumab, and cerebrovascular disease presented with fevers and respiratory symptoms, as well as acute treatment-refractory headache with associated neck stiffness and transient behavioral abnormalities. Although not confirmed with cerebrospinal fluid testing, we suspect this patient had COVID-19 meningoencephalitis, highlighting the need to consider secondary headaches in patients with coronavirus infection, even in the setting of chronic migraine. We offer anecdotal treatment recommendations for acutely refractory secondary headache and guidance for the consulting neurologist during the COVID-19 pandemic., Competing Interests: Conflict of InterestDr. Arca has no disclosures or conflict of interest. Dr. Starling has the following disclosures: consulting fees—Alder, Amgen, Eli Lilly & Company, Impel, Lundbeck, Novartis, Medscape., (© Springer Nature Switzerland AG 2020.)

Primary care physicians can help their patients with migraine modify their triggers, and thereby mitigate the severity and frequency of their symptoms, by offering lifestyle modification counseling based on the mnemonic SEEDS (sleep, exercise, eat, diary, and stress). The authors review evidence associated with each of these factors and provide best-practice recommendations., (Copyright © 2019 Cleveland Clinic.)

Background: In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs., Methods: SAMURAI and SPARTAN were similarly designed, Phase 3, randomized, double-blind, placebo-controlled trials in adults treating a single migraine attack with lasmiditan 50, 100, or 200 mg. Both studies included patients with CVRFs, and SPARTAN allowed patients with coronary artery disease, clinically significant arrhythmia, or uncontrolled hypertension. Efficacy and safety of lasmiditan in subgroups of patients with differing levels of CVRFs are reported. For efficacy analyses, logistic regression was used to assess treatment-by-subgroup interactions. For safety analyses, Cochran-Mantel-Haenszel test of general association evaluated treatment comparisons; Mantel-Haenszel odds ratio assessed significant treatment effects., Results: In this pooled analysis, a total of 4439 patients received ≥1 dose of study drug. A total of 3500 patients (78.8%) had ≥1 CVRF, and 1833 patients (41.3%) had ≥2 CVRFs at baseline. Both trials met the primary endpoints of headache pain freedom and most bothersome symptom freedom at 2 h. The presence of CVRFs did not affect efficacy results. There was a low frequency of likely CV treatment-emergent adverse events (TEAEs) overall (lasmiditan, 30 [0.9%]; placebo, 5 [0.4%]). There was no statistical difference in the frequency of likely CV TEAEs in either the absence or presence of any CVRFs. The only likely CV TEAE seen across patients with ≥1, ≥ 2, ≥ 3, or ≥ 4 CVRFs was palpitations., Conclusions: When analyzed by the presence of CVRFs, there was no statistical difference in lasmiditan efficacy or the frequency of likely CV TEAEs. Despite the analysis being limited by a single-migraine-attack design, the lack of differences in efficacy and safety with increasing numbers of CVRFs indicates that lasmiditan might be considered in the treatment algorithm for patients with CVRFs. Future studies are needed to assess long-term efficacy and safety., Trial Registration: ClinicalTrials.gov NCT02439320 (SAMURAI), registered 18 March 2015 and ClinicalTrials.gov NCT02605174 (SPARTAN), registered 11 November 2015.

Concussion is a public health crisis affecting vulnerable populations including youth athletes. As awareness increases, more patients with acute concussion are seeking medical evaluations. Internists are frontline medical providers and thus should be able to identify, diagnose, manage, and know when to refer patients with concussion. Management of concussion includes rapid removal from play, symptomatic treatment, and return to learn/play recommendations. Inappropriate management may lead to recurrent concussions, prolonged recovery, and potential long-term consequences. Understanding the key features of diagnosis, postinjury assessment tools, symptomatic treatment, and management of concussion, including return to learn/play recommendations, is essential for primary care providers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: Unusual headache disorders are less commonly discussed and may be misdiagnosed. These headache disorders frequently have a benign natural history; however, without reassurance, therapeutic education, and treatment, they can negatively affect the health and function of patients., Recent Findings: This article reviews the clinical features, diagnosis, workup, and proposed treatments for several unusual headache disorders including primary cough headache, primary headache associated with sexual activity, primary exercise headache, cold-stimulus headache, primary stabbing headache, nummular headache, hypnic headache, and headache attributed to travel in space. Exploding head syndrome is also discussed, which is a sleep disorder commonly confused with a headache disorder., Summary: Unusual headache disorders are usually benign, yet without the correct diagnosis can be very worrisome for many patients. Through greater awareness of these headache disorders, neurologists can evaluate and effectively manage unusual headache disorders, which offers significant benefits to patients and practice satisfaction to neurologists.

Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a -2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (-0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of -2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, -3.1 (6.4) ( p < 0.0001), and total headache days of any intensity -3.16 days (5.21) compared to the performance goal (-0.63 days) ( p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events. Conclusions This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention. Trial registration number NCT02357381.

Introduction: Greater occipital nerve (GON) blocks are frequently used to treat migraine headaches, although a paucity of supporting clinical evidence exists. The objective of this study was to assess the efficacy of GON block in acute treatment of migraine headache, with a focus on pain relief., Methods: This retrospective cohort study was undertaken between January 2009 and August 2014 and included patients who underwent at least 1 GON block and attended at least 1 follow-up appointment. Change in the 11-point numeric pain rating scale (NPRS) was used to assess the response to GON block. Response was defined as "minimal" (<30% NPRS point reduction), "moderate" (31-50% NPRS point reduction), or "significant" (>50% NPRS point reduction)., Results: A total of 562 patients met inclusion criteria; 423 were women (75%). Mean age was 58.6 ± 16.7 years. Of these 562, 459 patients (82%) rated their response to GON block as moderate or significant. No statistically significant relationship existed between previous treatment regimens and response to GON block. GON block was equally effective across the different age and sex groups., Conclusions: Greater occipital block seems to be an effective option for acute management of migraine headache, with promising reductions in pain scores., Competing Interests: Conflict of interest: AJS has received consulting fees from Amgen and eNeura., (© Copyright 2018 by the American Board of Family Medicine.)

Headache is a common, disabling neurologic problem in all age groups, including older adults. In older adults, headache is most likely a primary disorder, such as tension-type headache or migraine; however, there is a higher risk of secondary causes, such as giant cell arteritis or intracranial lesions, than in younger adults. Thus, based on the headache history, clinical examination, and presence of headache red flags, a focused diagnostic evaluation is recommended, ranging from blood tests to neuroimaging, depending on the headache characteristics. Regardless of the primary or secondary headache disorder diagnosis, treatment options may be limited in older patients and may need to be tailored to the presence of comorbid medical conditions. The purpose of this review is to provide an update on the management of headache in older adults, from diagnosis to treatment., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Chronic migraine is a debilitating neurobiological disorder that affects approximately 1.4-2.2% of the population worldwide. Patients with chronic migraine have 15 or more headache days per month, with at least 8 days per month that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a standardized injection protocol, was approved by the US Food and Drug Administration in 2010 for the treatment of chronic migraine. The approval was made based on results from two large, randomized, double-blind placebo-controlled trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Since then, numerous studies have been performed investigating the short-term and long-term benefits, risks and complications of the use of onabotulinumtoxinA injections for the treatment of chronic migraine. The purpose of this narrative review is to describe the currently available clinical evidence for the use of onabotulinumtoxinA injections for treating patients with chronic migraine., Competing Interests: Conflict of interest statement: Dr Chia Chun Chiang: None declared. Dr Amaal J. Starling: Amgen, Medical Advisory Board; Alder, Medical Advisory Board; Eli Lilly & Company, Medical Advisory Board; eNeura, Medical Advisory Board.

Background: Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms., Methods: Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores., Results: Among 141 players tested, 20 had clinically diagnosed concussion. All 20 had immediate postconcussion K-D times >5 seconds from baseline (average 7.3 seconds) and all but 2 had worse postseason scores (46.4 seconds vs 52.4 seconds, p < 0.05, Wilcoxon signed rank test). Nonconcussed athletes saw minimal improvement postseason (43.9 seconds vs 42.1 seconds, p < 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue., Conclusions: Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion., Classification of Evidence: This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

Concussion pathophysiology is complicated and involves numerous mechanisms, including excessive neurotransmitter release, metabolic derangements, neuroinflammation, cerebral blood flow changes, and axonal disruption. The initial biomechanical impact in a concussion results in abnormal function at the cellular level, which initiates a cascade of events that leads to microstructural changes and, in the minority of cases, more persistent, permanent damage., (Copyright © 2017 Elsevier Inc. All rights reserved.)