Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS:A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS:A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION/CONCLUSIONS:This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

This practice guideline provides updated evidence-based recommendations regarding the use of pharmacologic migraine prevention in adults. A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies published through June 6, 2024, and is available in a companion publication. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Recommendations are provided on how to decide when it is appropriate to start a pharmacologic migraine preventive medication and how to decide which migraine preventive medication to start. Recommendations address decision making on appropriate choices of migraine preventive medications in specific situations and populations, including patients with fibromyalgia, obesity, or hypertension; considerations for older adults; treatment during pregnancy and lactation; sex-related factors in choosing medications; and treatment for patients with medication overuse. Recommendations on assessment of treatment efficacy, adverse effects, and discontinuing migraine preventive medications are provided.

This practice guideline provides updated evidence-based recommendations regarding the use of pharmacologic migraine prevention in adults. A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies published through June 6, 2024, and is available in a companion publication. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Recommendations are provided on how to decide when it is appropriate to start a pharmacologic migraine preventive medication and how to decide which migraine preventive medication to start. Recommendations address decision making on appropriate choices of migraine preventive medications in specific situations and populations, including patients with fibromyalgia, obesity, or hypertension; considerations for older adults; treatment during pregnancy and lactation; sex-related factors in choosing medications; and treatment for patients with medication overuse. Recommendations on assessment of treatment efficacy, adverse effects, and discontinuing migraine preventive medications are provided.

BACKGROUND AND OBJECTIVES/OBJECTIVE:This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS:A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS:A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION/CONCLUSIONS:This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

OBJECTIVE:Our objectives were to understand migraine-related perceptions among college students and the lived experiences of those with migraine on college campuses and to generate recommendations for supporting college students with migraine. BACKGROUND:During young adulthood, there is a sharp growth in migraine prevalence and disability-adjusted life years. Migraine prevalence is approximately 16% among university students and negatively influences several aspects of a student's college experience. METHODS:This was a qualitative study using phenomenological inquiry via virtual semistructured focus groups. Recruitment took place between April 2025 and July 2025. An initial 60-min focus group was conducted in May 2025 with an all-women's college to assess our questions' relevance and comprehensiveness. We then conducted four national focus groups in June 2025 and July 2025 with college students from across the United States. All focus groups included students with and without severe headache or migraine (self-reported). Focus groups were transcribed and independently coded twice. We developed themes for the five focus groups using content analysis. Qualitative analysis was conducted between July 2025 and September 2025. RESULTS:Three students attended the all-women's college focus group and 47 students attended one of the four national focus groups (n = 50). The following themes emerged from the five focus groups: (1) Migraine is often misunderstood and not discussed on campus, with misconceptions surrounding severity and its distinction from headache. (2) The impact of migraine on campus is significant, with students reporting various triggering environments, difficulty maintaining focus, attending class, performing academically, preserving social relationships, and participating in extracurricular activities. (3) The most commonly reported accommodations for migraine were academic, specifically exam- and attendance-related, though not always honored by professors. (4) Access to migraine care for students is challenging, with reports that student health centers are typically unapproachable, inconvenient, and unhelpful, with students seeking external providers for migraine. Students recommended more awareness and education initiatives for improved understanding of migraine as well as increased access to migraine resources and accommodations. CONCLUSION/CONCLUSIONS:The experiences captured in our study provide unique qualitative insights by highlighting how misunderstanding of migraine on campus contributes to social and academic challenges faced by students with migraine. Students described unmet needs related to widespread misunderstanding of migraine, limited academic flexibility, environmental triggers, limited access to care, and inconsistent implementation of accommodations, highlighting that greater awareness of migraine, especially by professors and student health services, is crucial on college campuses. There are opportunities for migraine education programs on college campuses to increase knowledge and awareness about migraine and create a more supportive migraine environment.

BackgroundFew studies have examined which patients with migraine might be responders for mind-body interventions. Thus, we examined whether certain baseline mindfulness traits and interest in physical exercise might predict response to treatment.MethodsThis is a planned exploratory analysis of a phase 2 randomized controlled study (N  =  50; 25 per arm) comparing a 6-week physical therapist (PT)-delivered biofeedback-assisted relaxation (BAR) program vs. an Enhanced Usual Care (EUC) migraine self-management program (diary tracking and emailed migraine-related educational materials). We conducted moderation analyses to determine whether the Multidimensional Assessment of Interoceptive Awareness (MAIA), Difficulties in Emotion Regulation Scale (DERS) and Physical Activity Enjoyment Scale (PACES) at baseline influenced the effect of BAR on migraine-related outcomes (Migraine-Specific Quality of Life Role Function Restrictive (MSQv2.1-RFR) and Migraine-Related Disability (MIDAS)) at 6 months.ResultsAmong the n = 40 participants (BAR = 19; EUC = 21), the majority were female (95%), non-Hispanic (77.5%) and white (67.5%). Mean (SD) age was 45.6 (11.2) years. For the MAIA Not-Worrying subscale, BAR produced the greatest improvement in 6-month MSQv2.1-RFR scores among participants with low baseline Not-Worrying scores (those who tended to worry about bodily sensations/discomfort more) (BAR = 77.1 ± 6.6 vs. EUC = 48.9 ± 5.0; p = 0.002, g = 4.75). The benefit diminished at average levels (p = 0.060, g = 2.72) and was absent at high baseline Not-Worrying (p = 0.528, g =  -0.91). For the MAIA Self-Regulation subscale, BAR was most effective among those low in baseline self-regulation (BAR = 71.7 ± 5.3 vs. EUC = 44.3 ± 7.2; p = 0.004, g = 4.27). The DERS total score showed that BAR demonstrated little benefit among participants with better baseline emotion regulation (i.e. lower DERS score; p = 0.907, g = 0.17) but was more effective as baseline emotion regulation difficulties increased, showing a moderate benefit at average levels (BAR = 69.2 ± 4.2 vs. EUC = 55.8 ± 4.0, p = 0.027, g = 3.25) and a large, significant difference at high levels (BAR = 70.6 ± 6.3 vs. EUC = 44.7 ± 5.7; p = 0.004, g = 4.22). The PACES total score indicated that BAR benefits were strongest among those with low (BAR = 76.1 ± 7.0 vs. EUC = 47.1 ± 5.3, p = 0.002, g = 4.60) to average (BAR = 71.2 ± 4.2 vs. EUC = 58.6 ± 4.0, p = 0.035, g = 3.07) enjoyment of physical activity.ConclusionsWe found subgroups of individuals with migraine who may be better responders to PT-delivered BAR, specifically those who tend to worry more about bodily sensations (lower MAIA Not-Worrying score), those with low self-regulation (lower MAIA Self-Regulation score), those with worse emotion regulation (higher DERS score) and those with lower levels of physical activity enjoyment (lower PACES score) at baseline. This may help us determine who may benefit most from BAR.Trial RegistrationClinicalTrials.gov Identifier: NCT06077812.

Consumer wearable devices are commonly used by patients and consumers for several reasons with increasing application as new technologies are developed. Use of these devices is an emerging issue in Neurology because of increased adoption and the additional data reported to providers by patients. Understanding of possible functions, limitations, and effect on patients of non-US Food and Drug Administration (FDA)-cleared wearable technology to inform neurologic care is needed. A common theme in people with neurologic conditions regarding consumer wearables and associated tracking applications is that there is significant promise in these tools, but adherence (days per use/per week), continued engagement (attrition), and unintended consequences such as heightened anxiety remain important issues. Further understanding and validation of these devices is needed within the field of Neurology before full use and confidence can be achieved. Below, we provide examples of non-FDA-cleared wearable devices used in Neurology in the areas of epilepsy, headache, cardiac monitoring, and sleep.

OBJECTIVE:To update the 2016 American Headache Society (AHS) guideline on parenteral pharmacologic therapies for the management of migraine attacks in the emergency department (ED). METHODS:We conducted a systematic review and meta-analysis using the same methodology as the 2016 guideline. The original search strategy was repeated and expanded to include studies of nerve blocks and sphenopalatine ganglion (SPG) blocks. We searched Medline, Embase, Cochrane, clinicaltrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform through February 10, 2025. Eligible studies were randomized controlled trials (RCTs) involving adults diagnosed with migraine, treated in the ED with intravenous (IV), intramuscular (IM), subcutaneous (SC), or nerve block (including SPG block) interventions. Two reviewers independently screened titles/abstracts and full texts; a third reviewer resolved disagreements. Data were extracted using a standardized form and verified by a second reviewer. Risk of bias was assessed using the American Academy of Neurology (AAN) criteria. Where applicable, meta-analyses were performed. Efficacy was categorized as highly likely, likely, or possibly effective or ineffective. Clinical recommendations were developed using the AAN guideline development process. RESULTS:The search identified 26 new RCTs evaluating 20 injectable treatments. Of these, 12 were rated class I (low risk of bias), 9 class II, and 4 class III. Prochlorperazine IV, dexketoprofen IV, sumatriptan SC, and greater occipital nerve blocks (GONB) were considered highly likely to be effective based on multiple class I studies. Chlorpromazine IV, metoclopramide IV, eptinezumab IV, ketorolac IV, and supraorbital nerve blocks (SONB) were considered likely effective based on one class I or multiple class II studies. Hydromorphone IV, propofol IV, and paracetamol IV were considered likely ineffective based on class I or multiple class II studies. After review of the evidence and a consensus process, recommendations were made for each intervention. CONCLUSIONS:Prochlorperazine IV and GONB must be offered to eligible adults presenting to the ED with a migraine attack for treatment of headache requiring parenteral therapy (level A - must offer) in those without contraindications, while hydromorphone IV must not be offered (level A - must not offer). Treatments that should be offered when appropriate (level B - should offer) include dexketoprofen IV, ketorolac IV, metoclopramide IV, sumatriptan SC, and SONB. Chlorpromazine IV, dexamethasone IV, and valproate IV may be offered (level C - may offer). Paracetamol IV may not be offered (level C - should not offer). Eptinezumab should be offered (level B) only for patients matching the clinical trial population but is rated level U - no recommendation for an ED-specific population. Additional evidence is needed for caffeine, granisetron, ibuprofen, ketamine, lidocaine, normal saline, propofol, and SPG blocks, all currently rated level U - no recommendation.

OBJECTIVE:People with migraine have a higher prevalence and severity of insomnia. We examined the relationship between insomnia severity and migraine-related disability (MIDAS) and migraine-specific quality of life (MSQv2.1). METHODS:We conducted a post-hoc analysis of a pilot randomized controlled study assessing the RELAXaHEAD application in those with insomnia and comorbid migraine. Descriptive statistics were used to summarize demographic and clinical characteristics. Linear mixed model analysis was conducted to evaluate Insomnia Severity Index (ISI) as a predictor of each MSQv2.1 domain and MIDAS. RESULTS:Forty-two participants completed baseline and at least one follow-up survey. Mean age was 43.8 years (SD 12.6) and the majority (85.7%) were female. Most participants (81.0%) had severe migraine-related disability (median baseline MIDAS, 32 (IQR 52)). Over half (54.8%) of participants had moderate clinical insomnia (mean baseline ISI, 18.5 (SD 4.6)). Baseline median MSQv2.1 scores were 44.3 (IQR 31.4) for Role Function-Restrictive (RFR), 65.0 (IQR 45.0) for Role Function-Preventive (RFP), and 46.7 (IQR 46.7) for Emotional Function (EF). The effect of ISI on MIDAS was statistically significant (rate ratio (RR)=1.10, p < 0.05, 95%CI [1.028, 1.171], meaning each one-point increase in ISI was associated with a 10% higher MIDAS score). Additionally, a 1-point increase in ISI was associated with a decrease of 1.2 points in MSQ-RFR (B=-1.205, p = 0.001),1.0 point in MSQ-RFP (B=-0.981, p = 0.020), and 1.4 points in MSQ-EF (B=-1.66, p = 0.001). CONCLUSIONS:Our study revealed significant associations between insomnia severity and migraine-related disability and quality of life, highlighting the importance of prevention and sleep intervention for patients with migraine.

Mobile health (mHealth) tools can be used to deliver nonpharmacologic therapies to patients with migraine. However, mHealth studies often report poor treatment adherence. Neuroscience Education Therapy (NET), behavioral economics, and Digital Navigators have the potential to increase treatment adherence and thereby improve remote migraine self-management. We conducted a 6-month prospective pilot randomized controlled trial testing if a multi-component package of behavioral interventions increased treatment adherence among patients using one of two different mHealth migraine self-management programs (low-intensity program consisting only of a headache diary versus high-intensity program consisting of a headache diary and behavioral exercises). Our outcomes were the number of diary entries and behavioral exercises completed/week captured via back-end analytics of the mHealth application. We also compared our adherence data at 90-days (a secondary endpoint to assess the durability of the effect) with adherence data from similar published studies without the adherence-enhancing package. We enrolled 26 participants (n = 15 low intensity group, n = 11 high-intensity group). During the 6-week intervention period, we had a median of 7 headache diary entries/week in both groups and a median of 6 days/week of behavioral exercises in the high-intensity group. The rate of adherence with the adherence-enhancing package included was 2.9-8x higher compared to the median rates of the behavioral exercises to historical controls. With use of NET, behavioral economics, and digital navigators, participants achieved higher levels of adherence to both self-management programs compared to prior remote migraine self-management studies. Therefore, these tools may be beneficial to improving adherence to migraine self-management programs.