Long-Term Epidural Patching Outcomes and Predictors of Benefit in Patients With Suspected CSF Leak Nonconforming to ICHD-3 Criteria.

BACKGROUND AND OBJECTIVES: Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. METHODS: We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. RESULTS: The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. DISCUSSION: Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.

Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). BACKGROUND: Insurers mandate step therapy with NOEPs before approving CGRP mAbs. METHODS: Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days. RESULTS: Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]). CONCLUSIONS: There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.

Long-term persistence to OnabotulinumtoxinA to prevent chronic migraine: Results from 11 years of patient data from a tertiary headache center.

OBJECTIVE: To determine if patients with chronic migraine continue onabotulinumtoxinA (onabotA) long-term. METHODS: We performed a retrospective cohort analysis using aggregated, de-identified patient data from the Stanford Headache Center. We included patients in California who received at least one prescription for onabotA during the years of 2011-2021. The primary outcome was the number of onabotA treatments each patient received. Secondary outcomes included sex, age, race, ethnicity, body mass index (BMI), distance to the treatment facility, and zip code income quartile. RESULTS: A total of 1,551 patients received a mean of 7.60 ± 7.26 treatments and a median of 5 treatments, with 16.2% of patients receiving only one treatment and 10.6% receiving at least 19. Time-to-event survival analysis suggested 26.0% of patients would complete at least 29 treatments if able. Younger age and female sex were associated with statistically significant differences between quartile groups of number of onabotA treatments (p = 0.007, p = 0.015). BMI, distance to treatment facility, and zip code income quartile were not statistically significantly different between quartile groups (p > 0.500 for all). Prescriptions of both triptans and non-onabotA preventive medications showed a statistically significant increase with each higher quartile of number of onabotA treatments (p < 0.001; p < 0.001). DISCUSSION: We show long-term persistence to onabotA is high and that distance to treatment facility and income are not factors in continuation. Our work also demonstrates that as patients continue onabotA over time, there may be an increased need for adjunctive or alternative treatments.

Alcohol Use Disorder in Patients with Chronic Migraine: A Retrospective, Observational Study.

OBJECTIVE: The relationship between migraine and alcohol consumption is unclear. We assessed the association between chronic migraine and alcohol use disorder(AUD), relative to chronic disease controls, and in conjunction with common comorbidities. METHODS: We conducted a retrospective, observational study. The primary outcome was the odds ratio for AUD in patients with chronic migraine or with chronic migraine and additional comorbidities relative to controls. RESULTS: A total of 3701 patients with chronic migraine, 4450 patients with low back pain, and 1780 patients with type 2 diabetes mellitus met inclusion criteria. Patients with chronic migraine had a lower risk of AUD relative to both controls of low back pain (OR 0.37; 95% CI: 0.29-0.47, p < 0.001) and type 2 diabetes mellitus (OR 0.39; 95% CI: 0.29-0.52, p < 0.001). Depression was associated with the largest OR for AUD in chronic migraine (OR 8.62; 95% CI: 4.99-14.88, p < 0.001), followed by post-traumatic stress disorder (OR 6.63; 95% CI: 4.13-10.64, p < 0.001) and anxiety (OR 3.58; 95% CI: 2.23-5.75, p < 0.001). CONCLUSION: Patients with chronic migraine had a lower odds ratio of AUD relative to controls. But in patients with chronic migraine, those with comorbid depression, anxiety, or PTSD are at higher risk of AUD. When patients establish care, comorbid factors should be assessed and for those at higher risk, AUD should be screened for at every visit.

Complementary and Integrative Medicine for the Treatment of Trigeminal Neuralgia and Trigeminal Autonomic Cephalalgia.

PURPOSE OF REVIEW: Trigeminal neuralgia (TN) and trigeminal autonomic cephalalgias (TACs) are both painful diseases which directly impact the branches of the trigeminal nerve, which supply the face. Patients who have experienced adverse effects, have not responded to mainstream treatments, or have a personal preference for nonmedication options, often turn to complementary and integrative medicine (CIM). The aim of this review is to discuss the efficacy and safety of CIM therapies available for the treatment of TN and TACs. RECENT FINDINGS: Not only are there limited therapeutic options for TN and TAC patients, but also is there a proportion of patients who are intolerant to standard medical treatments. Recent findings have illustrated that 86% of patients with headache disorders utilize CIM modalities in combination with mainstream medical therapy. CIM modalities can be helpful for these diseases and have primarily been studied in combination with standard medical therapy. There is limited evidence for CIM and behavioral therapies in managing these conditions, and more research is needed to confirm which therapies are safe and effective.

The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis.

OBJECTIVE: To determine the effect of the introduction of the calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine. BACKGROUND: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market. METHODS: We performed a retrospective cohort analysis using the aggregated de-identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021. RESULTS: We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001). CONCLUSION: The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time.

The utility of ChatGPT in the assessment of literature on the prevention of migraine: an observational, qualitative study.

Background: It is not known how large language models, such as ChatGPT, can be applied toward the assessment of the efficacy of medications, including in the prevention of migraine, and how it might support those claims with existing medical evidence. Methods: We queried ChatGPT-3.5 on the efficacy of 47 medications for the prevention of migraine and then asked it to give citations in support of its assessment. ChatGPT's evaluations were then compared to their FDA approval status for this indication as well as the American Academy of Neurology 2012 evidence-based guidelines for the prevention of migraine. The citations ChatGPT generated for these evaluations were then assessed to see if they were real papers and if they were relevant to the query. Results: ChatGPT affirmed that the 14 medications that have either received FDA approval for prevention of migraine or AAN Grade A/B evidence were effective for migraine. Its assessments of the other 33 medications were unreliable including suggesting possible efficacy for four medications that have never been used for the prevention of migraine. Critically, only 33/115 (29%) of the papers ChatGPT cited were real, while 76/115 (66%) were "hallucinated" not real papers and 6/115 (5%) shared the names of real papers but had not real citations. Conclusion: While ChatGPT produced tailored answers on the efficacy of the queried medications, the results were unreliable and inaccurate because of the overwhelming volume of "hallucinated" articles it generated and cited.

Primary Cough Headache.

PURPOSE OF REVIEW: In this review article, we summarize the most recent findings and observations in patients experiencing primary cough headache. RECENT FINDINGS: Recent studies draw attention to further characterization of patients with primary cough headache in a pulmonology clinic. There have also been recent case studies describing new therapy considerations, including noninvasive vagus nerve stimulation and lumbar punctures. Primary cough headache has been a recognized entity since as early as 1932. Patients generally report a sudden onset, sharp headache lasting a few hours that is precipitated by Valsalva maneuver or coughing. It remains an uncommon diagnosis, and secondary causes are crucial to rule out with imaging studies. Additionally, there can be an overlap with other primary headache disorders such as primary exercise headache and headache associated with sexual activity, thus requiring a detailed history. Many hypotheses exist regarding the pathophysiology including relative pressure gradients and a crowded posterior fossa. Generally, patients are responsive to indomethacin, but more recent case reports have suggested benefits of other medications and procedures that may offer patients an alternative option, including vagus nerve stimulation, lumbar punctures, and beta blockers. Future case series and studies should focus on management of these patients, with a specific focus on individuals who do not tolerate indomethacin.

The Role of Step Therapy in the Treatment of Migraine.

PURPOSE OF REVIEW: This review examines recent evidence and applies bioethical principles to evaluate the benefits and risks of using step therapy in the treatment of migraine. RECENT FINDINGS: With the CGRP mAbs, gepants, and lasmiditan now on the market for up to 5 years, new research, including network meta-analyses and long-term use studies, can evaluate the comparative efficacy, tolerability, and adherence of these medications relative to older acute and preventive medications for the treatment of migraine. Deciding how medications are chosen for patients requires accounting for many factors including sustainability, efficacy, tolerability, and preference. Newer research can help give clarity on the appropriateness of gating certain treatment options behind others.

The Role of Manual Therapies in the Treatment of Headache Disorders.

PURPOSE OF REVIEW: A comprehensive headache treatment plan typically requires both medication and non-medication treatment strategies. Manual therapies offer another therapeutic approach to headache treatment. This article reviews the evidence for manual therapies in the treatment of headache disorders. RECENT FINDINGS: Current evidence shows potential benefit from myofascial trigger point injections, myofascial release, and massage for the treatment of various headache types. There is also evidence for strain counterstrain technique, ischemic compression, and spinal manipulative therapies for cervicogenic headache. Although larger randomized clinical trials are necessary for many of these modalities, recent findings show that manual therapies could be an important tool for the treatment of some headache disorders.

Migraine.

Migraine affects about 1 billion people worldwide, and up to 15% of adults in the United States have migraine attacks in any given year. Migraine is associated with substantial adverse socioeconomic and personal effects. It is the second leading cause of years lived with disability worldwide for all ages and the leading cause in women aged 15 to 49 years. Diagnostic uncertainty increases the likelihood of unnecessary investigations and suboptimal management. This article advises clinicians about diagnosing migraine, ruling out secondary headache disorders, developing acute and preventive treatment plans, and deciding when to refer the patient to a specialist.

Insomnia and Migraine: A Review of Evidence-Based, Biobehavioral Interventions.

PURPOSE OF REVIEW: The purpose of this review is to discuss the current evidence for Cognitive Behavioral Therapy for Insomnia (CBT-I) for patients with migraine and comorbid insomnia. In this article, we provide a narrative review of the literature on CBT-I and migraine, highlighting recent advances in research into this topic. Finally, we propose a way for clinicians to integrate CBT-I into clinical practice. RECENT FINDINGS: Multiple studies support CBT-I as a validated modality for the treatment of insomnia in migraine. CBT-I is used to treat insomnia and should be offered as first line therapy. Clinicians should screen for insomnia in all patients with headache, especially in those with migraine, to best manage this condition through the implementation of specific insomnia treatment.

Migraine and Diet: Updates in Understanding.

PURPOSE OF REVIEW: We explore recent developments in the prevention and treatment of migraine through dietary interventions. RECENT FINDINGS: Healthier diets (defined in multiple ways), meal regularity, and weight loss are associated with decreased headache burden. Specific diets including the ketogenic diet, the low-glycemic index diet, and the DASH diet are supported by modest evidence for the prevention of migraine. Neither a gluten-free diet, in patients without celiac disease, nor elimination diets have sufficient evidence for their routine consideration. Diet remains a crucial, but underexplored, component of comprehensive migraine management. Multiple interventions exist for providers and patients to consider integrating into their treatment plan. Larger studies are needed to support stronger recommendations for utilization of specific dietary interventions for the prevention and treatment of migraine.

Medication overuse headache in patients with chronic migraine using cannabis: A case-referent study.

OBJECTIVE: To examine whether cannabis use predicts medication overuse headache (MOH) in patients with chronic migraine (CM). METHODS: Electronic chart review was conducted by combining the terms "CM," "medication overuse," "cannabis," "cannabidiol," and "tetrahydrocannabinol" for patients seen at our headache clinics from 2015 to 2019. Of 729 charts consecutively screened, 368 met our inclusion criteria, that is, adult patients with CM with ≥1-year CM duration. The following variables were extracted from the included patient charts: MOH diagnosis, age, sex, migraine frequency, current CM duration, current cannabis use duration, overused acute migraine medications, current MOH duration, and types of cannabis products used. Logistic regression was used to identify variables predicting MOH while controlling for remaining predictors. Agglomerative hierarchical clustering (AHC) was conducted to explore natural clusters using all predictor variables. RESULTS: There were 212 patients with CM and MOH (cases; median age 43 years, interquartile range [IQR] 33-54; 177 [83%] females) and 156 patients with CM without MOH (referents; median age 40 years, IQR 31-49; 130 [83%] females). MOH was present in 81% (122/150) of current cannabis users compared with 41% (90/218) in those without cannabis use-adjusted odds ratio 6.3 (95% CI: 3.56 to 11.1, p < 0.0001). Current cannabis use was significantly associated with opioid use (Spearman's rho 0.26, p < 0.0001). Both current cannabis use (rho 0.40, p < 0.0001) and opioid use (rho 0.36, p < 0.0001) were significantly associated with MOH. Similarly, AHC revealed two major natural clusters. Cluster I patients featured 9.3 times higher current cannabis use, 9.2 times higher current opioid use, and 1.8 times higher MOH burden than those in Cluster II (p < 0.0001). CONCLUSION: Cannabis use was significantly associated with increased prevalence of MOH in CM. Bidirectional cannabis-opioid association was observed-use of one was associated with use of the other. Advising patients with CM and MOH to reduce cannabis use may help treat MOH effectively.

Headache in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Narrative Review.

OBJECTIVE: To summarize available literature regarding headache as a manifestation of coronaviruses and to describe potential underlying mechanisms. REVIEW METHODS: References for this review were identified by searches within PubMed without any date restrictions. The search terms used were coronavirus disease 2019 (COVID-19) clinical manifestation, COVID-19 epidemiology, neurologic findings in COVID-19, headache in COVID-19, neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and headache in SARS-CoV-2. RESULTS: Headache is one of the most common neurologic complaints in patients with SARS-CoV-2. While the pathophysiological connection between headache and SARS-CoV-2 is unclear, inflammatory mechanisms may play a key role. One of the mechanisms cited in the literature of migraine and other headache disorders is the activation of nociceptive sensory neurons by cytokines and chemokines. A similar mechanism has been reported in SARS-CoV-2 with the release of cytokines and chemokines by macrophages throughout the course of infection. Other mechanisms for headache in SARS-CoV-2 include (1) viral neuroinvasion as seen with viral encephalitis; (2) hypoxemia due to the well-described pulmonary manifestations of the disease; and (3) thrombosis secondary to COVID-19 induced hypercoagulable states. CONCLUSION: According to the Centers for Disease Control, common symptoms of human coronavirus include fever, cough, runny nose, sore throat, and headache. In the case of SARS-CoV-2, there are limited reports about headaches, one of the most common clinical manifestations. There are currently no studies that focus specifically on headache among patients with SARS-CoV-2 infection.

Introducing the National Headache Fellowship Opportunities Website.

OBJECTIVE: To build a national Headache Medicine fellowship opportunities website that promotes a unified application timeline and a more transparent application process. BACKGROUND: In July 2019, the Consortium of Academic Headache Program Directors unanimously accepted the recommendations of the American Academy of Neurology Fellowship Application Timing Position Statement. To implement the unified application timeline, the American Headache Society agreed to host a fellowship opportunities website with information on the application process and resources for each fellowship program. METHODS: We designed a main landing page that features the unified timeline for applications and offers. The page also features icons for all participating US fellowship programs (identified using the United Council for Neurologic Subspecialties certification database). The icons serve as links to each fellowship program's individual webpage. We sent an electronic form to each fellowship program director, asking them to submit program information to be included on each fellowship program's individual webpage. Key contents on each program webpage include an image of the program, brief program description, names of applicants who have filled positions, and open positions. Each institution webpage also includes an electronic form that allows applicants to directly send their name, contact, and a brief message to the program director. RESULTS: We launched the website on May 15, 2020. As of June 19, 2020, the website featured 24 participating headache fellowship programs, including 5 pediatric programs and 19 adult training programs, from all regions of the US. CONCLUSION: The website serves as a central resource for Headache Medicine fellowship applicants and promotes a unified application timeline and a more transparent application process.

Reimagining Headache Fellowships.

In March of 2020, the COVID-19 pandemic led to drastic changes in clinical practice and teaching methods. This article relates the experience of developing an almost virtual headache fellowship in response to the pandemic.