Jennifer Robblee’s research while affiliated with Barrow Neurological Institute and other places

Objective Survey Latin American (LATAM) neurologists on their comfort with prescribing triptans in the setting of common contraindications. Background Triptans are associated with multiple contraindications due to 5-HT 1B -mediated vasoconstriction. A previous survey study examined the comfort level of headache specialists from the American Headache Society (AHS) in prescribing triptans in the setting of various contraindications, but this has not been studied in LATAM countries. Methods We sent a modified and translated survey to LATAM neurologists with headache management expertise grouped in the Latin American Headache Association (ASOLAC). The survey was extended to local Neurology Associations to increase the sample. An eleventh question on selective serotonin reuptake inhibitors (SSRI) use was added to the original 10 questions. Responses were assessed with descriptive statistics. Results There were 225 surveys analyzed from 10 LATAM countries. Notable results include that 54.2% (122/225) never use triptans in the setting of stroke, 60.9% (137/225) said never for dissection, and 70.2% (158/225) said never for reversible cerebral vasoconstriction syndrome (RCVS), but for venous thromboembolism responses were sometimes in 26.7% (60/225), rarely in 20.9% (47/225), and never in 31.6% (71/225). 57.8% (130/225) responded never for hemiplegic migraine but prolonged aura responses were 25.3% (57/225) sometimes, 25.3% (58/225) rarely, and 40.4% (91/225) never. Responses for use with aneurysms included 23.6% (53/225) sometimes, 15.6% (25/225) rarely, and 44.0% (99/225) never. For poorly controlled hypertension, 58.2% (131/225) said never. For pregnancy, 57.3% (129/225) reported never. Responses for age over 65 years included 35.6% (80/225) sometimes, 32.0% (72/225) rarely, and 22.2% (50/225) never. For SSRI use, responses were 22.7% (51/225) frequently, 38.7% (87/225) sometimes, and 24.0% (54/225) rarely. Conclusion Triptan contraindications were often considered absolute for RCVS, stroke, dissection, hemiplegic migraine, hypertension, and pregnancy. More studies are needed to clarify the true danger of triptan contraindications.

Purpose of Review This review discusses the diagnosis and treatment of nervus intermedius neuralgia (NIN) and identifies gaps in the literature. Recent Findings The nervus intermedius is a branch of the facial nerve. NIN presents as a rare neuralgia of this nerve, causing deep ear pain, which may radiate to the auditory canal, auricle, mastoid, soft palate, temple, and angle of the jaw. NIN most commonly presents in middle-aged women; neurovascular compression involving the anterior inferior cerebellar artery is the most common etiology described. Despite its diagnostic criteria in the International Classification of Headache Disorders, 3rd edition (ICHD-3), NIN may lack a trigger zone and may manifest as achy or neuralgiform pain instead of the typically described sharp or shooting pain. Like trigeminal neuralgia, NIN can be divided into classic, idiopathic, secondary, or painful neuropathy. Although there are no established guidelines for treating NIN, many possible treatments are used. Experience from treating trigeminal neuralgia suggests that carbamazepine or oxcarbazepine can be considered first-line. Patients with medically refractory NIN may benefit from neurosurgery referral for microvascular decompression or nerve sectioning. Summary More research is needed to elucidate the range of clinical presentations in patients with NIN. Current data are limited and suggest that symptoms may diverge from the ICHD-3 diagnostic criteria. Although various treatments have been attempted, they often lack solid evidence and are typically derived from approaches used for other neuralgias. Proper diagnosis is crucial, particularly when considering surgical referral, due to the potential overlap of NIN with other neuralgias affecting the head and neck.

Objectives Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients. Background SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72‐h duration is required before the attack can be treated as SM. Methods The Refractory Headache Special Interest Group from AHS developed a four‐question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed. Results Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72‐h period had elapsed. Most (76.0%, 149/196) chose “treat remotely using outpatient medications at home” as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti‐inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196). Conclusions Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management.

Objectives The primary objective of this proposed guideline is to update the prior 2016 guideline on parenteral pharmacotherapies for the management of adults with a migraine attack in the emergency department (ED). Methods We will conduct an updated systematic review and meta‐analysis using the 2016 guideline methodology to provide clinical recommendations. The same search strategy will be used for studies up to 2023, with a new search strategy added to capture studies of nerve blocks and sphenopalatine blocks. Medline, Embase, Cochrane, clinicaltrials.gov , and the World Health Organization International Clinical Trial Registry Platform will be searched. Our inclusion criteria consist of studies involving adults with a diagnosis of migraine, utilizing medications administered intravenously, intramuscularly, or subcutaneously in a randomized controlled trial design. Two authors will perform the selection of studies based on title and abstract, followed by a full‐text review. A third author will intervene in cases of disagreements. Data will be recorded in a standardized worksheet and subjected to verification. The risk of bias will be assessed using the American Academy of Neurology tool. When applicable, a meta‐analysis will be conducted. The efficacy of medications will be evaluated, categorizing them as “highly likely,” “likely”, or “possibly effective” or “ineffective.” Subsequently, clinical recommendations will be developed, considering the risk associated with the medications, following the American Academy of Neurology recommendation development process. Results The goal of this updated guideline will be to provide guidance on which injectable medications, including interventional approaches (i.e., nerve blocks, sphenopalatine ganglion), should be considered effective acute treatment for adults with migraine who present to an ED. Conclusions The methods outlined in this protocol will be used in the design of a future systematic review and meta‐analysis‐informed guideline, which will then be assessed by and submitted for endorsement by the American Headache Society.

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.

Background Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene–related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. Methods This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). Results The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. Conclusions Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. Trial registration ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309). Graphical Abstract

Background Refractory migraine is a poorly described complication of migraine in which migraine has chronified and become resistant to standard treatments. The true prevalence is unknown, but medication resistance is common in headache clinic patient populations. Given the lack of response to treatment, this patient population is extremely difficult to treat with limited guidance in the literature. Objective To review the diagnostic, pathophysiological, and management challenges in the refractory migraine population. Discussion There are no accepted, or even ICHD-3 appendix, diagnostic criteria for refractory migraine though several proposed criteria exist. Current proposed criteria often have low bars for refractoriness while also not meeting the needs of pediatrics, lower socioeconomic status, and developing nations. Pathophysiology is unknown but can be hypothesized as a persistent “on” state as a progression from chronic migraine with increasing central sensitization, but there may be heterogeneity in the underlying pathophysiology. No guidelines exist for treatment of refractory migraine; once all guideline-based treatments are tried, treatment consists of n-of-1 treatment trials paired with non-pharmacologic management. Conclusion Refractory migraine is poorly described diagnostically, its pathophysiology can only be guessed at by extension of chronic migraine, and treatment is more the art than science of medicine. Navigating care of this refractory population will require multidisciplinary care models and an emphasis on future research to answer these unknowns.

Purpose of Review The purpose of the study is to review and discuss the use of telemedicine in headache medicine. Recent Findings Before the COVID-19 pandemic, the use of telemedicine for headache was most common in Europe. In recent years, however, telemedicine has been used broadly within headache medicine, including for pediatric patients and behavioral interventions. Several randomized clinical trials have shown that telemedicine is non-inferior to face-to-face visits. Multiple studies have reported substantial benefits associated with telemedicine, including high satisfaction rates, improved access to headache specialists, reduced travel, quicker visits, greater cost-effectiveness, reduced wait times, reduced no-show rates, and the increased comfort of remaining in one’s home environment. The main limitation reported is the lack of a physical examination, including fundus assessment. Summary Telemedicine has become a vital tool in headache patient care, with the data supporting its use for patient follow-up in particular.