Sustained response to atogepant in episodic migraine: post hoc analyses of a 12-week randomized trial and a 52-week long-term safety trial.

BACKGROUND: Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment. METHODS: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety issues. An initial response was defined as ≥50%, ≥75%, or 100% reduction from baseline in MMDs in month 1 for ADVANCE or quarter 1 for the LTS trial. The proportions of participants who continued to experience a response above each response-defining threshold through each subsequent month (for ADVANCE) or each quarter (for LTS) were calculated. RESULTS: In ADVANCE, sustained response rates during months 2 and 3 varied with dose and were as follows: 70.8-81.1% following an initial ≥50% response, 47.3-61.9% following an initial ≥75% response, and 34.8-41.7% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during month 1, more than 79% continued to experience at least a 50% response during both months 2 and 3. During the LTS trial, sustained response rates through quarters 2, 3, and 4 were 84.7% following an initial ≥50% response, 72.6% following an initial ≥75% response, and 37.8% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during quarter 1, more than 90% continued to experience at least a 50% response through quarters 2, 3, and 4. CONCLUSION: Over 70% of participants who experienced an initial response with atogepant treatment had a sustained response with continued treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03777059 (submitted: December 13, 2018); NCT03700320 (submitted: September 25, 2018).

Cranial Neuralgias.

OBJECTIVE: The cranial neuralgias are relatively rare, but recognizing these syndromes and distinguishing among them is critical to reducing unnecessary pain and disability for affected patients. Despite their distinctive features, cranial neuralgias may go undiagnosed or misdiagnosed for several years. A notable proportion of cranial neuralgia presentations are due to secondary causes and require targeted treatment. The purpose of this article is to review the diagnosis and management of cranial neuralgias encountered in clinical practice. LATEST DEVELOPMENTS: In 2020, the International Classification of Orofacial Pain was released for the first time. Modeled after the International Classification of Headache Disorders, it includes updated terminology for cranial neuralgias. The underlying pathophysiology of the cranial neuralgias is currently believed to be rooted in both peripheral and central nociceptive systems. In addition, a growing number of familial cases are being identified. Recent therapeutic advancements include a better understanding of how to utilize older therapies and procedures more effectively as well as the development of newer approaches. ESSENTIAL POINTS: Cranial neuralgia syndromes are rare but important to recognize due to their debilitating nature and greater likelihood of having potentially treatable underlying causes. While management options have remained somewhat limited, scientific inquiry is continually advancing the understanding of these syndromes and how best to address them.

Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials.

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).

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Risk factors for migraine disease progression: a narrative review for a patient-centered approach.

BACKGROUND: In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache subspecialty practice, but there may be less awareness in general neurology or primary care settings where most people with migraine who seek treatment consult. Herein, we review the definition of and risk factors for migraine progression and consider strategies that could reduce its risk. METHODS: A group of headache expert healthcare professionals, clinicians, and researchers reviewed published evidence documenting factors associated with increased or decreased rates of migraine progression and established expert opinions for disease management recommendations. Strength of evidence was rated as good, moderate, or based solely on expert opinion, using modified criteria for causation developed by AB Hill. RESULTS: Migraine progression is commonly operationally defined as the transition from ≤ 15 to ≥ 15 monthly headache days among people with migraine; however, this does not necessarily constitute a fundamental change in migraine biology and other definitions should be considered. Established and theoretical key risk factors for migraine progression were categorized into five domains: migraine disease characteristics, treatment-related factors, comorbidities, lifestyle/exogenous factors, and demographic factors. Within these domains, good evidence supports the following risk factors: poorly optimized acute headache treatment, cutaneous allodynia, acute medication overuse, selected psychiatric symptoms, extra-cephalic chronic pain conditions, metabolism-related comorbidities, sleep disturbances, respiratory conditions, former/current high caffeine intake, physical inactivity, financial constraints, tobacco use, and personal triggers as risk factors. Protective actions that may mitigate migraine progression are sparsely investigated in published literature; our discussion of these factors is primarily based on expert opinion. CONCLUSIONS: Recognizing risk factors for migraine progression will allow healthcare providers to suggest protective actions against migraine progression (Supplementary Fig. 1). Intervention studies are needed to weight the risk factors and test the clinical benefit of hypothesized mitigation strategies that emerge from epidemiological evidence.

Persistence to anti-CGRP monoclonal antibodies and onabotulinumtoxinA among patients with migraine: a retrospective cohort study.

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA. METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same drug (anti-CGRP mAb or onabotulinumtoxinA) without a ≥ 15-day gap in medication supply on/after June 25, 2020, to December 31, 2021. Patients were indexed at the start of their most recent episode. Patients were considered non-persistent and discontinued the therapy associated with their most recent episode if there was ≥ 15-day gap in medication supply. A Cox proportional-hazards model estimated the discontinuation hazard between treatments. The gap periods and cohort definition were varied in sensitivity analyses. RESULTS: The study included 66,576 patients (median age 46 years, 88.6% female). More eptinezumab-treated patients had chronic migraine (727/1074), ≥ 3 previous acute (323/1074) or preventive (333/1074) therapies, and more prior treatment episodes (3) than other treatment groups. Based on a 15-day treatment gap, patients on subcutaneous anti-CGRP mAbs had a 32% (95% CI: 1.19, 1.49; erenumab), 42% (95% CI: 1.27, 1.61; galcanezumab), and 58% (95% CI: 1.42, 1.80; fremanezumab) higher discontinuation hazard than those receiving eptinezumab, with this relationship attenuated, but still statistically significant based on 30-day and 60-day treatment gaps. There was no significant difference in the discontinuation hazard between eptinezumab and onabotulinumtoxinA. Based on a 15-day treatment gap among patients who newly initiated therapy, the discontinuation hazard of subcutaneous anti-CGRP mAbs remained significantly higher compared to eptinezumab and onabotulinumtoxinA. CONCLUSION: Patients treated with eptinezumab demonstrated persistency that was higher than subcutaneous anti-CGRP mAbs and similar to onabotulinumtoxinA.

The Safety of Celecoxib as an Acute Treatment for Migraine: A Narrative Review.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first-line choice for the acute treatment of migraine attacks for decades; however, the safety of a particular NSAID is related to its treatment dose, duration, and mechanism of action. Although adverse event (AE) risks differ substantially among individual migraine treatments, increased or prolonged exposure to any NSAID elevates risks and severity of AEs. METHODS: For this narrative review, we conducted a literature search of PubMed until July 2022, focusing on the history, mechanism of action, and treatment guidelines informing the safety and efficacy of celecoxib oral solution for the acute treatment of migraine attacks. RESULTS: Here we discuss the mechanisms of action of nonselective NSAIDs vs. cyclooxygenase-2 (COX-2) inhibitors, and how these mechanisms underlie the AEs associated with these treatments. We review the clinical trials that influenced the regulatory history of NSAIDs, specifically COX-2 inhibitors, the role of traditional and new formulations of NSAIDs including celecoxib oral solution, and special considerations in the acute treatment of migraine attacks. CONCLUSIONS: Low-dose formulations of NSAIDs, such as celecoxib oral solution, provide acute migraine analgesia with similar or fewer associated cardiovascular and gastrointestinal events than previous formulations.

Optimized Acute Treatment of Migraine Is Associated With Greater Productivity in People With Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: This study aimed to ascertain whether level of optimization of acute treatment of migraine is related to work productivity across the spectrum of migraine. METHODS: Data were from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, an internet-based longitudinal survey. Respondents with migraine who reported full-time employment and use of ≥1 acute prescription medication for migraine were included. We determined relationships among lost productive time (LPT; measured with the Migraine Disability Assessment Scale), acute treatment optimization (Migraine Treatment Optimization Questionnaire- ), and monthly headache days (MHDs). RESULTS: There was a direct relationship between LPT and MHD category. Greater acute treatment optimization was associated with lower total LPT, less absenteeism, and less presenteeism within each MHD category. CONCLUSIONS: Optimizing acute treatment for migraine may reduce LPT in people with migraine and reduce indirect costs.

Erenumab dosage for migraine prevention: An evidence-based narrative review with recommendations.

BACKGROUND: Therapeutic monoclonal antibodies against the calcitonin gene-related peptide (CGRP) receptor or its ligand have changed the landscape of treatment options for migraine. Erenumab is the first and only fully human monoclonal antibody designed to target and block the CGRP receptor. It is approved by the Food and Drug Administration for preventive treatment of migraine in adults. The recommended dose of erenumab is 70 mg monthly, with guidance that some patients may benefit from the 140 mg monthly dose. There is a need for information to guide clinical practice on the comparative efficacy and safety of these two dosing options. OBJECTIVE: To evaluate therapeutic and tolerability differences between erenumab 70 and 140 mg based on evidence from published literature. METHODS: This narrative review evaluates therapeutic and tolerability differences between erenumab 70 and 140 mg based on a literature search using PubMed interface, Embase and Ovid MEDLINE(R) databases. The key search terms included migraine, AMG 334, AMG334, erenumab, erenumab-aooe, and Aimovig. The search was limited to English language articles or conference abstracts published up to May 2021. RESULTS: From the literature search, we retrieved 23 relevant articles/conference abstracts (19 articles [5 randomized, double-blind studies] and 4 conference abstracts) for inclusion in this narrative review. Although the recommended starting dosage of erenumab is 70 mg, this narrative review of the literature indicates that some patients may benefit from a dosage of 140 mg erenumab once monthly-especially those with difficult-to-treat disease and prior treatment failures. The evidence indicates that erenumab at 140 mg has a numerically better efficacy than 70 mg across a broad spectrum of migraine outcomes, including preventing progression to chronic migraine. CONCLUSION: Cumulative data from the literature support a therapeutic gain with an increase from erenumab 70 to 140 mg and a rationale for initiating 140 mg in selected patients.

Beyond the Raskin Protocol: Ketamine, Lidocaine, and Other Therapies for Refractory Chronic Migraine.

PURPOSE OF REVIEW: The purpose of this review is to discuss the available evidence and therapeutic considerations for intravenous drug therapy for refractory chronic migraine. RECENT FINDINGS: In carefully monitored settings, the inpatient administration of intravenous lidocaine and ketamine can be successful in treating refractory chronic migraine. Many patients with refractory chronic migraine have experienced treatment failure with the Raskin protocol. The use of aggressive inpatient infusion therapy consisting of intravenous lidocaine or ketamine, along with other adjunctive medications, has become increasingly common for these patients when all other treatments have failed. There is a clear need for prospective studies in this population comprised of patients who have largely been excluded from other studies.

Efficacy and safety of fremanezumab in clinical trial participants aged ≥60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies.

BACKGROUND: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM). METHODS: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and FOCUS study in participants with EM or CM and prior inadequate response to 2-4 migraine preventive medication classes. Participants in all studies were randomized 1:1:1 to receive 12 weeks of subcutaneous treatment with quarterly fremanezumab (Months 1/2/3: EM/CM, 675 mg/placebo/placebo), monthly fremanezumab (Months 1/2/3: EM, 225 mg/225 mg/225 mg; CM, 675 mg/225 mg/225 mg), or matched monthly placebo. RESULTS: These pooled analyses included 246 participants aged ≥60 years. Reductions in monthly migraine days from baseline over 12 weeks were significantly greater with fremanezumab (least-squares mean change from baseline [standard error]: quarterly fremanezumab, - 4.3 [0.59]; monthly fremanezumab, - 4.6 [0.54]) versus placebo (placebo, - 2.3 [0.57]; both P < 0.01 vs placebo). As early as Week 1, significant reductions from baseline in weekly migraine days were observed with fremanezumab versus placebo (both P < 0.01). With fremanezumab treatment versus placebo, a significantly higher proportion of participants achieved ≥50% reduction in monthly migraine days, and significant improvements in disability and quality-of-life outcomes were observed (P < 0.05). Proportions of participants experiencing serious adverse events and adverse events leading to discontinuation were low and similar in the fremanezumab and placebo groups. Efficacy and safety results were comparable to the overall pooled population (N = 2843). CONCLUSIONS: This pooled subgroup analysis demonstrates that fremanezumab treatment is efficacious and well-tolerated over 12 weeks in participants aged ≥60 years with EM or CM. These data may help healthcare providers with clinical decision making and preventive treatment selection for older patients with migraine. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: HALO CM: NCT02621931 ; HALO EM: NCT02629861 ; FOCUS: NCT03308968 .

Cluster Headache and Other Trigeminal Autonomic Cephalalgias.

PURPOSE OF REVIEW: The trigeminal autonomic cephalalgias (TACs) are relatively rare, but they represent a distinct set of syndromes that are important to recognize. Despite their unique features, TACs often go undiagnosed or misdiagnosed for several years, leading to unnecessary pain and suffering. A significant proportion of TAC presentations may have secondary causes. RECENT FINDINGS: The underlying pathophysiology of TACs is likely rooted in hypothalamic dysfunction and derangements in the interplay of circuitry involving trigeminovascular, trigeminocervical, trigeminoautonomic, circadian, and nociceptive systems. Recent therapeutic advancements include a better understanding of how to use older therapies more effectively and the identification of new approaches. SUMMARY: TAC syndromes are rare but important to recognize because of their debilitating nature and greater likelihood for having potentially serious underlying causes. Although treatment options have remained somewhat limited, scientific inquiry is continually advancing our understanding of these syndromes and how best to manage them.

Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine.

OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine. BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks. METHODS: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a qualifying attack with M207 3.8 mg (intracutaneous zolmitriptan). Participants underwent clinical evaluations at specified intervals up to 12 months. RESULTS: Among 335 participants who treated ≥1 migraine attack, 257 completed 6 months and 127 completed 1 year of treatment. The most common reason for withdrawal from the study was a low frequency of reported attacks post randomization. Overall, 5963 migraine attacks were treated. Most participants (96%) experienced at least 1 adverse event, the vast majority of which concerned the application site, and > 95% of which were mild. Fifteen participants (4%) withdrew due to adverse events; 4 withdrew due to 7 application site reactions, 6 of which were mild. Participants achieved pain freedom in 2477/5617 (44%) of attacks, most bothersome symptom freedom in 3315/5330 (62%) of attacks, and pain relief 2 h post-dose in 4552/5617 (81%) of attacks. Sustained pain freedom 2-24 h was seen in 1761/4698 (38%) of attacks, and 2-48 h in 1534/4429 (35%) of attacks. CONCLUSIONS: The majority of participants experienced cutaneous adverse reactions such as application site erythema, swelling, and bleeding, and most reactions were scored as mild. These results are consistent with what was observed in the single migraine attack treatment ZOTRIP trial indicating that M207 is well tolerated in the setting of longer-term repeated use. Efficacy findings were also similar to those in the ZOTRIP trial. TRIAL REGISTRATION: Clinicaltrials.gov on September 13, 2017 ( NCT03282227 ).

Biomarkers in Migraine.

BACKGROUND: Disability from migraine has a profound impact on the world's economy. Research has been ongoing to identify biomarkers to aid in diagnosis and treatment. OBJECTIVE: The aim of this study was to highlight the purported diagnostic and therapeutic migraine biomarkers and their role in precision medicine. METHODS: A comprehensive literature search was conducted using PubMed, Google Scholar, and clinicaltrials.gov using keywords: "migraine" OR "headache" combined with "biomarkers" OR "marker." Other keywords included "serum," "cerebral spinal fluid," "inflammatory," and "neuroimaging." RESULTS: After a review of 88 papers, we find the literature supports numerous biomarkers in the diagnosis of migraine. Therapeutic biomarkers, while not as extensively published, highlight calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide-38 (PACAP-38) as biomarkers with the most substantiated clinical relevance. Genetic markers mainly focusing on gene mutations with resultant biochemical alterations continue to be studied and show promise. CONCLUSION: Although there are several proposed biomarkers for migraine, continued research is needed to substantiate their role in clinical practice.

Unusual Brain MRI Findings in Patients Imaged for Headache: a Case Series.

PURPOSE OF REVIEW: We describe a series of cases with unusual brain MRI findings in patients who present with headache disorders. RECENT FINDINGS: Incidental findings in patients imaged for headache include the following: aneurysm, arachnoid cyst, cerebral vascular malformations, Arnold-Chiari malformations, empty sella turcica, gray matter heterotopias, mastoiditis, mega cisterna magna, meningioma, normal variants of cerebral circulation, paranasal sinus disease, pineal cyst, pituitary tumor, Rathke's cleft cyst, skull hyperostosis, and vestibular schwannoma. The most common abnormal MRI findings encountered in migraine are nonspecific white matter lesions. The current 2019 guidelines from the American College of Radiology and American Headache Society recommend against ordering neuroimaging in patients with a high probability of a primary headache disorder not typically associated with diagnostic imaging findings and who have normal neurologic exam in addition to no red flags in history. Often, unnecessary neuroimaging yields incidental findings, and this typically results in patient anxiety and further unnecessary testing. Detailed below are a series of cases in which unusual findings were found in patients presenting to our clinic for further evaluation of headache disorders. Imaging may have been done prior to presentation to us or by us due to concern for secondary causes.

Updated Evaluation of IV Dihydroergotamine (DHE) for Refractory Migraine: Patient Selection and Special Considerations.

Dihydroergotamine (DHE) is an ergot alkaloid derivative of substances produced by rye fungus. Ergotamine was first used in the field of gynecology and obstetrics, then used for migraine treatment a few years later. DHE was developed as a derivative of ergotamine. DHE, when compared to ergotamine, demonstrates greater alpha-adrenergic antagonist activity, lower arterial vasoconstriction, less dopaminergic agonism, and lower emetic potential. DHE can be delivered via several routes including intravenous (IV), intramuscular (IM), subcutaneous (SC), intranasal (IN), oral, and orally inhaled (although the latter two are not available in the USA and the last remains experimental only). DHE can be used in an outpatient basis in infusion centers, emergency departments, and urgent care centers, as well as inpatient treatment for admitted patients. There are protocols for adults as well as pediatric migraine treatment. DHE and other ergot alkaloids are considered contraindicated in pregnant women as they decrease uterine blood flow and increase uterine muscle contractility predisposing to spontaneous abortion. DHE during lactation is also not recommended as it can lead to gastrointestinal distress and weakness in infants; it can also suppress milk production. Caution should be taken before administering DHE in patients with cardiovascular risk factors. DHE is an older drug with an interesting history, yet it is still clinically useful today for patients with migraine attacks not responsive to triptans, who have a greater burden from migraine, and in refractory migraine.

Correction to: Diving Headache.

The original version of this article incorrectly listed the second author's name. It should be Stephanie J. Nahas, not Stephanie J. Nahas-Geiger. The author name is corrected in this erratum.

Diving Headache.

This review will focus on the most recent information regarding the ICHD-3 definition of diving headache as well as other important causes of diving headache that are not listed in the ICHD-3 classification system. The paper will discuss etiology, diagnosis, and management of these disorders, focusing, when possible, on the newest research available. ICHD-3 diving headache is due to hypercapnia and is treated accordingly with oxygen. Other causes of diving headache range from decompression sickness to external compression headache to primary headache disorders, such as migraine. Correctly determining the underlying cause of the diving headache is critical to management and relies on history taking and physical exam. The pathophysiology of newly described types of diving headache, such as diving ascent headache, remains under investigation but may be related to other homeostatic headache causes, such as airplane headache. Further investigation may yield more information regarding management as well as possible insight into other headache disorders.

Nummular Headache.

PURPOSE OF REVIEW: This article reviews nummular headache (NH), including the latest literature on the epidemiological and clinical features, the most recent proposed pathophysiology, and novel management. RECENT FINDINGS: NH is characterized by continuous or intermittent head pain confined to a focal circumscribed area (1-6 cm in diameter). It is usually of mild to moderate intensity, although some patients have severe continuous pain or disabling exacerbations. NH is a primary headache, though many secondary cases have been described. Evaluation requires exclusion of systemic and structural diseases. Gabapentin can be recommended as a first-line preventive treatment. If poorly tolerated or in refractory cases, botulinum toxin is a reasonable alternative. NH is a fairly common disorder in patients presenting to a headache clinic. Increased understanding of NH will lead to improved outcomes. Clinical trials would lead to enhanced knowledge of NH.