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.

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 .

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.

Headache and temporal arteritis: when to suspect and how to manage.

Temporal arteritis, also termed giant cell arteritis, is one of the vasculitides affecting large and medium sized cranial arteries, particularly of the carotid tree. Clinical manifestations may vary from the classic constellation of temporal headache in the elderly accompanied by constitutional signs, jaw claudication, and visual symptoms; therefore, a high index of clinical suspicion may be necessary to identify the disorder. Once suspected, immediate treatment is crucial while exploring any number of diagnostic tools to confirm or refute the diagnosis, since morbidity from untreated temporal arteritis can be devastating. At the same time, achieving a definitive diagnosis is paramount, as treatment can be toxic with significant morbidity of its own. Temporal artery biopsy remains the gold standard, but noninvasive diagnostic approaches are being refined. Corticosteroids remain the cornerstone of treatment, but are ineffective for, not tolerated by, or contraindicated in some individuals, necessitating the exploration of alternatives.