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Migraine is a debilitating disease whose clinical and social impact is out of debate. Tolerability issues, interactions, contraindications, and inefficacy of the available medications make new options necessary. The calcitonin-gene-related peptide (CGRP) pathway has shown its importance in migraine pathophysiology and specific medications targeting this have become available. The first-generation CGRP receptor antagonists or gepants, have undergone clinical trials but their development was stopped because of hepatotoxicity. The new generation of gepants, however, are efficacious, safe, and well tolerated as per recent clinical trials. This led to the FDA-approval of rimegepant, ubrogepant, and atogepant. The clinical trials of the available gepants and some of the newer CGRP-antagonists are reviewed in this article.
Learn More >The aim of this study was to identify the manual therapy (MT) methods and techniques that have been evaluated for the treatment of cervicogenic headache (CH) and their effectiveness.
Learn More >Background Mutations in gene encoding the Na,K-ATPase α isoform are associated with familial hemiplegic migraine type 2. Migraine with aura is a known risk factor for heart disease. The Na,K-ATPase is important for cardiac function, but its role for heart disease remains unknown. We hypothesized that is a susceptibility gene for heart disease and aimed to assess the underlying disease mechanism. Methods and Results Mice heterozygous for the familial hemiplegic migraine type 2-associated G301R mutation in the gene (α mice) and matching wild-type controls were compared. Reduced expression of the Na,K-ATPase α isoform and increased expression of the α isoform were observed in hearts from α mice (Western blot). Left ventricular dilation and reduced ejection fraction were shown in hearts from 8-month-old α mice (cardiac magnetic resonance imaging), and this was associated with reduced nocturnal blood pressure (radiotelemetry). Cardiac function and blood pressure of 3-month-old α mice were similar to wild-type mice. Amplified Na,K-ATPase-dependent Src kinase/Ras/Erk1/2 (p44/42 mitogen-activated protein kinase) signaling was observed in hearts from 8-month-old α mice, and this was associated with mitochondrial uncoupling (respirometry), increased oxidative stress (malondialdehyde measurements), and a heart failure-associated metabolic shift (hyperpolarized magnetic resonance). Mitochondrial membrane potential (5,5´,6,6´-tetrachloro-1,1´,3,3´-tetraethylbenzimidazolocarbocyanine iodide dye assay) and mitochondrial ultrastructure (transmission electron microscopy) were similar between the groups. Proteomics of heart tissue further suggested amplified Src/Ras/Erk1/2 signaling and increased oxidative stress and provided the molecular basis for systolic dysfunction in 8-month-old α mice. Conclusions Our findings suggest that mutation leads to disturbed cardiac metabolism and reduced cardiac function mediated via Na,K-ATPase-dependent reactive oxygen species signaling through the Src/Ras/Erk1/2 pathway.
Learn More >Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse.
Learn More >Immunogenicity of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody developed for migraine prevention, has been evaluated throughout clinical development.
Learn More >It is important to find effective and safe pharmacological options for managing cluster headache (CH) because there is limited evidence from studies supporting the general efficacy and safety of pharmacological therapies. This systematic review and network meta-analysis (NMA) analyzed published randomized controlled trials (RCTs) to evaluate the efficacy and safety of pharmacological treatments in patients with CH. The PubMed and Embase databases were searched to identify RCTs that evaluated the efficacy and safety of pharmacological treatments for CH. Efficacy outcomes included frequency and duration of attacks, pain-free rate, and the use of rescue agents. Safety outcomes were evaluated based on the number of patients who experienced adverse events. A total of 23 studies were included in the analysis. The frequency of attacks was reduced (mean difference (MD) = -1.05, 95% confidence interval (CI) = -1.62 to -0.47; = 0.0004), and the pain-free rate was increased (odds ratio (OR) = 3.89, 95% CI = 2.76-5.48; < 0.00001) in the pharmacological treatment group, with a lower frequency of rescue agent use than the placebo group. Preventive, acute, and triptan or non-triptan therapies did not show significant differences in efficacy ( > 0.05). In the NMA, different results were shown among the interventions; for example, zolmitriptan 5 mg was more effective than zolmitriptan 10 mg in the pain-free outcome (OR = 0.40, 95% CI = 0.19-0.82; < 0.05). Pharmacological treatment was shown to be more effective than placebo to manage CH with differences among types of therapies and individual interventions, and it was consistently shown to be associated with the development of adverse events. Thus, individualized therapy approaches should be applied to treat CH in real-world practice.
Learn More >Postcraniotomy headache (PCH) is a highly underappreciated and very common adverse event following craniotomy.
Learn More >The Neck Disability Index (NDI) is a self-rated disability tool originally developed for whiplash associated disorders and validated in cervical musculoskeletal conditions. It is now commonly used to assess neck disability in migraine but it is unknown whether NDI scores relate to migraine and hypersensitivity, cervical musculoskeletal dysfunction or both. This single-blinded observational study aimed to determine whether the presence of cervical musculoskeletal dysfunction, migraine features and hypersensitivity predict NDI scores and whether alternate versions of the NDI (NDI-physical, NDI-8, NDI-5) relate more to cervical musculoskeletal dysfunction.
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