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.

Purpose of review: Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug–drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients. Recent findings: After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials. Summary: Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest efficacy. Atogepant has shown efficacy in migraine prevention in a phase II/III study. Most importantly, hepatotoxicity has not been reported in specifically designed phase I studies or long-term extension studies, with rimegepant or ubrogepant, or in a preventive study with atogepant. Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. Because of the particular benefit gepants may represent for these groups of patients, specific studies in patients with medication overuse headache, as well as those with comorbid cardiovascular diseases, would be of considerable interest.

Brain positron emission tomography imaging with 18Fluorine-fluorodeoxyglucose (FDG-PET) has demonstrated utility in suspected autoimmune encephalitis. Visual and/or assisted image reading is not well established to evaluate hypometabolism/hypermetabolism. We retrospectively evaluated patients with autoimmune encephalitis between 2003 and 2018. Patients underwent EEG, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) sampling and autoantibodies testing. Individual FDG-PET images were evaluated by standard visual reading and assisted by voxel-based analyses, compared to a normal database. For the latter, three different methods were performed: two based on statistical surface projections (Siemens syngo.via Database Comparison, and 3D-SSP Neurostat) and one based on statistical parametric mapping (SPM12). Hypometabolic and hypermetabolic findings were grouped to identify specific patterns. We found six cases with definite diagnosis of autoimmune encephalitis. Two cases had anti-LGI1, one had anti-NMDA-R and two anti-CASPR2 antibodies, and one was seronegative. ¹⁸F-FDG-PET metabolic abnormalities were present in all cases, regardless of the method of analysis. Medial–temporal and extra-limbic hypermetabolism were more clearly depicted by voxel-based analyses. We found autoantibody-specific patterns in line with the literature. Statistical surface projection (SSP) methods (Neurostat and syngo.via Database Comparison) were more sensitive and localized larger hypermetabolic areas. As it may lead to comparable and accurate results, visual analysis of FDG-PET studies for the diagnosis of autoimmune encephalitis benefits from voxel-based analysis, beyond the approach based on MRI, CSF sample and EEG.

Background: Indomethacin is a nonsteroidal anti‐inflammatory drug whose mechanism of action in certain types of headache disorders remains unknown. The so‐called indomethacin‐responsive headache disorders consist of a group of conditions with a very different presentation that have a particularly good response to indomethacin. The response is so distinct as to be used in the definition of two: hemicrania continua and paroxysmal hemicrania. Methods: This is a narrative literature review. PubMed and the Cochrane databases were used for the literature search. Results: We review the main pharmacokinetic and pharmacodynamics properties of indomethacin useful for daily practice. The proposed mechanisms of action of indomethacin in the responsive headache disorders, including its effect on cerebral blood flow and intracranial pressure, with special attention to nitrergic mechanisms, are covered. The current evidence for its use in primary headache disorders, such as some trigeminal autonomic cephalalgias, cough, hypnic, exertional or sexual headache, and migraine will be covered, as well as its indication for secondary headaches, such as those of posttraumatic origin. Conclusion: Increasing understanding of the mechanism(s) of action of indomethacin will enhance our understanding of the complex pathophysiology that might be shared by indomethacin‐sensitive headache disorders.

Vestibular migraine (VM) commonly causes recurrent vertigo, but diagnosing and managing it can be difficult due to symptom overlap with other vestibular and headache disorders. This review provides a comprehensive update on VM, beginning with the diagnostic criteria established by the International Headache Society and the Bárány Society, who have increased awareness of this condition. While the pathophysiology is not yet completely understood, there is evidence of a complex interaction between the nociceptive and vestibular systems. Treatment approaches are primarily empirical and lack robust, high-quality evidence. Often, antihistamines and benzodiazepines are used for quick symptom relief, while the efficacy of triptans is still uncertain. Preventive measures include lifestyle changes, vestibular rehabilitation, oral migraine prophylactics, Botulinum toxin type A, and, more recently, CGRP-targeted therapies. Due to diagnostic uncertainties and the absence of standardised treatment protocols, further research—particularly randomised controlled trials—is crucial for establishing evidence-based guidelines.