Novel knowledge about the interrelationships and reciprocal effects of migraine and epilepsy, migraine and mood disorders, or migraine and irritable bowel syndrome has emerged in recent decades. Over time, comorbid pathologies associated with migraine that share common physiopathological mechanisms were studied. Among these studied pathologies is epilepsy, a disorder with common ion channel dysfunctions as well as dysfunctions in glutamatergic transmission. A high degree of neuronal excitement and ion channel abnormalities are associated with epilepsy and migraine and antiepileptic drugs are useful in treating both disorders. The coexistence of epilepsy and migraine may occur independently in the same individual or the two may be causally connected. The relationship between cortical spreading depression (CSD) and epileptic foci has been suggested by basic and clinical neuroscience research. The most relevant psychiatric comorbidities associated with migraine are anxiety and mood disorders, which influence its clinical course, treatment response, and clinical outcome. The association between migraine and major depressive disorder can be explained by a robust molecular genetic background. In addition to its role as a potent vasodilator, CGRP is also involved in the transmission of nociception, a phenomenon inevitably linked with the stress and anxiety caused by frequent migraine attacks. Another aspect is the role of gut microbiome in migraine’s pathology and the gut–brain axis involvement. Irritable bowel syndrome patients are more likely to suffer migraines, according to other studies. There is no precise explanation for how the gut microbiota contributes to neurological disorders in general and migraines in particular. This study aims to show that migraines and comorbid conditions, such as epilepsy, microbiota, or mood disorders, can be connected from the bench to the bedside. It is likely that these comorbid migraine conditions with common pathophysiological mechanisms will have a significant impact on best treatment choices and may provide clues for future treatment options.

Background/Objectives: This study investigated the frequency and timing of optic neuritis (ON) episodes in relation to the onset of multiple sclerosis (MS) and examined the occurrence of Uhthoff’s phenomenon and Lhermitte’s sign to understand their roles in early diagnosis and disease progression. Methods: A longitudinal study was conducted with 127 MS patients. Clinical data, including ophthalmological examinations for ON, were collected and questionnaires assessed the presence of Uhthoff’s phenomenon and Lhermitte’s sign. Results: Results showed that 37% of patients experienced demyelinating retrobulbar ON, with 25.53% having ON as the initial symptom of MS. Residual visual acuity impairment (below 20/40) and dyschromatopsia were reported by 25.53% and 17.02% of patients, respectively. Uhthoff’s phenomenon and Lhermitte’s sign were present in 26.77% and 36.22% of patients, respectively. The findings underscore the importance of early ophthalmological assessments in diagnosing MS, as ON can be an initial indicator of the disease. Conclusions: The study highlights the need for precise diagnostic tools and personalized therapeutic strategies focused on specific biomarkers and pathways involved in neuroinflammation and demyelination. Early diagnosis through vigilant ophthalmologic evaluation can lead to interventions that significantly alter disease progression, improving patient outcomes and quality of life.

Multiple sclerosis is a chronic and progressive neurological disease, with an important socio-economic burden. Over time, an increased incidence of headaches like migraines and tension headaches has been observed among these patients. Headaches have not been considered as multiple sclerosis-related symptoms, even representing a red flag for multiple sclerosis diagnosis. It is uncertain whether the headache–multiple sclerosis association could be explained by the presence of common triggers or a common physiopathological mechanism (involvement of tertiary B-cell follicles). An important differential diagnosis is between multiple sclerosis attacks and migraines with aura, which can also be associated with neurological deficits. Another important aspect is the occurrence or exacerbation of the cephalalgic syndrome after the initiation of therapy for multiple sclerosis (DMTs), or the improvement of headache after the initiation of certain DMT drugs. In addition to headaches, individuals diagnosed with multiple sclerosis often report experiencing diverse pain syndromes, contributing to an additional decline in their overall quality of life. These syndromes are frequently neglected, the focus being on slowing down the progression of neurological deficits. This review aims to evaluate the characteristics of multiple-sclerosis-related headaches (frequency, possible correlation with attacks, and disease-modifying therapies) and the key distinctions in imaging characteristics between demyelinating lesions in multiple sclerosis and those observed in cases of primary headaches.

Migraine severely impacts the quality of life of young adults. During the past few years, many studies have been done regarding the pathophysiology of this condition. There has been intense debate regarding CGRP, but research is still underway about the glymphatic system and PACAP. This review provides an overview of the current literature in this area of migraine pathophysiology. The inflammatory mediators and neuropeptides that activate trigeminovascular pathways can be accumulated during migraine attacks as a result of a failure of glymphatic clearance. Neuroinflammation, CGRP, CSD, and sleep have all been linked to the glymphatic system and migraine. In this article, we also discuss the latest hypotheses regarding the PACAP pathway in the neurophysiology of migraine. Additionally, recent research suggests that glymphatic dysfunction could enhance PACAP-mediated signaling. This article will explore possible correlations between these mechanisms and migraine pathophysiology.

Migraine affects over one billion individuals worldwide and is increasingly recognized as a systemic disorder with broad cardiovascular comorbidities extending beyond its neurological profile. Despite growing epidemiological evidence, the intersections of migraine with cardiovascular risk stratification, stroke mechanisms, endothelial dysfunction, neuroimaging findings, and neurocognitive profiles remain incompletely mapped. Following the PRISMA-ScR framework, we searched PubMed/MEDLINE for recent (2015–2025) English-language human studies with large sample sizes (≥400) examining cardiovascular outcomes, vascular biomarkers, neuroimaging, or endothelial function in adult migraine populations. The protocol was preregistered on OSF. Forty-three studies encompassing more than 1,500,000 participants across seven thematic domains were included. Migraine with aura was consistently associated with increased ischemic stroke risk in a non-atherosclerotic pattern, with evidence suggesting potential cardioembolic mechanisms including patent foramen ovale and atrial fibrillation. Active episodic migraine paradoxically showed inverse associations with traditional cardiovascular risk scores, while inflammatory biomarkers such as high-sensitivity C-reactive protein and fibrinogen remained interictally elevated, and white matter hyperintensity burden was substantially higher than controls, though available evidence did not indicate increased dementia risk. Cardiovascular disease may represent a clinically relevant comorbidity of migraine, warranting integrated multidisciplinary management. Future studies should prioritize sex-stratified longitudinal designs with aura-specific risk modeling and cerebral endothelial assessment.

Background: Real-world evidence regarding the effectiveness and safety of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies in Eastern European populations remains limited. We aimed to evaluate treatment outcomes and safety in Romanian patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM). Methods: We conducted a multicenter retrospective observational cohort study including 113 adults with HFEM (n = 38) or CM (n = 75) who initiated treatment with galcanezumab, erenumab, fremanezumab, or eptinezumab at specialized headache centers in Romania. Monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM were assessed at the baseline and during follow-up. Treatment outcomes, discontinuation, persistence, and adverse events were evaluated during routine clinical follow-up. Results: At month 6, headache frequency was substantially reduced in both groups, with median MMDs decreasing from 10 to 2 in patients with HFEM and median MHDs decreasing from 25 to 6 in patients with CM. A ≥50% reduction in headache frequency was achieved by 78.9% of patients with HFEM and 64.0% of those with CM. Among the patients with CM, 70.7% met the predefined criterion for conversion to episodic migraine at month 6. During follow-up, 22 patients discontinued treatment. Adverse events were reported in 28 patients (24.8%), were predominantly non-serious, and resulted in treatment discontinuation in 3 patients (2.7%). No serious adverse events were documented. Treatment persistence at 12 months was 82.3%. Conclusions: In this Romanian real-world cohort, anti-CGRP monoclonal antibody treatment was associated with substantial reductions in migraine/headache frequency in patients with HFEM and CM. The treatment was generally well-tolerated, with predominantly non-serious adverse events and a low rate of discontinuation due to adverse events. These findings provide real-world evidence from Romania and support further prospective evaluation of the long-term effectiveness and safety of anti-CGRP monoclonal antibodies.