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Molecular and Clinical Aspects of Migraine and Its Comorbidities: Epilepsy, Stroke, and Restless Leg Syndrome

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 4303

Special Issue Editors

Prof. Dr. Janusz Blasiak

E-Mail Website
Guest Editor
Faculty of Medicine, Collegium Medicum, The Mazovian Academy in Plock, 09-402 Plock, Poland
Interests: DNA; RNA; gene expression; cancer; AMD; epigenetics; stem cells
Special Issues, Collections and Topics in MDPI journals
Dr. Michał Fila

E-Mail Website
Guest Editor
Department of Developmental Neurology and Epileptology, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, Poland
Interests: migraine; headaches; stroke; electromyography; neuropathy

Special Issue Information

Dear Colleagues,

Although migraines are one of the leading causes of disability worldwide, they are still an underdiagnosed and undertreated disease, which is a consequence of the incomplete knowledge of migraine pathogenesis. One of the main reasons for that is the restrictive access to human target material and the limited value of experimental animals to model human migraines. Sensitization of the trigeminovascular system and cortical hyperexcitability are essential mechanisms in migraine pathogenesis, but their molecular basis remains unclear. Migraines are frequently associated with comorbidities such as mental disorders, cardiovascular disease, epilepsy, stroke, restless leg syndrome, among others. In many of these comorbidities, it is not clear whether there is a cause–effect relationship or if they are merely associated with migraines. This Special Issue focuses on migraines and their frequent comorbidities, including epilepsy, stroke, and restless leg syndrome. We welcome original and review papers not only investigating the coexistence of migraines with epilepsy, stroke, and restless leg syndrome but also exploring these three syndromes to provide information on their potential links with migraines. Both experimental and clinical research work are welcome.

Prof. Dr. Janusz Blasiak
Dr. Michał Fila
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • migraine
  • genetics and epigenetics of migraine
  • migraine comorbidities
  • omics in migraine studies
  • stem cells in migraine studies
  • epilepsy
  • stroke
  • restless leg syndrome

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Published Papers (2 papers)

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Review

22 pages, 2406 KiB  
Review
Sirtuins Contribute to the Migraine–Stroke Connection
by Jan Krekora, Michal Fila, Maria Mitus-Kenig, Elzbieta Pawlowska, Justyna Ciupinska and Janusz Blasiak
Int. J. Mol. Sci. 2025, 26(14), 6634; https://doi.org/10.3390/ijms26146634 - 10 Jul 2025
Viewed by 198
Abstract
The prevalence of stroke in patients with migraine is higher than in the general population, suggesting certain shared mechanisms of pathogenesis. Migrainous infarction is a pronounced example of the migraine–stroke connection. Some cases of migraine with aura may be misdiagnosed as stroke, with [...] Read more.
The prevalence of stroke in patients with migraine is higher than in the general population, suggesting certain shared mechanisms of pathogenesis. Migrainous infarction is a pronounced example of the migraine–stroke connection. Some cases of migraine with aura may be misdiagnosed as stroke, with subsequent mistreatment. Therefore, it is important to identify these shared mechanisms of pathogenesis contributing to the migraine–stroke connection to improve diagnosis and treatment. Sirtuins (SIRTs) are a seven-member family of NAD+-dependent histone deacetylases that can epigenetically regulate gene expression. Sirtuins possess antioxidant properties, making them a first-line defense against oxidative stress, which is important in the pathogenesis of migraine and stroke. Mitochondrial localization of SIRT2, SIRT3, and SIRT4 supports this function, as most reactive oxygen and nitrogen species are produced in mitochondria. In this narrative review, we present arguments that sirtuins may link migraine with stroke through their involvement in antioxidant defense, mitochondrial quality control, neuroinflammation, and autophagy. We also indicate mediators of this involvement that can be, along with sirtuins, therapeutic targets to ameliorate migraine and prevent stroke. Full article
(This article belongs to the Special Issue Molecular and Clinical Aspects of Migraine and Its Comorbidities: Epilepsy, Stroke, and Restless Leg Syndrome)
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15 pages, 1623 KiB  
Review
Novel Calcitonin Gene-Related Peptide (CGRP) Interfering Migraine Therapies and Stroke—A Review
by Michael Thomas Eller, Florian Frank, Katharina Kaltseis, Anel Karisik, Michael Knoflach and Gregor Broessner
Int. J. Mol. Sci. 2024, 25(21), 11685; https://doi.org/10.3390/ijms252111685 - 30 Oct 2024
Cited by 1 | Viewed by 3653
Abstract
Migraine and stroke are neurological disorders with significant global prevalence and impact. Recent advances in migraine therapy have focused on the calcitonin gene-related peptide (CGRP) pathway. This review examines the shared pathomechanisms between migraine and stroke, with emphasis on the role of CGRP. [...] Read more.
Migraine and stroke are neurological disorders with significant global prevalence and impact. Recent advances in migraine therapy have focused on the calcitonin gene-related peptide (CGRP) pathway. This review examines the shared pathomechanisms between migraine and stroke, with emphasis on the role of CGRP. We analyze the current literature on CGRP’s functions in cerebrovascular regulation, edema formation, neuroinflammation, and neuroprotection. CGRP acts as a potent vasodilator and plays a crucial role in trigeminovascular activation during migraine attacks. In stroke, CGRP has demonstrated neuroprotective effects by improving collateral circulation and reducing ischemia-reperfusion injury. Concerns have been raised about the potential impact of CGRP inhibitors on stroke risk and outcomes. Studies in animals suggest that CGRP receptor antagonists may worsen cerebral ischemia by impairing collateral flow. We discuss the implications of these findings for the use of CGRP-targeting therapies in migraine patients, especially those at increased risk of stroke. Additionally, we explore the complex interplay between CGRP, endothelial function, and platelet activity in both conditions. This review highlights the need for further research to elucidate the long-term cerebrovascular safety of CGRP pathway inhibitors and to identify potential subgroups of migraine patients who may be at higher risk of adverse cerebrovascular events with these novel therapies. Full article
(This article belongs to the Special Issue Molecular and Clinical Aspects of Migraine and Its Comorbidities: Epilepsy, Stroke, and Restless Leg Syndrome)
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