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Advances and Updates in Migraine
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Advances and Updates in Migraine

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: 25 August 2026 | Viewed by 2900

Special Issue Editors

Prof. Dr. Hartmut Göbel

E-Mail Website
Guest Editor
Kiel Migraine and Headache Center, 24149 Kiel, Germany
Interests: migraine; headache; neurology; pain management; diagnosis; comorbidity
Special Issues, Collections and Topics in MDPI journals
Dr. Carl H. Göbel

E-Mail Website
Guest Editor
1. Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, 24149 Kiel, Germany
2. Kiel Migraine and Headache Center, 24149 Kiel, Germany
Interests: migraine; headache; neurology

Special Issue Information

Dear Colleagues,

Migraine is the most prominent headache disorder and ranks third among all diseases worldwide, affecting nearly 15% of the global population annually. It is most prevalent in women aged 30 to 40 and is more common than diabetes, asthma, and epilepsy combined. Chronic migraine alone impacts approximately 2% of the world’s population. The WHO lists migraine as the leading cause of disability under the age of 50, especially in women. Headache disorders account for over 75% of all years lived with disability due to neurological diseases—surpassing stroke, dementia, Parkinson’s disease, multiple sclerosis, and epilepsy. Despite this immense burden, headache disorders are still underdiagnosed and undertreated. Comorbidities such as depression, anxiety, cardiovascular disease, and stroke—especially in young women—underline the urgent need for improved care structures.

This Special Issue aims to highlight cutting-edge advances in migraine research, diagnosis, and treatment. We welcome contributions addressing novel pathophysiological insights, genetic risk factors, precision medicine approaches, and innovations in acute and preventive therapies, including CGRP-antibodies, gepants, ditans, and neuromodulation. By bringing together clinical and translational research, this Special Issue seeks to catalyze change and mobilize the scientific community to reduce the individual and societal burden of migraine and headache disorders.

Prof. Dr. Hartmut Göbel
Dr. Carl H. Göbel
Guest Editors

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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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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
  • chronic migraine
  • headache disorders
  • CGRP antibodies
  • gepants
  • ditans
  • triptans
  • precision medicine
  • neuromodulation
  • comorbidities
  • disability burden
  • pediatric migraine
  • ICHD-3 classification
  • neurotransmitters
  • preventive therapy
  • translational headache research

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Published Papers (3 papers)

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Research

12 pages, 1853 KB  
Article
Neurologic Symptoms and Cerebrovascular Events During Atogepant Therapy: A Case Series with Contextual Comparison with a Non-Gepant–Treated Migraine Cohort
by Carl H. Göbel, Axel Heinze, Katja Heinze-Kuhn, Anna Cirkel and Hartmut Göbel
J. Clin. Med. 2026, 15(5), 1930; https://doi.org/10.3390/jcm15051930 - 3 Mar 2026
Viewed by 699
Abstract
Background: CGRP contributes to cerebrovascular regulation, mainly based on experimental and translational data; human evidence remains limited. Gepants, including atogepant, are effective migraine preventives and achieve partial penetration across the blood–brain barrier. However, their neurologic and cerebrovascular safety in heterogeneous patient populations remains [...] Read more.
Background: CGRP contributes to cerebrovascular regulation, mainly based on experimental and translational data; human evidence remains limited. Gepants, including atogepant, are effective migraine preventives and achieve partial penetration across the blood–brain barrier. However, their neurologic and cerebrovascular safety in heterogeneous patient populations remains incompletely characterized. Objective: To describe acute neurologic events observed during atogepant therapy, provide contextual information regarding their baseline occurrence, and explore potential mechanisms by which CGRP receptor blockade may influence neurovascular resilience. Methods: We report five adults treated with atogepant (30–60 mg/day) who developed acute neurologic symptoms prompting emergency hospital admission. All patients underwent comprehensive diagnostic assessment including neuroimaging, vascular studies, cardiac evaluation, and laboratory testing. To provide context, a retrospective comparison cohort of migraine patients not treated with gepants during a similar period was analyzed. Baseline characteristics were summarized, and event occurrence was compared using Fisher’s exact test. Results: Among 575 individuals treated with atogepant, five experienced acute neurologic events, including one cerebellar infarction and several transient focal syndromes without structural correlates. No cerebrovascular events requiring hospitalization were identified in the non-gepant cohort (n = 610). In an unadjusted analysis, this difference was statistically significant (p = 0.027). The events were clinically heterogeneous, and several lacked radiologic confirmation of ischemia. Conventional vascular risk factors were present in some patients. Conclusions: These findings do not imply causality but raise the possibility that CGRP receptor blockade may reduce cerebrovascular adaptability in susceptible individuals. Clinicians should remain vigilant for ischemia or microvascular dysfunction when patients receiving atogepant present with acute vertigo, diplopia, ptosis, or hemisensory symptoms—even when CT and CTA are normal—and obtain timely MRI and vascular assessment. The absence of comparable events in a retrospective non-gepant cohort provides contextual information but does not permit inference regarding increased risk due to potential confounding and unmeasured factors. The findings are exploratory and hypothesis-generating, underscoring the need for prospective controlled studies to clarify the cerebrovascular safety of CGRP receptor antagonists in routine clinical practice. Full article
(This article belongs to the Special Issue Advances and Updates in Migraine)
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15 pages, 978 KB  
Article
Clinical and Genetic Factors Associated with Non-Response to Erenumab
by Giulia Mallucci, Salvatore Terrazzino, Martina Giacon, Alberto Cordella, Sarah Cargnin, Christoph Schankin, Claudio Gobbi and Chiara Zecca
J. Clin. Med. 2025, 14(24), 8922; https://doi.org/10.3390/jcm14248922 - 17 Dec 2025
Viewed by 713
Abstract
Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, such as erenumab (ERE), are effective migraine-preventive therapies for many patients. Identifying clinical and genetic factors associated with treatment failure is crucial for optimizing patient management. Methods: This multicenter, prospective observational [...] Read more.
Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, such as erenumab (ERE), are effective migraine-preventive therapies for many patients. Identifying clinical and genetic factors associated with treatment failure is crucial for optimizing patient management. Methods: This multicenter, prospective observational study included patients with episodic or chronic migraine treated with ERE for 12 months. Demographics, migraine history, comorbidities, treatment outcomes, and genetic variants in CGRP receptor-related genes (CALCRL and RAMP1) were evaluated for associations with non-response to ERE, defined as a <50% reduction in monthly migraine days. Results: Of the 140 patients starting ERE, 11 were lost to follow up, 12 stopped ERE due to side effects; 18 patients were non-responders and were compared to 99 responders. Arterial hypertension [adjusted OR (aOR): 7.77, p = 0.007], smoking (aOR: 4.98, p = 0.014), and insomnia requiring medication (aOR: 4.51, p = 0.027) were associated with non-responder status. Genetic analysis revealed a nominal association between the RAMP1 rs6431564 polymorphism and non-responder status (nominal p = 0.025), which did not survive Bonferroni correction. The G allele was linked to a reduced risk (aOR per G allele: 0.28, p = 0.025) and caused the increased expression of RAMP1 in an allele-dose manner. Conclusions: Hypertension, smoking, insomnia requiring medication, and, nominally, the RAMP1 rs6431564 polymorphism were associated with non-responder status to ERE in migraine patients. Further validation of the present results in larger cohorts is needed. Full article
(This article belongs to the Special Issue Advances and Updates in Migraine)
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16 pages, 1737 KB  
Article
miR-197, miR-101, and miR-143 and Pro-Inflammatory Cytokines in Migraine
by Roberto Carlos Rosales-Gómez, Beatriz Teresita Martín-Márquez, Alvaro Jovanny Tovar-Cuevas, Omar Cárdenas-Saenz, Patricia Orozco-Puga, Milton Omar Guzmán-Ornelas, Nathan Alejandro Peña-Dueñas, Flavio Sandoval-García, Daniela Ortiz-Ríos, Mariana Chávez-Tostado, Diana Mercedes Hernández-Corona, Miriam Méndez-del Villar and Fernanda-Isadora Corona-Meraz
J. Clin. Med. 2025, 14(18), 6410; https://doi.org/10.3390/jcm14186410 - 11 Sep 2025
Viewed by 1099
Abstract
Background: Migraine is a disabling neurological disorder where the release of neuropeptides and a local and systemic proinflammatory state prevail. MicroRNAs (miRs) are epigenetic regulators that control the expression of genes involved in inflammation, neovascularization, and pain-related processes. Cytokines mediate the inflammatory [...] Read more.
Background: Migraine is a disabling neurological disorder where the release of neuropeptides and a local and systemic proinflammatory state prevail. MicroRNAs (miRs) are epigenetic regulators that control the expression of genes involved in inflammation, neovascularization, and pain-related processes. Cytokines mediate the inflammatory state, while miRs can modulate their expression. Methods: This is an analytical and observational study in which subjects with a diagnosis of chronic and episodic migraine and healthy controls were recruited, and the migraine patients were classified by episodic or chronic migraine, as well as with or without aura. Cytokines were measured using the ELISA technique, and the microRNAs hsa-miR-197-3p, hsa-miR-101-3p, and hsa-miR-143-3p were evaluated using qPCR methodology. We also utilized bioinformatic tools, such as miRBase, TargetScan, miRNet, and miRPath, to analyze the interactions and pathways involved. Results: Our findings revealed that hsa-miR-197-3p is elevated in patients without aura (29.91 ± 11.14 with aura vs. 81.10 ± 53.85 without aura, RU; p = 0.021), whereas hsa-miR-143-3p is elevated in episodic migraine (0.0639 ± 0.0227 in EM vs. 0.0308 ± 0.0174, RU p = 0.011). Furthermore, we found higher levels of IL-17 (9.46 ± 1.06 in CM vs. 7.61 ± 2.12 in EM, p = 0.030), IL-6 (4.95 ± 2.84 in CM vs. 1.52 ± 0.98 non-migraine subjects, p = 0.016), and TNFα in chronic migraine patients (0.46 ± 0.24 in CM vs. 0.20 ± 0.05 in non-migraine, p = 0.011 and vs. 0.20 ± 0.13 in EM, p = 0.016). Conclusions: Inflammation is present in migraine regardless of the clinical characteristics of the patients, although it may be accentuated in chronic migraine. Our preliminary findings suggest a potential role for peripheral inflammatory markers, including specific microRNAs (miR-197, miR-101, and miR-143) and cytokines (TNF-α, IL-6, and IL-17A), in the pathophysiology of migraine. These results, although limited by sample size and cross-sectional design, highlight molecular pathways that warrant further investigation. Full article
(This article belongs to the Special Issue Advances and Updates in Migraine)
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