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Headache Disorders: New Advances in Management and Treatment Strategies

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

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 17051

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Special Issue Editors

Dr. Andreas A. Argyriou

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Guest Editor

Neurology Department, Agios Andreas State General Hospital of Patras, 26335 Patras, Greece
Interests: headache; pain; neuromuscular disorders; epilepsy; neurooncology

Dr. Vikelis Michail

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Guest Editor

Headache Clinic, Mediterraneo Hospital, 166 75 Glyfada, Greece
Interests: headache; migraine; pain

Dr. Emmanouil V. Dermitzakis

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Guest Editor

Euromedica General Clinic, 546 45 Thessaloniki, Greece
Interests: headache; migraine; pain

Special Issue Information

Dear Colleagues,

The recent market release of monoclonal antibodies (MAbs), specifically targeting the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP MAbs), based on the results of clinical trials and real-life data, appeared as a promising preventative option in both episodic and chronic migraine patients with a much higher efficacy/tolerability ratio, compared to the already available oral and injectable prophylactic treatment of armamentarium. Four anti-CGRP MAbs are currently in use for the prevention of episodic and chronic migraines, including erenumab used to target the CGRP-receptor and fremanezumab, galcanezumab and eptinezumab used to target the CGRP ligand. In addition, anti-CGRP MAbs can be used wth some degree of success as preventives in other headache disorders, such as cluster and post-traumatic headaches. There are, however, unmet needs associated with the prophylactic management of these headache disorders, because of inadequate headache frequency reduction in about one third of migraine patients and an even higher percentage of treatment failure in cluster and post-traumatic headache patients. Significant unmet needs are also present in the symptomatic management of these headache disorders. To overcome these issues, new acute pharmacological options for headaches have been studied in the last few years, including gepants, a class of small molecules that target the CGRP receptor, and ditans, a class of non-triptan serotonin receptor antagonists. Gepants have been also explored in migraine prevention.

The scope of this Special Issue is to summarize our existing knowledge on the pros and cons of modern therapies for headache disorders, to examine open clinical and pathogenetic issues and to explore future perspectives for future research to pursue. As such, both research papers and reviews are welcome. Thank you for agreeing to contribute towards the successful release of this Special Issue for the Journal of Clinical Medicine. The Co-Editors and I are confident that it will become a reference point for all those who want to know why, when, and how to treat headache patients with monoclonal antibodies that target the CGRP, gepants or ditans.

Dr. Andreas A. Argyriou
Dr. Vikelis Michail
Dr. Emmanouil V. Dermitzakis
Guest Editors

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Keywords

headache
migraine
cluster headache
post-traumatic headache
acute treatment
prophylaxis
calcitonin gene-related peptide
monoclonal antibodies
gepants
ditans

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Published Papers (8 papers)

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Research

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11 pages, 253 KiB

Open AccessArticle

Efficacy of Desvenlafaxine in Reducing Migraine Frequency and Severity: A Retrospective Study

by Marina Stoupa Hadidi, Murad Rasheed, Yanal M. Bisharat, Heba H. Al Helou, Hussam A. El Aina, Hala M. Batayneh, Alaa A. A. Aljabali and Omar Gammoh

J. Clin. Med. 2024, 13(17), 5156; https://doi.org/10.3390/jcm13175156 - 30 Aug 2024

Viewed by 2745

Abstract

Background: Migraine is characterized by sudden acute episodes of pain, with a global prevalence of 18% among all age groups. It is the second leading cause of years lived with disability worldwide. Prophylactic treatment is important in managing migraine; however, its efficacy and safety are debated. This study aimed to evaluate the efficacy of desvenlafaxine in female patients with migraine. Methods: We conducted a retrospective observational case study involving 10 women diagnosed with migraine who were treated with desvenlafaxine. We measured the number of migraine days per month, average headache duration in minutes, headache severity using a visual analog scale, use of acute medications, and frequency of acute medication use per week. Results: Desvenlafaxine significantly reduced the number of migraine days from 14.70 ± 3.68 at baseline to 2.50 ± 2.50 at follow-up (p < 0.05). The average headache duration dropped from 131.25 ± 32.81 min to 52.50 ± 44.64 min. Headache severity scores improved from 6.80 ± 1.49 at baseline to 0.80 ± 0.92 at follow up, the frequency of acute medication use per week reduced from 3.30 ± 1.49 at baseline to 0.80 ± 0.92, and the frequency of acute medication use decreased from 3.30 ± 1.49 times per week to 0.80 ± 0.92. Conclusions: Desvenlafaxine shows potential as an effective prophylactic therapy for migraine. Larger-scale studies are necessary to further explore its benefits. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

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12 pages, 251 KiB

Open AccessArticle

Predictors of Headaches and Quality of Life in Women with Ophthalmologically Resolved Idiopathic Intracranial Hypertension

by Anat Horev, Sapir Aharoni-Bar, Mark Katson, Erez Tsumi, Tamir Regev, Yair Zlotnik, Ron Biederko, Gal Ifergane, Ilan Shelef, Tal Eliav, Gal Ben-Arie and Asaf Honig

J. Clin. Med. 2024, 13(13), 3971; https://doi.org/10.3390/jcm13133971 - 7 Jul 2024

Cited by 1 | Viewed by 1180

Abstract

Background/objectives: The aim of this study was to evaluate the long-term outcomes of a cohort of ophthalmologically resolved female idiopathic intracranial hypertension (IIH) patients. Methods: Our cross-sectional study included adult females with at least 6 months of ophthalmologically resolved IIH. Patients with papilledema or who underwent IIH-targeted surgical intervention were excluded. Participants completed a questionnaire consisting of medical information, the Migraine Disability Assessment Scale (MIDAS) and the Headache Impact Test (HIT-6). Electronic medical records and the results of imaging upon diagnosis were retrospectively reviewed. Results: One-hundred-and-four participants (mean age 35.5 ± 11.9 years) were included (7.85 ± 7 years post-IIH diagnosis). Patients with moderate–severe disability according to the MIDAS scale (n = 68, 65.4%) were younger (32.4 ± 8.9 vs. 41.5 ± 14.4 year-old, p < 0.001), had a shorter time interval from IIH diagnosis (5.9 ± 5.3 vs. 11.7 ± 8.5 years, p < 0.001), and had lower FARB scores (indicating a more narrowed transverse-sigmoid junction; 1.28 ± 1.82 vs. 2.47 ± 2.3, p = 0.02) in comparison to patients with low–mild disability scores. In multivariate analysis, a lower FARB score (OR 1.28, 95% CI 0.89–1.75, p = 0.12) and younger age (OR 1.09, 95% CI 0.98–1.19, p = 0.13) showed a trend toward an association with a moderate–severe MIDAS score. Moreover, in the sub-analysis of patients with a moderate–severe MIDAS scale score, the 10 patients with the highest MIDAS scores had a low FARB score (1.6 ± 1.1 vs. 2.7 ± 2.4, p = 0.041). Conclusions: High numbers of patients with ophthalmologically resolved IIH continue to suffer from related symptoms. Symptoms may be associated with the length of time from the diagnosis of IIH and a lower FARB score. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

8 pages, 209 KiB

Open AccessArticle

A Novel Virtual-Based Comprehensive Clinical Approach to Headache Care

by Thomas Berk, Stephen Silberstein and Peter McAllister

J. Clin. Med. 2023, 12(16), 5349; https://doi.org/10.3390/jcm12165349 - 17 Aug 2023

Cited by 1 | Viewed by 1907

Abstract

One major innovation, a result of the coronavirus pandemic, has been the proliferation of telemedicine. Telehealth can help solve the access problems that plague headache medicine, allowing patients in areas with no headache expertise to consult and work with a headache specialist. This is a retrospective chart review of patients seen by Neura Health, a comprehensive app-based telehealth headache center. Patients are seen by a specialist and, in addition to any medical recommendations, are given care plans individualized to their condition and recommendations at the end of their clinical appointments. The primary outcome of this study is a decrease in monthly headache days after 90 days; secondary outcomes include disability as determined by MIDAS score, depression determined by PHQ-9, patients’ utilization of emergency department or urgent care resources, as well as their global impression of improvement. The deidentified outcomes of consecutive patients of Neura Health were evaluated from March 2022–March 2023. Subjects were excluded if they did not complete all forms, or if they did not receive a clinical or coaching follow-up appointment within 90 days. A total of 186 consecutive patients at Neura Health were identified during the review period. The median decrease in monthly headache days was 55.0% after a 90 day period, headache severity was decreased by 16.7%, global impression of improvement increased by 60.9%, disability decreased by 38.7%, depression decreased by 12.5% and ER/urgent care visits were decreased by 66.1%. A comprehensive, telehealth-based virtual headache-care model significantly decreased migraine frequency, severity and disability, and is able to decrease ER or urgent care visits. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

10 pages, 1230 KiB

Open AccessArticle

Effects of Fremanezumab on Psychiatric Comorbidities in Difficult-to-Treat Patients with Chronic Migraine: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry

by Michail Vikelis, Emmanouil V. Dermitzakis, Georgia Xiromerisiou, Dimitrios Rallis, Panagiotis Soldatos, Pantelis Litsardopoulos, Dimitrios Rikos and Andreas A. Argyriou

J. Clin. Med. 2023, 12(13), 4526; https://doi.org/10.3390/jcm12134526 - 6 Jul 2023

Cited by 10 | Viewed by 2360

Abstract

Objective: this post hoc analysis aimed to evaluate the efficacy of fremanezumab in difficult-to-treat chronic migraine (CM) patients with and without psychiatric comorbidities (PCs), mainly anxiety and/or depression. Methods: We assessed data from CM patients with and without PCs who failed at least 3 preventives and eventually received at least 3 consecutive monthly doses of fremanezumab 225 mg. Outcomes included the crude response (≥50% reduction in monthly headache days (MHDs)) rates to fremanezumab from the baseline to the last clinical follow-up. The changes in MHDs; MHDs of moderate/greater severity; monthly days with intake of abortive medication; and the proportion of patients’ changing status from with PCs to decreased/without PCs were also compared. Disability and quality of life (QOL) outcomes were also assessed. Results: Of 107 patients enrolled, 65 (60.7%) had baseline PCs. The percentage of patients with (n = 38/65; 58.5%) and without (n = 28/42; 66.6%) PCs that achieved a ≥50% reduction in MHDs with fremanezumab was comparable (p = 0.41), whereas MHDs were significantly reduced (difference vs. baseline) in both patients with PCs (mean −8.9 (standard error: 6.8); p < 0.001) and without PCs (−9.8 (7.5); p < 0.001). Both groups experienced significant improvements in all other efficacy, disability, and QOL outcomes at comparable rates, including in MHD reduction. A significant proportion of fremanezumab-treated patients with baseline PCs de-escalated in corresponding severities or even reverted to no PCs (28/65; 43.1%) post-fremanezumab. Conclusions: fremanezumab appears to be effective as a preventive treatment in difficult-to-treat CM patients with and without PCs while also being beneficial in reducing the severity of comorbid anxiety and/or depression. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

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10 pages, 267 KiB

Open AccessArticle

Predictors of Response to Fremanezumab in Migraine Patients with at Least Three Previous Preventive Failures: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry

by Andreas A. Argyriou, Emmanouil V. Dermitzakis, Georgia Xiromerisiou, Dimitrios Rallis, Panagiotis Soldatos, Pantelis Litsardopoulos and Michail Vikelis

J. Clin. Med. 2023, 12(9), 3218; https://doi.org/10.3390/jcm12093218 - 29 Apr 2023

Cited by 10 | Viewed by 2159

Abstract

Objective: To define, in a real-world population of patients with high-frequency episodic (HFEM) or chronic migraine (CM), the predictive role of socio-demographic or phenotypic profiling of responders to fremanezumab. Patients and methods: Two-hundred and four adult fremanezumab-treated patients with either HFEM or CM, who failed to at least three preventive treatments, provided data at baseline on several individual socio-demographic and phenotypic variables. These variables were analyzed for their ability to independently predict the response (50–74% response rates) or super-response (≥ 75% response rates) to fremanezumab. Patients were followed from 3–18 months of fremanezumab exposure. Results: The main finding to emerge from univariate analyses was that three baseline socio-demographic/clinical variables, i.e., age group 41–70 years (p = 0.02); female gender (p = 0.03); patients with HFEM (p = 0.001), and three clinical phenotypic variables, i.e., strict unilateral pain (p = 0.05); pain in the ophthalmic trigeminal branch (p = 0.04); and the “imploding” quality of pain (p = 0.05), were significantly related to fremanezumab response. However, in multivariate analysis, only HFEM (p = 0.02), the presence of strict unilateral (p = 0.03), and pain location in the ophthalmic trigeminal branch (p = 0.036) were independently associated with good fremanezumab response. Allodynia (p = 0.04) was the only clinical predictive variable of super-responsiveness to fremanezumab. Conclusions: A precise phenotypic profiling with identification of pain characteristics consistent with peripheral and/or central sensitization might reliably predict the responsiveness to fremanezumab in migraine prophylaxis. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

Review

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14 pages, 697 KiB

Open AccessReview

Telecoaching and Migraine: Digital Approach to Physical Activity in Migraine Management. A Scoping Review

by Ignazio Leale, Vincenzo Di Stefano, Angelo Torrente, Paolo Alonge, Roberto Monastero, Michele Roccella, Filippo Brighina, Valerio Giustino and Giuseppe Battaglia

J. Clin. Med. 2025, 14(3), 861; https://doi.org/10.3390/jcm14030861 - 28 Jan 2025

Cited by 1 | Viewed by 1200

Abstract

Migraine is a common neurological disorder, affecting approximately 15% of the European population and is among the main causes of years lived with disability. In the context of increasing digitalisation, telecoaching (TC) is a new training modality that involves the use of digital tools to access and manage training services remotely. Given the well-documented benefits of physical activity in migraine management and the rapid expansion of digital health services following the COVID-19 pandemic, this scoping review aims to evaluate the use and feasibility of TC-based training programs in individuals with migraine. A systematic search was conducted on multiple databases (PubMed, Web of Science, and Scopus) identifying 1507 studies, of which only 3 met the inclusion criteria. These studies collectively involved 181 participants with migraine and assessed various training programs, including aerobic training, resistance training, and physical therapy. Most training programs showed statistically significant improvements in several variables, including severity, duration, and frequency of migraine attacks. However, based on our study, there is limited evidence to suggest that TC training is beneficial for migraine patients. These findings underscore the need for further investigation, with more rigorous methodologies, higher-quality trials, and larger sample sizes to better establish the efficacy of TC training as a preventive and therapeutic approach for migraine. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

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30 pages, 1100 KiB

Open AccessFeature PaperReview

The Dawn and Advancement of the Knowledge of the Genetics of Migraine

by Nader G. Zalaquett, Elio Salameh, Jonathan M. Kim, Elham Ghanbarian, Karen Tawk and Mehdi Abouzari

J. Clin. Med. 2024, 13(9), 2701; https://doi.org/10.3390/jcm13092701 - 4 May 2024

Cited by 2 | Viewed by 2074

Abstract

Background: Migraine is a prevalent episodic brain disorder known for recurrent attacks of unilateral headaches, accompanied by complaints of photophobia, phonophobia, nausea, and vomiting. Two main categories of migraine are migraine with aura (MA) and migraine without aura (MO). Main body: Early twin and population studies have shown a genetic basis for these disorders, and efforts have been invested since to discern the genes involved. Many techniques, including candidate-gene association studies, loci linkage studies, genome-wide association, and transcription studies, have been used for this goal. As a result, several genes were pinned with concurrent and conflicting data among studies. It is important to understand the evolution of techniques and their findings. Conclusions: This review provides a chronological understanding of the different techniques used from the dawn of migraine genetic investigations and the genes linked with the migraine subtypes. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

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Other

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19 pages, 2565 KiB

Open AccessSystematic Review

Safety and Efficacy of Atogepant for the Preventive Treatment of Migraines in Adults: A Systematic Review and Meta-Analysis

by Abdulrahim Saleh Alrasheed, Taif Mansour Almaqboul, Reem Ali Alshamrani, Noor Mohammad AlMohish and Majed Mohammad Alabdali

J. Clin. Med. 2024, 13(22), 6713; https://doi.org/10.3390/jcm13226713 - 8 Nov 2024

Viewed by 2446

Abstract

Background: Migraine is a common neurological condition marked by unilateral recurrent pulsating headaches, often associated with systemic signs and symptoms. Recently, calcitonin gene-related peptide (CGRP) antagonists, including atogepant, an oral CGRP receptor antagonist, have emerged as effective and safe treatments. The current study sought to assess the efficacy and safety of atogepant for preventing episodic migraines in adults. Methods: A comprehensive search, following PRISMA guidelines, was conducted using PubMed, Web of Science, and Cochrane Library to identify randomized, double-blind, placebo-controlled trials published up to June 2024. Results: The studies included adult participants with episodic migraine treated with atogepant. The primary outcomes assessed were changes in mean monthly migraine days (MMDs) and monthly headache days (MHDs) over 12 weeks. Secondary outcomes included reduction in acute medication use, 50% responder rates, and adverse events. A meta-analysis using a random-effects model was performed to evaluate efficacy and safety. Six trials with 4569 participants were included. Atogepant significantly reduced mean monthly migraine days (MMDs) and monthly headache days (MHDs) compared to placebo at all doses (10 mg, 30 mg, 60 mg), with the 60 mg dose showing the greatest reduction (mean difference: −1.48 days, p < 0.001). Significant reductions in acute medication use and improved 50% responder rates were also observed for all doses. The safety profile of atogepant was favorable, with common adverse events being mild to moderate, such as constipation and nausea. There were no significant differences in serious adverse events between the atogepant and placebo groups. Conclusions: Atogepant is an effective and well-tolerated option for preventing episodic migraines, showing significant reductions in migraine frequency and acute medication use. However, further studies are necessary to assess its long-term safety and efficacy, especially at higher doses, and to investigate its potential role in personalized treatment strategies for migraine prevention. Full article

(This article belongs to the Special Issue Headache Disorders: New Advances in Management and Treatment Strategies)

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