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Frontiers in Nutrition 2023Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising...
INTRODUCTION
Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising approach is ketogenic therapy, which replaces the brain's glucose fuel source with ketone bodies, potentially reducing the frequency or severity of headaches.
AIM
This study aims to conduct a systematic review of the scientific literature on the impact of ketosis on migraine, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.
RESULTS
After a careful selection process and bias evaluation, 10 articles were included in the review, primarily from Italy. The bias assessment indicated that 50% of the selected articles had a low risk of bias in all domains, with the randomization process being the most problematic domain. Unfortunately, the evaluation of ketosis was inconsistent between articles, with some assessing ketonuria, some assessing ketonemia, and some not assessing ketosis levels at all. Therefore, no association could be made between the level of ketosis and the prevention or reduction of migraine attacks. The ketogenic therapies tested in migraine treatments included the very low-calorie ketogenic diet (VLCKD, = 4), modified Atkins diet (MAD, = 3), classic ketogenic diet (cKDT, = 2), and the administration of an exogenous source of beta-hydroxybutyrate (BHB). The meta-analysis, despite reporting high heterogeneity, found that all interventions had an overall significant effect ( = 9.07, < 0.00001; subgroup differences, Chi2 = 9.19, dif = 3, = 0.03; , 67.4%), regardless of the type of endogenous or exogenous induction of ketosis.
CONCLUSION
The initial findings of this study suggest that metabolic ketogenic therapy may provide some benefit in treating migraines and encourage further studies, especially randomized clinical trials with appropriate and standardized methodologies. The review strongly recommends the use of the adequate measurement of ketone levels during ketogenic therapy to monitor adherence to the treatment and improve knowledge of the relationship between ketone bodies and efficacy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022330626.
PubMed: 37377485
DOI: 10.3389/fnut.2023.1204700 -
European Journal of Neurology Mar 2022Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial... (Review)
Review
BACKGROUND AND PURPOSE
Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial fibrillation, which is a relevant risk factor for stroke.
METHODS
PubMed was searched for 'migraine' AND 'atrial fibrillation' and selected original investigations on the association of migraine and atrial fibrillation for our analysis. Articles without original data, such as guidelines, narrative reviews, editorials and others, were excluded.
RESULTS
In all, 109 publications were found. Twenty-two were included and analysed for this review. The population-based Atherosclerosis Risk in Communities study showed a significant association of migraine with visual aura and incident atrial fibrillation (hazard ratio 1.30, 95% confidence interval 1.03-1.62, p = 0.02), but not for migraine without aura, compared to non-headache persons after multivariable adjustment for vascular risk factors. An even larger population-based study in Denmark confirmed this association (odds ratio 1.25, 95% confidence interval 1.16-1.36). Studies investigating patients with ischaemic stroke and migraine are methodologically insufficient and provide contradictory results. Ablation therapy for atrial fibrillation in patients with migraine might reduce migraine attacks, but transient post-ablation new-onset migraine-like headaches in persons without a history of migraine have also been reported.
CONCLUSION
Population-based studies indicate a significant association of migraine with aura and atrial fibrillation. In practical terms, screening for atrial fibrillation in patients who have a long history of migraine might be reasonable, whereas in patients with stroke or other disorders and migraine extensive screening for atrial fibrillation should be performed as in all patients without migraine.
Topics: Atrial Fibrillation; Brain Ischemia; Humans; Migraine Disorders; Migraine with Aura; Risk Factors; Stroke
PubMed: 34826198
DOI: 10.1111/ene.15198 -
BioPsychoSocial Medicine Jun 2023Irritable bowel syndrome (IBS) and migraines are often comorbid each other. These disorders are likely to be bidirectionally linked through the gut-brain axis and share...
BACKGROUND
Irritable bowel syndrome (IBS) and migraines are often comorbid each other. These disorders are likely to be bidirectionally linked through the gut-brain axis and share several underlying mechanisms including central nervous system sensitization. However, quantitative analysis of comorbidity was not reported enough. The aim of this systematic review and meta-analysis was to calculate the present degree of comorbidity of these two disorders.
METHODS
A literature search was performed searching for articles describing IBS or migraine patients with the same inverse comorbidity. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were then extracted. The total effect estimates were determined and presented by random effect forest plots for the group of articles with IBS patients with migraine and the group of articles on migraine sufferers with comorbid IBS separately. The average results of these plots were compared.
RESULTS
The literature search resulted in initial 358 articles and final 22 articles for the meta-analysis. The total OR values obtained were 2.09 [1.79 - 2.43] in IBS with comorbid migraine or headache, 2.51 [1.76 - 3.58] for migraineurs with comorbid IBS and an overall HR of 1 .62 [1.29 - 2.03] was found for cohort studies of migraine sufferers with comorbid IBS. A similar expression of a selection of other comorbidities was found in IBS and migraine patients, especially for depression and fibromyalgia a strong similarity was found in their expression rate.
CONCLUSIONS
This systematic review with meta-analysis was the first to combine data on IBS patients with comorbid migraine and migraineurs with comorbid IBS. The fact that closely related existential rates were observed between these two groups should be used as motivation for future research to further investigate these disorders for why this similarity occurs. Mechanisms involved in central hypersensitivity such as genetic risk factors, mitochondrial dysfunction and microbiota are particularly good candidates. Experimental designs in which therapeutic methods for these conditions can be exchanged or combined may also lead to the discovery of more efficient treatment methods.
PubMed: 37291550
DOI: 10.1186/s13030-023-00275-4 -
The Journal of Headache and Pain Jun 2022Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize... (Review)
Review
Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing.We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N = 4), migraine with aura (N = 8), both migraine with and without aura (N = 3), or hemiplegic migraine (N = 5).In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.
Topics: Epilepsy; Hemiplegia; Humans; Migraine with Aura; Migraine without Aura; Phenotype
PubMed: 35650524
DOI: 10.1186/s10194-022-01430-y -
Epilepsy & Behavior : E&B Oct 2023The seizure subtype of functional neurological disorder (FND-seizures) is a common neuropsychiatric condition manifesting with episodic epilepsy-like events. Despite the...
BACKGROUND
The seizure subtype of functional neurological disorder (FND-seizures) is a common neuropsychiatric condition manifesting with episodic epilepsy-like events. Despite the common belief that FND-seizures are precipitated by psychological stressors, neurological disorders may also be triggers. In 1890, Babinski described four cases of FND symptoms associated with migraine attacks. Despite the passing of more than 130 years since this first clinical observation, the relationship between FND-seizures and migraine is not fully elucidated.
OBJECTIVES
(1) To complete a systematic review of the literature that investigated potential associations between FND-seizures and migraine and the response of FND seizures to treatment with migraine prophylactic medications (2). To undertake a retrospective study of patients with FND-seizures and migraine, including response to migraine prophylaxis.
METHODS
(1) Using PRISMA methods, we completed a systematic review of EMBASE and Scopus databases from inception to March 31, 2021, for literature on FND-seizures and migraine. (2) Our multi-disciplinary team, including subspecialists in psychosomatic medicine, epilepsy, and headache disorders, reviewed consecutive patients diagnosed with FND-seizures and migraine to assess potential causal associations and responses to standard migraine prophylactic medications.
RESULTS
(1) The search yielded seven studies from 126 screened manuscripts (N = 1,186 patients with FND-seizures; mean age 38.7 years; 72.6% female). They varied substantially in design, population, diagnostic measures, and outcomes. Nevertheless, all studies found associations between FND-seizures and migraine, which were stronger than those between epileptic seizures and migraine in comparative investigations, but provided limited information on treatment response. (2) In our case series, investigators reached unanimous consensus that migraine attacks triggered FND-seizures in 28/43 (65.1%) patients reviewed (mean age, 38.8 years; 74% female). In 19/26 (73%) patients with adequate follow-up data, treatment with migraine prophylactic medications alone (no behavioral interventions) concomitantly reduced FND-seizure and headache frequency by >50%.
CONCLUSION
Our systematic review and case series indicate that migraine attacks may trigger FND-seizures, perhaps more often that currently understood, and suggest that migraine prophylaxis may reduce FND-seizure frequency in such cases. To validate these observations, fully powered prospective investigations are required.
PubMed: 37717461
DOI: 10.1016/j.yebeh.2023.109437 -
European Stroke Journal Dec 2023Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have suggested an elevated risk of cervical artery dissection (CeAD) in patients with a history of migraine. We aimed to investigate this potential association using systematic review and meta-analytic methods.
PATIENTS AND METHODS
We utilized a pre-defined search protocol to identify and screen studies related to migraine and CeAD in PubMed, Embase, and the Web of Science Core Collection. We assessed the risk of bias and performed a meta-analysis of selected studies to assess the association between migraine and CeAD. We also performed subgroup analyses by migraine subtype, biological sex, and the use of stroke versus non-stroke controls.
RESULTS
We identified 11 studies ( = 9857 patients) for inclusion in the meta-analysis. Meta-analysis showed an association between migraine and CeAD with an odds ratio of 1.74 (95%CI 1.38-2.19). There was high heterogeneity among the included studies ( = 61%). Publication bias was present but the Trim-Fill imputation suggested that the impact on results was likely minimal. Subgroup analyses revealed an association between migraine without aura and CeAD (OR 1.86, 95%CI 1.55-2.24) but not migraine with aura and CeAD (OR 1.15, 95%CI 0.71-1.88). There was no difference in the association between migraine and CeAD in men compared to women.
DISCUSSION AND CONCLUSION
A history of migraine is associated with an increased risk of CeAD. Further studies are needed to elucidate the potential pathophysiologic mechanisms underlying this association.
Topics: Male; Humans; Female; Risk Factors; Stroke; Migraine Disorders; Aortic Dissection; Arteries
PubMed: 37555306
DOI: 10.1177/23969873231191860 -
Life Sciences Aug 2023Cortical spreading depolarization (CSD) is a wave of pathologic neuronal dysfunction that spreads through cerebral gray matter, causing neurologic disturbance in... (Review)
Review
AIMS
Cortical spreading depolarization (CSD) is a wave of pathologic neuronal dysfunction that spreads through cerebral gray matter, causing neurologic disturbance in migraine and promoting lesion development in acute brain injury. Pharmacologic interventions have been found to be effective in migraine with aura, but their efficacy in acutely injured brains may be limited. This necessitates the assessment of possible adjunctive treatments, such as nonpharmacologic methods. This review aims to summarize currently available nonpharmacological techniques for modulating CSDs, present their mechanisms of action, and provide insight and future directions for CSD treatment.
MAIN METHODS
A systematic literature review was performed, generating 22 articles across 3 decades. Relevant data is broken down according to method of treatment.
KEY FINDINGS
Both pharmacologic and nonpharmacologic interventions can mitigate the pathological impact of CSDs via shared molecular mechanisms, including modulating K/Ca/Na/Cl ion channels and NMDA, GABA, serotonin, and CGRP ligand-based receptors and decreasing microglial activation. Preclinical evidence suggests that nonpharmacologic interventions, including neuromodulation, physical exercise, therapeutic hypothermia, and lifestyle changes can also target unique mechanisms, such as increasing adrenergic tone and myelination and modulating membrane fluidity, which may lend broader modulatory effects. Collectively, these mechanisms increase the electrical initiation threshold, increase CSD latency, slow CSD velocity, and decrease CSD amplitude and duration.
SIGNIFICANCE
Given the harmful consequences of CSDs, limitations of current pharmacological interventions to inhibit CSDs in acutely injured brains, and translational potentials of nonpharmacologic interventions to modulate CSDs, further assessment of nonpharmacologic modalities and their mechanisms to mitigate CSD-related neurologic dysfunction is warranted.
Topics: Humans; Cortical Spreading Depression; Migraine Disorders; Serotonin; Neurons; Brain Injuries
PubMed: 37302793
DOI: 10.1016/j.lfs.2023.121833 -
Journal of Neurology Jan 2023To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine.
METHODS
Neuroimaging studies published from origin to August 1, 2021 were searched in six databases including PubMed, Web of Science, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP. Study selection, quality assessment, and data extraction were conducted by two independent researchers. Anisotropic effect size-signed differential mapping (AES-SDM) and activation likelihood estimation (ALE) were used to perform the meta-analysis of available studies reporting whole-brain gray matter (GM) structural data in migraine patients. Clinical variables correlation analysis and migraine subgroup analysis were also conducted.
RESULTS
40 articles were included after the strict screening, containing 1616 migraine patients and 1681 matched healthy subjects (HS) in total. Using the method of AES-SDM, migraine patients showed GM increase in the bilateral amygdala, the bilateral parahippocampus, the bilateral temporal poles, the bilateral superior temporal gyri, the left hippocampus, the right superior frontal gyrus, and the left middle temporal gyrus, as well as GM decrease in the left insula, the bilateral cerebellum (hemispheric lobule IX), the right dorsal medulla, the bilateral rolandic operculum, the right middle frontal gyrus, and the right inferior parietal gyrus. Using the method of ALE, migraine patients showed GM increase in the left parahippocampus and GM decrease in the left insula. The results of correlation analysis showed that many of these brain regions were associated with migraine headache frequency and migraine disease duration. Migraine patients in different subtypes (such as migraine without aura (MwoA), migraine with aura (MwA), episodic migraine (EM), chronic migraine (CM), vestibular migraine (VM), etc.), and in different periods (in the ictal and interictal periods) presented not entirely consistent GM alterations.
CONCLUSION
Migraine patients have GM alterations in multiple brain regions associated with sensation, affection, cognition, and descending modulation aspects of pain. These changes might be a consequence of repeated migraine attacks. Further studies are required to determine how these GM changes can be used to diagnose, monitor disease progression, or exploit potential therapeutic interventions for migraine patients.
Topics: Humans; Brain; Gray Matter; Frontal Lobe; Prefrontal Cortex; Migraine without Aura; Magnetic Resonance Imaging
PubMed: 36098838
DOI: 10.1007/s00415-022-11363-w -
The Journal of Laryngology and Otology Sep 2023Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a systematic review and meta-analysis to determine the effectiveness of available prophylactic medication.
METHOD
literature search was performed using PubMed, Ovid and Embase databases. Qualitative and quantitative analysis were performed as well as risk of bias analysis. Meta-analysis for the mean differences for pre- and post-treatment impact based on Dizziness Handicap Inventory and Vertigo Symptom Scale were performed. Proportionate transformation meta-analysis for the successful event rate based on complete symptoms control was explored.
RESULTS
Thirteen publications were identified: 3 were randomised, controlled trials and 10 were non-randomised, controlled trials. Propranolol and venlafaxine improved the Vertigo Symptom Scale score by -13.31 points and -4.16 points, respectively, and the Dizziness Handicap Inventory score by -32.24 and -21.24, respectively. Only propranolol achieved statistically significant impact with 60 per cent of patients achieving complete symptom control.
CONCLUSION
Propranolol should be offered as the first-line treatment for vestibular migraine followed by venlafaxine. Amitriptyline, flunarizine and cinnarizine showed a trend for symptom improvement, but this was not statistically significant.
Topics: Humans; Dizziness; Propranolol; Venlafaxine Hydrochloride; Vertigo; Migraine Disorders
PubMed: 36200521
DOI: 10.1017/S0022215122001979 -
Neurology May 2023Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies.
METHODS
A librarian created search criteria in MEDLINE Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Separate from the systematic review/meta-analysis, we performed a genetic analysis for genes with a circadian pattern of expression (clock-controlled genes or CCGs) by cross-referencing genome-wide association studies (GWASs) of headache, a nonhuman primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders. Altogether, this allowed us to catalog circadian features at the behavioral level (circadian timing, time of day, time of year, and chronotype), systems level (relevant brain areas where CCGs are active, melatonin and corticosteroid levels), and cellular level (core circadian genes and CCGs).
RESULTS
For the systematic review and meta-analysis, 1,513 studies were found, and 72 met the inclusion criteria; for the genetic analysis, we found 16 GWASs, 1 nonhuman primate study, and 16 imaging reviews. For cluster headache behavior, meta-analyses showed a circadian pattern of attacks in 70.5% (3,490/4,953) of participants across 16 studies, with a clear circadian peak between 21:00 and 03:00 and circannual peaks in spring and autumn. Chronotype was highly variable across studies. At the systems level, lower melatonin and higher cortisol levels were reported in cluster headache participants. At the cellular level, cluster headache was associated with core circadian genes and , and 5 of the 9 cluster headache susceptibility genes were CCGs. For migraine behavior, meta-analyses showed a circadian pattern of attacks in 50.1% (2,698/5,385) of participants across 8 studies, with a clear circadian trough between 23:00 and 07:00 and a broad circannual peak between April and October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in participants with migraine and even lower during an attack. At the cellular level, migraine was associated with core circadian genes and , and 110 of the 168 migraine susceptibility genes were CCGs.
DISCUSSION
Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiologic foundation for circadian-targeted research into these disorders.
TRIAL REGISTRATION INFORMATION
The study was registered with PROSPERO (registration number CRD42021234238).
Topics: Animals; Cluster Headache; Melatonin; Genome-Wide Association Study; Migraine Disorders; Primates
PubMed: 36990725
DOI: 10.1212/WNL.0000000000207240