-
The Journal of Headache and Pain Jan 2024Migraine and epilepsy are two paroxysmal chronic neurological disorders affecting a high number of individuals and being responsible for a high individual and... (Review)
Review
BACKGROUND
Migraine and epilepsy are two paroxysmal chronic neurological disorders affecting a high number of individuals and being responsible for a high individual and socioeconomic burden. The link between these disorders has been of interest for decades and innovations concerning diagnosing and treatment enable new insights into their relationship.
FINDINGS
Although appearing to be distinct at first glance, both diseases exhibit a noteworthy comorbidity, shared pathophysiological pathways, and significant overlaps in characteristics like clinical manifestation or prophylactic treatment. This review aims to explore the intricate relationship between these two conditions, shedding light on shared pathophysiological foundations, genetic interdependencies, common and distinct clinical features, clinically overlapping syndromes, and therapeutic similarities. There are several shared pathophysiological mechanisms, like CSD, the likely underlying cause of migraine aura, or neurotransmitters, mainly Glutamate and GABA, which represent important roles in triggering migraine attacks and seizures. The genetic interrelations between the two disorders can be observed by taking a closer look at the group of familial hemiplegic migraines, which are caused by mutations in genes like CACNA1A, ATP1A2, or SCN1A. The intricate relationship is further underlined by the high number of shared clinical features, which can be observed over the entire course of migraine attacks and epileptic seizures. While the variety of the clinical manifestation of an epileptic seizure is naturally higher than that of a migraine attack, a distinction can indeed be difficult in some cases, e.g. in occipital lobe epilepsy. Moreover, triggering factors like sleep deprivation or alcohol consumption play an important role in both diseases. In the period after the seizure or migraine attack, symptoms like speech difficulties, tiredness, and yawning occur. While the actual attack of the disease usually lasts for a limited time, research indicates that individuals suffering from migraine and/or epilepsy are highly affected in their daily life, especially regarding cognitive and social aspects, a burden that is even worsened using antiseizure medication. This medication allows us to reveal further connections, as certain antiepileptics are proven to have beneficial effects on the frequency and severity of migraine and have been used as a preventive drug for both diseases over many years.
CONCLUSION
Migraine and epilepsy show a high number of similarities in their mechanisms and clinical presentation. A deeper understanding of the intricate relationship will positively advance patient-oriented research and clinical work.
Topics: Humans; Migraine Disorders; Epilepsy; Migraine with Aura; Anticonvulsants; Comorbidity
PubMed: 38273253
DOI: 10.1186/s10194-024-01719-0 -
International Journal of Molecular... Jul 2023Migraine is a common condition with disabling attacks that burdens people in the prime of their working lives. Despite years of research into migraine pathophysiology... (Review)
Review
Migraine is a common condition with disabling attacks that burdens people in the prime of their working lives. Despite years of research into migraine pathophysiology and therapeutics, much remains to be learned about the mechanisms at play in this complex neurovascular condition. Additionally, there remains a relative paucity of specific and targeted therapies available. Many sufferers remain underserved by currently available broad action preventive strategies, which are also complicated by poor tolerance and adverse effects. The development of preclinical migraine models in the laboratory, and the advances in human experimental migraine provocation, have led to the identification of key molecules likely involved in the molecular circuity of migraine, and have provided novel therapeutic targets. Importantly, the identification that vasoconstriction is neither necessary nor required for headache abortion has changed the landscape of migraine treatment and has broadened the therapy targets for patients with vascular risk factors or vascular disease. These targets include nitric oxide synthase (NOS) and several neuropeptides that are involved in migraine. The ability of NO donors and infusion of some of these peptides into humans to trigger typical migraine-like attacks has supported the development of targeted therapies against these molecules. Some of these, such as those targeting calcitonin gene-related peptide (CGRP), have already reached clinical practice and are displaying a positive outcome in migraineurs for the better by offering targeted efficacy without significant adverse effects. Others, such as those targeting pituitary adenylate cyclase activating polypeptide (PACAP), are showing promise and are likely to enter phase 3 clinical trials in the near future. Understanding these nitrergic and peptidergic mechanisms in migraine and their interactions is likely to lead to further therapeutic strategies for migraine in the future.
Topics: Humans; Migraine Disorders; Headache; Pituitary Adenylate Cyclase-Activating Polypeptide; Calcitonin Gene-Related Peptide; Nitric Oxide Synthase
PubMed: 37569369
DOI: 10.3390/ijms241511993 -
Neurology India 2023The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo.
METHODS
Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3).
RESULTS
Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)].
,
although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence).
CONCLUSION
Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.
Topics: Humans; Vitamin D; Vitamin D Deficiency; Migraine Disorders; Odds Ratio
PubMed: 37635492
DOI: 10.4103/0028-3886.383862 -
The Journal of Headache and Pain Dec 2023Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence.
AIM
To assess the cost-effectiveness of drugs used to treat adults with chronic migraine.
METHODS
We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes.
RESULTS
Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY.
CONCLUSIONS
Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.
Topics: Adult; Humans; Topiramate; Migraine Disorders; Headache; Cost-Benefit Analysis; Decision Making; Quality-Adjusted Life Years
PubMed: 38053051
DOI: 10.1186/s10194-023-01686-y -
Pediatric Blood & Cancer Jul 2023Maternal migraine has been linked to adverse birth outcomes including low birth weight and preterm birth, as well as congenital anomalies in offspring. It has been...
BACKGROUND
Maternal migraine has been linked to adverse birth outcomes including low birth weight and preterm birth, as well as congenital anomalies in offspring. It has been speculated that this may be due to the use of medications in pregnancy, but lifestyle, genetic, hormonal, and neurochemical factors could also play a role. There is evidence for varying cancer incidences among adults with migraine. Here, we utilized data from national registries in Denmark to examine associations between maternal diagnoses of migraine and risk for cancer in offspring.
METHODS
We linked several national registries in Denmark to identify cases from the Cancer Registry among children less than 20 years (diagnoses 1996-2016) and controls from the Central Population Register, matched to cases by birth year and sex (25:1 matching rate). Migraine diagnoses were identified from the National Patient Register using International Classification of Diseases, versions 8 and 10 codes and migraine-specific acute or prophylactic treatment recorded in the National Pharmaceutical Register. We used logistic regression to estimate the risk of childhood cancers associated with maternal migraine.
RESULTS
Maternal migraine was positively associated with risk for non-Hodgkin lymphoma (odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.01-2.86), central nervous system tumors ([OR = 1.31, 95% CI: 1.02-1.68], particularly glioma [OR = 1.64, 95% CI: 1.12-2.40]), neuroblastoma (OR = 1.75, 95% CI: 1.00-3.08), and osteosarcoma (OR = 2.60, 95% CI: 1.18-5.76).
CONCLUSIONS
Associations with maternal migraine were observed for several childhood cancers, including neuronal tumors. Our findings raise questions about the role of lifestyle factors, sex hormones, genetic, and neurochemical factors in the relationship between migraine and childhood cancers.
Topics: Pregnancy; Child; Adult; Female; Infant, Newborn; Humans; Premature Birth; Central Nervous System Neoplasms; Migraine Disorders; Pregnancy Complications; Lymphoma, Non-Hodgkin; Risk Factors; Registries
PubMed: 37101365
DOI: 10.1002/pbc.30385 -
Frontiers in Public Health 2023Adults who suffer from migraines are highly susceptible to mental illnesses that may have significant association with their HRQoL. Therefore, this study aimed to...
BACKGROUND
Adults who suffer from migraines are highly susceptible to mental illnesses that may have significant association with their HRQoL. Therefore, this study aimed to investigate how anxiety and depression related to HRQoL in adults with Migraine.
METHODS
Data from the Medical Expenditure Panel Survey for 2017 to 2020 were used to identify adult patients 18 years of age and older with a migraine diagnosis. The Physical and Mental Component Summary (PCS & MCS) scores from the SF-12 were used to calculate HRQoL. To adjust for a wide range of variables, multivariate linear regressions were used to evaluate the association between depression and anxiety and HRQoL among adults with migraine.
RESULTS
Among the 1,713 identified adults with migraines, 11.2% experienced depression, 14.6% experienced anxiety, and 13.7% had both conditions. Compared to migraineurs who had only migraine, adults with comorbid depression and anxiety had the lowest mean scores on the PCS and MCS. Additionally, migraineurs who had depression had significantly lower HRQoL MCS scores (depression: β = -7.552, < 0.001), and those with anxiety had significantly lower HRQoL MCS scores (anxiety: β = -4.844, p < 0.001) compared to those without these comorbidities. Notably, individuals with migraines who exercise had higher scores on both PCS and MCS than those who did not exercise.
CONCLUSION
This nationally representative sample provides insights into the associations between depression and anxiety with poor HRQoL among individuals with migraines. Additionally, it revealed the negative impact of concurrent chronic diseases, and poor socioeconomic status on HRQoL, while emphasizing the beneficial effects of regular exercise. This study highlights the clinical, policy, and public health implications for improving healthcare planning, resource allocation, and promoting lifestyle changes to reduce depression and anxiety in migraine sufferers.
Topics: Adult; Humans; Adolescent; Quality of Life; Depression; Anxiety; Comorbidity; Migraine Disorders
PubMed: 37860801
DOI: 10.3389/fpubh.2023.1241800 -
Complementary Therapies in Medicine Nov 2023Migraine is a prevalent and disabling neurological disorder affecting a significant proportion of the global population. Although medications are the primary treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Migraine is a prevalent and disabling neurological disorder affecting a significant proportion of the global population. Although medications are the primary treatment option, their efficacy remains unclear. Thus, alternative therapies such as scalp acupuncture have gained momentum; however, evidence for the effectiveness of scalp acupuncture remains insufficient. Therefore, this review provides evidence regarding the effectiveness and safety of scalp acupuncture for the treatment of migraines.
DESIGN
PubMed, EMBASE, CENTRAL, Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Korean Medical Database, NDSL, Citation Information by NII, and China National Knowledge Infrastructure were searched from their inception to September 2022 to identify randomised controlled trials (RCTs) without language restrictions. Data were collected and analysed independently by two reviewers. The RoB 2.0 tool was used to evaluate the risk of bias, and a meta-analysis was conducted using RevMan software (V5.4).
SETTING
Eight RCTs including 874 patients were selected.
RESULTS
Scalp acupuncture had a higher total effective rate (relative risk [RR]:1.24; 95% confidence interval [CI]:1.08-1.43; P < 0.01) than that of ordinary acupuncture. The headache index decreased significantly (standardised mean differences [SMD]:-1.27; 95% CI:-2.06 to -0.48; P < 0.01), and the total effective rate was higher (RR:1.20; 95% CI:1.06-1.37; P < 0.01) with scalp acupuncture than with medications. However, evidence supporting the effectiveness of scalp acupuncture was not robust. No adverse events were reported.
CONCLUSION
Scalp acupuncture appears to be more effective than other treatments for migraines. However, their safety remains uncertain.
PROSPERO REGISTRATION NUMBER
CRD42022348879.
Topics: Humans; Scalp; Migraine Disorders; Acupuncture Therapy; Medicine, East Asian Traditional; Headache
PubMed: 37783377
DOI: 10.1016/j.ctim.2023.102991 -
Current Pain and Headache Reports Nov 2023Historical evidence suggests a shared underlying etiology for migraine and gastrointestinal (GI) disorders that involves the gut-brain axis. Here we provide narrative... (Review)
Review
PURPOSE OF REVIEW
Historical evidence suggests a shared underlying etiology for migraine and gastrointestinal (GI) disorders that involves the gut-brain axis. Here we provide narrative review of recent literature on the gut-brain connection and migraine to emphasize the importance of tailoring treatment plans for patients with episodic migraine who experience GI comorbidities and symptoms.
RECENT FINDINGS
Recent population-based studies report the prevalence of migraine and GI disorders as comorbidities as well as overlapping symptomology. American Headache Society (AHS) guidelines have integrated GI symptoms as part of migraine diagnostic criteria and recommend nonoral therapies for patients with GI symptoms or conditions. Nasal delivery is a recommended nonoral alternative; however, it is important to understand potential adverse events that may cause or worsen GI symptoms in some patients due to the site of drug deposition within the nasal cavity with some nasal therapies. Lastly, clinical perspectives emphasize the importance of identifying GI symptoms and comorbidities in patients with episodic migraine to best individualize migraine management. Support for an association between the gut-brain axis and migraine continues to prevail in recent literature; however, the relationship remains complex and not well elucidated. The presence of GI comorbidities and symptoms must be carefully considered when making treatment decisions for patients with episodic migraine.
Topics: Humans; Migraine Disorders; Brain; Headache; Comorbidity
PubMed: 37792173
DOI: 10.1007/s11916-023-01175-6 -
Translational Psychiatry Feb 2024Previous studies have observed a significant comorbidity between Alzheimer's disease (AD) and some other neuropsychiatric disorders. However, the mechanistic connections...
Previous studies have observed a significant comorbidity between Alzheimer's disease (AD) and some other neuropsychiatric disorders. However, the mechanistic connections between neuropsychiatric disorders and AD are not well understood. We conducted a Mendelian randomization analysis to appraise the potential influences of 18 neurodegenerative and neuropsychiatric disorders on AD. We found that four disorders are causally associated with increased risk for AD, including bipolar disorder (BD) (OR: 1.09), migraine (OR: 1.09), schizophrenia (OR: 1.05), and Parkinson's disease (PD) (OR: 1.07), while attention-deficit/hyperactivity disorder (ADHD) was associated with a decreased risk for AD (OR: 0.80). In case of amyotrophic lateral sclerosis (OR: 1.04) and Tourette's syndrome (OR: 1.05), there was suggestive evidence of their causal effects of on AD. Our study shows that genetic components predisposing to BD, migraine, schizophrenia, and PD may promote the development of AD, while ADHD may be associated with a reduced risk of AD. The treatments aimed at alleviating neuropsychiatric diseases with earlier onset may also influence the risk of AD-related cognitive decline, which is typically observed later in life.
Topics: Humans; Alzheimer Disease; Schizophrenia; Parkinson Disease; Attention Deficit Disorder with Hyperactivity; Migraine Disorders; Genome-Wide Association Study
PubMed: 38395927
DOI: 10.1038/s41398-024-02822-1 -
The Journal of Headache and Pain Jan 2024Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which... (Review)
Review
BACKGROUND
Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways.
METHODS
A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review.
RESULTS
We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development.
CONCLUSIONS
Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.
Topics: Animals; Mechanotransduction, Cellular; Pain; Migraine Disorders; Nociception
PubMed: 38221631
DOI: 10.1186/s10194-023-01710-1