Migraines and ME/CFS - Discussion on how they may be related

Genetic correlation

A recent preprint found a genetic correlation of rg=0.45 between ME/CFS (DecodeME) and a USA migraine cohort. This figure is similar to the genetic correlation value I found when testing correlation of DecodeME with other migraine cohorts (UK BioBank and FinnGen).

Insights into Pathophysiological Pathways in ME/CFS Through Genetic Correlation and Mendelian Randomization, 2026, Wielscher et al
Migraine, a common comorbidity of POTS reflecting impaired neurovascular reactivity (10), showed a clear positive genetic correlation with ME/CFS (rg = 0.45, p < 10⁻⁶). PHBC [pleiotropic heritability with bias correction] analyses mirrored this result: migraine exhibited substantial single-trait shared pleiotropy with ME/CFS, and its removal from the multi-trait model produced a marked reduction in shared pleiotropy, indicating that neurovascular dysregulation represents a key pleiotropic axis underlying ME/CFS risk.
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Google search interest

In a more unconventional analysis on the forum, doing a wide-scale search for correlations between Google search interest in "chronic fatigue syndrome" and many other terms, I found that search interest in US states and US metro areas for "chronic fatigue syndrome" is highly correlated to search interest in terms related to migraines.


Bimodal distribution for age of onset

Several papers that found a bimodal age distribution in migraine incidence or prevalence rates are compiled on this thread: Migraine prevalence by age and sex in the United States: A life-span study, 2010, Victor et al

Two studies of ME/CFS have also found a bimodal distribution for age of onset [1,2].


Female sex bias

Migraine [3] and ME/CFS [4] are both more prevalent in females than in males.


Light/sound sensitivity

Sensitivity to light and sound are common symptoms in both migraine [5-7] and ME/CFS [8,9]


1. Bakken, Inger Johanne et al. “Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012.” BMC medicine vol. 12 167. 1 Oct. 2014, https://doi.org/10.1186/s12916-014-0167-5

2. McGrath, Simon J et al. “Incidence age is bimodal for myalgic encephalomyelitis/chronic fatigue syndrome, with higher severity burden for early onset disease.” Oxford open immunology vol. 7,1 iqag007. 17 Mar. 2026, https://doi.org/10.1093/oxfimm/iqag007

3. Victor, T W et al. “Migraine prevalence by age and sex in the United States: a life-span study.” Cephalalgia : an international journal of headache vol. 30,9 (2010): 1065-72. https://doi.org/10.1177/0333102409355601

4. Lim, Eun-Jin et al. “Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).” Journal of translational medicine vol. 18,1 100. 24 Feb. 2020, https://doi.org/10.1186/s12967-020-02269-0

5. Ishikawa, Tomoharu et al. “Identification of Everyday Sounds Perceived as Noise by Migraine Patients.” Internal medicine (Tokyo, Japan) vol. 58,11 (2019): 1565-1572. https://doi.org/10.2169/internalmedicine.2206-18

6. Artemenko, Ada R et al. “Migraine and light: A narrative review.” Headache vol. 62,1 (2022): 4-10. https://doi.org/10.1111/head.14250

7. Vingen, J V et al. “Phonophobia in migraine.” Cephalalgia : an international journal of headache vol. 18,5 (1998): 243-9. https://doi.org/10.1046/j.1468-2982.1998.1805243.x

8. Maeda, Kensei I et al. “Health outcomes of sensory hypersensitivities in myalgic encephalomyelitis/chronic fatigue syndrome and multiple sclerosis.” Psychology, health & medicine vol. 28,10 (2023): 3052-3063. https://doi.org/10.1080/13548506.2023.2195670

9. Chang, Chia-Jung et al. “A Comprehensive Examination of Severely Ill ME/CFS Patients.” Healthcare (Basel, Switzerland) vol. 9,10 1290. 29 Sep. 2021, https://doi.org/10.3390/healthcare9101290
 
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Sly Saint said:
there are quite a few threads that touch on this subject.
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Here are links to some of them:

General discussions

Migraines caused by ME - How to discuss with Neuro?

Migraine treatments

Are there symptoms you had in the early stages of ME that you no longer get? - Some mentions of migraine

Why has 'persistent enteroviral infection' been dropped as a research strand in ME/CFS? (Jen Brea asking) - Some discussion about weakness in ME/CFS showing up on one side of the body, and how migraine can be one-sided.

One-sided weakness

Ketogenic diet - Discussion about diet effect on migraines

Do you have ME/CFS related pain? - Just a couple posts mentioning migraine

Sensory sensitivities: research and theories?

Primary Exertion Headaches

Ocular and visual migraine, retinal migraine

Do others find that migraines trigger PEM (without a delay)?

Needing to lie flat - Some discussion about migraine sufferers also needing to lie flat

Poll: Do you or the person you care for with ME suffer migraines or other headaches? - (Members only)

ME muscle pain: type, location, triggers and consequences - (Members only)

Migraines and PEM? - (Members only)

Do you often, or ever have a feeling of pressure in your head? - (Members only)


Specific study/news threads

Women Suffer Worse Migraines Than Men. Now Scientists Think They Know Why

Can a Chronic BPPV w/a History of Trauma be the Trigger of Symptoms in Vestibular Migraine, ME/CFS & Whiplash Associated Disorders?, 2018, Carsten

The prevalence of papilledema in patients with migraine: a crucial cooccurrence of migraine & idiopathic intracranial hypertension, 2020, Onder et al

Increased intracranial pressure in migraine? Neuroimaging study on a cohort of migraineurs (nearly all had CFS), 2020, Onder et al

Daily persistent headache after viral illness during a worldwide pandemic ...: Lessons from 1890 Russian/Asiatic flu, 2020, Rosen

OnabotulinumtoxinA Is an Effective Treatment for Chronic Migraine in Patients With Comorbid Fibromyalgia, 2020, Real and de Teran

Migraine headaches in Chronic Fatigue Syndrome (CFS): Comparison of two prospective cross-sectional studies, Baraniuk et al, 2011

Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue & Mood Disorders Simply Due to Shared Biological Systems?, 2021, Karsan & Goadsby

Autonomic Dysfunction among Migraineurs with and without Complaints of Orthostatic Intolerance: Evidence for Small Fiber Nerve Damage, 2021, Stillman

Recording of Dr James Baraniuk's May 17, 2022 webinar, "Nociplastic pain in ME/CFS and overlap with migraine and other disorders"

Bidirectional Association Between Fibromyalgia and Migraine Among Probands and Unaffected Non-Twin Siblings, 2022, Po-Chun et al

Migraine in the context of chronic primary pain, chronic overlapping pain disorders, and functional somatic disorders 2022 Henningsen et al

Fatigue, CFS and migraine: Intersecting the lines through a cross-sectional study in patients with episodic and chronic migraine, 2023, Kumar

How Migraine & Chronic Fatigue Syndrome (ME/CFS) Are Connected: interview with James Baraniuk

Sex-related differences in the association between migraine, COVID-19, and long COVID: A population-based cohort, 2025, Al-Hassany et al

Migraine and functional neurological disorder (FND)—a review of comorbidity and potential overlap 2025 Stone et al

Insights into Pathophysiological Pathways in ME/CFS Through Genetic Correlation and Mendelian Randomization, 2026, Wielscher et al

A multi-ancestry meta [GWAS] of migraine among veterans: associations with traumatic brain injury, depression, and [PTSD], 2025, Gasperi et al


There are currently over 1500 posts and over 70 thread titles that mention "migraine".
 
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SCN2A variants are associated with familial and sporadic hemiplegic migraine

May or may not be related to ME.

Abstract​

Familial hemiplegic migraine (FHM) is a severe autosomal dominant subtype of migraine with aura, characterized by transient motor weakness during attacks. Known genes (CACNA1A, ATP1A2, SCN1A, PRRT2) account for fewer than 20% of genetically diagnosed cases.

To identify novel genetic contributors to FHM, we performed whole-genome linkage analysis and partial exome sequencing in a four-generation pedigree. A candidate ion channel gene (SCN2A) was subsequently screened in six additional pedigrees with multiple affected members and in a cohort of 594 unrelated probands with familial or sporadic hemiplegic migraine without mutations in known FHM genes. Functional consequences of identified variants were assessed using heterologous expression and automated patch clamp recording. The neurophysiological impact of SCN2A dysfunction was investigated using computational neuron models.

We identified a heterozygous missense mutation (c.4438A>G, p.Lys1480Glu) in SCN2A, encoding the neuronal voltage-gated sodium channel NaV1.2, which co-segregated with the FHM phenotype. Additional SCN2A variants (c.769T>A, p.Phe257Ile, and c.3955C>G, p.Arg1319Gly) were found in a second family and a sporadic case, respectively. All variants were absent from the gnomAD database. All ten individuals carrying a SCN2A variant experienced typical hemiplegic migraine attacks beginning in childhood. Two children heterozygous for p.Phe257Ile also had self-limited infantile seizures during the first year of life. None of the affected individuals exhibited permanent cerebellar ataxia, intellectual disability, or recurrent febrile coma. Functional studies revealed altered voltage-dependent and kinetic properties in all three variants that elicited abnormal action potential firing in a computer model of a neuron, supporting their pathogenicity.

These findings implicate SCN2A dysfunction in both familial and sporadic hemiplegic migraine, expanding the genetic landscape of migraine and the phenotypic spectrum associated with SCN2A variants.
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Epilepsy Gene Implicated in Severe Migraine Disorder

"The new genetic study revealed evidence that mutations in the gene SCN2A — which was previously associated with epilepsy and neurodevelopmental disorders, including autism spectrum disorder — can also cause both familial and sporadic hemiplegic migraine. The findings expand the genetic landscape of migraine and add to the growing list of neurological conditions linked to SCN2A dysfunction".

"The discovery places SCN2A alongside a small but growing group of ion channel genes implicated in migraine and reinforces the idea that migraine is fundamentally a disorder of brain excitability, George said. It also broadens knowledge of SCN2A-related disease.

The findings may eventually improve genetic diagnosis and counseling, George said. More broadly, the study adds momentum to efforts to better understand migraine at a molecular level — knowledge that could ultimately inform new therapies".
 
forestglip said:
I thought it'd be good to have a public thread for general discussion about how ME/CFS and migraines may be related. We have a members only thread for sharing experiences as well.
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FYI - you did have the observation that migraine and ME/CFS both share increased prolactin in the Buspirone Challenge test.

forestglip said:
It seems the debate has been going on for a while. This one from 2004 is two authors debating whether the increased prolactin response in migraine is related to serotonin or dopamine receptors: Buspirone Challenge is not a valid Probe of Central 5-HT1A Receptor Function
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And for me now that I'm lucky enough to now experience vestibular like migraines as well as, or as part of, ME/CFS I think the link is interesting.
 
Dysautonomia and POTS in the ENT Clinic: Differentiating Orthostatic Dizziness From Vestibular Migraine and Persistent Postural-Perceptual Dizziness (PPPD)

Published: May 15, 2026

Abstract​

One of the most common complaints in ENT clinics is dizziness. Although most cases are caused by vestibular neuritis and benign paroxysmal positional vertigo (BPPV), a significant number of patients experience non-vestibular dizziness. One non-vestibular cause is postural orthostatic tachycardia syndrome (POTS), which presents with symptoms similar to vestibular migraine (VM) and persistent postural perceptual dizziness (PPPD). Dizziness from POTS is related to dysautonomia rather than the vestibular system. In otolaryngology, understanding the autonomic nature of non-vestibular dizziness is important for accurate diagnosis. This study aims to review the clinical characteristics and pathophysiology of POTS, vestibular migraine, and PPPD; examine historical, physical, and diagnostic findings that differentiate autonomic and vestibular causes of dizziness; and develop a more specific model for evaluating chronic dizziness in the ENT setting. Literature on dizziness, vestibular and autonomic pathophysiology, and the clinical presentation of POTS, VM, and PPPD is reviewed in this paper. The timing of symptoms, their triggers, and objective assessment are key differentiating factors for these disorders. Various diagnostic tools, including orthostatic vital signs, oculomotor assessment, gait and balance evaluation, vestibular function assessment, tilt table testing, and neuroimaging, are also reviewed. Clear distinctions among POTS, VM, and PPPD are made.
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