Tag: migraine

A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS

Abstract:

Transient receptor potential vanilloid 1 (TRPV1) is a ligand and heat-gated ion channel expressed on nociceptors that plays a central role in thermal and chemical pain signaling. Loss-of-function variants in TRPV1 have been associated with reduced nociception. We report a 65-year-old woman with disabling polyneurofunctional/neuropathic symptomatology including migraine, functional gastrointestinal disorders, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Diagnostic evaluation revealed sensory polyneuropathy and autonomic instability. Whole genome sequencing reanalysis identified a heterozygous TRPV1 c.2174A > T (p.Lys725Met) Likely Pathogenic variant that is very rare and highly conserved.

Our patient reports consistent, longstanding, marked hypersensitivity to heat, capsaicin, and alcohol, all of which are known TRPV1 agonists, supporting a gain-of-function mechanism for this variant. Furthermore, prior studies have implicated TRPV1 hyperactivity in migraine, nociceptive sensitization, and ME/CFS. Despite the excellent clinical correlation, causality of the variant cannot be definitively established without functional studies.

This case expands the potential phenotypic spectrum associated with TRPV1, and highlights a possible role for TRPV1-mediated channelopathies in complex neurofunctional disorders including ME/CFS.

Source: Zimmermann PM, Boles RG. A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS. Case Rep Genet. 2026 Nov 3;2026:1920171. doi: 10.1155/crig/1920171. PMID: 42979319; PMCID: PMC13729082. https://pmc.ncbi.nlm.nih.gov/articles/PMC13729082/ (Full text)

Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome

Abstract:

Background: Hypermobility Spectrum Disorders (HSD) and hypermobile Ehlers-Danlos syndrome (h-EDS) are multisystemic connective tissue disorders involving joint hypermobility and numerous other manifestations. Autonomic dysfunction, chronic pain, and chronic fatigue are known comorbidities of HSD and h-EDS that can affect patient quality of life (QoL), but there are limited data on the severity of autonomic symptoms, prevalence of comorbid conditions and QoL in patients with HSD/h-EDS.

Methods: We utilized the Composite Autonomic Symptom Scale (COMPASS-31) to assess autonomic symptom severity, Short-Form 36 (SF-36) to assess QoL, and the Beck Depression Inventory Second Edition (BDI-II) in a cohort of women with physician-diagnosed HSD or h-EDS, who completed these questionnaires anonymously.

Results: 84 women (mean age of 37.1 ± 8.4 years) completed the study. 58.3 % reported having physician-diagnosed postural orthostatic tachycardia syndrome (POTS), 32.1 % had mast cell activation syndrome (MCAS), 54.8 % had migraine, 26.2 % had myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and 98.8 % reported experiencing chronic pain. Importantly, 25 % of patients reported having all three diagnoses: HSD/h-EDS, POTS and MCAS. Mean COMPASS-31 score was 54.45 (range 18.79-80.93), indicating severe autonomic dysfunction, which was significantly higher than in patients with multiple sclerosis, diabetic neuropathy, scleroderma, and psoriatic arthritis as shown in prior studies. Mean SF-36 score was 32.38 (SD = 22.91) indicating poor QoL, which was worse than in patients with POTS, multiple sclerosis, rheumatoid arthritis, and lupus as determined by prior studies.

Conclusions: This study demonstrates that women with HSD/h-EDS experience severe autonomic dysfunction, chronic pain, chronic comorbid conditions and reduced QoL. More than half of participants in this cohort had POTS and migraine, with one in four having a clinical triad of HSD/h-EDS, POTS and MCAS.

Source: Collins Hutchinson ML, Liang E, Fuster E, Blitshteyn S. Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome. Auton Neurosci. 2025 Oct 14;262:103356. doi: 10.1016/j.autneu.2025.103356. Epub ahead of print. PMID: 41118678. https://pubmed.ncbi.nlm.nih.gov/41118678/

Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome

Abstract:

Thoracic outlet syndrome (TOS) is characterized by compression of nerves or blood vessels as they pass through the scalene triangle and the costoclavicular space, and under the pectoralis minor. Common symptoms include arm fatigue and heaviness, paresthesias, and neck and upper back pain, provoked by arm extension or elevation.

We have recently reported that some myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients report symptoms suggestive of TOS, specifically with respect to overhead activity, but there is uncertainty whether this overlap in symptoms is more related to ME/CFS itself or a direct contribution by TOS. This case report describes an ME/CFS patient diagnosed with TOS, who experienced major decreases in many expected and unexpected symptoms after bilateral TOS surgery.

A 19-year-old female patient with ME/CFS and the hypermobile Ehlers-Danlos syndrome (hEDS) developed progressive symptoms of numbness and tingling in the upper limbs, which did not improve after two months of physical therapy. The patient elected to undergo the rib resection with neurolysis and scalenectomy surgery on her left side. Due to the success in the reduction of symptoms, she elected to undergo the same procedure on the right side three months later.

By eight weeks after the second surgery, the patient had experienced an expected complete resolution of upper limb numbness and tingling. She also reported a complete resolution of migraines, occipital neuralgia, vertigo, and visual disturbances, along with a marked improvement in cognitive fogginess and lightheadedness.

This case report highlights the potential for marked improvements in clinical function after recognition and surgical treatment of TOS in a patient with comorbid hEDS and ME/CFS. In addition to expected improvement in upper limb symptoms and the resolution of occipital headaches, our patient noted improvement in systemic symptoms of lightheadedness, cognitive dysfunction, and visual disturbances.

This experience suggests that those with hEDS and ME/CFS should be more carefully screened for brachial plexus dysfunction. Conversely, ascertainment of systemic symptoms may enhance the diagnosis of TOS and the items assessed in surgical treatment outcome studies.

Source: Christoforou ME, Lum YW, Sroge SC, Azola AM, Rowe PC. Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome. Cureus. 2025 Aug 19;17(8):e90494. doi: 10.7759/cureus.90494. PMID: 40978926; PMCID: PMC12445393. https://pmc.ncbi.nlm.nih.gov/articles/PMC12445393/ (Full text)

Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank

Abstract:

Background: Diagnosing complex illnesses like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is complicated due to the diverse symptomology and presence of comorbid conditions. ME/CFS patients often present with multiple health issues, therefore, incorporating comorbidities into research can provide a more accurate understanding of the condition’s symptomatology and severity, to better reflect real-life patient experiences.

Methods: We performed association studies and machine learning on 1194 ME/CFS individuals with blood plasma nuclear magnetic resonance (NMR) metabolomics profiles, and seven exclusive comorbid cohorts: hypertension (n = 13,559), depression (n = 2522), asthma (n = 6406), irritable bowel syndrome (n = 859), hay fever (n = 3025), hypothyroidism (n = 1226), migraine (n = 1551) and a non-diseased control group (n = 53,009).

Results: We present a lipoprotein perspective on ME/CFS pathophysiology, highlighting gender-specific differences and identifying overlapping associations with comorbid conditions, specifically surface lipids, and ketone bodies from 168 significant individual biomarker associations. Additionally, we searched for, trained, and optimised a machine learning algorithm, resulting in a predictive model using 19 baseline characteristics and nine NMR biomarkers which could identify ME/CFS with an AUC of 0.83 and recall of 0.70. A multi-variable score was subsequently derived from the same 28 features, which exhibited ~2.5 times greater association than the top individual biomarker.

Conclusions: This study provides an end-to-end analytical workflow that explores the potential clinical utility that association scores may have for ME/CFS and other difficult to diagnose conditions.

Source: Huang K, G C de Sá A, Thomas N, Phair RD, Gooley PR, Ascher DB, Armstrong CW. Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank. Commun Med (Lond). 2024 Nov 26;4(1):248. doi: 10.1038/s43856-024-00669-7. PMID: 39592839; PMCID: PMC11599898.  https://pmc.ncbi.nlm.nih.gov/articles/PMC11599898/ (Full text)

Fatigue, chronic fatigue syndrome and migraine: Intersecting the lines through a cross-sectional study in patients with episodic and chronic migraine

Abstract:

Objectives: Fatigue is a common symptom occurring in a variety of disorders. Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue as the core symptom. The risk of CFS is nearly 1.5 times higher in migraine while headaches have been reported in 59% of cases with CFS. However, details of its occurrence and severity remain largely unexplored.

The primary objective of our study was to determine the occurrence and severity of fatigue and CFS in patients with episodic and chronic migraine. The secondary objectives were to define their relationship with other common comorbidities.

Materials and methods: 60 migraine patients (30 each, episodic [EM] and chronic migraine [CM]) were recruited from Neurology Outpatient Department, GIPMER a tertiary referral center in New Delhi, India. Patients’ headache severity was analyzed using the Headache impact test-6 (HIT-6) score while fatigue and other migraine accompaniments were assessed using Fatigue severity scale (FSS), Chalder fatigue scale, CDC diagnostic criteria for CFS, American College of Rheumatology Diagnostic Criteria for fibromyalgia, Hamilton Depression Scale, the Generalized Anxiety Disorder 7-Item Scale, and Epworth sleepiness Scale (ESS). Comparative analysis was further done among migraine patients with and without fatigue and CFS.

Results: The mean HIT-6 score was significantly higher in CM versus EM. The CM group had a higher mean FSS score (47.87 vs. 37.3 in EM; P = 0.004), a percentage of patients with severe fatigue (60% vs. 20% in EM; P = 0.004), and a higher percentage of patients with pathological fatigue (83.3% vs. 63.3% in EM; P = 0.04). Around 23.33% of CM patients fulfilled the criteria of CFS. Fatigue correlated positively with severity, frequency, attack duration and chronicity of the migraine episodes, along with depression, anxiety, and excessive daytime sleepiness.

Conclusion: Fatigue and related comorbid disorders are significantly more common in CM than in EM, expanding the morbidity of the condition and underscores the need to address these accompanying symptoms for devising a holistic treatment plan.

Source: Kumar H, Dhamija K, Duggal A, Khwaja GA, Roshan S. Fatigue, chronic fatigue syndrome and migraine: Intersecting the lines through a cross-sectional study in patients with episodic and chronic migraine. J Neurosci Rural Pract. 2023 Jul-Sep;14(3):424-431. doi: 10.25259/JNRP_63_2022. Epub 2023 Apr 20. PMID: 37692810; PMCID: PMC10483198. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10483198/ (Full text)

Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study

Abstract:

Background: The burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group.

Methods: Two groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale.

Results: The Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04-2.45, P-value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064-2.596, P-value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645, P-value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145-6.195, P-value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975, P-value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108, P-value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739, P-value = 0.003), and headache (OR = 3.148, 95%CI = 1.616-6.136, P-value = ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (P-value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3-7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2-5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1-6).

Conclusion: The study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.

Source: Magdy R, Elmazny A, Soliman SH, Elsebaie EH, Ali SH, Abdel Fattah AM, Hassan M, Yassien A, Mahfouz NA, Elsayed RM, Fathy W, Abdel-Hamid HM, Mohamed J, Hussein M. Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study. J Headache Pain. 2022 Aug 12;23(1):101. doi: 10.1186/s10194-022-01468-y. PMID: 35962348; PMCID: PMC9372973. https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-022-01468-y (Full text)

Exposure-response relationship between K. brevis blooms and reporting of upper respiratory and neurotoxin-associated symptoms

Abstract:

In southwest Florida, Karenia brevis (K. brevis) blooms occur frequently, can be very intense and persist over several years. Individuals living in coastal communities around the Gulf of Mexico are particularly vulnerable to brevetoxins released by K. brevis in seawater and carried inland within marine aerosol. Exposure to K. brevis occurs during residential, recreational, and occupational activities and has been associated with upper respiratory tract (URT) symptoms in healthy and medically vulnerable individuals. Additionally, ingestion of brevetoxin-contaminated seafood causes neurotoxic shellfish poisoning (NSP), and severe headaches prompting emergency department visits which occur in excess during K. brevis blooms.

The current study examined a dose-response relationship between K. brevis in coastal waters and URT and NSP-like symptoms and headaches among southwest Florida residents. Data on past medical history (PMH) and medical symptoms were collected from the participants (n = 258) in five southwest Florida counties between June 2019 to August 2021. A dose-response relationship was observed between K. brevis blooms and reporting of URT and NSP-like symptoms and headaches. Reporting of NSP-like symptoms was higher among participants with a PMH of migraines, chronic fatigue syndrome (CFS) and mild memory loss, while the association of headaches with K. brevis blooms was accentuated among individuals with a PMH of migraines.

These results suggest further investigations into the threshold of aerosolized brevetoxin dose required to elicit URT, headaches and/or NSP-like symptoms. These symptoms ultimately cause significant public health safety concerns, primarily among vulnerable populations with preexisting neurological conditions.

Source: Abdullah L, Ferguson S, Niedospial D, Patterson D, Oberlin S, Nkiliza A, Bartenfelder G, Hahn-Townsend C, Parks M, Crawford F, Reich A, Keegan A, Kirkpatrick B, Mullan M. Exposure-response relationship between K. brevis blooms and reporting of upper respiratory and neurotoxin-associated symptoms. Harmful Algae. 2022 Aug;117:102286. doi: 10.1016/j.hal.2022.102286. Epub 2022 Jul 12. PMID: 35944953. https://pubmed.ncbi.nlm.nih.gov/35944953/

An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes

Abstract:

Objectives: Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses.

Methods: A brief online survey was offered to members of a PCS support group website. Responses were assessed for self-reported co-existing symptoms and formal diagnoses, including: chronic fatigue syndrome, fibromyalgia, postural tachycardia syndrome, irritable bowel syndrome, migraines, interstitial cystitis, and temporomandibular joint dysfunction.

Results: Of a total of 6000 members, there were 398 respondents; 232 (59%) had not yet been treated for PCS. Among these, the most prevalent co-existing symptoms were as follows: severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%). These are much higher than reported for the general female population. The most commonly self-reported comorbid syndrome diagnoses for the overall group of 398 were: irritable bowel syndrome (29%), fibromyalgia (13%), spinal nerve problems (18%), interstitial cystitis (10%), postural tachycardia syndrome (9%), hypertension (11%), chronic fatigue syndrome (10%), and Ehlers-Danlos syndrome (6%). Other than with hypertension, these rates are variably higher than in the general population.

Conclusion: Several self-reported co-existing symptoms and syndromes are more prevalent in members of a PCS support group relative to the reported prevalence in the general population. More formal investigation is warranted to evaluate this finding and to investigate potential etiologic links. Ehlers-Danlos Syndrome appears to be common in self identifying PCS women.

Source: Smith SJ, Sichlau M, Sewall LE, Smith BH, Chen B, Khurana N, Rowe PC. An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes. Phlebology. 2022 Jul 13:2683555221112567. doi: 10.1177/02683555221112567. Epub ahead of print. PMID: 35831253. https://pubmed.ncbi.nlm.nih.gov/35831253/

Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems?

Abstract:

Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients can experience symptoms hours to days prior to migraine pain, which can warn of impending headache. These symptoms can include mood and cognitive change, fatigue, and neck discomfort. Some epidemiological studies have suggested that migraine is associated in a bidirectional fashion with other disorders, such as mood disorders and chronic fatigue, as well as with other pain conditions such as fibromyalgia. This review will focus on the literature surrounding alterations in fatigue, mood, and cognition in particular, in association with migraine, and the suggested links to disorders such as chronic fatigue syndrome and depression.

We hypothesize that migraine should be considered a neural disorder of brain function, in which alterations in aminergic networks integrating the limbic system with the sensory and homeostatic systems occur early and persist after headache resolution and perhaps interictally. The associations with some of these other disorders may allude to the inherent sensory sensitivity of the migraine brain and shared neurobiology and neurotransmitter systems rather than true co-morbidity.

Source: Karsan N, Goadsby PJ. Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems? Front Hum Neurosci. 2021 Jun 3;15:646692. doi: 10.3389/fnhum.2021.646692. PMID: 34149377; PMCID: PMC8209296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209296/ (Full text)

Can a Chronic BPPV With a History of Trauma be the Trigger of Symptoms in Vestibular Migraine, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Whiplash Associated Disorders (WAD)? A Retrospective Cohort Study

Abstract:

BACKGROUND: In patients with chronic benign paroxysmal positional vertigo (BPPV), i.e., chronic vestibular multicanalicular canalithiasis (CVMCC), abnormal signals are transmitted from diseased labyrinths via the healthy vestibular nuclei complex to their end organs. The vestibulo-thalamo-cortical reflex as proposed in vestibular migraine is just one of these reflexes. In a group of patients diagnosed with CVMCC otolith repositioning maneuvers specific for each semicircular canal (SCC) ameliorated pain and other symptoms in 90%. Increased awareness of CVMCC may reduce suffering and continuous medication.

OBJECTIVE: To evaluate if CVMCC can be the trigger of symptoms in vestibular migraine, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and whiplash associated disorders (WAD).

STUDY DESIGN: Retrospective consecutive observational cohort study.

SETTING: Ambulatory at a private Otoneurology Centre.

PATIENTS: One hundred sixty-three patients with CVMCC and a history of trauma.

INTERVENTION: Based on the symptoms (structured symptom questionnaire), the patients are post hoc sub grouped according to the criteria of the different diagnoses.

MAIN OUTCOME MEASURE: Frequency of patients with CVMCC who fulfill the criteria of the different diagnoses.

RESULTS: 98% of all patients with CVMCC fulfill the Barany Society criteria of a probable vestibular migraine; 17% fulfill the International Classification of Headache Disorders defined vestibular migraine criteria; 63% fulfill the Fukuda criteria of ME/CFS; 100% of the patients with WAD suffer from CVMCC.

CONCLUSION: This survey supports the hypothesis that CVMCC can be the trigger of symptoms in vestibular migraine, ME/CFS, and WAD. The actual diagnosis the patient receives is often in accordance with the patient’s dominant symptom.

Source: Tjell C, Iglebekk W, Borenstein P. Can a Chronic BPPV With a History of Trauma be the Trigger of Symptoms in Vestibular Migraine, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Whiplash Associated Disorders (WAD)? A Retrospective Cohort Study. Otol Neurotol. 2018 Oct 9. doi: 10.1097/MAO.0000000000002020. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30303941