Tag: 2025

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)

Exploration of Intersections and Divergences of Long COVID and Chronic Fatigue Syndrome

Abstract:

Background: Fatigue is the most common symptom of Long COVID (LC), defined by persistent or newly emerging symptoms that develop at least three months after an initial SARS-CoV-2 infection, in the absence of other identifiable cause. This study investigates the prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as a potential comorbidity of LC.

Methods: The study enrolled 37 adult controls with no documented SARS-CoV-2 infection and 32 individuals with a history of infection, categorized as LC-yes (with LC symptoms) and LC-no (without LC symptoms). ME/CFS diagnosis was based on the International Consensus Criteria (ICC).

Results: Among LC-yes cases, the most frequently reported symptoms included post-exertional malaise (PEM); neurosensory, perceptual, or motor disturbances; cognitive impairment; sleep disturbances; pain; impaired thermoregulation; and flu-like symptoms, all occurring significantly more than in the LC-no or control groups. All individuals in the LC-yes group reported PEM. ME/CFS was diagnosed in three LC-yes cases (18.8%), one LC-no case (6.7%), and four control subjects (10.8%), with no statistically significant differences observed among groups. Experiencing more than six symptoms during acute infection, such as fatigue, loss of taste or smell, headache, fever, cough, myalgia, sore throat, shortness of breath, rhinorrhea, and diarrhea, was associated with a twofold higher risk of developing LC.

Conclusion: A substantial proportion of LC-yes individuals experienced PEM; neurosensory, perceptual, or motor disturbances; cognitive impairment; and sleep disturbances, with rates significantly exceeding those in the LC-no and control groups. Nevertheless, only a minority of LC-yes cases (18.8%) satisfied criteria for the ME/CFS, and the prevalence did not significantly differ from LC-no and controls. These findings suggest that while many symptoms of LC overlap with those of ME/CFS, only a subset of LC cases meet established ME/CFS diagnostic criteria.

Source: Kouyoumdjian JA, Yamamoto LA, Graca CR. Exploration of Intersections and Divergences of Long COVID and Chronic Fatigue Syndrome. Cureus. 2025 Aug 20;17(8):e90607. doi: 10.7759/cureus.90607. PMID: 40978825; PMCID: PMC12448662. https://pmc.ncbi.nlm.nih.gov/articles/PMC12448662/ (Full text)

Abnormal Brain Activation Patterns in Patients With Post-Acute Sequelae of COVID-19 (PASC) During Recovery: A fNIRS Study

Abstract:

COVID-19 has increased the likelihood of cognitive impairment in patients with post-acute sequelae of COVID-19 (PASC). There is a lack of direct evidence regarding the working memory performance of mild patients during the recovery period. This study employed functional near-infrared spectroscopy (fNIRS) to construct a mixed effects model for PASC patients performing the N-back task, assessing brain activation levels and brain connectivity.

PASC patients exhibited abnormally low activation in the parietal lobe (β = −0.21) and abnormally high activation in the occipital lobe (β = 0.40). There was a significant reduction in brain connectivity within the frontal–parietal and frontal–occipital networks.

These findings suggest that PASC patients experience impaired fronto-parietal network connectivity, rely more on the visual cortex to compensate for executive function deficits, and use this as a compensatory mechanism to reduce overall cerebral blood oxygenation. This study provides evidence of altered brain activation patterns in PASC patients during the recovery period due to cognitive impairment.

Source: Y. Ran, S. Wu, S. Liu, et al., “ Abnormal Brain Activation Patterns in Patients With Post-Acute Sequelae of COVID-19 (PASC) During Recovery: A fNIRS Study,” Journal of Biophotonics (2025): e202500206, https://doi.org/10.1002/jbio.202500206. https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbio.202500206

Long COVID Incidence Proportion in Adults and Children Between 2020 and 2024: An Electronic Health Record-Based Study From the RECOVER Initiative

Abstract:

Background: Incidence estimates of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, also known as long COVID, have varied across studies and changed over time. We estimated long COVID incidence among adult and pediatric populations in 3 nationwide research networks of electronic health records (EHRs) participating in the RECOVER (Researching COVID to Enhance Recovery) Initiative using different classification algorithms (computable phenotypes).

Methods: This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and 2 control groups: contemporary coronavirus disease 2019 (COVID-19)-negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative [N3C], National Patient-Centered Clinical Research Network [PCORnet], and PEDSnet) implemented its own long COVID definition. We introduced a harmonized definition for adults in a supplementary analysis.

Results: Overall, 4% of children and 10%-26% of adults developed long COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5% to 6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants.

Conclusions: Our findings indicate that preventing and mitigating long COVID remains a public health priority. Examining temporal patterns and risk factors for long COVID incidence informs our understanding of etiology and can improve prevention and management.

Source: Mandel H, Yoo YJ, Allen AJ, Abedian S, Verzani Z, Karlson EW, Kleinman LC, Mudumbi PC, Oliveira CR, Muszynski JA, Gross RS, Carton TW, Kim C, Taylor E, Park H, Divers J, Kelly JD, Arnold J, Geary CR, Zang C, Tantisira KG, Rhee KE, Koropsak M, Mohandas S, Vasey A, Mosa ASM, Haendel M, Chute CG, Murphy SN, O’Brien L, Szmuszkovicz J, Guthe N, Santana JL, De A, Bogie AL, Halabi KC, Mohanraj L, Kinser PA, Packard SE, Tuttle KR, Hirabayashi K, Kaushal R, Pfaff E, Weiner MG, Thorpe LE, Moffitt RA. Long COVID Incidence Proportion in Adults and Children Between 2020 and 2024: An Electronic Health Record-Based Study From the RECOVER Initiative. Clin Infect Dis. 2025 Jul 18;80(6):1247-1261. doi: 10.1093/cid/ciaf046. PMID: 39907495; PMCID: PMC12272849. https://pubmed.ncbi.nlm.nih.gov/39907495/

Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID are complex, disabling conditions that have emerged as significant public health challenges, affecting millions worldwide. Despite their growing prevalence, effective diagnostics and treatments remain limited, largely due to an incomplete understanding of their underlying pathophysiology. Both conditions share hallmark symptoms of chronic fatigue, cognitive dysfunction, and postexertional malaise, but their biological underpinnings remain to be elucidated. Neuroimaging offers a promising, noninvasive window into the brain’s metabolic landscape and has the potential to uncover objective biomarkers for these conditions.

In this mini review, we highlight recent advancements in metabolic neuroimaging, particularly positron emission tomography and magnetic resonance imaging/magnetic resonance spectroscopy, that reveal alterations in glucose and oxygen metabolism, neurotransmitter balance, and oxidative stress. These insights point toward shared disruptions in brain energy metabolism and neuroinflammatory processes, which may underlie the persistent symptoms in both ME/CFS and Long-COVID.

Importantly, while some findings overlap, inconsistencies in metabolite profiles between ME/CFS and Long-COVID underscore the need for further stratification and longitudinal research. Standardizing definitions, such as identifying Long-COVID patients who meet ME/CFS diagnostic criteria, could help improve study comparability.

By summarizing current imaging evidence, this review underscores the potential of neuroimaging to identify imaging biomarkers to advance the clinical diagnosis of Long-COVID and identify therapeutic targets for treatment development. As we continue to face the growing burden of Long-COVID and ME/CFS, metabolic imaging may serve as a powerful tool to bridge gaps in knowledge and accelerate progress toward effective care.

Source: Zhu Y, Quan P, Yamazaki T, Norweg A, Natelson B, Xu X. Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID. Immunometabolism (Cobham). 2025 Sep 12;7(4):e00068. doi: 10.1097/IN9.0000000000000068. PMID: 40958852; PMCID: PMC12435251. https://pmc.ncbi.nlm.nih.gov/articles/PMC12435251/ (Full text)

Solriamfetol improves daily fatigue symptoms in adults with myalgic encephalomyelitis/chronic fatigue syndrome after 8 weeks of treatment

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term illness with no treatment options that address the disease directly. Solriamfetol is a selective dual norepinephrine-dopamine reuptake inhibitor that promotes wakefulness in obstructive sleep apnea and narcolepsy.

Aims: This study evaluated the efficacy and safety of solriamfetol for fatigue symptoms in adults with ME/CFS over 8 weeks of treatment.

Methods: This was a phase 4, double-blind, randomized, placebo-controlled trial of solriamfetol in adults with ME/CFS. Eligible participants (N = 38) were randomly assigned to receive 75 mg (titrated to 150 mg as needed) solriamfetol or placebo. Participants completed a battery of assessments at weekly visits. The primary outcome was Fatigue Symptom Inventory (FSI) scores, and the secondary outcome measure was Behavioral Rating Inventory of Executive Function for Adults (BRIEF-A), at Weeks 6 and 8. T-tests assessed the differences in mean change from baseline between solriamfetol and placebo. Adverse events were monitored throughout the study.

Results: At Week 8 (p = 0.039), but not Week 6 (p = 0.270), solriamfetol improved FSI severity compared to placebo. On the BRIEF-A global executive composite, solriamfetol improved more than placebo at Week 8 (p = 0.012), driven by improved metacognition index (p = 0.004), but not behavioral regulation index (p = 0.574). Solriamfetol was well tolerated, with most common AEs being sleep loss and headaches.

Conclusions: Solriamfetol demonstrated good safety and efficacy in improving fatigue and executive functioning in patients with ME/CFS. As a dual norepinephrine-dopamine reuptake inhibitor and wakefulness-promoting factors, solriamfetol has the potential to improve fatigue symptoms of ME/CFS.

Clinical trial number: NCT04622293.

Source: Young JL, Powell RN, Powell A, Welling LLM, Granata L, Saal J. Solriamfetol improves daily fatigue symptoms in adults with myalgic encephalomyelitis/chronic fatigue syndrome after 8 weeks of treatment. J Psychopharmacol. 2025 Sep 16:2698811251368371. doi: 10.1177/02698811251368371. Epub ahead of print. PMID: 40958377. https://journals.sagepub.com/doi/10.1177/02698811251368371

A multi-omics recovery factor predicts long COVID in the IMPACC study

Abstract:

Background. Following SARS-CoV-2 infection, ~10-35% of COVID-19 patients experience long COVID (LC), in which debilitating symptoms persist for at least three months. Elucidating biologic underpinnings of LC could identify therapeutic opportunities.

Methods. We utilized machine learning methods on biologic analytes provided over 12-months after hospital discharge from >500 COVID-19 patients in the IMPACC cohort to identify a multi-omics “recovery factor”, trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood CyTOF protein levels. Recovery factor scores were tested for association with LC, disease severity, clinical parameters, and immune subset frequencies. Enrichment analyses identified biologic pathways associated with recovery factor scores.

Results. LC participants had lower recovery factor scores compared to recovered participants. Recovery factor scores predicted LC as early as hospital admission, irrespective of acute COVID-19 severity. Biologic characterization revealed increased inflammatory mediators, elevated signatures of heme metabolism, and decreased androgenic steroids as predictive and ongoing biomarkers of LC. Lower recovery factor scores were associated with reduced lymphocyte and increased myeloid cell frequencies. The observed signatures are consistent with persistent inflammation driving anemia and stress erythropoiesis as major biologic underpinnings of LC.

Conclusion. The multi-omics recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.

Trial Registration. ClinicalTrials.gov NCT04378777.

Funding. This study was funded by NIH, NIAID and NSF.

Source: Gisela Gabernet, Leying Guan, Lauren I.R. Ehrlich, et al. A multi-omics recovery factor predicts long COVID in the IMPACC study. J Clin Invest. September 9, 2025. https://doi.org/10.1172/JCI193698. https://www.jci.org/articles/view/193698/ (Full study available as PDF file)

Hormonal Fluctuations and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Women: The Role of Menstrual Cycle and Menopause

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem disease, predominantly affecting women as compared to men and showing extreme symptom variability across reproductive life stages. The aim of this research was to determine the effects of hormonal changes, menopause status, and symptom severity in individuals with ME/CFS.

This was a prospective observational cohort study conducted at JPMC, Karachi from January 2024 to June 2025. Final recruitment was of 150 women with ME/CFS (90 were in the premenopausal, 30 in the perimenopausal and 30 in the postmenopausal strata). Baseline demographic and clinical profiling, laboratory hormonal assays (estradiol, progesterone, LH, FSH), symptom daily profiles and monthly activity data, and objective autonomic probe reflex testing (tilt-table studies) were obtained.

The findings revealed a clear hormonal gradient across the groups (ANOVA p < 0.001), with estradiol and progesterone levels becoming lower and gonadotropins higher with older reproductive age.

Symptom trajectories varied according to for premenopausal women: fatigue and pain peaked pre menstrually (CFQ p = 0.01, VAS p = 0.02) and cognitive impairment was lowest at ovulation (p = 0.04).

When comparing across menopause groups, symptom burden was greater in the perimenopausal and postmenopausal participants and the perimenopausal and postmenopausal participants had lower SF-36 quality-of-life component scores (physical functioning 0.01, mental health 0.04).

Tilt-table findings from the cohort suggest age-related differences in autonomic dysfunction with postmenopausal women more likely to exhibit orthostatic hypotension (36.7%) and premenopausal women more likely to express POTS (38.9%).

The correlation analysis revealed that low levels of estradiol and progesterone were significantly correlated with higher levels of fatigue and pain, whereas the opposite association was found for LH and FSH, the latter two being positively correlated with fatigue and orthostatic symptoms.

These findings provide the first quantifiable evidence for reproductive hormonal dynamics substantially modulating the clinical expression of ME/CFS in women and the need for hormone-sensitive management approaches.

Source: Mehak Khan, Sidra Anees, Muhammad Muthar Anees, Komal Khalid Chaudhry, Syeda Marium Rashid Zaidi, Vishan Das, Rimal Rashid. Hormonal Fluctuations and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Women: The Role of Menstrual Cycle and Menopause. The Research of Medical Science Review; Volume 3, Issue 8, 2025. ISSN: 3007-1208 & 3007-1216. https://medscireview.net/index.php/Journal/article/view/2032 (Full text available as PDF file)

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options

Abstract:

With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies.

Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea.

We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.

Source: Yong SJ, Kenny TA, Halim A, Munipalli B, Alhashem YN, AlSaihati H, Al-Subaie MF, Al Kaabi NA, Al Fares MA, Garout M, Sabour AA, Alshiekheid MA, Almansour ZH, Alotaibi J, Alrasheed HA, Alamri AA, Albayat H, Alamodi AS, Tombuloglu H, Mohapatra RK, Hazazi A, Rabaan AA. Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options. Rev Med Virol. 2025 Sep;35(5):e70070. doi: 10.1002/rmv.70070. PMID: 40944962. https://pubmed.ncbi.nlm.nih.gov/40944962/

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis

Abstract:

Myalgic Encephalomyelitis (ME) is a complex, multisystem disorder with poorly understood pathophysiological mechanisms. SMPDL3B, a membrane-associated protein expressed in renal podocytes, is essential for lipid raft integrity and glomerular barrier function. We hypothesize that reduced membrane-bound SMPDL3B may contribute to podocyte dysfunction and impaired renal physiology in ME. To investigate this, we quantified soluble SMPDL3B in plasma and urine as a surrogate marker of membrane-bound SMPDL3B status and assessed renal clearance and plasma metabolomic profiles.
In a cross-sectional study of 56 ME patients and 16 matched healthy controls, ME patients exhibited significantly lower urine-to-plasma ratios of soluble SMPDL3B and reduced renal clearance, suggesting podocyte-related abnormalities. Plasma metabolomics revealed dysregulation of metabolites associated with renal impairment, including succinic acid, benzoic acid, phenyllactic acid, 1,5-anhydroglucitol, histidine, and citrate.
In ME patients, plasma SMPDL3B levels inversely correlated with 1,5-anhydroglucitol concentrations and renal clearance. Multivariable modeling identified the urine-to-plasma SMPDL3B ratio as an independent predictor of clearance. Female ME patients showed more pronounced SMPDL3B alterations, reduced clearance, and greater symptom severity. Non-linear associations between soluble SMPDL3B and lipid species further suggest systemic metabolic remodeling.
These findings support soluble SMPDL3B as a potential non-invasive biomarker of renal-podocyte involvement in ME, highlighting sex-specific differences that may inform future therapeutic strategies.
Source: Rostami-Afshari B, Elremaly W, McGregor NR, Huang KJK, Armstrong CW, Franco A, Godbout C, Elbakry M, Abdelli R, Moreau A. Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis. International Journal of Molecular Sciences. 2025; 26(18):8882. https://doi.org/10.3390/ijms26188882 https://www.mdpi.com/1422-0067/26/18/8882 (Full text)