Tag: 2026

FreeSurfer-based amygdala subfield volumetry in long COVID and ME/CFS: clinical and immunological correlations

Abstract:

Background: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share debilitating symptoms and have been associated with limbic-system dysfunction. We investigated amygdala subfield volumes to identify disease-specific neuroanatomical features and their clinical and immunological correlates.

Methods: We prospectively examined 27 patients with long COVID, 38 patients with ME/CFS, and 47 healthy controls (HCs). Amygdala subfields were segmented using high-resolution 3-T MRI and FreeSurfer software. Group comparisons were performed using analysis of covariance, and partial correlations with clinical and immunological indices, including autoantibodies, plasmablasts, regulatory T cells (Tregs), and Eomesodermin-positive helper T cells (Eomes+ Th cells), were assessed.

Results: Patients with long COVID had nominally larger right cortical nucleus volumes than HCs (raw p = 0.040; Bonferroni-adjusted p = 0.119), whereas patients with ME/CFS had a nominally larger left paralaminar nucleus (raw p = 0.048; Bonferroni-adjusted p = 0.145). In long COVID, G-protein-coupled receptor (GPCR) autoantibodies were nominally negatively associated with right medial nucleus volume. In ME/CFS, performance status was nominally positively associated with the right basal nucleus, right paralaminar nucleus, and right whole amygdala, and plasmablasts were nominally positively associated with the right corticoamygdaloid transition area. No group difference or partial correlation remained significant after correction for multiple testing.

Conclusion: Although no finding survived correction for multiple testing, the exploratory results suggest that amygdala-related structural variation may be relevant to both long COVID and ME/CFS. The nominal, uncorrected within-group patterns centered on olfactory-related amygdala nuclei and GPCR autoantibodies in long COVID, and on amygdala structure, functional severity, and plasmablasts in ME/CFS; however, these patterns do not support a conclusion of between-group differences. These observations are hypothesis-generating and do not establish disease-specific mechanisms. Prespecified validation in larger longitudinal and independent cohorts is required.

Source: Kimura Y, Sato W, Shigemoto Y, Kagaya R, Hayakawa A, Kumazawa Y, Shin I, Amano K, Yamamura T, Sato N. FreeSurfer-based amygdala subfield volumetry in long COVID and ME/CFS: clinical and immunological correlations. Front Neurol. 2026 Sep 16;17:1913553. doi: 10.3389/fneur.2026.1913553. PMID: 42819213; PMCID: PMC13623709. https://pmc.ncbi.nlm.nih.gov/articles/PMC13623709/ (Full text)

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia are overlapping chronic disorders characterized by fatigue, pain, cognitive dysfunction, sleep disturbance, and multisystem symptoms. Whether peripheral blood DNA methylation reflects diagnostic categories, quantitative symptom burden, or both remains unclear. We aimed to identify DNA methylation axes associated with diagnosis, symptom dimensions, and clinical differences between these conditions.

Methods: This cross-sectional study included 188 women: 73 healthy controls, 71 with ME/CFS, and 44 with fibromyalgia. DNA methylation was profiled in peripheral blood mononuclear cells using the Illumina MethylationEPIC v2 array. Principal component analysis identified latent methylation axes. Linear models adjusted for age, body mass index, and estimated immune-cell composition tested associations with diagnostic group and clinical measures. Region-level methylation analyses, functional enrichment, bootstrap resampling, permutation testing, leave-one-out analyses, and medication/comorbidity sensitivity analyses were performed.

Results: Both patient groups had greater symptom burden than healthy controls but differed clinically. Fibromyalgia showed greater widespread pain, pain catastrophizing, central sensitization inventory scores, and temporal summation, whereas ME/CFS showed greater post-exertional malaise, cognitive symptoms, and lower physical activity. Two methylation axes showed clinically relevant associations. PC5 differentiated ME/CFS from fibromyalgia and healthy controls and was associated mainly with post-exertional malaise and cognitive symptoms. PC6 separated both patient groups from healthy controls but not from each other, and was associated with broader symptom burden, including widespread pain, pain impact, sleep disturbance, visceral symptoms, and temporal summation. The temporal summation association, together with higher widespread pain and temporal summation in fibromyalgia, suggests that PC6 includes a pain-related component extending to experimentally assessed nociceptive summation. Region-level analyses identified 591 PC5-associated and 54 PC6-associated high-confidence differentially methylated regions. Enrichment implicated neuroimmune, metabolic, cytokine, NF-κB, JAK-STAT, TGF-β, and immune-regulatory pathways. Sensitivity analyses supported the stability of the main associations.

Conclusions: Peripheral blood DNA methylation profiles identified partly distinct but overlapping DNA methylation axes in ME/CFS and fibromyalgia. PC5 was aligned with post-exertional malaise and cognitive symptoms, whereas PC6 was aligned with broader pain-related multisystem burden. Independent replication and longitudinal studies are needed to establish clinical utility.

Source: Polli A, Hendrix J, Wyns A, Van Campenhout J, Allard S, Aerts JL, Laeremans T, Xiong H, Buntinx Y, Michiels J, Ben Amar J, Godderis L, Thienpont B, Nijs J. Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden. J Transl Med. 2026 Aug 22;24(1):1222. doi: 10.1186/s12967-026-08824-5. PMID: 42811334. https://link.springer.com/article/10.1186/s12967-026-08824-5 (Full text)

Persistent symptom burden in long-standing systemic lupus erythematosus: a subgroup-focused hypothesis for an SLE-ME/CFS research phenotype

Abstract:

Background: Despite improved control of inflammatory disease activity in systemic lupus erythematosus (SLE), many patients experience persistent fatigue, impaired physical function, cognitive symptoms, sleep disturbance, and reduced exercise tolerance, including during remission. These symptoms are multifactorial and may not be adequately explained by conventional measures of inflammatory activity. Clinical and biological parallels with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that interacting immune, metabolic, vascular, and autonomic mechanisms may contribute to persistent symptom burden in a subgroup of patients with long-standing SLE.

Objective: To develop a subgroup-focused, non-linear, and testable framework for persistent symptoms in SLE by integrating established SLE evidence with carefully distinguished mechanistic insights from ME/CFS research.

Methods: This Commentary is based on a targeted, non-systematic literature synthesis of publications identified in PubMed and Web of Science. Evidence was categorized as direct SLE evidence, evidence from ME/CFS, or cross-condition mechanistic inference. Priority was given to human studies, systematic reviews, meta-analyses, and translational research addressing persistent symptoms, autonomic and endothelial dysfunction, mitochondrial and redox alterations, and neurocognitive manifestations.

Results: We propose a hypothesized SLE-ME/CFS research phenotype characterized by persistent, functionally limiting symptoms despite low inflammatory disease activity or remission. The phenotype includes fatigue lasting at least six months together with post-exertional symptom exacerbation, unrefreshing sleep, cognitive symptoms, and/or orthostatic intolerance, following structured exclusion or assessment of alternative explanations and comorbidities. Direct SLE evidence supports the relevance of residual immune activation, oxidative stress, mitochondrial alterations, endothelial dysfunction, and dysautonomia. Findings from ME/CFS further suggest potentially convergent mechanisms involving impaired cellular energetics, autonomic dysfunction, altered cerebral perfusion, and neuroimmune dysregulation. However, these cross-condition inferences require direct validation in SLE.

Conclusions: Persistent symptom burden in long-standing SLE may reflect a biologically distinct subgroup in which immune, autonomic, vascular, metabolic, and neurocognitive mechanisms interact dynamically. The proposed framework does not define a new diagnostic entity or fixed disease trajectory but provides a hypothesis-generating basis for prospective longitudinal studies. Multidimensional phenotyping may improve patient stratification, biomarker discovery, and supportive care for patients whose symptoms remain disproportionate to conventional measures of disease activity.

Source: Habermann-Horstmeier L. Persistent symptom burden in long-standing systemic lupus erythematosus: a subgroup-focused hypothesis for an SLE-ME/CFS research phenotype. J Transl Med. 2026 Sep 25;24(1):1215. doi: 10.1186/s12967-026-08867-8. PMID: 42806386. https://link.springer.com/article/10.1186/s12967-026-08867-8 (Full text)

Muscle symptoms and a latent physiological symptom-dysregulation factor in ME/CFS: exploratory analyses by sex and age-defined menopausal-status proxy group

Abstract:

Background: Muscle-related symptoms are among the most disabling manifestations of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), yet their position within the broader symptom architecture of the disease remains unclear. We hypothesized that muscle symptoms may represent a candidate integrative symptom within a broader shared symptom-dysregulation structure and their symptom associations differ according to sex and menopausal status.

Methods: Cross-sectional data from 736 individuals with physician-diagnosed ME/CFS enrolled in the APAV-ME/CFS registry were analysed. Muscle problems served as the primary outcome variable. Associations with 14 symptom domains were examined using multivariable logistic regression. Pearson and tetrachoric correlations, exploratory factor analysis, and structural equation modeling (SEM) were used to identify latent symptom structures. Exploratory analyses were stratified by sex, menopausal status, and disease duration.

Results: In the full multivariable model (non-robust estimates), breathing problems (OR 2.49 [95% Conf. Interval: 1.42-4.38], p = 0.001), flu-like symptoms (OR 1.97 [1.14-3.42], p = 0.015), and temperature-regulation disorders (OR 1.97 [1.10-3.51], p = 0.021) independently predicted muscle problems. A reduced physiological model (not-robust estimates) additionally identified cardiovascular symptoms (OR 1.87 [1.09-3.24], p = 0.024) as a significant predictor. Tetrachoric correlations demonstrated substantial latent associations between muscle problems and breathing difficulties (ρ = 0.52), cardiovascular symptoms (ρ = 0.49), temperature-regulation disorders (ρ = 0.49), visual disturbances (ρ = 0.39), and flu-like symptoms (ρ = 0.39). Factor analysis and SEM supported a single latent physiological dysregulation factor with good model fit (RMSEA = 0.046, CFI = 0.971, TLI = 0.952, SRMR = 0.026).

The sex-stratified analyses revealed differences in the pattern of statistically significant symptom associations across the subgroups. However, the overall test of the symptom-by-sex interaction terms did not provide evidence for a statistically established difference in the symptom associations by sex. Thus, the subgroup-specific patterns should primarily be interpreted as descriptive and exploratory. At the individual symptom level, the association between breathing-related symptoms and muscle problems showed a statistically significant interaction with sex, suggesting that this association may differ between women and men. However, this finding should be interpreted cautiously given the non-significant overall interaction test and the wide confidence interval of the interaction estimate.

In women, all five physiological symptoms independently predicted muscle problems, whereas in men only breathing problems and temperature-regulation disorders remained significant. Women classified as premenopausal and postmenopausal based on an age-defined proxy showed different patterns of symptom associations with muscle problems in subgroup-specific analyses. Women in the premenopausal age-proxy group showed significant associations with cardiovascular symptoms, visual disturbances, and temperature-regulation disorders, whereas women classified as postmenopausal showed significant associations with breathing difficulties and flu-like symptoms. However, the overall menopausal-by-symptom interaction was not statistically significant (Wald χ2 (5)=5.96, p = 0.310).

The specified latent physiological factor showed statistical comparability across the cross-sectional disease-duration groups. Gastrointestinal complaints loaded substantially on the latent factor despite lacking an independent association with muscle problems in multivariable regression. Urogenital symptoms also showed a smaller but significant association with the latent factor and substantial item-specific variance.

Conclusions: Muscle symptoms may represent a candidate integrative symptom within a latent physiological symptom-dysregulation factor encompassing respiratory, cardiovascular, thermoregulatory, visual, and flu-like symptoms in this ME/CFS sample. Secondary analyses suggested that gastrointestinal complaints were also part of the broader physiological symptom pattern, although they were not independently associated with muscle problems. The specified latent physiological factor showed no overall statistical evidence of measurement differences across the cross-sectional disease-duration groups. However, subgroup-specific symptom patterns differed descriptively by sex and age-defined menopausal-status proxy group.

Women classified as premenopausal were characterized primarily by cardiovascular, visual, and thermoregulatory symptom associations, whereas women classified as postmenopausal and men showed greater prominence of breathing-related symptoms. Flu-like symptoms were independently associated with muscle problems in the postmenopausal subgroup but not in the premenopausal subgroup. Because the corresponding interaction term was not statistically significant, this subgroup contrast should be interpreted as an exploratory difference in association rather than as evidence of a menopause-specific effect. More broadly, the findings are compatible with the hypothesis that the latent symptom-dysregulation factor may reflect a chronic PEM-associated multisystem response.

Whether this symptom-dysregulation factor corresponds to interacting autonomic, vascular, immunological, and metabolic processes remains to be determined by longitudinal and biomarker-based studies. ME/CFS phenotyping may improve patient stratification and facilitate the development of mechanism-based therapeutic approaches.

Source: Habermann-Horstmeier L, Horstmeier LM. Muscle symptoms and a latent physiological symptom-dysregulation factor in ME/CFS: exploratory analyses by sex and age-defined menopausal-status proxy group. J Transl Med. 2026 Sep 28;24(1):1216. doi: 10.1186/s12967-026-09018-9. PMID: 42806383. https://link.springer.com/article/10.1186/s12967-026-09018-9 (Full text)

High Frequency of HHV-7 Reactivation in Neurological and Neuropsychiatric Long COVID: A Retrospective Observational Study

Abstract:

The neurological and neuropsychiatric manifestations of long COVID remain incompletely understood. Reactivation of latent herpesviruses has been proposed as a contributing mechanism, but human herpesvirus 7 (HHV-7) has received limited attention despite its neurotropic potential. We conducted a retrospective analysis of HHV-7 polymerase chain reaction (PCR) results in 30 patients (18 women and 12 men; age range, 21-55 years) with a neurological/neuropsychiatric long COVID phenotype tested within 24 months of SARS-CoV-2 infection at R.E.D. Laboratories SA, Belgium.

HHV-7 positivity was compared with a historical pre-COVID-19 laboratory reference cohort comprising 320 diagnostic tests performed from 2012 to 2019. HHV-7 positivity was 29.1% (93/320; 95% CI, 24.4-34.3%) in the historical reference cohort and 76.7% (23/30; 95% CI, 59.1-88.2%) in the neurological/neuropsychiatric long COVID cohort. The between-cohort difference was significant using a two-sided Fisher’s exact test (p < 0.000001). All six patients tested within the first 12 months were HHV-7-positive. HHV-7-positive patients frequently reported neuropsychiatric symptoms, and in one longitudinal index case, viral load tracked self-reported symptom severity.

In this patient-initiated retrospective study, HHV-7 positivity was substantially more frequent in the long COVID cohort than in the historical reference cohort. These findings are hypothesis-generating and support prospective investigation of HHV-7 in neurological and neuropsychiatric long COVID.

Source: Ducret D, Mijatovic T. High Frequency of HHV-7 Reactivation in Neurological and Neuropsychiatric Long COVID: A Retrospective Observational Study. Viruses. 2026 Sep 20;18(9):1043. doi: 10.3390/v18091043. PMID: 42797874. https://www.mdpi.com/1999-4915/18/9/1043 (Full text)

Knowing or not knowing: the practical and moral complexity of diagnostic-seeking pathways in situations of medical uncertainty

Abstract:

In this paper, we discuss the practical and moral complexities of diagnostic-seeking pathways for three uncertain medical conditions: fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and long COVID. We analyse qualitative data collected in the UK between 2023 and 2025, comprising in-depth interviews with medical professionals, researchers, and patients, as well as documentary sources.

Drawing on the anthropology and sociology of diagnosis, this paper discusses how chronic illness can be marked by challenging and unstable pathways, influenced by the organisation of the medical system and the resources patients have to navigate it. Diagnoses further do not guarantee a solution to the condition, and can, on the other hand, produce stigma. Medical professionals recognise the uncertain nature of these conditions and emphasise how diagnosis can play an instrumental role in providing patients with access to therapies, benefits, or acceptance. Patients discuss the complexity of the strategies they deploy not only to obtain a diagnosis but also to navigate the practical and moral complexities associated with their condition.

Analysing the practical and moral complexity of diagnostic-seeking pathways represents a way to enrich anthropological reflections on diagnosis by demonstrating how this key concept of biomedicine is strongly influenced by social, economic, and moral, as well as biological, factors.

Source: Greco C, Cross S. Knowing or not knowing: the practical and moral complexity of diagnostic-seeking pathways in situations of medical uncertainty. Anthropol Med. 2026 Sep 25:1-16. doi: 10.1080/13648470.2026.2709278. Epub ahead of print. PMID: 42788232. https://www.tandfonline.com/doi/full/10.1080/13648470.2026.2709278 (Full text)

DNA methylation: unifying framework for complex chronic conditions

Abstract:

Complex chronic conditions represent a growing health burden that is poorly understood and inadequately managed within current health systems. This review focuses on the potential of epigenetic DNA methylation to provide a pathway for better understanding of four closely related conditions: myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID (LC), fibromyalgia (FM), and hypermobile Ehlers-Danlos syndrome (hEDS).

These conditions have extensive overlapping symptoms, suggesting shared underlying pathophysiological mechanisms. Epigenetic regulation, particularly DNA methylation, provides a powerful framework for comparative and longitudinal studies across these clinically overlapping conditions.

Here, we synthesise evidence from current DNA methylation studies in ME/CFS, LC, and FM, and consider how an integrated cross-condition approach could advance mechanistic insight, enable diagnostic stratification, and improve patient outcomes.

Source: Sharma S, Rodger EJ, Chatterjee A, Tate WP. DNA methylation: unifying framework for complex chronic conditions. Trends Genet. 2026 Sep 24:S0168-9525(26)00221-0. doi: 10.1016/j.tig.2026.09.001. Epub ahead of print. PMID: 42786072. https://www.cell.com/trends/genetics/fulltext/S0168-9525(26)00221-0 (Full text)

Hemodynamic Phenotyping in ME/CFS and ANOCA: Complementary Insights from Coronary Function Testing and Invasive Cardiopulmonary Exercise Testing

Abstract:

This single-center cohort study sought to evaluate the association between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Angina with Non-Obstructive Coronary Arteries (ANOCA), by determining the observed frequency of ME/CFS among patients with ANOCA diagnosed by coronary function testing (CFT). Additionally, we performed an exploratory analysis of the diagnostic utility of invasive cardiopulmonary exercise testing (iCPET) in ME/CFS patients with CFT-confirmed ANOCA, with the aim of identifying the predominant physiological mechanism responsible for exertional limitation in this population.

Systematic medical record review of 261 patients with CFT-confirmed ANOCA was performed using standardized diagnostic criteria to identify concurrent ME/CFS diagnosis. ME/CFS was identified in 47 patients, representing an observed frequency of 18%. The only statistically significant difference between ANOCA patients with and without ME/CFS was a higher frequency of connective tissue disease in the ME/CFS group (p = 0.0221). In a separate cohort of 27 patients with ME/CFS who underwent iCPET, 24 patients (89%) had CFT-confirmed ANOCA.

The diagnosis of ANOCA by CFT prompted a change in medical management in 81% of patients in this cohort. iCPET revealed a primary peripheral limitation to exercise, characterized by impaired peak systemic oxygen extraction despite normal peak oxygen delivery. This study demonstrates a clinically significant association between ME/CFS and ANOCA.

These findings underscore the clinical value of CFT in patients with ME/CFS and exertional chest pain and highlight iCPET as a complementary tool for hemodynamic phenotyping in this population. Prospective studies incorporating simultaneous CFT and iCPET with molecular phenotyping are warranted.

Source: Mackay Z, Shah S, Villalobos JG, Latif N, Arun A, Joseph P, Heerdt P, Singh I. Hemodynamic Phenotyping in ME/CFS and ANOCA: Complementary Insights from Coronary Function Testing and Invasive Cardiopulmonary Exercise Testing. Am J Physiol Heart Circ Physiol. 2026 Sep 21. doi: 10.1152/ajpheart.90080.2026. Epub ahead of print. PMID: 42767811. https://journals.physiology.org/doi/abs/10.1152/ajpheart.90080.2026 (Full text available as PDF file)

Clinical Symptomatology, Cognition and Psychosocial Wellbeing in Adolescents With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Cross-Sectional Observational Study

Abstract:

Aim: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling illness that frequently begins in adolescence, yet adolescents with ME/CFS remain an under-researched population. We aimed to characterise the cognitive and psychosocial wellbeing of adolescents with ME/CFS relative to normative benchmarks and unaffected age-peers.

Methods: Adolescents with mild-to-moderate ME/CFS (n = 25) and healthy controls (n = 25) aged 10-19 years were recruited in Melbourne, Australia. Each completed a set of clinical questionnaires and cognitive assessments to assess ME/CFS symptomatology, school functioning, psychosocial wellbeing and cognition. Their caregivers also completed questionnaires regarding their psychosocial wellbeing and everyday executive functioning.

Results: Adolescents with ME/CFS showed significantly reduced information processing speed, though other measures of intellectual functioning did not differ consistently between groups. The ME/CFS group also reported significantly poorer sleep, quality of life and higher levels of anxiety and depression. Caregivers further identified significant attention and working memory concerns in the ME/CFS group, but reported no differences in internalising behaviours between groups.

Conclusion: Adolescents with ME/CFS experience substantial psychosocial and physical burden because of their illness. Cognitive difficulties in ME/CFS may reflect inefficiencies in information processing speed and fluctuating symptom burden. Discrepancies between adolescent self-report and caregiver ratings underscore the importance of inclusive perspectives in ME/CFS management. These findings support the need for flexible, paced educational and clinical accommodations and for further research into the dynamic cognitive profile of adolescents with ME/CFS across a more representative population.

Source: Chau T, Josev EK, Scheinberg A, Thomas N, McDonald F, Reveley C, Gooley PR, Armstrong C, Knight S. Clinical Symptomatology, Cognition and Psychosocial Wellbeing in Adolescents With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Cross-Sectional Observational Study. J Paediatr Child Health. 2026 Sep 20. doi: 10.1111/jpc.70587. Epub ahead of print. PMID: 42764669. https://onlinelibrary.wiley.com/doi/10.1111/jpc.70587 (Full text)

Postural orthostatic tachycardia syndrome in adolescents with ME/CFS – a case control study

Abstract:

Introduction: Postural orthostatic tachycardia syndrome (PoTS) can be associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Pediatric PoTS requires a “sustained” rise in orthostatic heart rate ≥40 bpm above supine heart rate (relative limit), often >120 bpm (absolute limit). However, the diagnostic criteria for PoTS in adolescents remain underexplored, particularly regarding the definition of “sustained” tachycardia, which poses challenges in clinical and research settings. This study examined orthostatic intolerance criteria, including PoTS, in adolescents with ME/CFS and healthy controls.

Methods: Medical history of orthostatic intolerance was assessed by a semi-structured interview with 18 ME/CFS patients and 18 matched healthy controls (14-17 years). A passive 10-min standing test with minute-by-minute heart rate and blood pressure registration was performed. PoTS was diagnosed by a clinical expert based on current consensus criteria. Data were analyzed using Fisher’s exact test and receiver operating characteristic analysis.

Results: Although history of orthostatic intolerance was positive in 15/18 ME/CFS [83%, 0.95 CI (61; 94)] and 3/18 healthy controls [17%, 0.95 CI (5.9; 39)], PoTS was diagnosed in only 7/18 ME/CFS [39%, 0.95 CI (20; 61)] vs. no healthy controls [0%, 0.95 CI (0; 18)]. Subgroups were identified, e.g., positive history of orthostatic intolerance yet physiological passive 10-min standing test, or negative history of orthostatic intolerance yet tachycardia in passive 10-minute standing test. PoTS diagnosis by the clinical expert matched best with the passive 10-min standing test alone when at least 60% of upright heart rate values were above one or both limits. The absolute limit was superior to the relative limit in distinguishing adolescents with and without PoTS.

Discussion: PoTS was observed only in ME/CFS. In adolescents with ME/CFS, positive history of orthostatic intolerance, along with at least 60% of heart rate values above published upright-position limits, may allow non-experts to make a valid diagnosis, facilitating clinical care and future studies. Further research will show if these results can be generalized.

Source: Leone A, Gerrer K, Viereck A, Grabbe A, Kircher A, Behrends U, Maier A. Postural orthostatic tachycardia syndrome in adolescents with ME/CFS – a case control study. Front Pediatr. 2026 Sep 1;14:1836407. doi: 10.3389/fped.2026.1836407. PMID: 42746015; PMCID: PMC13574936. https://pmc.ncbi.nlm.nih.gov/articles/PMC13574936/ (Full text)