AMMES WANTS YOU!

AMMES needs volunteers! AMMES is actively recruiting volunteers to help AMMES grow and prosper.

Fundraising coordinator –  should have experience fundraising for non-profits (We usually run fundraisers once or twice a year.)

IT Person – keeps website  up to date – experience with WordPress a must! (Time commitment: 1 hour a month)

Patient Advocate – ideally someone with Social Work background. Occasionally we get requests from patients who need help finding housing programs or other types of government assistance. (Time commitment:1 hour a month)

We are also looking for board members. Board members do not need to have ME/CFS, but must demonstrate knowledge about the disease and share a commitment to serve the community. Because we are a nationally-focused nonprofit, board members must be US citizens or residents.

Read more about what we do on our website HERE.

Please contact us at admin@ammes.org if you are interested in being a part of this wonderful organization.

AMMES is a 501(c)(3) national nonprofit. Your donations are tax deductible.

You can donate HERE.

WE WANT TO HELP!

Getting help is a priority for people who are ill. This is especially important for ME/CFS patients who have lost their incomes because they are too ill to work. People who are so impoverished that they can’t afford food, clothing, and shelter face a struggle for survival on a daily basis. That struggle can overshadow all others – including the search for physicians and treatments – while patients scramble for their basic needs. The effort to stay alive is all-encompassing.

How will these patients get food to eat, pay their rent, and buy such bare essentials as shoes?

Who will help them when their options run out?

We will! AMMES has distributed over $85,000 to patients who are severely ill to help them with their basic necessities. We have helped pay for housing, medical care, food, utilities, and other essential needs. Please help us help them by spreading the word.

Read more about how AMMES helps people with their basic needs here>>

AMMES is a 501(c)(3) national nonprofit. Your donations are tax deductible.

You can donate to our financial crisis fund HERE.

Covid and ME/CFS

Announcement:

AMMES has recently added an informational page about COVID-19 and ME/CFS. The page includes physicians’ recommendations regarding the COVID vaccine for people with ME/CFS, patient surveys on how the vaccine has affected them, research articles on long-Covid and ME/CFS, related news items, and tips from doctors on how to treat patients with ME/CFS who contract COVID-19. You can find the page here:  https://ammes.org/covid-19/

Overcoming barriers in myalgic encephalomyelitis/chronic fatigue syndrome research: the CureME participatory model

Abstract:

Research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents unique challenges. These stem from the logistical difficulties created by the degree of disability experienced and heterogeneous diagnostic criteria driven by etiological uncertainty. This is compounded by distrust of research institutions within the ME/CFS community, due to historical mischaracterization of ME/CFS as a psychosomatic disease. This commentary proposes a framework to address the resulting methodological and practical barriers.

The CureME Framework draws on the UK ME/CFS Biobank’s extensive experience of participatory research and incorporates strategies for effective recruitment and data collection. It is informed by collaborations with individuals with lived experience of ME/CFS including severely affected individuals. This is achieved by integrating co-produced study design, community-engaged recruitment, and adaptations that minimize the cognitive and physical burden of participation.

This increases access to research participation, reduces selection bias, and strengthens cohort representativeness. Adopting this approach may enhance methodological rigor, accessibility, trust, cohort representativeness, statistical power, and ethical integrity in ME/CFS research.

Source: Abken E, Tyson S, Kingdon C. Overcoming barriers in myalgic encephalomyelitis/chronic fatigue syndrome research: the CureME participatory model. Front Hum Neurosci. 2026 Jul 7;20:1826525. doi: 10.3389/fnhum.2026.1826525. PMID: 42483535; PMCID: PMC13385095. https://pmc.ncbi.nlm.nih.gov/articles/PMC13385095/ (Full text)

Inflammatory and neuroinjury blood biomarkers across COVID-19 severity groups in individuals with persistent neurological symptoms

Abstract:

Persistent neurological symptoms such as cognitive impairment, fatigue, and neuropsychiatric disturbances are increasingly reported in patients with long COVID, with chronic neuroinflammation and neuronal injury proposed as potential contributors. To characterize inflammatory and neuroinjury-related biomarker patterns, we conducted a case-control study including 325 participants recruited at King Chulalongkorn Memorial Hospital between January 2022 and December 2023, comprising 265 individuals with persistent neurological symptoms following COVID-19 infection and 60 asymptomatic COVID-19 participants who did not develop long COVID symptoms.

Blood samples were analysed for inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, IFN-α, IL-4) using multiplex immunoassays, and for neuroinflammatory and neurodegenerative biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, and beta-amyloid peptides (Aβ40, Aβ42) using SIMOA and ELISA platforms. Among 265 participants with complete data (critical = 7, severe = 22, moderate = 79, mild = 157), patients with severe and critical COVID-19 exhibited significantly higher concentrations of IL-6, IL-1β, TNF-α, and IL-8, together with elevated NfL, GFAP, and phosphorylated tau181 levels, and reduced Aβ42/40 ratios.

Strong positive correlations between neurodegenerative biomarkers and pro-inflammatory cytokines were observed in critically ill patients, whereas these associations were weak or absent in mild and moderate cases. Older age was also associated with greater disease severity and increased risk of persistent neurological complications.

These findings indicate that individuals with persistent neurological symptoms following COVID-19, particularly those with a history of severe or critical disease, exhibited higher inflammatory and neuroinjury-related biomarker levels, while blood-based biomarkers such as NfL, GFAP, and phosphorylated tau181 may serve as minimally invasive tools for characterizing neurological involvement and identifying patients at risk of long-term neurological sequelae.

Source: Ruchisrisarod C, Kaewpom T, Wanthong P, Luechaipanit W, Bunprakob S, Ampoot W, Yomrat S, Hemachudha P, Supharatpariyakorn T, Thanapornsangsuth P, Tammachote R, Saraya AW. Inflammatory and neuroinjury blood biomarkers across COVID-19 severity groups in individuals with persistent neurological symptoms. Int J Immunopathol Pharmacol. 2026 Jan-Dec;40:3946320261465568. doi: 10.1177/03946320261465568. Epub 2026 Jul 16. PMID: 42460883; PMCID: PMC13376473. https://pmc.ncbi.nlm.nih.gov/articles/PMC13376473/ (Full text)

Multimodal approach to identify neuropsychophysiological subgroups in myalgic encephalomyelitis/chronic fatigue syndrome and their relevance for rehabilitation: protocol for a mechanistic cross-sectional and longitudinal study

Abstract:

Introduction: Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) is a debilitating condition characterized by severe fatigue and post-exertional malaise (PEM). Reported neuropsychophysiological abnormalities suggest ME/CFS is multifactorial, but current knowledge remains fragmented. This study protocol outlines a multimodal investigation designed to (1) compare neuropsychophysiological mechanisms between ME/CFS patients and healthy participants, (2) test an integrative model of ME/CFS, (3) identify neuropsychophysiological subgroups within the patient population, and (4) identify predictors of symptom response during rehabilitation.

Methods and analysis: This study will enroll 115 ME/CFS patients and 55 healthy participants. Groups will be comparable in age, sex, and education level, with a larger patient sample enabling subgroup and longitudinal analyses. A cross-sectional assessment at baseline will be carried out in both groups. Patients will then be evaluated longitudinally throughout a standardized cognitive-behavioral therapy rehabilitation program delivered as routine care.

Baseline measures include systemic inflammation and general health biomarkers, measures of autonomic and central nervous system function, neuroinflammation (magnetic resonance spectroscopy, [18F]DPA714 PET in a subsample), serum short-chain fatty acid levels, gut microbiota composition and function, and neuroendocrine and self-reported responses to psychosocial stress. Fatigue severity (physical and cognitive) and PEM will be assessed through validated questionnaires, ecological momentary assessment, and laboratory tasks.

These will be re-evaluated during therapy, and all non-neuroimaging measures will be repeated after the rehabilitation program. Statistical analyses will comprise multivariate analysis of variance, general linear models, classification algorithms, structural equation models, least absolute shrinkage selection operator principal component regression (LASSO-PCR), cluster analysis and latent class growth analysis (LCGA).

Source: Dooms Y, Qiu L, Coppieters I, Vergaelen E, Claes S, Dupont P, Hehl M, Cuypers K, Engler H, Dombrowski K, Verbeke K, Van den Bergh O, Raes J, Van Oudenhove L, Van Den Houte M, Bogaerts K. Multimodal approach to identify neuropsychophysiological subgroups in myalgic encephalomyelitis/chronic fatigue syndrome and their relevance for rehabilitation: protocol for a mechanistic cross-sectional and longitudinal study. Brain Behav Immun Health. 2026 Jul 6;56:101299. doi: 10.1016/j.bbih.2026.101299. PMID: 42472232; PMCID: PMC13380062. https://pmc.ncbi.nlm.nih.gov/articles/PMC13380062/ (Full text)

Perioperative outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome undergoing general anesthesia: a retrospective matched-pair study

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Despite features with potential relevance for anesthesia and perioperative care, empirical data on perioperative outcomes in patients with ME/CFS remains limited. We therefore performed a retrospective matched-pair analysis to generate clinical data on perioperative responses and identify areas for future research.

Methods: We conducted a retrospective matched-pair analysis at a single tertiary center. All patients with ME/CFS undergoing general anesthesia from 2015 to 2026 were identified using ICD-10-GM codes with additional manual verification and matched 1:1 to controls for comparison. Patients with confounding diagnoses or American Society of Anesthesiologists physical status above III were excluded. The analysis focused on intraoperative hemodynamic parameters, including baseline, post-induction, median, and lowest recorded systolic blood pressure and heart rate, as well as early postoperative outcomes in the post-anesthesia care unit (PACU), including maximum pain scores and requirement for rescue analgesia.

Results: Out of 189 individuals identified through ICD-10 codes, 15 matched pairs were included after application of exclusion criteria. Patients with ME/CFS exhibited lower minimum intraoperative systolic blood pressure (90.0 [82.5-95.0] vs. 100.0 [90.0-110.0] mmHg, p = 0.044) and lower minimum heart rate (50.0 [40.0-57.5] vs. 60.0 [50.0-65.0] bpm, p = 0.012). Vasopressor use and fluid administration did not differ, and no episodes of severe hypotension or perioperative adverse events were observed. Postoperative pain was higher in ME/CFS, with higher maximum pain scores (NRS 5.0 [4.0-6.0] vs. 1.0 [0.0-4.0], p = 0.008) and more frequent opioid rescue analgesia (80% vs. 33%, p = 0.039). Postoperative nausea or vomiting, oxygen supplementation, and PACU length of stay were similar between groups.

Conclusions: In this small exploratory cohort, general anesthesia was not associated with clinically relevant hemodynamic instability in patients with ME/CFS. Postoperative pain scores and opioid rescue requirements were higher in the ME/CFS group. Post-exertional malaise, a key disease feature with potentially delayed onset and significant impact, was not captured and remains an important target for future research. These findings should be considered hypothesis-generating and support prospective studies evaluating perioperative management and patient-relevant outcomes in ME/CFS.

Source: Steinkirchner FM, Kaufmann CK, Kraus RF, Käss M, Schieffer E, Graf BM, Lassen C, Kimmerling V, Dejaco A. Perioperative outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome undergoing general anesthesia: a retrospective matched-pair study. BMC Anesthesiol. 2026 Jul 16;26(1):426. doi: 10.1186/s12871-026-04102-5. PMID: 42464211. https://link.springer.com/article/10.1186/s12871-026-04102-5 (Full text available as PDF file)

Handgrip strength in children, adolescents, and young adults with suspected myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children, young people (CYP) lacks validated diagnostic biomarkers. Post-exertional malaise (PEM) is central to case definitions and is usually assessed by patient report. We evaluated the feasibility and clinical value of handgrip strength (HGS) testing in PEM-reporting CYP referred for suspected ME/CFS.

Methods: In this prospective observational study at the Munich Chronic Fatigue Center for Young People (November 2022-November 2024), 147 patients (10-25 years) referred for the assessment of ME/CFS with positive DSQ-PEM screening and 83 healthy controls (HC) completed two HGS sessions (10 maximal grips/session; 3-s contraction/5-s rest; 60-minute inter-session break) using a digital dynamometer. We derived maximal force (Fmax), mean force (Fmean), fatigue ratio (FR = Fmax/Fmean), and recovery ratio (RR = Fmean session 2 / session 1). Analyses used repeated-measures ANCOVA, linear regression, partial Spearman correlations (adjusted for sex, age, and BMI), and proportional odds models for group membership (HC, noME/CFS, ME/CFS), reporting accuracy, and the C-statistic. Sensitivity analyses compared noME/CFS with confirmed CCC-ME/CFS.

Results: After clinical work-up, 84/147 (57%) patients were classified as ME/CFS (confirmed or probable) and 63/147 (43%) as noME/CFS. HGS test completion rate was high (session 1: 146/147, 99.3%; session 2: 142/147, 96.6%). Compared with HC, patients had substantially lower HGS (mean difference -9.93 kg, 95% CI: -12.00 to -7.85), and HGS indices correlated modestly with physical functioning (SF-12 PCS), but not with PEM duration. Both noME/CFS and ME/CFS groups differed from HC in absolute strength indices (Fmean, Fmax) and FR. RR differed between ME/CFS and HC, whereas no HGS index significantly separated noME/CFS from ME/CFS. In proportional odds models, each HGS index improved fit (all p < 0.001), but discrimination across HC, noME/CFS, and ME/CFS patients was moderate (accuracy 49.2-57.3% vs no-information rate 36.5%, with best performance for Fmean in session 2). In the CCC-restricted sensitivity analysis, discrimination between confirmed CCC-ME/CFS and noME/CFS was moderate (accuracy 62.8-70.7%; C-statistic 0.63-0.73), with best performance for absolute strength indices and RR.

Conclusions: Standardized two-session repeated HGS testing is feasible in CYP with chronic fatigue and self-reported PEM and provides an objective marker of functional impairment that aligns with physical health status but not with PEM duration. However, HGS alone shows limited ability to discriminate ME/CFS from other fatiguing noME/CFS conditions. HGS may be useful for quantitative phenotyping, patient stratification, and longitudinal outcome assessment rather than as a standalone diagnostic biomarker.

Source: Mihatsch L, Schartner L, de Luna JL, Höhler C, Bucka L, Lovrenovic L, Eidenschink S, Schmuck B, Bienemann V, Christa C, Mittelstraß K, Hausruckinger A, Warlitz C, Michel K, Gerrer K, Freitag H, Scheibenbogen C, Pricoco R, Behrends U. Handgrip strength in children, adolescents, and young adults with suspected myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2026 Jul 15. doi: 10.1186/s12967-026-08654-5. Epub ahead of print. PMID: 42458481. https://link.springer.com/article/10.1186/s12967-026-08654-5 (Full text available as PDF file)

Biomarkers of post-acute infection syndrome: a systematic literature review

Abstract:

Background: Post-acute infection syndrome (PAIS) remained underrecognized before the COVID-19 pandemic, which further increased exposure by introducing a novel global cause. The global burden of post-acute COVID syndrome (PACS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) alone is estimated at several tens of millions affected worldwide. Biomarker discovery is central to improving PAIS diagnosis and may provide therapeutic targets. This review summarizes current knowledge on biomarkers for PAIS, including PACS and ME/CFS.

Methods: A systematic literature search was conducted in PubMed and Web of Science. Inclusion criteria were: (1) studies including PAIS patients; (2) reporting laboratory or omics biomarkers; and (3) investigating biomarkers or pathomechanisms of PAIS. Although Guillain-Barré syndrome (GBS) is not PAIS, we have included it as a separate mechanistic comparator due to its prevalence in search results and its clinical and immunological similarities to PAIS.

Results: A total of 142 studies analyzing PAIS biomarkers were included. GBS was analyzed separately and later compared with the other results. Overall, the reviewed studies employed heterogeneous approaches. While similar types of data were frequently investigated, analytical methods varied and often focused only on a subset of molecules. The results indicate that amino acid, energy, and lipid metabolism, microbiome, mitochondrial stress, and miRNA networks are affected. All pathways are connected via NF-κB.

Discussion: PAIS is a multisystem disorder rooted in persistent immune activation, metabolic reprogramming, and systemic inflammation, driven not by active viral infection, but by dysregulated host responses. The NF-κB pathway serves as a unifying hub, connecting molecular, cellular, and clinical phenotypes. Our framework enables a shift from symptom-based to mechanism-based classification, paving the way for biologically grounded interventions.

Conclusion: This review synthesizes a broad spectrum of biomarkers in PAIS, integrating findings across pathogens and molecular levels rather than restricting to individual conditions or symptom clusters. This study highlights the differences and commonalities among pathogens and diseases that lead to post-acute sequelae, fills a critical knowledge gap, and provides a foundation for future research and clinical practice. Future studies incorporating multi-omics approaches, longitudinal designs, and larger patient cohorts are needed to validate specific biomarkers and advance the understanding of PAIS.

Source: Wendt K, Schieck M, Gille C, Marschollek M, Illig T, Wolff D, Nee S. Biomarkers of post-acute infection syndrome: a systematic literature review. Front Immunol. 2026 Jun 30;17:1741761. doi: 10.3389/fimmu.2026.1741761. PMID: 42454043; PMCID: PMC13365053. https://pmc.ncbi.nlm.nih.gov/articles/PMC13365053/ (Full text)

Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterised by post-exertional malaise, non-restorative sleep, and cognitive impairment, yet no objective diagnostic biomarkers have been established. Untargeted plasma metabolomics provides a broad view of the biochemical disturbances underlying ME/CFS; however, the high dimensionality of omics datasets and the limited interpretability of conventional classifiers nevertheless hinder translation into clinical practice. This study evaluates three ensemble classifiers-Explainable Boosting Machine (EBM), XGBoost, and LightGBM-for binary ME/CFS classification using plasma metabolomic and lipidomic profiles from 197 participants (106 ME/CFS; 91 healthy controls; 888 features).

Feature dimensionality was reduced using a Pareto-Guided Recursive Neural Network (PRNN) pipeline. Model performance was assessed via 50-repeat stratified hold-out validation. EBM achieved the highest accuracy (0.909; 95% CI: 0.868-0.949) and area under the receiver operating characteristic curve (AUC: 0.940; 95% CI: 0.909-0.983), with XGBoost and LightGBM performing comparably. Interpretability analyses revealed that pairwise metabolite interaction terms-particularly proline & indole-3-lactate, tyrosine & N-acetylornithine, and maleic acid & arachidic acid-contributed the greatest discriminative signal.

An ablation analysis comparing the full interaction-augmented EBM (AUC = 0.940) with a main-effects-only EBM (AUC = 0.882) confirmed that pairwise metabolite co-variation contributes additional discriminative value beyond individual metabolite levels, implicating amino acid catabolism, tryptophan-kynurenine pathway dysregulation, mitochondrial energy impairment, and lipid remodelling as central pathophysiological features. Global and instance-level explanations jointly demonstrated population-level metabolic signatures alongside individual heterogeneity, highlighting the added clinical value of explainable artificial intelligence (XAI) in metabolomics.

These findings support EBM-based metabolomic profiling as an internally validated approach for ME/CFS classification, subject to external validation, calibration assessment, and prospective testing.

Source: Yagin FH, Korkmaz Y, Colak C, Alzakari SA, Alkhalifa AK, Al-Hashem F, Aghaei M. Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection. Int J Mol Sci. 2026 Jun 30;27(13):5920. doi: 10.3390/ijms27135920. PMID: 42450188. https://www.mdpi.com/1422-0067/27/13/5920 (Full text)

Australian registry reports poor health and wellbeing in people living with ME/CFS

Abstract:

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition hallmarked by post-exertional malaise accompanied by an array of multisystemic symptoms. Consequently, people living with ME/CFS experience significant health impacts and report poor health-related quality of life (HRQoL). Living with a condition of an area of unmet need, there is a call for a greater understanding of the health impacts of ME/CFS in Australia. Despite growing recognition and awareness, large-scale national comparative investigations using ME/CFS cohorts have not been reported.

Methods: The National Centre for Neuroimmunology and Emerging Diseases houses a significant Australian registry of people with ME/CFS. Self-reported questionnaire data collected from people with ME/CFS and non-fatigued controls (NFC) between 2014 and February 2026 was exported from applications including Research Electronic Data Capture (REDCap) and LimeSurvey. Data was collected pertaining to the sociodemographic background, medical history, symptom presentation (for people with ME/CFS), and validated patient reported outcome measures to assess HRQoL. The questionnaire covered medical history, routine medications, symptom presentation, and HRQoL, using validated tools including the 36-item short form health survey (SF-36). Data was analysed using independent student’s t and chi-square tests, linear regression analysis, principal component analysis (PCA), and k-means clustering. Data was presented as mean and standard deviation or percentages. Statistical analysis was completed using SPSS and RStudio with a significance set at p < 0.05.

Results: Responses were analysed from n = 797 NFC (41.72 ± 13.86 years, 62.6% female) and n = 2,873 people with ME/CFS (44.85 ± 13.77 years, 75.2% female). Participants with ME/CFS fulfilled Fukuda (39.0%), CCC (30.4%) and ICC (30.6%) case definitions. Analysis of symptom presentation differed in both severity and frequency according to the most stringent case definition met; however, this did not predict poor HRQoL outcomes. HRQoL was significantly impaired compared with NFC, and people fulfilling ICC were more likely to report poorer outcomes. Regression analysis revealed the impact of multisystemic symptoms on both physical and mental functioning. K means clustering returned four clusters which differed according to stringent case criteria met, severity and frequency of symptoms.

Conclusion: This large-scale national investigation highlights the significant symptom burden and reduced HRQoL in people with ME/CFS. These findings emphasise the need for tailored clinical approaches and further research into symptom clustering for the purpose of identifying clinical subtypes.

Source: Eaton-Fitch N, Marshall-Gradisnik S. Australian registry reports poor health and wellbeing in people living with ME/CFS. J Transl Med. 2026 Jul 13. doi: 10.1186/s12967-026-08618-9. Epub ahead of print. PMID: 42443918. https://link.springer.com/article/10.1186/s12967-026-08618-9 (Full text available as PDF file)

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study

Abstract:

Background and rationale: In our ongoing phase II observational pilot trial, the compounded formulation of low-dose rapamycin significantly reduced fatigue-related clinical symptoms in ME/CFS subjects. Although the underlying molecular mechanism remains unclear, exploring metabolic pathways involving circulating blood-borne factors is warranted. Recent studies suggest that increased levels of purines may exacerbate oxidative stress in ME/CFS patients. It is not known if rapamycin modulates purine biosynthesis and improves disease symptoms.

Methods and results: To address, we performed a comprehensive LCMS-based quantification of purine biosynthetic intermediates in plasma from responder cohort of ME/CFS participants, both at baseline (BSL) and after 90 days of rapamycin therapy (T3). Notably, differential regulation was observed in the enzymatic conversion of inosine monophosphate (IMP) to xanthosine-5-monophosphate (XMP) and hypoxanthine (HPX) between BSL and T3 samples. Flow cytometry assays on PBMCs confirmed that rapamycin reduces IMP dehydrogenase activity, thereby limiting the conversion of IMP to XMP. Further analyses, including mitochondrial oxidative stress assessments, Seahorse OCR following purine supplementation, and flow cytometry indicate that altered purine levels can impair mitochondrial energy metabolism, and may contribute to inflammatory processes in microglia.

Conclusion: Collectively, these findings highlight the therapeutic potential of rapamycin to enhance energy metabolism in patients with ME/CFS.

Major limitations: There is no placebo group, and molecular results are somewhat biased to responders.

Trial registration: CLINICALTRIALS.GOV, NCT06257420. Registered 11 December 2023, https://clinicaltrials.gov/study/NCT06257420.

Source: Gile B, Bulbule S, Toriola MA, Ruan BT, Marium S, Benko A, Grach S, Mueller M, Bateman L, Bell J, Yellman B, Berner J, Chheda B, Kaufman D, Gottschalk G, Roy A. Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study. J Transl Med. 2026 Jul 10. doi: 10.1186/s12967-026-08575-3. Epub ahead of print. PMID: 42432754. https://link.springer.com/article/10.1186/s12967-026-08575-3 (Full text available as PDF file)

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS

Abstract:

The glymphatic system is a recently discovered brain waste clearance system that is mostly active during sleep and disengaged during wakefulness. Impaired glymphatic function leads to the deposition of metabolic waste products in the brain potentially causing inflammation leading to various symptoms in ME/CFS. While the glymphatic function has been assessed in other neurodegenerative diseases using ‘diffusion tensor imaging along the perivascular space’ (DTI-ALPS), it has not been studied in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

This preliminary study investigates glymphatic function in 58 participants (ME/CFS = 31 and healthy controls = 27) using the DTI-ALPS index derived from DTI data acquired with 3 T MRI. The bilateral hemispheric DTI-ALPS index was estimated to assess glymphatic function, and an asymmetry index was calculated to determine interhemispheric asymmetry in glymphatic function.

We found that the global DTI-ALPS index was significantly lower in ME/CFS patients compared to healthy controls (ME/CFS: 1.44 ± 0.086; healthy controls: 1.51 ± 0.11, p = 0.014), indicating reduced glymphatic function in ME/CFS. Examining the hemispheres separately, showed the right hemisphere DTI-ALPS index was lower in ME/CFS than healthy controls (ME/CFS = 1.41 ± 0.097; healthy controls = 1.49 ± 0.12; p = 0.009) but not different on the left. Additionally, we did not find any significant difference in asymmetry index between ME/CFS and healthy controls. We observed an association between the global DTI-ALPS index and severity of ‘sleep disturbance’ (p = 0.013, r = -0.47) and “impaired concentration” (p = 0.026, r = -0.43).

This study demonstrated impaired glymphatic function in ME/CFS which may lead to symptoms such as cognitive dysfunction and sleep disturbance experienced by ME/CFS.

Source: Thapaliya K, Marshall-Gradisnik S, Inderyas M, Barnden L. Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS. Front Neurosci. 2026 Jun 19;20:1875420. doi: 10.3389/fnins.2026.1875420. PMID: 42403482; PMCID: PMC13329448. https://pmc.ncbi.nlm.nih.gov/articles/PMC13329448/ (Full text)