J Transl Med. 2026 Jul 15. doi: 10.1186/s12967-026-08654-5. Online ahead of print.
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.
TRIAL REGISTRATION: Not applicable.
PMID:42458481 | DOI:10.1186/s12967-026-08654-5
