E2 ModerateModerate confidencePEM not requiredLongitudinalPeer-reviewedReviewed
Orthostatic tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis.
Katz, Ben Z, Stewart, Julian M, Shiraishi, Yukiko et al. · Clinical pediatrics · 2012 · DOI
Quick Summary
This study looked at whether teenagers with ME/CFS have trouble standing up for long periods (a condition called orthostatic intolerance). Researchers tested 36 teens with ME/CFS and 43 recovered teens, all about 6 months after having infectious mononucleosis. Surprisingly, they found that similar numbers of both groups had difficulty with standing tolerance, suggesting this may not be a key difference between those who recover and those who develop ME/CFS.
Why It Matters
Orthostatic intolerance is commonly reported by ME/CFS patients and has been proposed as a potential biomarker. This study helps clarify whether it is a specific feature of ME/CFS or a more general consequence of post-viral illness, which is important for understanding the mechanisms underlying the condition and developing diagnostic tests.
Observed Findings
- 25% (9/36) of adolescents with CFS had abnormal standing orthostatic tolerance testing
- 21% (9/43) of recovered controls had abnormal standing orthostatic tolerance testing
- No statistically significant difference was found between the two groups in SOT abnormality rates
- Both groups were comparable in age, weight, and body mass index
- 6 months post-infectious mononucleosis, 13% of the original cohort met CFS criteria
Inferred Conclusions
- Orthostatic intolerance is not a distinguishing pathophysiologic feature of post-IM CFS in adolescents
- Abnormal orthostatic tolerance may represent a non-specific consequence of acute mononucleosis rather than a CFS-specific finding
- Other mechanisms besides orthostatic intolerance may underlie the development of CFS following infectious mononucleosis
Remaining Questions
- Why do some adolescents develop CFS after IM while others recover, if orthostatic intolerance is not a distinguishing factor?
- Would findings differ in adult populations or in ME/CFS cases with different etiologies?
- What other pathophysiologic mechanisms might explain the development of CFS post-IM if not orthostatic intolerance?
What This Study Does Not Prove
This study does not prove that orthostatic intolerance plays no role in ME/CFS generally, only that it was not a distinguishing feature in this specific post-IM adolescent cohort. It does not establish causation or explain why some people develop ME/CFS after mononucleosis while others recover. The study's small sample size and focus on adolescents limits generalization to adults or other ME/CFS populations.
Tags
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Blood Biomarker
Phenotype:Infection-TriggeredPediatric
Method Flag:PEM Not DefinedWeak Case DefinitionSmall SampleExploratory Only
Metadata
- DOI
- 10.1177/0009922812455094
- PMID
- 22850676
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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