Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients.
Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Barth, Markus et al. · Frontiers in neuroscience · 2023 · DOI
Quick Summary
Researchers used advanced MRI scans to examine a part of the brain called the brainstem in patients with ME/CFS and long COVID, comparing them to healthy people. They found that both patient groups had larger volumes in certain brainstem areas compared to healthy controls. The size of specific brainstem regions also correlated with symptom severity, particularly pain and breathing difficulties.
Why It Matters
This study provides objective neuroimaging evidence that ME/CFS and long COVID involve measurable brain structure changes, which helps validate the neurobiological basis of these conditions. Finding correlations between brainstem volume and specific symptoms (pain, breathing difficulty) offers potential biomarkers and suggests the brainstem's role in the symptom pathophysiology, which could inform future therapeutic targets.
Observed Findings
ME/CFS patients showed significantly larger pons (p=0.004) and whole brainstem (p=0.01) volumes compared to healthy controls.
Long COVID patients showed significantly larger pons (p=0.003), superior cerebellar peduncle (p=0.009), and whole brainstem (p=0.005) volumes compared to healthy controls.
In ME/CFS, pons and whole brainstem volumes positively correlated with pain severity.
In both ME/CFS and long COVID, midbrain volume negatively correlated with breathing difficulty severity.
No significant volume differences were detected between the ME/CFS and long COVID groups.
Inferred Conclusions
Abnormal brainstem volumes are a shared neurobiological feature of both ME/CFS and long COVID, consistent with their overlapping symptom profiles.
Brainstem structural abnormalities may represent a biomarker associated with specific symptoms, particularly pain and respiratory dysfunction.
The brainstem's role in autonomic regulation, pain processing, and respiratory control makes its involvement plausible for the multi-system dysfunction observed in both conditions.
Remaining Questions
Are brainstem volume changes present before illness onset, or do they develop during disease progression?
What This Study Does Not Prove
This study does not prove that brainstem volume changes cause ME/CFS or long COVID symptoms—correlation alone cannot establish causation. The small sample size (10 ME/CFS, 8 long COVID patients) limits statistical power and generalizability to the broader patient population. It also does not explain whether these volume changes develop during illness or are pre-existing factors.
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 →