Biomarkers associated with blood-brain interface regulation and relationships to exercise and epilepsy: a brief review.
M David Diggs, Christopher G Ballmann, James T Houston and 1 others
PMID 42553138WHAT IT FOUND
A narrative review of blood biomarkers in epilepsy, not a clinical trial.
It finds S100β, GFAP, and NfL are promising but unvalidated markers, and that exercise evidence in epilepsy is still too thin to guide prescribing.
Key findings
01Blood-brain interface disruption is increasingly recognised as an active driver of epileptogenesis — not just a byproduct of seizures — through a self-reinforcing cycle of glial activation, neuroinflammation, and network hyperexcitability.
02S100β and GFAP index acute astroglial and barrier perturbation, while NfL reflects more sustained neuroaxonal damage over weeks to months; none is yet validated for routine clinical use in epilepsy, and NfL is best used as part of a multimodal panel rather than a standalone test.
03The authors state that evidence for exercise as an adjunct therapy in epilepsy is lacking, with very few studies examining exercise effects across epilepsy subtypes using fluid biomarkers; much of what is known comes from healthy or other neurological populations.
STILL TO COME
How it was doneWhat they foundWhat it means for PTs
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What it does not show
Narrative (non-systematic) review with no formal risk-of-bias assessment, no meta-analysis, and no PRISMA flow diagram; the authors acknowledge this explicitly. Much of the exercise–epilepsy evidence is drawn from healthy or other neurological populations rather than from people with epilepsy. Biomarker findings are limited by heterogeneity in sampling time points, assay platforms, and cutoffs across studies, making cross-study comparison difficult. S100β is influenced by extracranial sources (trauma, stroke, melanoma, intense physical activity, systemic inflammation), complicating interpretation in epilepsy. GFAP and NfL are not yet validated for routine use in epilepsy; the authors describe them as promising but unproven. The review is a single-author synthesis (or small team) without systematic screening, so coverage may be incomplete.
Declared interests
Funded by NIH training and research grants (T32 HD071866 and R01 HD102723). No industry funding, no conflicts of interest declared, and no sponsor involvement in study design or manuscript preparation is mentioned.
The easy way to misread this
Do not read this review as evidence that exercise reduces seizures in epilepsy or that S100β, GFAP, or NfL are ready for routine clinical use. The authors state the exercise evidence in epilepsy is lacking and that GFAP is not yet validated, and the biomarker findings come from heterogeneous, mostly cross-sectional studies with inconsistent results.