Inflammatory activation—particularly increased hsCRP and Cathepsin-S levels—was associated with reduced motor recovery and characterized individuals who subsequently had major adverse cardiovascular events during subacute stroke rehabilitation.
Key Findings
Results
Increases in hsCRP during treatment were associated with less upper-extremity motor improvement from baseline to end-of-treatment.
The association was statistically significant: β = -0.75 ± 0.26, p = 0.01
Motor function was assessed using the Fugl-Meyer Assessment for Upper Extremity (FMA-UE)
The relationship was evaluated using mixed-effects regression across longitudinal timepoints
The study population consisted of 24 patients with subacute ischemic stroke (21 completers)
Results
Cathepsin-B, Cathepsin-S, and E-selectin were not significantly associated with FMA-UE motor improvement.
All four biomarkers (plasma Cathepsin-B, Cathepsin-S, E-selectin, and hsCRP) were assessed longitudinally
Only hsCRP reached statistical significance in association with motor recovery
Analyses were conducted at baseline, end-of-treatment (4 weeks), and 12-week follow-up
Substantial interindividual variability was noted across all biomarker measurements
Results
Four participants who later experienced major adverse cardiovascular events showed high levels of hsCRP and Cathepsin-S at baseline.
This was an exploratory observation within the 24-patient cohort
Both hsCRP (inflammatory marker) and Cathepsin-S (lysosomal protease associated with inflammation and vascular disease) were elevated at baseline in these individuals
The finding suggests these biomarkers may indicate vascular risk in addition to recovery potential
The small number of events (n=4) limits statistical inference but highlights a potential clinical signal
Results
No significant associations were found between any biomarker and changes in cognition, depression, or quality of life.
Cognition was measured using the Montreal Cognitive Assessment (MoCA)
Depression was measured using the Beck Depression Inventory-II (BDI-II)
Quality of life was measured using EQ-5D-5L
A trend-level positive association was observed between E-selectin and MoCA score, but did not reach statistical significance
These were sensitivity analyses within the exploratory substudy design
Methods
The study was an exploratory substudy of the PRACTISE trial in which patients with subacute ischemic stroke received patient-tailored transcranial direct current stimulation (tDCS) or sham during four weeks of upper-extremity rehabilitation.
Trial registration: NCT05355831
Total enrollment: 24 patients; 21 completers
Assessments occurred at baseline, end-of-treatment (4 weeks), and 12-week follow-up
Baseline MRI was rated for small-vessel disease (SVD) burden using STRIVE criteria
Biomarkers reflecting neuroplasticity, inflammation, and vascular integrity were the focus of the substudy
What This Means
This research examined whether certain proteins measurable in the blood could help explain why some stroke patients recover better than others after rehabilitation. The study followed 24 patients with recent ischemic strokes who were undergoing upper-arm rehabilitation combined with either brain stimulation (tDCS) or a sham procedure. Blood samples were taken at the start, after four weeks of treatment, and at a 12-week follow-up to measure four biomarkers: two cathepsins (enzymes linked to inflammation and brain plasticity), E-selectin (a marker of blood vessel inflammation), and high-sensitivity C-reactive protein (hsCRP, a general marker of inflammation).
The main finding was that patients whose hsCRP levels increased during the treatment period showed less improvement in arm and hand motor function compared to patients whose hsCRP did not rise. Additionally, four patients who later suffered serious heart or vascular events (such as heart attacks or strokes) had notably high levels of both hsCRP and Cathepsin-S at the very beginning of the study. The other biomarkers were not significantly linked to motor recovery, though there was a weak, non-significant trend suggesting E-selectin might relate to cognitive outcomes.
This research suggests that measuring inflammation in the blood during stroke rehabilitation could provide useful information about both how well a patient is likely to recover and their future cardiovascular risk. Because the study was small and exploratory, the findings need to be confirmed in larger trials, but they point toward inflammatory biomarkers—particularly hsCRP and Cathepsin-S—as potentially valuable tools for personalizing stroke rehabilitation and identifying patients who may need closer cardiovascular monitoring.
Kolmos M, Sørensen N, Gandrup K, Larsson A, Dunø M, Kruuse C. (2026). Biomarkers of plasticity and recovery after stroke: Insights from the PRACTISE trial.. Clinical neurology and neurosurgery. https://doi.org/10.1016/j.clineuro.2026.109492