Comprehensive Plasma Biomarker Profiling Identifies Inflammatory and Glial Pathways Linked to Severity in Status Epilepticus
Karnig Kazazian1, Hannah Gray1, Danelle Czink1, Victoria Labuda1, Aleksandra Leligdowicz1, Teneille Gofton1
1Western University
Objective:
To characterize the pathobiology of status epilepticus (SE) in critically illness.
Background:
SE is a neurological emergency with high morbidity, especially when refractory to treatment. The biological mechanisms driving refractory SE remain unclear. Inflammatory, endothelial, and glial activation may underlie treatment resistance and poor outcomes. Identifying circulating biomarkers of these pathways could enable early prognostication and personalized management in SE.
Design/Methods:
Adults with SE admitted to intensive care were prospectively enrolled. Blood samples were collected on day 7 after SE onset and used to quantify 22 circulating proteins representative of inflammation, endothelial activation, and neuronal/glial injury using the Luminex platform. Protein concentrations were compared in patients with SE responsive to therapy and refractory SE. Refractory SE was adjudicated based on treatment response and EEG.
Results:
Thirty-four patients were included (responsive SE n=25, refractory SE n=9). Patients with refractory SE showed prolonged coma and hospitalization, higher mortality (p<0.01), and worse 6-month outcomes (GOSE=2.4 vs 5.4, p=0.001; DRS = 18.6 vs 4.6, p=0.04). On day 7, patients with refractory SE compared to self-limited SE had higher IL-6 (34.70 pg/mL vs 14.55 pg/mL, p=0.04), YKL-40 (83771.91 pg/mL vs 34331.35 pg/mL p=.006), and Neurosin (3955.95 pg/mL vs 2289.36 pg/m p<0.001) levels. Other markers (angiopoietin-2, CXCL10, S100B) were similarly higer in patients with refractory SE but, the associations did not reach significance.
Conclusions:
Immune and glial activation is present one week after SE onset and is greater among patients with refractory SE. These findings suggest the presence of inflammation may be driving refractory SE. If validated in larger cohorts, such plasma-based signatures could enable rapid, low-cost risk stratification of SE patients and predicting who may be more likely to develop refractory SE. This would be particularly valuable in under-resourced settings where advanced neurodiagnostics are limited and help identify those who may benefit from aggressive therapies.
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