Reduction in Cerebrospinal Fluid Volume as an Early Quantitative Biomarker of Cerebral Edema After Ischemic Stroke.

Background and Purpose- Cerebral edema (CED) develops in the hours to days after stroke; the resulting increase in brain volume may lead to midline shift (MLS) and neurological deterioration. The time course and implications of edema formation are not well characterized across the spectrum of stroke. We analyzed displacement of cerebrospinal fluid (ΔCSF) as a dynamic quantitative imaging biomarker of edema formation. Methods- We selected subjects enrolled in a stroke cohort study who presented within 6 hours of onset and had baseline and ≥1 follow-up brain computed tomography scans available. We applied a neural network-based algorithm to quantify hemispheric CSF volume at each imaging time point and modeled CSF trajectory over time (using a piecewise linear mixed-effects model). We evaluated ΔCSF within the first 24 hours as an early biomarker of CED (defined as developing MLS on computed tomography beyond 24 hours) and poor outcome (modified Rankin Scale score, 3-6). Results- We had serial imaging in 738 subjects with stroke, of whom 91 (13%) developed CED with MLS. Age did not differ (69 versus 70 years), but baseline National Institutes of Health Stroke Scale was higher (16 versus 7) and baseline CSF volume lower (132 versus 161 mL, both