Investigation of the Role of Inflammatory Markers in the Early Detection of Cerebral Vasospasm, Delayed Cerebral Ischemia, and Meningitis Associated With External Cerebrospinal Fluid Drainage After Non-Traumatic Subarachnoid Hemorrhage - A Prospective Case-Control Study

Background Non-traumatic subarachnoid haemorrhage (SAH) is frequently complicated by delayed cerebral ischaemia (DCI) and by ventriculitis/meningitis when external CSF drains are used; bedside TCCD has limited accuracy for vasospasm detection, creating a need for early biomarkers.

Objective To assess the predictive and diagnostic performance of IL-6, IL-1β, TNFα, procalcitonin (PCT), C-reactive protein (CRP) and adrenomedullin (ADM) measured in CSF and serum for vasospasm, DCI, and drain-associated ventriculitis/meningitis after SAH; to test whether combining biomarkers improves accuracy versus routine parameters; and to explore associations with admission and day-14 serum 25-hydroxy-vitamin D.

Methods Prospective case-control study at the University of Debrecen (planned n≈100; enrolment 01-Nov-2024-31-Dec-2029). Adults with angiography-verified SAH requiring lumbar/ventricular drainage are included; traumatic SAH, prior 6-month meningitis, and immunosuppression are excluded. TCCD is performed daily for 14 days; suspected vasospasm is defined by mean flow velocity \>120 cm/s, severe by \>200 cm/s, with monitoring extended to day 21 if severe. Sampling: daily CSF IL-6/PCT/CRP until drain removal; IL-1β/TNFα/ADM at 0-2, 3-5, 6-8, 9-11, 12-14 days and at meningitis detection; serum 25-OH-D on drain insertion day and day 14. Outcomes at days 30/90/180: mortality, GOSE, Barthel, Karnofsky, mRS. Statistics: normality testing; t-test or non-parametric equivalents; χ² with Yates' correction; Bonferroni for multiplicity; ROC analysis for diagnostic/predictive performance.

Endpoints DCI: new unexplained CT ischaemia or a new unexplained neurological deficit \>1 h. Drain-associated infection: infectologist-adjudicated ventriculitis/meningitis. Vasospasm: TCCD-suggested or DSA-confirmed.

Expected impact An accessible CSF/serum biomarker panel may enable earlier risk stratification and treatment for vasospasm, DCI, and drain-associated infections, and inform future randomized trials of vitamin-D supplementation in SAH.