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

Brief Summary This single-centre prospective case-control study will evaluate whether a CSF/serum biomarker panel (IL-6, IL-1β, TNFα, PCT, CRP, adrenomedullin) can improve the early diagnosis and risk stratification of cerebral vasospasm, delayed cerebral ischaemia (DCI), and drain-associated ventriculitis/meningitis in adults treated for non-traumatic SAH with external CSF drainage. The study also explores associations with serum 25-hydroxy-vitamin D.

Detailed Description Background: Bedside TCCD is non-invasive but has limited accuracy for vasospasm; DSA is the gold standard but invasive and not easily repeatable. Early, reliable biomarkers could identify high-risk patients sooner. External CSF drainage is standard after SAH but carries a 5-22% risk of ventriculitis/meningitis.

Objectives: Assess diagnostic/predictive performance (including ROC analyses) of IL-6, IL-1β, TNFα, PCT, CRP and adrenomedullin (ADM) in CSF and serum for vasospasm, DCI and drain-associated infection; compare against routine parameters; evaluate combined-biomarker utility; explore associations with 25-OH-vitamin D.

Sampling/monitoring: Daily TCCD for 14 days (extend to day 21 if severe vasospasm); suspected vasospasm if MFV \>120 cm/s, severe if \>200 cm/s. CSF IL-6/PCT/CRP daily until drain removal; IL-1β, TNFα, ADM at 0-2, 3-5, 6-8, 9-11, 12-14 days and at infection detection; serum 25-OH-vitamin D on drain-insertion day and day 14. Outcomes collected at days 30/90/180 (mortality, GOSE, Barthel, Karnofsky, mRS).

Study Type Observational (Prospective; Case-Control).

Observational Model / Time Perspective Case-Control; Prospective.

Estimated Enrollment

\~100 participants.

Outcome Measures Primary Outcome Measures Vasospasm occurrence (binary): TCCD suggestive (MFV \>120 cm/s; severe \>200 cm/s) and/or DSA-confirmed; diagnostic/predictive performance of biomarkers (e.g., ROC AUC). Time Frame: first 14 days post-ictus (to day 21 if severe vasospasm).

Delayed cerebral ischaemia (DCI) (binary): new unexplained ischaemia on native cranial CT or new unexplained neurological deficit lasting \>1 hour; biomarker performance vs DCI status. Time Frame: during acute hospital course (typically within first 14 days).

Drain-associated ventriculitis/meningitis (binary): infectologist-adjudicated diagnosis during drainage; biomarker performance vs infection status. Time Frame: through duration of external drainage.

Secondary Outcome Measures Functional outcomes: mortality; Extended Glasgow Outcome Scale; Barthel Index; Karnofsky; modified Rankin Scale at days 30/90/180 post-ictus.

Comparative accuracy: biomarkers vs routine CSF/blood parameters (e.g., CSF cell count/composition/lactate; albumin \& glucose ratios; serum CRP/PCT/IL-6).

Combined-biomarker utility: added value of multi-marker panels over single markers.

Vitamin D exploratory analysis: correlation of biomarkers with admission and day-14 serum 25-OH-vitamin D.

Biospecimen CSF and blood samples collected for biomarker measurements (lab values used for analysis).

Eligibility Criteria

Inclusion:

* Adults (≥18 years). * Angiography-identifiable non-traumatic SAH (regardless of source). * Requires lumbar or ventricular drain as part of treatment.

Exclusion:

* Traumatic SAH. * Patient/legal representative does not consent. * Meningitis within 6 months prior to ictus. * Immunosuppressed state (disease or medications affecting WBC number/function).

Groups/Cohorts (for analyses)

* Vasospasm (+/-) (TCCD-suggested or DSA-confirmed vs. absent). * DCI (+/-) (meets DCI definition vs. absent). * Drain-associated ventriculitis/meningitis (+/-) (infectologist-adjudicated vs. excluded).

Statistical Plan Normality testing; t-test or non-parametric equivalents; χ² with Yates' correction where appropriate; Bonferroni for multiplicity; ROC analysis for diagnostic/predictive performance.

Location University of Debrecen, Clinical Centre - Department of Anaesthesiology and Intensive Care, Debrecen, Hungary (Neurosurgical Intensive Care Unit).

Contacts Principal Investigator: Prof. Dr. Csilla Molnár - University of Debrecen, Clinical Centre, Department of Anaesthesiology and Intensive Care. (Phone/Email per site policy.)

Keywords Subarachnoid haemorrhage; vasospasm; delayed cerebral ischaemia; ventriculitis; meningitis; IL-6; IL-1β; TNFα; procalcitonin; CRP; adrenomedullin; CSF biomarkers; TCCD; vitamin D.