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Observational Study
. 2025 Jan;32(1):e16456.
doi: 10.1111/ene.16456. Epub 2024 Oct 30.

Cerebrospinal fluid red blood cells and total protein are associated with clinical outcome in spontaneous subarachnoid hemorrhage

Klaus Berek  1 , Anna Lindner  1 , Philipp Kindl  1 , Franziska Di Pauli  1 , Alois J Schiefecker  1 , Bettina Pfausler  1 , Raimund Helbok  1   2 , Florian Deisenhammer  1 , Ronny Beer  1 , Verena Rass  1 , Harald Hegen  1
Affiliations
Observational Study

Cerebrospinal fluid red blood cells and total protein are associated with clinical outcome in spontaneous subarachnoid hemorrhage

Klaus Berek et al. Eur J Neurol. 2025 Jan.

Abstract

Background and purpose: Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis.

Methods: Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real-world, observational study. Longitudinal CSF samples were collected as part of routine diagnostics. RBC count and CSF TP at the time of admission (RBCfirst, TPfirst), in Week 1 (RBCDays1-7, TPDays1-7), Week 2 (RBCDays8-14, TPDays8-14), and Week 3 or thereafter (RBCDay>14, TPDay>14), the highest detected value (RBChighest, TPhighest), as well as the RBC count adjusted for disease duration (RBCadjusted) were assessed. Primary outcomes were good functional outcome after 3 months, defined as modified Rankin scale score ≤2 and ICU survival.

Results: A total of 183 SAH patients with a female predominance (69%), a median (interquartile range [IQR]) age of 60 (50-70) years and median (IQR) Hunt and Hess score of 4 (3-5) were included. Multivariable analyses revealed that lower values of RBCfirst, RBCadjusted, RBChighest, TPfirst and TPhighest were associated with good functional outcome and hospital survival. Lower TP concentrations in Weeks 1, 2 and 3 were associated with good functional outcome, and in Weeks 1 and 2 with ICU survival. Early RBC measurements (Week 1) were associated with good functional outcome and ICU survival.

Conclusions: Low CSF RBC counts and TP concentrations were associated with good functional outcome and ICU survival in a real-world cohort of SAH patients requiring external ventricular drainage.

Keywords: cerebrospinal fluid; prognosis; red blood cells; subarachnoid hemorrhage; total protein.

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Conflict of interest statement

Klaus Berek has participated in meetings sponsored by and received travel funding or speaker honoraria from Roche, Teva, Merck, Biogen, Sanofi and Novartis. He is Associate Editor of Frontiers in Immunology and Frontiers in Neurology (Section Multiple Sclerosis and Neuroimmunology). Anna Lindner has nothing to disclose. Philipp Kindl has nothing to disclose. Franziska Di Pauli has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene‐BMS, Celgene, Horizon, Janssen‐Cilag, Merck, Novartis, Sanofi‐Genzyme, Roche and Teva. Her institution has received research grants from Roche. Alois J. Schiefecker has nothing to disclose. Bettina Pfausler has nothing to disclose. Raimund Helbok has nothing to disclose. Florian Deisenhammer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene‐BMS, Genzyme‐Sanofi, Horizon, Janssen, Merck, Novartis Pharma and Roche. His institution has received research grants from Biogen and Genzyme Sanofi. He is Section Editor of the MSARD Journal (Multiple Sclerosis and Related Disorders) and Review Editor of Frontiers in Neurology. Ronny Beer has nothing to disclose. Verena Rass has nothing to disclose. Harald Hegen has participated in meetings sponsored by and received speaker honoraria or travel funding from Bayer, Biogen, Bristol Myers Squibb, Horizon, Janssen, Merck, Novartis, Sanofi‐Genzyme, Siemens and Teva, and received honoraria for acting as consultant for Biogen, Bristol Myers Squibb, Novartis, Roche, Sanofi‐Genzyme and Teva. He is Associate Editor of Frontiers in Neurology.

Figures

FIGURE 1
FIGURE 1
Inclusion flow chart. CSF, cerebrospinal fluid; ICU, intensive care unit; SAH, subarachnoid hemorrhage.
FIGURE 2
FIGURE 2
Cerebrospinal fluid (CSF) red blood cell (RBC) counts (a), total protein (TP) concentrations (b) and number of samples (c) per day. CSF RBC counts are shown as 10×/μL. TP concentrations are given in mg/dL.
FIGURE 3
FIGURE 3
Cerebrospinal fluid (CSF) red blood cell (RBC) counts and total protein (TP) concentrations according to good functional outcome (a) and hospital survival (b). CSF RBC counts are shown as 10×/μL. TP concentrations are given in mg/dL. Good functional outcome is defined as modified Rankin scale score ≤2. Statistical significance for group comparisons is given at a p value of *p < 0.05; **p < 0.01; ***p < 0.001. RBC adjusted = calculated RBC count at admission; RBC first, RBC count at first measurement; RBC highest, highest RBC count of all measurement; TP first, CSF TP at first measurement; TP highest, highest CSF TP measurement.
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