Granulocytes in cerebrospinal fluid of adults suspected of a central nervous system infection: a prospective study of diagnostic accuracy

Abstract

Purpose: Cerebrospinal fluid (CSF) granulocytes are associated with bacterial meningitis, but information on its diagnostic value is limited and primarily based on retrospective studies. Therefore, we assessed the diagnostic accuracy of CSF granulocytes.

Methods: We analyzed CSF granulocytes (index test) from all consecutive patients in two prospective cohort studies in the Netherlands. Both studies included patients ≥ 16 years, suspected of a central nervous system (CNS) infection, who underwent a diagnostic lumbar puncture. All episodes with elevated CSF leukocytes (≥ 5 cells per mm³) were selected and categorized by clinical diagnosis (reference standard).

Results: Of 1261 episodes, 625 (50%) had elevated CSF leukocytes and 541 (87%) were included. 117 of 541 (22%) were diagnosed with bacterial meningitis, 144 (27%) with viral meningoencephalitis, 49 (9%) with other CNS infections, 76 (14%) with CNS autoimmune disorders, 93 (17%) with other neurological diseases and 62 (11%) with systemic diseases. The area under the curve to discriminate bacterial meningitis from other diagnoses was 0.97 (95% confidence interval [CI] 0.95-0.98) for CSF granulocyte count and 0.93 (95% CI 0.91-0.96) for CSF granulocyte percentage. CSF granulocyte predominance occurred in all diagnostic categories. A cutoff at 50% CSF granulocytes gave a sensitivity of 94% (95% CI 90-98), specificity of 80% (95% CI 76-84), negative predictive value of 98% (95% CI 97-99) and positive predictive value of 57% (95% CI 52-62).

Conclusion: CSF granulocytes have a high diagnostic accuracy for bacterial meningitis in patients suspected of a CNS infection. CSF granulocyte predominance occurred in all diagnostic categories, limiting its value in clinical practice.

Keywords: Bacterial meningitis; Central nervous system infection; Cerebrospinal fluid; Diagnostic accuracy; Granulocytes.

Fig. 1

Flowchart of episodes through the study. Cerebrospinal fluid (CSF), central nervous system (CNS)

Fig. 2

Violin plots depicting CSF granulocyte percentage per diagnostic category. Red dashed line represents a cerebrospinal fluid granulocytes percentage of 50%. Patients above demonstrated granulocyte predominance. Cerebrospinal fluid (CSF), central nervous system (CNS)

Fig. 3

Scatterplot depicting granulocyte percentage in relation to leukocyte count in the CSF. Vertical dashed line represents a cerebrospinal fluid leukocyte count of 5. Crosses represent patients diagnosed with bacterial meningitis. Cerebrospinal fluid (CSF)

Fig. 4

a ROC curves of leukocytes and granulocytes in the CSF of all episodes. b ROC curves of leukocytes and granulocytes in the CSF of episodes with 5–3000/mm³ CSF leukocytes. The AUCs of leukocytes, granulocytes and granulocyte percentage in the CSF as a single predictor for bacterial meningitis are depicted in, respectively, black, yellow and blue. The AUCs of a logistic regression model using bacterial meningitis as the dependent variable and leukocytes together with a cutoff point for granulocyte percentage at either granulocyte predominance (> 50%) or the Youden index as the independent variables are depicted in, respectively, in grey and green. Receiver operator characteristics (ROC), cerebrospinal fluid (CSF), area under the curve (AUC).