Adults with suspected central nervous system infection: A prospective study of diagnostic accuracy

Abstract

Objectives: To study the diagnostic accuracy of clinical and laboratory features in the diagnosis of central nervous system (CNS) infection and bacterial meningitis.

Methods: We included consecutive adult episodes with suspected CNS infection who underwent cerebrospinal fluid (CSF) examination. The reference standard was the diagnosis classified into five categories: 1) CNS infection; 2) CNS inflammation without infection; 3) other neurological disorder; 4) non-neurological infection; and 5) other systemic disorder.

Results: Between 2012 and 2015, 363 episodes of suspected CNS infection were included. CSF examination showed leucocyte count >5/mm³ in 47% of episodes. Overall, 89 of 363 episodes were categorized as CNS infection (25%; most commonly viral meningitis [7%], bacterial meningitis [7%], and viral encephalitis [4%]), 36 (10%) episodes as CNS inflammatory disorder, 111 (31%) as systemic infection, in 119 (33%) as other neurological disorder, and 8 (2%) as other systemic disorders. Diagnostic accuracy of individual clinical characteristics and blood tests for the diagnosis of CNS infection or bacterial meningitis was low. CSF leucocytosis differentiated best between bacterial meningitis and other diagnoses (area under the curve [AUC] 0.95) or any neurological infection versus other diagnoses (AUC 0.93).

Conclusions: Clinical characteristics fail to differentiate between neurological infections and other diagnoses, and CSF analysis is the main contributor to the final diagnosis.

Keywords: Cerebrospinal fluid; Diagnostic test assessment; Encephalitis; Meningitis.

Figure 1. Diagnosis in patients with suspected neurological infection.

Abbreviations: CNS=Central nervous system, HaNDL=Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis. ^aHistoplasma encephalitis, neuroborreliosis, neurosyphilis and brain abscess (n=1). ^bTraumatic brain injury, benign intracranial hypertension, cerebral lymphoma, peripherial neuropathy.

Figure 2

Scatter plot displaying individual values of age (A), C-reactive protein levels (B), blood leukocyte count (C), CSF leukocyte count (D), total protein level (E) and CSF to blood glucose ratio levels (F) per diagnosis category. Footnote: Categories left of the vertical line consider neurological infections, right of the line other diagnostic categories. Each dot represents one episodes, the grey box in panel A indicates the age category of patients who were not included in the study, the dashed horizontal lines in panel B-E indicate the upper limit of normal (C-reactive protein 5 mg/L, blood leukocyte count 10.5x10⁹/L, CSF leukocyte count 5/mm³, CSF protein 0.60 g/L), and in panel F the lower limits of normal (CSF to blood glucose ratio 0.6).