Convergence of Cerebrospinal Fluid Neuronal Biomarker Burden and MRI Lesion Pattern and Its Association With Short‐Term Outcome in Neuroinfectious Diseases

BACKGROUND: Neuroinfectious diseases (NDs) are potentially treatable conditions associated with substantial morbidity, but their clinical course remains difficult to predict. While specific MRI patterns are characteristic of distinct aetiologies, their prognostic value remains poorly investigated. Cerebrospinal fluid (CSF) biomarkers of neuroaxonal and synaptic damage have been linked to clinical outcome. We investigated the association of CSF biomarkers and MRI findings with short-term outcome in NDs. METHODS: In this multicentre cohort study, CSF was analysed in 123 patients with NDs and in 95 non-neuroinflammatory controls. Concentrations of beta-synuclein, SNAP-25, neurogranin and neurofilament light chain protein (NfL) were measured. MRI findings were classified by topography and lesion pattern. Clinical outcome at discharge was assessed using the modified Rankin Scale and degree of recovery. RESULTS: All CSF biomarkers were higher in ND patients with MRI abnormalities than in those without MRI abnormalities and/or controls, also within the (meningo-)encephalitis group. Temporal lobe involvement was the MRI pattern most consistently associated with elevated CSF biomarkers, even after multivariable adjustment including aetiology, and was independently associated with poor functional outcome and incomplete recovery. A global neuronal biomarker burden derived by principal component analysis (PC1) improved the fit of outcome models including MRI lesion pattern, with both temporal lobe involvement and PC1 remaining independently associated with outcome at discharge. CONCLUSIONS: MRI lesion pattern and CSF biomarkers of synaptic and neuroaxonal damage were independently associated with short-term outcome in NDs, suggesting that they capture complementary aspects of disease severity. Prospective studies are needed to establish their prognostic value.