Abstract
BackgroundEncephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.MethodsWe measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.ResultsHeat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).ConclusionsMediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.
Highlights
Encephalitis is a neurological emergency, which presents as headache, cognitive and behavioural disturbance, sometimes with focal neurological signs; many cases progress to seizures, coma and death [1]
Heat-map analysis of cerebrospinal fluid (CSF) mediator interactions was different for infectious and immunemediated cases, and that of the unknown aetiology group was similar to the infectious pattern
CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p
Summary
Encephalitis is a neurological emergency, which presents as headache, cognitive and behavioural disturbance, sometimes with focal neurological signs; many cases progress to seizures, coma and death [1]. The most common aetiologies are infectious, typically viruses, or immune-mediated processes, which are often associated with specific antibodies [2,3]. Whilst there may be overlap in the clinical presentations of these different aetiologies, early distinction is critical, as specific antiviral or immunosuppressive treatment is required depending on the cause [1,4]. Despite the increasing recognition of immunemediated causes of encephalitis, the aetiology of encephalitis remains unknown in 15–60% in most studies [10]. Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immunemediated cases, and whether this may give a clue to aetiology in those of unknown cause
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