Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology

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.

Many encephalitis cases still a medical mystery

“…Other micro‐organisms of which we are currently unaware may be causing disease and hence there are no diagnostic tools. Recent research shows an immunological profile suggestive of infection in a majority of unspecified cases 11 . This has given us greater impetus in the search for new aetiological agents.…”

“…Recent research shows an immunological profile suggestive of infection in a majority of unspecified cases. 11 This has given us greater impetus in the search for new aetiological agents.…”

Decoding the association between herpes simplex virus and antibody‐mediated encephalitis

“…Recently, the diagnosis and management of encephalitis has become more complex, with the awareness that herpes simplex virus encephalitis (HSE) can be associated with a secondary anti‐ N ‐methyl‐ d ‐aspartate receptor (anti‐NMDAR) encephalitis. There is early evidence of inflammatory mediators being distinct between infective and antibody‐mediated encephalitis . However, the number of patients is small, and no studies have examined host responses in anti‐NMDAR encephalitis following HSE.…”

“…There is early evidence of inflammatory mediators being distinct between infective and antibody-mediated encephalitis. 1 However, the number of patients is small, and no studies have examined host responses in anti-NMDAR encephalitis following HSE.…”

“…Paediatric and adult researchers should pool their clinical resources to gain better understanding and develop new treatments for these devastating conditions. Simonati et al 1 describe the natural history of 15 children with late infantile CLN5 disease. This disease is caused by mutations in the CLN5 gene and begins between the ages of 2 to 7 years.…”