Cerebrospinal fluid metabolite profiles in encephalitis reveal potential biomarkers for diagnosis and prognosis

<h3></h3> Encephalitis is a condition of devastating inflammation of the brain. Most commonly encephalitis is caused by either viral infection or antibody-mediated autoimmunity, which can be difficult to distinguish from each other, but distinguishing aetiology is crucial to determining timely and appropriate treatment. It is also difficult to distinguish encephalitis from other causes of encephalopathy where the primary pathology is outside the central nervous system. We analysed cerebrospinal fluid (CSF) samples from 51 prospectively recruited patients in the United Kingdom with encephalitis owing to viral infection, autoimmune encephalitis and mimicking conditions by ¹H nuclear magnetic resonance spectroscopy. We identified significant differences in levels of phenylalanine, leucine, isoleucine, valine, glucose and 2-hydroxybutyric acid between viral encephalitis and mimics. Glucose was significantly lower in autoimmune encephalitis than mimics, although overall the metabolite profiles of autoimmune and viral encephalitis were similar. Several metabolites correlated with poor outcome in viral encephalitis, including threonine, myo-inositol, creatine and creatinine. Glucose and 2-hydroxy-3-methylbutyric acid were lower in those patients who had seizures. CSF metabolites have potential as biomarkers of diagnosis and prognosis which, with validation in further studies, may be of clinical utility as well as improving understanding of the mechanisms of cerebral dysfunction and injury in encephalitis.