Encephalitis in Immunocompromised vs Immunocompetent Patients: A Comparative Study

Encephalitis is characterized by brain parenchymal inflammation caused by infection or autoimmunity. There are limited recent data on how immunocompromised patients with encephalitis differ from the general encephalitis population.

This retrospective study of 2 large medical institutions compares clinical characteristics and outcomes of immunocompromised and immunocompetent patients with all-cause encephalitis.

Of the 657 patients, 151 (23%) were immunocompromised. Immunocompromised patients were more likely to have an infectious etiology, comorbidities, inflammatory cerebrospinal fluid (CSF) profile, abnormal neuroimaging, and worse clinical outcomes as assessed by discharge Glasgow Outcome Scale (GOS) and in-hospital mortality (all P < .05). The most commonly identified etiologies in immunocompromised patients were herpes simplex virus (HSV) and varicella zoster virus. HSV accounted for similar proportions in the immunocompromised (18%) and immunocompetent (14%) groups, though it was more commonly associated with a CSF neutrophilia in the immunocompromised group (P = .001). Strikingly, >10% of immunocompromised patients with encephalitis had autoimmune causes, two-thirds of which were checkpoint inhibitor associated. Factors associated with poor GOS on discharge differed, with poorer outcomes in the infectious group associated with immunocompromised state and poorer outcomes in the autoimmune group associated with immunocompetent state.

Immunocompromised patients with encephalitis have differing causes, atypical clinical presentations, higher in-hospital mortality, and distinct factors associated with poor outcome as compared with immunocompetent patients. While HSV and opportunistic infections cause encephalitis in the immunocompromised, the diagnosis of autoimmune encephalitis should also be considered and can be checkpoint inhibitor associated.