Objective:

To characterize immune-related encephalitis (irE) disease trajectory and identify predictors of recovery.

Background:

Immune checkpoint inhibitors (ICI) are increasingly used and have improved outcomes in cancer treatment; however, a subset of patients experience immune-related adverse events (irAEs), including autoimmune encephalitis (irE). 

Design/Methods:

We retrospectively reviewed patients who received ICI and had treating physician-documented diagnosis of irE. We fit a multivariable ordinal regression model after screening candidate predictors of irE recovery.

Results:

We identified 41 patients (median age 71.7, 29.3% female) with irE. Melanoma (46.3%) and lung cancer (22.0%) were most frequently represented. 48.8% of patients had received ≥2 ICIs. 29.3% had CNS cancer involvement and 19.5% had prior CNS radiation. Presenting symptoms of irE included encephalopathy (90.2%), gait instability (24.4%), psychiatric/behavioral changes (19.5%), and movement disorder (17.1%). 67.5% of patients had lymphocytic pleocytosis with 2 patients testing positive for clinically significant autoantibodies (1 in serum, 1 in CSF). 10% had MRI findings of encephalitis. Only 3 patients fit definite or probable autoimmune encephalitis 2016 Graus criteria. 53.7% of patients had other systemic irAEs at time of presentation. All patients were treated with steroids: 52.5% had full and 35.0% had partial recovery, with 31 days median recovery time. 56.1% were deceased at the last follow up (median 8.4 months). ICI was discontinued in all cases and 4 patients were re-challenged (2 partial remission, 1 no remission, 1 deceased); none had recurrence of irE at last follow up. Higher antibody prevalence in epilepsy/encephalopathy (APE2) score (OR 0.20) and prior CNS radiation (OR 0.03) were significantly associated with lower odds of better recovery. 

Conclusions:

Traditional clinical and imaging markers of autoimmune encephalitis are insensitive for irE. Patients with irE were steroid-responsive with most patients having a monophasic course. Higher APE2 scores and prior CNS radiation portend worse outcomes.