Clinical characterization of patients with autoimmune encephalitis (AE) enrolled in Project BIG (Brain Immune Gut), the Stanford biorepository for central nervous system (CNS) disease.

AE is a heterogeneous group of disorders defined by immune-mediated attack of the CNS; the spectrum of clinical presentations remains broad. Given the rarity of AE, management is often guided by limited data and varies with severity of disease. Project BIG is an interdisciplinary effort to collect cerebrospinal fluid (CSF), serum, and fecal samples from patients with inflammatory CNS disease seen at Stanford; clinical characterization of enrolled AE patients is crucial to supporting further analyses to identify immune profiles that may guide future treatment.

We reviewed the clinical course and initial diagnostic studies, including electroencephalogram (EEG), imaging, and CSF results, of AE patients enrolled in Project BIG (n=18). Longitudinal records were reviewed to assess acute treatment and any chronic immunosuppression.

The most common AE were NMDAR and LGI1 encephalitis. Initial EEG studies were largely abnormal, ranging from diffuse slowing to focal seizures; notably, one LGI1 patient had a normal initial EEG. CSF results were notable for lack of pleocytosis in LGI1 patients. In the acute treatment phase, most patients (n=15) were treated with high-dose steroids; 13 patients were subsequently started on long-term immunosuppression (rituximab or IVIG). Seizures, neuropsychiatric symptoms, and cognitive impairment were common on initial clinical presentation.

The clinical presentations of AE patients were consistent with existing clinical criteria. Interestingly, CSF pleocytosis was not seen in LGI1 patients, reinforcing that a high index of clinical suspicion should be maintained for LGI1 encephalitis with the appropriate clinical syndrome. Despite appropriate acute treatment with high-dose steroids, most patients required escalation of treatment and long-term immunosuppression, reflecting the persistent impairment often seen in AE patients. Future directions include cytokine profiling and single-cell transcriptomics to define immune signatures.