To describe a case of ICI-induced encephalitis with initial presentation concerning for infectious encephalitis and imaging appearance similar to low-grade glioma,  to highlight the importance of prompt consideration of this diagnosis, discuss the differential, as well as demonstrate clinical improvement with immunotherapy. 

Immune checkpoint inhibitors (ICI) are revolutionary immunomodulatory antibodies used in malignancy treatment, that are associated with adverse neurologic immune-related adverse events (irAEs), including ICI-related autoimmune encephalitis (ICI-AE). ICI-AE can be difficult to diagnose, with a broad differential, including infectious and neoplastic considerations; prompt recognition and treatment are crucial.

A 51 year-old Caucasian female with pT3a clear cell renal cell carcinoma status post recent right radial nephrectomy, was on the PDL1 inhibitor Pembrolizumab for three months. She then presented with three weeks of fatigue, transient diplopia and personality changes. MRI on admission showed non-enhancing FLAIR hyperintensities in the left thalamus and basal ganglia, concerning for encephalitis versus low-grade glioma. She was febrile on admission, prompting concern for an infectious encephalitis, and was empirically started on broad-spectrum antimicrobials with CNS coverage. Brain MRI revealed a Chiari malformation with cerebellar herniation, necessitating external ventricular drain (EVD) placement to obtain cerebrospinal fluid (CSF). While CSF white blood cell count and protein were normal, she did have seven CSF-unique oligoclonal bands. She was treated with 1g IV methylprednisolone daily for five days, followed by 2g/kg IVIg divided over four days, with subsequent clinical and radiographic improvement. She was discharged to rehab on a prednisone taper, with planned outpatient Autoimmune Neurology follow-up.

ICI-AE, while rare, is an important diagnostic consideration in patients who present with acute or subacute encephalopathy and/or personality changes, even with low-grade fever. CSF profile can show pleocytosis and/or elevated protein, but testing for other markers of inflammation, such as oligoclonal bands, to further evaluate for this diagnosis, is important.