To report a case of immune-checkpoint inhibitor associated meningoencephalitis with significant cerebrospinal fluid (CSF) pleocytosis and good outcome 

Post immune-checkpoint inhibitor autoimmune meningoencephalitis is rare with variable outcomes.  

Case report 

A 65-year-old male with thymic metastatic squamous cell carcinoma, status-post thymectomy and chemoradiation (carboplatin and paclitaxel) complicated by chemotherapy-induced neuropathy, presented with a three-day history of altered mental status a week after his first pembrolizumab infusion. At neurological nadir, he was not communicating or following simple commands and had meningismus. MRI brain demonstrated leptomeningeal enhancement and CSF demonstrated 1,562 nucleated cells/mcL, with lymphocytic predominance (89%), elevated protein (199 mg/dL) and normal glucose. No malignant cells were present but there was marked increase in CD4+ T cells without immunophenotypic aberrancy. Neural antibodies were negative in both serum and CSF. Bacterial/fungal/mycobacterial cultures, meningoencephalitis multiplex PCR and metagenomic sequencing for microorganisms were negative. The patient was initially treated with broad-spectrum antimicrobials and completed a full course of ceftriaxone. Due to negative infectious studies, he was treated with high-dose methylprednisolone for five days and plasma exchange followed by an oral prednisone taper over multiple weeks. Mental status improved within three days of treatment. Repeat MRI showed resolution of leptomeningeal enhancement. Repeat exam four weeks following presentation showed improved cognition (Kokmen STM 35/38) and known peripheral neuropathy. Repeat CSF showed 35 nucleated cells/mcl. CSF cytokine testing at nadir showed very high IL6, IL10, CXCL10, CXCL9, CXCL13, IFN g and to a lesser extent IL1b, GM-CSF, BAFF and CXCL8 that improved on repeat CSF. 

This case demonstrates an unusually significant CSF pleocytosis in the context of an immune-checkpoint inhibitor-associated meningoencephalitis. The cytokine signature and the cytology data suggest a predominant T-cell mediated inflammatory process (mainly CD4+ T-cells) responsive to immunotherapy.