ICI-mediated limbic encephalitides are increasingly being recognized in the literature, but atypical cases may be missed or misdiagnosed. Recent efforts are directed to identify biomarkers to help elucidate early diagnosis and treatment.

 Retrospective chart review and literature review

Case-1 A 71-year-old-male with epithelioid neoplasm of the lung who presented with confusion, personality changes, and loss of appetite after cycle 6 of pembrolizumab. Laboratory findings were suggestive of ICI mediated central adrenal insufficiency. Correction of metabolic derangements did not lead to improvement. MRI Brain with and without contrast and routine EEG were unremarkable. Lumbar puncture revealed protein of 44, glucose of 86, white blood cells of 1 and red blood cells of 1. The infectious panel and cytology were negative. sNfL was found to be elevated (326). The patient was started on plasmapheresis for clinical suspicion of ICI-mediated limbic encephalitis. He was seen in clinic one month after discharge with only mild residual slowing while performing complex-task. Repeat sNfL was normal.

Case-2 A 62-year-old-female with stage-IV adenocarcinoma of the lung and brain metastasis on nivolumab and ipilimumab presented to the hospital with worsening alerted mentation. MRI Brain showed new increased T2 signal intensity in hypothalamic and parahippocampal regions raising concern for ICI mediated limbic encephalitis. Serial lumbar punctures revealed lymphocytic pleocytosis without evidence of metastatic disease. sNfL was elevated (111). Patient was started on steroids and plasmapheresis with transient improvement. Novel tacrolimus therapy was initiated. Repeat sNfL continued to increase (182). Hospital course was complicated by a new DVT and pulmonary embolism. Patient transitioned to hospice and expired due to sepsis.

Increased sNfL levels reflect neuroaxonal damage and may serve as a novel biomarker to determine neurological outcomes and prognosis.