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A 79-year-old man with metastatic Merkel cell carcinoma presented one week after receiving pembrolizumab with bilateral upper and lower extremity tremor and nearly continuous involuntary facial movements exacerbated by purposeful movement. One year prior to presentation he also received pembrolizumab and developed mild tremor and dysarthria.

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Exam revealed jerky facial movements that worsened with activation, dysarthria with tremulous speech, intention tremors of the head and extremities, distally diminished vibration sense with hyporeflexia, bilateral upper extremity dysdiadochokinesis, bilateral lower extremity dysmetria, and truncal ataxia. MRI brain showed no acute abnormalities. Lumbar puncture revealed lymphocytic pleocytosis (26 nucleated cells/ml [normal <5], 77% lymphocytes), total protein of 107.3 mg/dL (normal 10-44), and glucose of 166 mg/dL (normal 40-70), which was concordant with serum glucose. Kappa free light chains were 0.501 mg/dl (normal <0.1) without oligoclonal bands. Mayo Clinic Movement Disorder Panels (MDC2, MDS2) were positive for neuronal intermediate filament (NIF) antibodies in both serum (titer 1:122,880, normal <1:240) and CSF (titer ≥1:1,024, normal <1:2) via cell-based assays for alpha internexin, NIF heavy chain, and NIF light chain. He was treated with IV methylprednisolone 1g daily for 5 days followed by oral prednisone taper and IVIG 2g/kg over 4 days with improvement in symptoms.

This patient met criteria for definite immunotherapy related encephalitis, subtype cerebellitis, associated with NIF autoantibodies. Merkel cell carcinoma can cause paraneoplastic NIF autoimmunity, raising the question of if pre-existing NIF autoimmunity was enhanced by immune checkpoint inhibitor (ICI) therapy. Though not recognized at the time, he may have had mild cerebellitis after his first dose of pembrolizumab, which primed the immune system and contributed to severe cerebellitis following second pembrolizumab dose. ICI use is becoming more common, and it is important that neurologists recognize and treat neurologic immune related adverse events of ICIs.