NCMP-30. Anti-Hu antibody associated paraneoplastic cerebellar degeneration (PCD) and dysautonomia in a patient with Merkel cell carcinoma: A rare case report

Paraneoplastic syndromes (PNS) are effects of cancer associated with pathogenic immune-mediated antibodies expressed by tumor cells. We present a case of a 74-year-old male with Merkel cell carcinoma on lenvatinib plus pembrolizumab who presented with gait instability and frequent falls. MRI brain and total spine unremarkable. CSF revealed elevated nucleated cells (13), protein (61 mg/dL), and myelin basic protein (6). Serum neurofilament light chains (NfL) were markedly elevated at 141 pg/mL. After treatment with five days of high dose IVMP followed by two days of IVIG for presumed ICI-induced cerebellitis, the patient’s truncal ataxia resolved. One month later, while tapering oral prednisone, symptoms recurred with severe orthostatic hypotension, prompting an additional dose of IVIG. Due to limited improvement, rituximab (375 mg/m2) was administered, leading to the resolution of symptoms. Paraneoplastic evaluation showed significantly elevated anti-Hu antibodies in the CSF (titers >1:1024) and serum (titers 1:30720) resulting in a diagnosis of anti-Hu associated paraneoplastic cerebellar degeneration (PCD) and dysautonomia. A severe sensorimotor axonal polyneuropathy with a proximal to distal gradient of involvement was identified on EMG. Despite aggressive immunosuppression and physical therapy, symptoms returned with progressive dysarthria, dysphagia, and pronounced functional deterioration. Repeat MRI brain/spine stable. NfL (26 pg/mL) and anti-Hu antibodies (titers 1:15360) in the serum had improved. Although reduced, inflammatory markers persisted in the CSF. In the context of clinical instability and ongoing inflammation, three subsequent doses of rituximab were administered, without response. A recent PET scan showed cancer remission. He started cyclophosphamide (750 mg/m2) and aggressive rehabilitation with the Curren Foundation. This case is rare and illustrates a prolonged recovery in a patient with anti-Hu PNS and Merkel cell carcinoma. We shed light on the importance of suspecting PNS to avoid misdiagnosis. Our case opens discussion regarding the perceived risk of PNS in patients being treated with ICI.