To describe a case of paraneoplastic neuronal intermediate filament (NIF) encephalitis associated with chronic lymphocytic leukemia (CLL), highlighting postmortem neuropathological findings.

NIF IgG is a recently identified autoantibody that has been associated with a variety of neurological presentations including encephalopathy, cerebellar ataxia, and myelopathy. The majority of cases are associated with an underlying malignancy. To our knowledge, neuropathological examination of postmortem brain tissue in NIF-associated encephalitis has not been reported in the literature.

A case report.

We present the case of a 76-year-old woman with a history of breast cancer and CLL (both in remission) who presented with several months of progressive cognitive decline, gait impairment, and prominent neuropsychiatric disturbances. Magnetic resonance imaging of the brain revealed two remote lacunar infarcts but was otherwise normal. Computed tomography imaging of the body revealed diffuse axillary, mesenteric, and retroperitoneal adenopathy concerning for CLL recurrence, and this was confirmed on peripheral flow cytometry of blood. Given the sudden onset of progressive and prominent neuropsychiatric changes without a clear etiology, a paraneoplastic evaluation was pursued. Serum autoantibody testing revealed positivity for NIF antibody by immunofluorescence assay and subsequent cell-based assay confirmed NIF heavy chain antibody at high titers (1:960). The patient was treated with a trial of high-dose intravenous methylprednisolone and plasma exchange with moderate clinical improvement. Ultimately, her cancer progressed, and she died approximately six months later. Neuropathological brain examination revealed the presence of inflammatory infiltrate in the cortex and cerebellum, and immunohistochemical analysis demonstrated reduced staining for intermediate filaments. There was also evidence of neurofibrillary tangles and neuritic plaques, findings typically seen in Alzheimer’s disease. There was no pathological evidence of CNS involvement of CLL.

Our case highlights neuropathological findings seen in paraneoplastic NIF autoimmunity and a possible association with CLL recurrence.