Anti-Tr/DNER Paraneoplastic Cerebellar Degeneration with Marked Cerebellar and Psychological Symptoms Responsive to Plasma Exchange

Abstract

Objective We present a patient who developed cerebellar degeneration and severe psychological symptoms leading to the diagnosis of Hodgkin's disease and detection of anti-Tr/DNER antibodies. The patient failed to respond methylprednisolone intravenous immunoglobulin G, rituximab, and tumor treatment but had significant improvement with plasma exchange (PLEX). Background Paraneoplastic cerebellar degeneration accompanying Hodgkin's disease may have its onset prior to detection of the underlying malignancy, during its course, or following treatment. The associated autoantibody, anti-Tr, is reactive with neuronal delta/notch-like epidermal growth factor-related receptors (DNER), an autoantibody not included in all paraneoplastic testing screens. The condition characterized by progressive cerebellar injury, and response to immunosuppressive therapy and tumor treatment is generally poor. Design/Methods Case Presentation: A 60-year-old male presented with diplopia, progressive loss of balance, and ataxia, with impaired short-term memory, confusion, and anger outbursts. Initial commercial screen for paraneoplastic autoantibodies was negative. Two months following his initial presentation he developed inguinal lymphadenopathy. He was diagnosed as having Hodgkin's Lymphoma Stage 1B and found by a second laboratory to have anti-TR/DNER antibodies (Titer 1:3480; Reference range <1:240), an antibody not included in the initial testing panel. CSF analysis was notable for a protein of 92 mg/dL. MRI demonstrated normal findings for age. Results Treatment with Doxorubicin-Bleomycin-Vinblastine-Dacarbazine (ABVD), pulse methylprednisolone, and intravenous immunoglobulin did not affect disease progression. Plasma exchange PLEX resulted in marked improvement. Symptoms worsened during subsequent treatment with intravenous immunoglobulins and rituximab but improved with further plasma exchange. Conclusions Although Hodgkin's disease is an important malignancy in paraneoplastic cerebellar degeneration, its associated autoantibody is not necessarily included in commercial paraneoplastic autoantibody screens, potentially leading to delay in diagnosis. Our patient's dramatic improvement with PLEX suggests that PLEX should be considered early in treatment, or where there is poor response to other treatment modalities.