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  • Updated 09.14.2020
  • Released 02.22.1994
  • Expires For CME 09.14.2023

Paraneoplastic cerebellar degeneration

Introduction

Overview

Paraneoplastic neurologic syndromes are characterized by a diverse array of phenotypic neurologic manifestations associated with an underlying malignancy. Paraneoplastic cerebellar degeneration is an uncommon but often devastating complication of malignancy in adults. The syndrome manifests as an acute or subacute onset of ataxia, vertigo, oscillopsia, and other cerebellar symptoms with mechanisms such as primary malignancy, infection, and nutritional or toxic and metabolic deficiencies excluded at diagnostic evaluation. The syndrome is often associated with occult small cell lung cancer, gynecologic cancers, breast cancer, and lymphoma. The immunopathogenesis of neuronal injury in paraneoplastic cerebellar degeneration is poorly understood but is thought to be related to antibody and cytotoxic T-cell mediated immune responses. Many patients have defined circulating autoantibodies but often no underlying antibody is identified. The authors review the clinical features, autoimmune aspects, and practical management of this important condition.

Key points

• Antibody-mediated cerebellar ataxia can be classified as paraneoplastic based on association with cancer or presence of autoantibody with a high pretest probability of cancer greater than 70% or autoimmune.

• Paraneoplastic cerebellar degeneration may present as an isolated subacute pancerebellar syndrome or a multifocal neurologic disorder and is most commonly seen in association with breast cancer, small cell lung cancer, and lymphoma.

• Two well-recognized autoantibodies syndromically associated with paraneoplastic cerebellar degeneration include Purkinje cell cytoplasmic antibody 1 (PCA1, or anti-Yo) associated with breast cancer and Purkinje cell cytoplasmic antibody Tr (anti-Tr or anti-delta/notch-like epidermal growth factor-related receptor [DNER]) associated with lymphoma. Autoantibodies targeting metabotropic glutamate receptor 1 (mGLuR1) cause autoimmune ataxia, in some cases associated with lymphoma.

• In patients with paraneoplastic cerebellar degeneration circulating autoantibodies, when present, can guide the search for an underlying neoplasm and provide insight into outcomes.

• Paraneoplastic cerebellar degeneration can be a disabling condition and patients may not have significant neurologic improvement despite successful tumor treatment and/or immunosuppressive therapies.

Historical note and terminology

The occurrence of subacute cerebellar degeneration in patients with systemic cancer was noted more than 60 years ago (49). Subsequently, an etiologic association between cancer and cerebellar degeneration was first clearly postulated by Lord Russell Brain in 1951 (06).

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