Paraneoplastic cerebellar degeneration

Abstract

Paraneoplastic cerebellar degeneration (PCD) is an unusual, remote effect of certain systemic cancers and is characterized by subacute cerebellar symptoms. PCD cases exhibit varying clinical features: In some cases only cerebellar involvement is noted, whereas in others, cerebellar involvement is accompanied by nervous system involvement at various levels. This article describes the knowledge on PCD, with emphasis on certain clinical-immunological associations. Recent studies have revealed the presence of various autoantibodies in the serum or cerebrospinal fluid of PCD patients. The antibodies associated with PCD are Yo, Hu, Ri, Ma, CV2/CRMP-5, P/Q-type VGCC, GAD, mGluR, ANNA-3, PCA-2, Tr, Zic and CARPVIII antibodies. The antigens recognized by these autoantibodies are membrane proteins or proteins expressed within cerebellar neurons. The pathogenic role played by the autoantibodies in PCD is unknown. In some PCD cases, it is unlikely that these autoantibodies play a pathogenic role; in such cases, cytotoxic T cells are assumed to play a crucial role in the pathogenesis of PCD. However, some autoantibodies, especially those directed against membrane proteins, have been shown to be directly involved in the pathogenesis of PCD. Detection of these autoantibodies is important for a correct diagnosis of PCD. The effect of immunotherapy is unclear in most PCD cases. Clarification of the relevant clinical-immunological associations is crucial for the developent of new therapeutic strategies for PCD.