| Paraneoplastic cerebellar degeneration | |
|---|---|
| Classification and external resources | |
| ICD-10 | G13.0 |
| ICD-9 | 334.9 |
| DiseasesDB | 33977 |
| eMedicine | neuro/299 |
| MeSH | D020362 |
Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome associated with lung, ovarian, breast, and other cancers.
As is the case with other paraneoplastic syndromes,[1] PCD is believed to be due to an autoimmune reaction targeted against components of the central nervous system (in PCD, this is specifically Purkinje cells)[2]. It is thought to be triggered when tumor cells (in PCD, most commonly ovarian or breast cancer[3][4]) express a protein normally expressed in the brain (in PCD, this is the Purkinje neuronal protein termed cdr2). This is believed to trigger an anti-tumor immune response that may be clinically significant, but also an anti-neuronal immune response[5]. PCD patients harbor an anti-neuronal antibody known as anti-Yo (named after the first two letters of the index patient). PCD may be associated with other tumors--when associated with small cell lung cancer, it is associated with an antibody termed "anti-Hu" (more commonly associated with paraneoplastic subacute sensory neuropathy and/or limbic encephalitis).
The clinical cerebellar ataxia evident in patients with PCD are caused by Purkinje neuronal loss in the cerebellum; it is manifested by dysarthria, limb and gait ataxia, and nystagmus. Radiologic imaging occasionally reveals cerebellar atrophy. Other paraneoplastic antibodies may be associated with PCD symptoms, including anti-Tr and antibodies to glutamate receptor.
The anti-Purkinje cell antibodies originally described in PCD led to the hypothesis that the antibody might be pathogenic, much as earlier studies had demonstrated pathogenicity of anti-acetylcholine receptor antibodies in myasthenia gravis. However, when the antibody was used to clone the cDNA encoding the cdr2 antigen, it was found to be an intracellular protein. This led to the suggestion[6] that there might be a cell-mediated component (T cell) in disease pathogenesis. cdr2 antigen-specific CD8+ T cells were subsequently described[7] in all PCD patients[8], making them a hallmark of the disease, and likely components in both the anti-tumor immune response and in the neuronal degeneration.