Paraneoplastic Cerebellar Degeneration

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Pathogenesis and Pathophysiology. Anti-Yo, an antibody of 34 and 62 kd that binds to a cytoplasmic antigen, is associated with ovarian cancer, breast cancer, and other gynecological malignancies and rarely to adenocarcinoma of the lung or unknown primary lesions. In contrast to the anti-Yo associated paraneoplastic cerebellar degeneration, in which patients are usually older women, a subset of paraneoplastic cerebellar degeneration is associated with Hodgkin's disease, in which patients are predominantly younger men.y A further subgroup of cerebellar degeneration is associated with small cell lung carcinoma and Lambert-Eaton myasthenic syndrome and an antibody against the presynaptic voltage-gated calcium channel. y

Epidemiology and Risk Factors. This entity, the most common paraneoplastic syndrome affecting the brain, may complicate any malignant tumor but is most commonly associated with lung cancer, particularly small cell lung cancer, and gynecological cancers, including endometrial, fallopian, ovarian, and breast cancer and lymphoma.

Clinical Features and Associated Findings. Neurological manifestations can precede detection of the associated cancer in more than one half of patients by months and, occasionally, up to 4 years, or manifestations may develop 2 years after the diagnosis of cancer. Although a more rapid onset within a few hours or days can occur, neurological signs usually develop over weeks to months. These signs include gait ataxia, which, over a few weeks to months, may progress to severe symmetrical or asymmetrical truncal and appendicular ataxia, dysarthria, and nystagmus.

Evaluation and Differential Diagnosis. Although no abnormalities exist on MRI in the acute setting, cerebellar atrophy can be seen later in the course of the illness. At autopsy the cerebellum is atrophic with near-complete loss of Purkinje cells throughout the cerebellar cortex. The differential diagnosis includes direct metastatic lesion of the cerebellum or outflow pathways, medication effects, or cerebrovascular accidents.

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