Paraneoplastic Cerebellar Degeneration

Excerpt

Paraneoplastic syndromes constitute a group of uncommon manifestations that are noted in patients with different types of malignancies. The underlying mechanism is not a direct spread but could be hormonal, caused by active proteins or peptides secreted by malignant cells such as antidiuretic hormone (ADH), parathyroid hormone-related peptide (PTHrP) or adrenocorticotrophic hormone (ACTH). They also can be autoimmune, caused by crossreacting antibodies or immune cells produced in the human body in response to malignant tumors, such as Lambert Eaton syndrome, paraneoplastic cerebellar degeneration, and limbic encephalitis. They can also be related to cytokines produced by tumor cells or the immune system. Paraneoplastic syndromes can occur with multiple types of malignancies, including but not limited to breast cancer, small cell lung cancer, squamous cell lung cancer, Hodgkin lymphoma, mesothelioma, renal cell carcinoma, and multiple other malignancies.

Clinicians need to be familiar with the presentations of paraneoplastic syndromes as they can be the first presenting symptoms of an underlying malignancy. Failure to identify these syndromes may result in delayed diagnosis of cancer and poor clinical outcomes. These syndromes are not directly related to tumor invasion, metastatic disease symptoms, or due to adverse treatment effects.

Paraneoplastic neurological syndromes (PNS) are a unique subset of paraneoplastic syndromes. Caused by cross-reactive antibodies called onconeural antibodies, these are antibodies produced by the immune system in response to malignant tumors. These onconeural antibodies can attack different parts of the nervous system resulting in various neurological manifestations.

Paraneoplastic cerebellar degeneration (PCD) is one of the more commonly seen paraneoplastic neurological syndromes. It is caused by immune-mediated injury to cerebellar Purkinje cells. It is associated with multiple malignancies but, most commonly, breast and pelvic malignancies. PCD has also been reported in patients with Hodgkin lymphoma, gastric cancer, prostate cancer, and small cell lung cancer. PCD can progress rapidly over a few weeks and can result in severe disability.