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Paraneoplastic cerebellar degeneration

Authors
Josep Dalmau, MD, PhD
Myrna R Rosenfeld, MD, PhD
Section Editor
Patrick Y Wen, MD
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

Paraneoplastic neurologic syndromes are a heterogeneous group of neurologic disorders associated with systemic cancer and caused by mechanisms other than metastases, metabolic and nutritional deficits, infections, coagulopathy, or side effects of cancer treatment.

Paraneoplastic cerebellar degeneration is an uncommon disorder that can be associated with any cancer; the most commonly associated are lung cancer (particularly small cell lung cancer (SCLC)), gynecologic and breast cancer, and lymphoma (particularly Hodgkin disease) [1]. The neurologic symptoms frequently precede the diagnosis of cancer, sometimes by an interval of years.

This topic discusses paraneoplastic cerebellar degeneration (PCD). An overview of paraneoplastic syndromes and other paraneoplastic disorders are discussed separately. (See "Overview of paraneoplastic syndromes of the nervous system" and "Paraneoplastic syndromes affecting peripheral nerve and muscle" and "Paraneoplastic syndromes affecting the spinal cord and dorsal root ganglia" and "Paraneoplastic and autoimmune encephalitis".)

PATHOGENESIS

The cerebellum is a frequent target of paraneoplastic autoimmunity. All paraneoplastic antibodies have been reported in association with PCD [2-17]. Some of these autoantibodies are associated with specific clinical settings (table 1) that may help focus the search for an underlying occult malignancy. Only two antibodies, anti-Yo and anti-Tr, predominantly associate with cerebellar dysfunction; the other paraneoplastic antibodies often associate with symptoms involving other areas of the nervous system.

The most common among the associated antibodies, anti-Yo antibodies (also called Purkinje cell antibody type 1 or PCA-1) primarily occur in patients with PCD who have breast cancer or tumors of the ovary, endometrium, and fallopian tube (picture 1) [4,5,18-20]. Rare cases of anti-Yo associated PCD have been described in men with adenocarcinoma [21-25]. The target antigens of anti-Yo antibodies are the cdr proteins that are expressed by Purkinje cells and ovarian and breast cancers [6,7,26]. A cytotoxic T cell response against cdr2 has also been identified in these patients [7].

      

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Literature review current through: Nov 2016. | This topic last updated: Fri Jul 17 00:00:00 GMT+00:00 2015.
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