Paraneoplastic cerebellar degeneration

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: Cerebellar ataxia due to neoplasia;

Paraneoplastic cerebellar degeneration (PCD) is a rare paraneoplastic syndrome associated with lung, ovarian, breast, Hodgkin’s lymphoma, and other types of tumors. Paraneoplastic cerebellar degeneration occurs in less than 1 to 3% of cancer patients. The pathogenesis of paraneoplastic cerebellar degeneration is due to an autoimmune reaction targeted against components of the central nervous system. The presence of anti-Purkinje cell is triggered by tumor cells, that normally express a Purkinje neuronal protein termed CDR2 antibodies. The antibodies that have been associated with the development of paraneoplastic cerebellar degeneration include anti-P/Q type calcium channel antibodies, anti-Tr antibodies, anti-Ri (ANNA-2), anti-CV2, antibodies to Ma proteins, and antibodies to the Zic4. Paraneoplastic cerebellar degeneration is more commonly observed among patients between 40 to 60 years old. Paraneoplastic cerebellar degeneration affects females more commonly than males. The majority of patients with paraneoplastic cerebellar degeneration are typically symptomatic. Early clinical features include dizziness, nausea, and vomiting. The diagnosis of paraneoplastic cerebellar degeneration is made with the following criteria: positive antibody-mediated immune response, diffuse cerebellar atrophy on imaging, and positive medical history of cancer. Common medical therapies for paraneoplastic cerebellar degeneration include intravenous immunoglobulins, cyclophosphamide, and methylprednisolone. There are no primary and secondary preventive measures available for paraneoplastic cerebellar degeneration.

• Paraneoplastic cerebellar degeneration was first described in early 1980.

• Paraneoplastic cerebellar degeneration may be classified according to the presence or absence of an antibody.

• The pathogenesis of paraneoplastic cerebellar degeneration is characterized by the presence of anti-Purkinje cell antibodies.
• The pathogenesis of paraneoplastic cerebellar degeneration is due to an autoimmune reaction targeted against components of the central nervous system.
• The pathogenesis of paraneoplastic cerebellar degeneration is triggered by tumor cells, that normally express a protein (Purkinje neuronal protein termed cdr2). This protein is believed to trigger an anti-tumor immune and anti-neuronal immune response.
• The antibodies that have been associated with the development of paraneoplastic cerebellar degeneration include:^[1]

• Anti – P/Q type calcium channel antibodies
• Anti -Tr antibodies
• Anti – Ri (ANNA-2)
• Anti – CV2
• Antibodies to Ma proteins
• Antibodies to the Zic4

• Causes of paraneoplastic cerebellar degeneration include:^[2]

• Lung cancer
• Ovarian cancer
• Breast cancer
• Hodgkin’s lymphoma

• Paraneoplastic cerebellar degeneration must be differentiated from other diseases that cause ataxia, dizziness, and nausea such as:
  • Cerebellar metastasis
  • Brainstem metastasis
  • Metabolic derangement
  • Intoxication

• Paraneoplastic cerebellar degeneration affects approximately 1 – 3% of all cancer patients.^[2]

• Paraneoplastic cerebellar degeneration is more commonly observed among patients between 40 to 60 years old.
• Paraneoplastic cerebellar degeneration is more commonly observed among middle aged adults.

• Paraneoplastic cerebellar degeneration affects females more commonly than males.

• There is no racial predilection to paraneoplastic cerebellar degeneration.

• There are no known risk factors for paraneoplastic cerebellar degeneration.^[3]

• There is insufficient evidence to recommend routine screening for paraneoplastic cerebellar degeneration.

• The majority of patients with paraneoplastic cerebellar degeneration are typically symptomatic.
• Early clinical features include dizziness, nausea, and vomiting.^[3]
• If left untreated, the majority of patients with paraneoplastic cerebellar degeneration may progress to develop severe disability with inability to walk.
• The most common complication of paraneoplastic cerebellar degeneration is cerebellar dysfunction.
• Prognosis is generally poor, and the median survival rate of patients with paraneoplastic cerebellar degeneration is approximately 13 months.^[1]

• The diagnosis of paraneoplastic cerebellar degeneration is made with the following criteria:^[1]

• Positive antibody-mediated immune response
• Diffuse cerebellar atrophy on imaging
• Positive medical history of cancer

• Symptoms of paraneoplastic cerebellar degeneration may include the following:^[1]

• Dysarthria
• Truncal, limb and gait ataxia
• Vertigo
• Nausea
• Vomiting
• Double vision
• Slurred speech
• Difficulty swallowing
• Nystagmus

• Patients with paraneoplastic cerebellar degeneration usually appear confused, or lethargic.^[3]
• Neurological examination may be remarkable for:^[1]

• Hyperactive reflexes
• Gait disturbance
• Babinski sign
• Speech disturbance
• Lack of coordination
• Nystagmus

• There are no specific laboratory findings associated with paraneoplastic cerebellar degeneration.
• Laboratory testing may include thyroid function tests, vitamin levels, and antibody titers (anti-gliadin, or anti-GAD antibodies).

• There are no ECG findings associated with paraneoplastic cerebellar degeneration.

• There are no x-ray findings associated with paraneoplastic cerebellar degeneration.

• There are no echocardiography/ultrasound findings associated with paraneoplastic cerebellar degeneration.

• There are no CT scan findings associated with paraneoplastic cerebellar degeneration.

• MRI is the imaging modality of choice for paraneoplastic cerebellar degeneration.
• On MRI, findings of paraneoplastic cerebellar degeneration include:^[1]

• Diffuse cerebellar atrophy
• No atrophy of the cerebral cortex, midbrain, pons, or medulla

• There are no other imaging findings associated with paraneoplastic cerebellar degeneration.

• Paraneoplastic cerebellar degeneration may also be diagnosed using PET scan.
• Findings on PET scan are often unspecific, but may include hypermetabolism.^[2]

• The mainstay of therapy for paraneoplastic cerebellar degeneration is supportive care.
• Common medical therapies for paraneoplastic cerebellar degeneration include:^[1]

• Intravenous immunoglobulins
• Cyclophosphamide
• Methylprednisolone

• Surgery is not recommended for patients with paraneoplastic cerebellar degeneration.

• There are no primary preventive measures available for paraneoplastic cerebellar degeneration.

• There are no secondary preventive measures available for paraneoplastic cerebellar degeneration.