Medication Summary
There is no specific medication approved for treatment of paraneoplastic cerebellar degeneration. Treatment is mainly directed at the underlying malignancy. However, immunotherapy may also be tried, such as the medications listed below. These may also be used in combination with plasmapheresis.
Immune Globulins
Class Summary
IVIg is a purified preparation of gamma globulin. It is derived from large pools of human plasma and is composed of 4 subclasses of antibodies, approximating the distribution of human serum.
Immune globulin IV (IVIG, Octagam, Gammagard, Bivigam)
Intravenous immune globulin neutralizes circulating myelin antibodies through anti-idiotypic antibodies. It downregulates proinflammatory cytokines (eg, interferon gamma), blocks Fc receptors on macrophages, suppresses inducer T and B cells, and augments suppressor T cells. IVIg also blocks the complement cascade and promotes remyelination. In addition, it may increase IgG in cerebrospinal fluid.
Antineoplastics, Anti-CD20 Monoclonal Antibodies
Class Summary
Monoclonal antibodies are used to bind to specific antigens, thereby stimulating the immune system to target these antigens.
Rituximab (Rituxan, Rituximab-abbs, Truxima)
Rituximab is a monoclonal antibody directed against the CD20 antigen on B-lymphocytes. It is recommended as second-line therapy in immune tolerance induction regimens for patients with FVIII inhibitors, especially those with high inhibitor titers. This agent binds to, and mediates destruction of, B-cells, thereby decreasing production of FVIII inhibitors and autoimmunization.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli and inhibit the synthesis of tumor necrosis factor (TNF)-alpha, interleukin-2 (IL-2), IL-6, and interferon (IFN)-gamma. In addition, glucocorticoids modulate serum and leukocyte-bound levels of cell adhesion molecules.
Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol)
Methylprednisolone decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability. This agent is slightly more potent than prednisone; 4 mg of methylprednisolone is equivalent to 5 mg of prednisone.
Prednisolone (Orapred ODT, Millipred, Millipred DP)
Prednisolone decreases inflammation by suppressing migration of PMNs and reducing capillary permeability.
Antineoplastics, Alkylating
Class Summary
Cancer chemotherapy is based on an understanding of tumor cell growth and on how drugs affect this growth. After cells divide, they enter a period of growth (G1 phase), followed by DNA synthesis (S phase). The next phase is a premitotic phase (G2 phase), then finally a phase mitotic cell division (M phase).
Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant ones. This is partly the rationale for current cyclic dosage schedules.
Cyclophosphamide
Exerts its cytotoxic effect by alkylation of DNA, which leads to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.
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The workup of paraneoplastic cerebellar degeneration.
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MRI of a 29-year-old female with ARCA1. Sagittal T1 shows marked diffuse cerebellar atrophy with no atrophy of the cerebral cortex, midbrain, pons, or medulla. Image from National Institutes of Health.
Tables
Antibodies Predominantly Associated With PCD |
Predominant Syndrome |
Associated Cancer |
Anti-Yo (PCA-1) antibodies |
PCD |
Ovarian Breast cancers |
Anti-Tr antibodies |
PCD |
Hodgkin's lymphoma |
Anti-mGluR1 antibodies** |
PCD |
Hodgkin's lymphoma |
Anti-Zic4 antibodies† |
PCD |
Small-cell lung cancer |
Sometimes Associated With PCD |
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Anti-VGCC antibodies |
Eaton-Lambert syndrome, PCD |
Small-cell lung cancer Lymphoma |
Anti-Hu (ANNA-1) antibodies |
Encephalomyelitis, PCD, sensory neuronopathy |
Small-cell lung cancer Other cancers |
Anti-Ri (ANNA-2) antibodies |
PCD, brain-stem encephalitis, paraneoplastic opsoclonus-myoclonus |
Breast cancer Gynecologic cancer Small-cell lung cancer |
Anti-CV2/CRMPS antibodies |
Encephalomyelitis, PCD, chorea, peripheral neuropathy, uveitis |
Small-cell lung cancer Thymoma Other cancers |
Anti-Ma protein antibodies‡ |
Limbic, hypothalamic, brain-stem encephalitis (infrequently PCD) |
Testicular cancer Lung cancer Other cancers |
Anti-amphiphysin antibodies |
Stiff-person syndrome, encephalomyelitis, PCD |
Breast cancer Small-cell lung cancer |
*There is no uniform nomenclature for some of these antibodies; variant names appear in parentheses. mGluR1: metabotropic glutamate receptor 1, Zic4: zing finger of the cerebellum 4, and VCGG: voltage-gated calcium channel. **Anti-mGluR1 antibodies have been identified in only 2 patients. † Anti-Zic4 antibodies are predominantly associated with PCD only when no other paraneoplastic antibodies are detectable. ‡Ma proteins include Ma1 and Ma2. Patients with brain-stem and cerebellar dysfunction usually have antibodies against both MA1 and Ma2. |
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