Approach Considerations
Two approaches can be used to treat paraneoplastic neurologic syndrome. The first treatment is directed toward the underlying tumor, while the second approach is toward the autoimmune disease causing the cerebellar dysfunction.
Since neurologic paraneoplastic syndromes are immune-mediated, 2 distinct approaches to therapy have been reported: removal of the antigen source by treatment of the underlying tumors and suppression of the immune response. Immunosuppression can be beneficial for some conditions. [27]
Medical Care
Paraneoplastic syndromes are a therapeutic challenge for the neurologist, and treatment of paraneoplastic syndromes is generally unsatisfactory.
Early tumor detection and treatment with resection, sometimes the addition of chemotherapy, should be the primary objective in these patients.
The response of the paraneoplastic neurologic syndromes to immunosuppressive agents or antitumor treatment is influenced greatly by the underlying neuropathology
The effect of the combination of intravenous immunoglobulins (IVIG), cyclophosphamide, and methylprednisolone on the clinical course of patients with paraneoplastic neurologic syndrome or paraneoplastic cerebellar degeneration and antineuronal antibodies is poor. This may be partly due to T-cell involvement in the cerebellar damage. However, due to the severe disability of the condition and the presence of some positive responders found in the literature, it is reasonable to trial a course of immunotherapy in an attempt to reduce morbidity.
Some reports indicate partial or complete remission of cerebellar symptoms after treating the primary neoplasm. This has been observed only in small-cell carcinomas and is not reported in gynecologic malignancies.
In a minority of patients who are not disabled severely at the onset of treatment, a transient stabilization is possible if the tumor is appropriately treated.
After review of the current literature regarding immune-mediated cerebellar ataxias, Hiroshi et al have proposed the following treatment strategy for paraneoplastic cerebellar degeneration. [48]
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Immediate attention to the treatment of neoplasm should be the first objective of treatment.
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Immediate induction of immunotherapy using corticosteroids (intravenous methylprednisolone or oral prednisolone), IVIg, plasmapheresis, immunosuppressants, or rituximab, either alone or in different combinations. There are no significant differences in the response to these types of immunotherapies.
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The anti-neoplasm therapies and immunotherapies have no benefits in most cases, with a relatively short median survival time (10.2 to 43 months), although retrospective studies on a few responders have identified some prognostic factors (for example, anti-Tr or anti-Ro antibody).
Surgical Care
Surgical care is required for patients who undergo tumor resection.
Consultations
A team approach is required in treating patients with paraneoplastic cerebellar degeneration.
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Neurologic consultation is needed for basic workup and to exclude other possible causes of cerebellar dysfunction.
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Oncology consultation is needed for tumor workup and treatment protocols.
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Surgical consultation is needed in patients for whom tumor resection is recommended.
Diet
The patient may require nutritional support in severe cases of nausea and vomiting.
Activity
Patients with severe cerebellar dysfunction are at high risk of falls and thus fall precautions must be taken, which may limit patient activity.
Most patients require assistance with ambulation and many progress to become wheelchair-bound.
Long-Term Monitoring
Long-term surveillance is necessary in patients without an identified underlying mailignancy.
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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 |
|
|
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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