Sunday, April 22, 2007

Paraneoplastic syndromes involving the nervous system

Darnell R B and Posner JB. NEJM2003; 349:1543-54. Review article . Mechanisms of disease.

Authors discuss immune mediated diseases, affecting 0.01 percent of patients with cancer. However some are more common. LEMS affects 3 % of patients with small cell lung cancer, and mg affects 15 % of patients with thymoma, and demyelinating neuropathy affects 50 % of patients with sclerotic form of multiple myeloma (rare form).

Neurologic condition usually appears first, and cancer searches may be unrewarding, and whole body PET scan should be considered. CSF pleocytosis may dissipate but elevated IgG may persist. The predominant cell type is T cells.

Clinical conditions include
Limbic encephalitis
brain stem encephalitis
cerebrellar degeneration
visual syndromes ((cancer associated retinopathy and ON)
necrotizing myelopathy
inflammatory myelitis
motor neuron disease
subacute motor neuropathy
stiff person syndrome
sensory neuronopathy
autonomic neuropathy
acute sensorimotor neuropathy
polyradiculpathy (GBS)
brachial neuritis
chronic sensorimotor neuropathy
vasculitic neuropathy
myasthenia gravis
necrotizing myopathy

Antigens that are present do not cause neurologic disease unless they cross the blood brain barrier and react with neurons expressing the onconeural antigen.

patients with Hu antigens mayhave small cell lung cancer restricted to a nodule despite that most small cell lung cancers are metastatic at diagnosis. The prognosis of the cancer may also be better, even, eg. among patients with anti Hu antibodies who lack a paraneoplastic syndrome. T cells are critical elements of the response. They may be activated by apoptotic tumor cells. In a few conditions, antibody responses are more important, including LEMS, MG and a rare form of cerebellar degeneration. These forms have antigens that are cell surface receptors. Anti Sox antibodies are thought predictive of SCCL in LEMS

Immune treatments are widely used but not known to be effective. Keine-Guibert protocols IVIG .5 g/kg for five days, iv methylprednisolone at 1 g/d for 3 days and iv cyclophosphamide at 600 mg/m(2) of body surface area for one day on day 4. The treatment can be repeated if it appears effective, at 3 week intervals, or if prednisolone was effective, using one day per month of ivig/steroid/cytoxan together. Also used is tacrolimus, .15 mg/kg/d for 14 days, then .3 mg/kg for 7 days.

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