Paraneoplastic neurologic disorders (PNDs) are cancer-related syndromes that can affect any part of the nervous system; caused by mechanisms other than metastasis or by complications of cancer such as coagulopathy, stroke, metabolic and nutritional conditions, infections, and side effects of cancer therapy. In 60% of pts the neurologic symptoms precede cancer diagnosis. PNDs occur in 0.5–1% of all cancer pts, but they occur in 2–3% of pts with neuroblastoma or small cell lung cancer (SCLC), and in 30–50% of pts with thymoma or sclerotic myeloma.
Recognition of a distinctive paraneoplastic syndrome (Table 79-1) should prompt a search for cancer, because treatment of tumor may improve the course of PNDs; many of these disorders also occur without cancer. Diagnosis is based on the clinical pattern, exclusion of other cancer-related disorders, confirmatory serum or CSF antibodies, or occasionally electrodiagnostic testing. Most PNDs are mediated by immune responses triggered by neuronal proteins expressed by tumors. PNDs associated with immune responses against intracellular antigens often respond poorly to treatment (Table 79-2), whereas those associated with antibodies to synaptic or neuronal cell surface proteins are more responsive to immunotherapy (Table 79-3). For any type of PND, if antibody testing is negative, the diagnosis rests on the demonstration of cancer and the exclusion of other cancer-related or independent disorders. Combined whole-body CT and PET scans often uncover tumors undetected by other tests.
MRI and CSF studies are important to rule out neurologic complications due to direct spread of cancer. In most PNDs the MRI findings are nonspecific. CSF findings typically consist of mild to moderate pleocytosis (<200 mononuclear cells, predominantly lymphocytes), an increase in the protein concentration, and a variable presence of oligoclonal bands.
TABLE 79-1Paraneoplastic Syndromes of the Nervous System ||Download (.pdf) TABLE 79-1Paraneoplastic Syndromes of the Nervous System
|CLASSIC SYNDROMES: USUALLY OCCUR WITH CANCER ASSOCIATION ||NONCLASSIC SYNDROMES: MAY OCCUR WITH AND WITHOUT CANCER ASSOCIATION |
Cerebellar degeneration (adults)
Subacute sensory neuronopathy
Gastrointestinal paresis or pseudo-obstruction
Lambert-Eaton myasthenic syndrome
Cancer- or melanoma-associated retinopathy
Progressive encephalomyelitis with rigidity and myoclonus
Motor neuron disease
Subacute and chronic mixed sensory-motor neuropathies
Neuropathy associated with plasma cell dyscrasias and lymphoma
Vasculitis of nerve
Pure autonomic neuropathy
Acute necrotizing myopathy
Peripheral nerve hyperexcitability (neuromyotonia)
TABLE 79-2Antibodies to Intracellular Antigens, Syndromes, and Associated Cancers ||Download (.pdf) TABLE 79-2Antibodies to Intracellular Antigens, Syndromes, and Associated Cancers
|ANTIBODY ||ASSOCIATED NEUROLOGIC SYNDROME(S) ||TUMORS |
|Anti-Hu (ANNA1) ||Encephalomyelitis, subacute sensory neuronopathy ||SCLC |
|Anti-Yo (PCA1) ||Cerebellar degeneration ||Ovary, breast |
|Anti-Ri (ANNA2) ||Cerebellar degeneration, opsoclonus, brainstem encephalitis ||Breast, gynecologic, SCLC |
|Anti-CRMP5 (CV2) ||Encephalomyelitis, chorea, optic neuritis, uveitis, peripheral neuropathy ||SCLC, ...|