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Paraneoplastic autoimmune neurological disorders reflect a patient's humoral and cellular immune responses to cancer. The cancer may be new or recurrent, is usually limited in metastatic volume, and is often occult by standard imaging procedures. Autoantibodies specific for onconeural proteins found in the plasma membrane, cytoplasm, and nucleus of neurons or muscle are generated in this immune response, and serve as serological markers of paraneoplastic autoimmunity. The most commonly recognized cancers in this context are small-cell lung carcinoma (SCLC), thymoma, ovarian (or related mullerian) carcinoma, breast carcinoma, and Hodgkin's lymphoma. Pertinent childhood neoplasms recognized thus far include neuroblastoma, thymoma, Hodgkin's lymphoma, and chondroblastoma. An individual patient's autoantibody profile can predict a specific neoplasm with 90% certainty, but not the neurological syndrome.
Three classes of autoantibodies are recognized in the spinal fluid analysis:
-Neuronal nuclear (antineuronal nuclear antibody-type 1 [ANNA-1], ANNA-2, ANNA-3)
-Neuronal and muscle cytoplasmic (Purkinje cell cytoplasmic antibody, type 1 [PCA-1]; PCA-2; PCA-Tr, CRMP-5, and amphiphysin)
-Glial nuclear (anti-glial nuclear antibody: AGNA)
Seropositive patients usually present with subacute neurological symptoms and signs. The patient may present with encephalopathy, cerebellar ataxia, myelopathy, radiculopathy, plexopathy, sensory, sensorimotor, or autonomic neuropathy, with or without coexisting evidence of a neuromuscular transmission disorder: Lambert-Eaton syndrome (LES), myasthenia gravis, or neuromuscular hyperexcitability. Initial signs may be subtle, but a subacute multifocal and progressive syndrome usually evolves. Sensorimotor neuropathy and cerebellar ataxia are common presentations, but the clinical picture in some patients is dominated by striking gastrointestinal dysmotility, limbic encephalopathy, basal ganglionitis, or cranial neuropathy (especially loss of vision, hearing, smell, or taste). Cancer risk factors include past or family history of cancer, history of smoking, or social/environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favor less neurological morbidity and offer the best hope for survival.
Monitoring patients who have previously tested positive for 1 or more antibodies in a Neuroimmunology Laboratory evaluation
Antibodies directed at onconeural proteins shared by neurons, muscle, and certain cancers are valuable serological markers of a patient's immune response to cancer. They are not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs. Several autoantibodies have a syndromic association, but no known autoantibodies predicts a specific neurological syndrome. Conversely, a positive autoantibody profile has 80% to 90% predictive value for a specific cancer. It is not uncommon for more than 1 paraneoplastic autoantibodies to be detected, each predictive of the same cancer.
This test should only be utilized when the presence of paraneoplastic autoantibodies has been previously documented.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Antibody-Type 1 (ANNA-1)
Antineuronal Nuclear Antibody-Type 2 (ANNA-2)
Antineuronal Nuclear Antibody-Type 3 (ANNA-3)
Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)
NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES
Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)
Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)
Purkinje Cell Cytoplasmic Antibody, Type TR (PCA-TR)
Collapsin Response-Mediator Protein-5 Neuronal (CRMP-5-IGG)
AMPA-RECEPTOR ANTIBODY BY CBA
GABA-B-RECEPTOR ANTIBODY BY CBA
NMDA-RECEPTOR ANTIBODY BY CBA
Neuronal Voltage-Gated Potassium Channel-Complex Autoantibody
< or =0.02 nmol/L
Paraneoplastic Autoantibody, Western Blot Confirmation
Collapsin Response-Mediator Protein-5-IGG (CRMP-5-IGG) Western Blot
Amphiphysin Antibody Western Blot