Chapter 097. Paraneoplastic Neurologic Syndromes (Part 3)

Neuronal cell-surface antigens can be the target of antibodies in some patients with paraneoplastic encephalitis. A few of these antigens have been identified, including the NR1/NR2 subunits of NMDA receptors (Fig. 97-1) and voltage-gated potassium channels (VGKC). These disorders are more responsive to immunotherapy than those associated with immune responses to intracellular antigens.Figure 97-1Antibodies to NR1/NR2 subunits of the NMDA receptor in a patient with paraneoplastic encephalitis and ovarian teratoma. Panel A is a section of dentate gyrus of rat hippocampus immunolabeled (brown staining) with the patients antibodies. The reactivity predominates in the molecular layer, which is highly enriched...
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Chapter 097. Paraneoplastic Neurologic Syndromes (Part 3) Chapter 097. Paraneoplastic Neurologic Syndromes (Part 3) Neuronal cell-surface antigens can be the target of antibodies in somepatients with paraneoplastic encephalitis. A few of these antigens have beenidentified, including the NR1/NR2 subunits of NMDA receptors (Fig. 97-1) andvoltage-gated potassium channels (VGKC). These disorders are more responsiveto immunotherapy than those associated with immune responses to intracellularantigens. Figure 97-1 Antibodies to NR1/NR2 subunits of the NMDA receptor in a patientwith paraneoplastic encephalitis and ovarian teratoma. Panel A is a section ofdentate gyrus of rat hippocampus immunolabeled (brown staining) with thepatients antibodies. The reactivity predominates in the molecular layer, which ishighly enriched in dendritic processes. Panel B shows the antibody reactivity withcultures of rat hippocampal neurons; the intense green immunolabeling is due tothe antibodies against the NR1/NR2 subunits of NMDA receptors. Only four of the antibodies listed in Table 97-2 have been shown to play adirect pathogenic role in PNDs; all produce distinctive disorders of the peripheralnervous system. These are: antibodies to P/Q-type voltage-gated calcium channels(VGCC) in patients with the Lambert-Eaton myasthenic syndrome (LEMS);antibodies to acetylcholine receptors in patients with myasthenia gravis; antibodiesto VGKC in some patients with peripheral nerve hyperexcitability(neuromyotonia); and antibodies to ganglionic acetylcholine receptors in somepatients with autonomic neuropathy. Common features of these four antibodies arethat they target cell-surface molecules and that their passive transfer to animalsreproduces the disorders. Plasma exchange or immunomodulation withintravenous immunoglobulin (IVIg) usually produces neurologic improvement.Each of these disorders can occur without cancer, and therefore detection of theseantibodies does not predict the presence of cancer. Other PNDs are likely immune-mediated, although their antigens areunknown. These include several syndromes of inflammatory neuropathies andmyopathies. In addition, many patients with typical PND syndromes are antibody-negative. For still other PNDs, the cause remains quite obscure. These include,among others, several neuropathies that occur in the terminal stages of cancer anda number of neuropathies associated with plasma cell dyscrasias or lymphomawithout evidence of inflammatory infiltrates or deposits of immunoglobulin,cryoglobulin, or amyloid. Approach to the Patient: Paraneoplastic Neurologic Disorders The diagnosis and management of PNDs may be difficult for severalreasons. First, it is common for symptoms to appear before the presence of a tumoris known. Second, the neurologic syndrome can evolve in a rapidly progressivefashion, producing a severe and usually irreversible neurologic deficit in a shortperiod of time. There is evidence that prompt tumor control improves the course ofPNDs. Therefore, the major concern of the physician is to recognize a disorderpromptly as paraneoplastic in order to identify and treat the tumor.