Chapter 097. Paraneoplastic Neurologic Syndromes (Part 3) doc

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 97-1 Antibodies 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 patient's antibodies. The reactivity predominates in the molecular layer, which is highly enriched in dendritic processes. Panel B shows the antibody reactivi ty with cultures of rat hippocampal neurons; the intense green immunolabeling is due to the antibodies against the NR1/NR2 subunits of NMDA receptors. Only four of the antibodies listed in Table 97-2 have been shown to play a direct pathogenic role in PNDs; all produce distinctive disorders of the peripheral nervous 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; antibodies to VGKC in some patients with peripheral nerve hyperexcitability (neuromyotonia); and antibodies to ganglionic acetylcholine receptors in some patients with autonomic neuropathy. Common features of these four antibodies are that they target cell-surface molecules and that their passive transfer to animals reproduces the disorders. Plasma exchange or immunomodulation with intravenous immunoglobulin (IVIg) usually produces neurologic improvement. Each of these disorders can occur without cancer, and therefore detection of these antibodies does not predict the presence of cancer. Other PNDs are likely immune-mediated, although their antigens are unknown. These include several syndromes of inflammatory neuropathies and myopathies. 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 and a number of neuropathies associated with plasma cell dyscrasias or lymphoma without 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 several reasons. First, it is common for symptoms to appear before the presence of a tumor is known. Second, the neurologic syndrome can evolve in a rapidly progressive fashion, producing a severe and usually irreversible neurologic deficit in a short period of time. There is evidence that prompt tumor control improves the course of PNDs. Therefore, the major concern of the physician is to recognize a disorder promptly as paraneoplastic in order to identify and treat the tumor. . Chapter 097. Paraneoplastic Neurologic Syndromes (Part 3) Neuronal cell-surface antigens can be the target of antibodies in some patients with paraneoplastic encephalitis antigens are unknown. These include several syndromes of inflammatory neuropathies and myopathies. In addition, many patients with typical PND syndromes are antibody- negative. For still other. 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 several