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 ha
Trang 1Chapter 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
Trang 3Antibodies 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 reactivity 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
Trang 4Each 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