Neurologic Complications of Systemic Diseases and Pregnancy
Which of the following statements is correct regarding neurologic involvement in patients with plasma cell dyscrasias and other hematologic disorders?
ExplanationC. The plasma cell dyscrasias include Waldenström macroglobulinemia (smoldering or symptomatic), monoclonal gammopathy of unknown significance (MGUS), multiple myeloma (smoldering or symptomatic), plasmacytomas (bone and extramedullary), primary amyloidosis, idiopathic Bence Jones proteinuria, among others. Neurologic complications of the plasma cell dyscrasias include a wide spectrum of manifestations. Neuropathy in patients with plasma cell dyscrasias can be due to infiltration of the peripheral nervous system by abnormal cells, amyloidosis, or a paraneoplastic syndrome. Infiltration of peripheral nerves would typically cause a sensorimotor predominantly axonal neuropathy. Infiltration of vertebral bodies can be extensive enough to lead to nerve root as well as spinal cord compression. Patients with plasma cell dyscrasias may develop encephalopathy due to hypercalcemia, hyperviscosity syndrome (due to hypergammaglobulinemia), and CNS infections, which such patients are prone to due to their immunocompromised state. Direct CNS involvement in plasma cell dyscrasias can occur but is relatively rare. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a constellation of abnormalities seen in some patients with plasma cell dyscrasias, particularly plasmacytoma, and not with leukemias. Question 3 depicts a patient with immunoglobulin M (IgM) monoclonal gammopathy associated with antibodies against myelin-associated glycoprotein (MAG). Patients with MGUS (which is characterized by the presence of a monoclonal protein in the absence of significant bone marrow involvement, anemia, renal failure, lytic lesions, or hypercalcemia) are at risk of developing symptomatic multiple myeloma. However, MGUS without evidence of other hematologic disorders can be associated with neuropathy. The neuropathy is often primarily demyelinating, and in some cases, particularly in patients with IgM MGUS, antibodies against MAG are detected in the serum. Neuropathy in patients with monoclonal proteinemias can also occur because of the presence of cryoglobulins. Cryoglobulins are serum protein complexes that precipitate at specific temperatures. They occur in a variety of conditions as follows: Type I cryoglobulins are isolated monoclonal proteins (usually IgM) seen in the monoclonal paraproteinemias such as multiple myeloma and Waldenström macroglobulinemia. Type II cryoglobulins are polyclonal immunocomplexes (formed by monoclonal IgM and IgG), usually seen in lymphoproliferative and autoimmune disorders, and Hepatitis C virus infection. Type III cryoglobulins are polyclonal immunocomplexes (formed by polyclonal IgM and IgG) seen with underlying infectious and autoimmune disorders (e.g., systemic lupus erythematosus and rheumatoid arthritis). The most common neuropathic complication of cryoglobulinemia is generalized neuropathy, although mononeuritis or mononeuritis multiplex and cerebral vasculitis with ischemic stroke can also occur. While Charcot–Marie–Tooth disease can present in adulthood, it is unlikely in the absence of family history or other evidence of a hereditary neuropathy on examination , and a costly genetic panel would not be of high yield. A technetium bone scan is not useful in investigating for the presence of bone lesions due to multiple myeloma (rather, plane film radiographs are used). Anti-GQ1b antibodies are typically seen in the Miller– Fisher variant of Guillain–Barré syndrome. Genetic abnormalities of superoxide dismutase are detected in some patients with familial amyotrophic lateral sclerosis which is not the diagnosis in this case.
