Neurologic aspects of plasma cell disorders

Plasma cell disorders make up a broad spectrum of diseases that are characterized by the appearance of an abnormal clone of plasma cells, which typically manifests as a production of monoclonal immunoglobulin protein (monoclonal gammopathy). The overproduction of plasma cells and subsequent monoclonal gammopathy may be malignant or a premalignant process. Monoclonal gammopathy of undetermined significance (MGUS) is an example of a benign process with a malignant potential. Multiple myeloma, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, and AL amyloidosis (immunoglobulin light chain amyloidosis) are examples of malignant plasma cell disorders which require treatment. Neurologic manifestations of an underlying plasma cell disorder can be variable and typically challenging to treat. They can range from mild symptoms resulting from therapy to treat the disorder to clinically significant and life-threatening complications related to the disease itself. The peripheral nervous system is more commonly affected than the central nervous system. Peripheral neuropathy is a frequent manifestation and is associated with all of the plasma cell disorders (MGUS, multiple myeloma, POEMS syndrome, Waldenström macroglobulinemia and AL amyloidosis) with notable differences in the signs and symptoms among the different groups. Examples of central nervous system manifestations include spinal cord pathology, such as spinal cord compression from vertebral collapse or plasmacytoma. Intracranial involvement is rare but can occur from brain parenchyma infiltration, leptomeningeal involvement, and tumor-like lesions, such as amyloidoma in AL amyloidosis and plasmacytoma in multiple myeloma. Encephalopathy can occur due to metabolic disturbances related to the underlying plasma cell disorder, including hypercalcemia and uremia in multiple myeloma and hyperviscosity in Waldenström macroglobulinemia. Included in this chapter is a detailed discussion of the various plasma cell disorders and their spectrum of neurologic manifestations.