Waldenstrom's and Neuropathy
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: Symptoms and signs of polyneuropathy are common (47%) in patients with Waldenstrom's macroglobulinemia.
Source: Levine T, et al. Peripheral Neuropathies in Waldenstrom's Macroglobulinemia. J Neurol Neurosurg Psychiatry. 2006;77;224-228.
At the 2003 international waldenstrom's Macroglobulinemia (WM) Foundation meeting, 119 patients with WM were examined and compared to 58 controls to determine the prevalence, clinical, and laboratory features of polyneuropathy in WM. All WM patients demonstrated monoclonal serum IgM immunoglobulin (IgM M-protein), and none had myeloma, other lymphoma, or monoclonal gammopathy of undetermined significance. Patients and controls all underwent neurological examination and electrodiagnostic studies by blinded, board-certified, neurologists. Vibration sensation was quantified using a graduated Rydel-Seiffer 64 Hz tuning fork, and strength was graded using the Medical Research Council scale. Nerve conduction studies included unilateral tibial motor and sural sensory examination, with extension of the study as appropriate if the initial findings were abnormal, allowing for classification of patients into axonal or demyelinating neuropathy categories. Serum M-proteins were studied for binding to antigens, including myelin associated glycoprotein (MAG) and sulphatide, using ELISA and Western blot techniques. Fisher's exact, chi-square, 2-sided Wilcoxon signed ranks or t tests were used for statistical analysis.
Polyneuropathy was significantly more common in WM patients compared to controls, with pain, burning, paresthesias, and/or sensory loss in the legs found in 47% of the WM patients vs. 9% of the controls (p<0.001). Quantitative vibratory score was 35% lower in the toes and fingers, pinprick sensation was 3.4 fold lower in the distal legs, and tandem gait abnormalities 5.5 fold more common in WM. No difference in deep tendon reflexes, toe strength, or joint position was found between controls and the WM group without demyelinating features on nerve conduction studies. WM patients with sulphatide-binding IgM antibody (5% of all WM) demonstrated axonal polyneuropathy, those binding MAG (4% of all WM) had mixed axonal and demyelinating sensorimotor neuropathy, and both groups demonstrating more severe sensory axonopathy than other WM patients. In the absence of MAG IgM binding, 4% had demyelinating neuropathy. Sensory neuropathy is frequent in WM, is associated with gait ataxia, and is more frequent and severe in the presence of serum anti-MAG or anti-sulphatide antibodies.
Commentary
First described in 1944, Waldenstrom's macroglobulinemia is a disease of elderly men, usually Caucasian, presenting with weakness, fatigue, lymphadenopathy and splenomegaly. Neurologic complications occur in 20%, generally related to a hyperviscosity syndrome. Usually involving the peripheral nervous system and presenting as peripheral polyneuropathy, WM may also affect the central nervous system, and is then referred to as the Bing-Neel syndrome. CNS presentations include multifocal leukoencephalopathy, sudden sensorineural deafness, headache, or impaired mental status. Recently, slowly progressive myelopathy due to WM has also been reported (Liberato B, et al. J Neurooncol. 2003;63;207-211). Pathology is characterized by perivascular and leptomeningeal lymphoplasmacytoid infiltrates. Treatment for this B-cell disorder includes chlorambucil, corticosteroids, cyclophosphamide, alkylating agents, gamma globulin, and plasmapheresis. Rituximab (Rituxan), a recently developed anti-CD20 antibody, has also shown promise (Welch D, et al. Arch Pathol Lab Med. 2002:126:1243-1244).
Symptoms and signs of polyneuropathy are common (47%) in patients with Waldenstrom's macroglobulinemia.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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