Contributed by Vanessa Tseng, MD, Elijah W. Stommel, MD, PhD, Dept of Neurology and Brent T. Harris, MD, PhD Dept of Pathology (Neuropathology) Dartmouth Medical School and Jayashri Srinivasan MBBS, PhD, Lahey Clinic
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Contributed by Vanessa Tseng, MD, Elijah W. Stommel, MD, PhD, Dept of Neurology and Brent T. Harris, MD, PhD Dept of Pathology (Neuropathology) Dartmouth Medical School and Jayashri Srinivasan MBBS, PhD, Lahey Clinic |
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DIAGNOSIS AND DISCUSSION:
Dx: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).
This is a report of two siblings with clinical and electrophysiologic features typical for an anti-MAG-associated demyelinating neuropathy. Although there are 3 reports of the familial association of monoclonal gammopathy and polyneuropathy, none were associated with the presence of anti-MAG antibodies (1-3). Genetic factors may also be operative in the development of monoclonal gammopathy, and multiple myeloma (4). Monoclonal gammopathies of unknown significance are identified in 3% of individuals over age 70 years and occur in 10% of patients with peripheral neuropathies of unknown etiology, although the association may be fortuitous (5). Up to 50% of patients with IgM monoclonal gammopathies develop polyneuropathy (5). Anti-MAG antibodies occur in patients with IgM kappa monoclonal gammopathy, although there are rare reports of the occurrence of anti-MAG antibodies without detectable monoclonal gammopathy. These antibodies are thought to have a pathophysiologic role; they intercalate within the layers of myelin leading to widening of lamellae and architectural derangement, resulting in demyelinating polyneuropathy (5).
Patients with CIDP who have monoclonal gammopathy (CIDP-MGUS) are distinct from classic CIDP (5). CIDP-MGUS patients tend to be males over 60 years, with a progressive, sensory-predominant demyelinating polyneuropathy. Immunomodulatory therapies are characteristically unsuccessful in these patients. Patients with anti-MAG antibodies and demyelinating neuropathy are a select subset of the CIDP-MGUS. On electrodiagnostic studies they have disproportionate distal slowing on nerve conduction studies. The anti-MAG syndrome does not respond to standard immunomodulating therapies including plasma exchange, intravenous immunoglobulin, corticosteroids or cyclophosphamide. Rituximab, a monoclonal antibody directed against the B cell surface membrane marker CD20, is well tolerated and early reports suggest that this may be a promising agent in the anti-MAG neuropathy syndrome, our experience to date is similar (6). We recommend evaluation for monoclonal gammopathy and anti-MAG antibodies in symptomatic relatives of patients with acquired demyelinating polyneuropathy.
References:
1. Busis NA, Halperin JJ, Stefansson K, Kwiatkowski DJ, et al. Peripheral neuropathy, high serum IgM, and paraproteinemia in mother and son. Neurology 1985;35:679-683.
2. Jensen TS, Schroder HD, Jonsson V, et al. IgM monoclonal gammopathy and neuropathy in two siblings. J Neurol Neurosurg Psychiatry 1988;51:1308-1315.
3. Manschot SM, Notermans NC, van den Berg LH, Verschuuren JJ, Lokhorst HM. Three families with polyneuropathy associated with monoclonal gammopathy. Arch Neurol 2000;57:740-742.
4. Grosbois B, Jego P, Attal M, et al. Familial multiple myeloma: report of fifteen families. Br J Haematol 1999;105:768-770.
5. Ropper AH, Gorson KC. Neuropathies associated with paraproteinemia. N Engl J Med 1998;338:1601-1607.
6. Pestronk A, Florence J, Miller T, Choksi R, Al-Lozi MT, Levine TD. Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry 2003;74:485-9.