Diagnosis: distal acquired demyelinating symmetric (DADS) neuropathy; i.e. demyelinating neuropathy secondary to IgM paraprotein + myelin associated glycoprotein (MAG) antibodies.
There was seropositivity to myelin associated glycoprotein (MAG) and sulfatide antibodies.
An IgM paraprotein is detected in about 5-10% of patients with otherwise unexplained polyneuropathy, about 40–70 % of which are seropositive to MAG 1. MAG is highly expressed in the CNS but is present only in small amounts in the peripheral nerves. It has however been suggested that the pathogenicity of anti-MAG antibodies could arise from their reactivity to a peripheral nervous system specific glycolipid, SGPG 2. Anti- MAG related neuropathy is clinically a predominant sensory neuropathy with sensory ataxia and impaired gait; motor deficits are rather distal and mild, specially early in the course. The diagnosis is made based on the findings of the nerve conduction studies, the presence of IgM paraprotein and seropositivity to MAG antibodies. CSF protein is typically increased (up to 250 mg/dl), but CSF studies are often not necessary. Although this patient had a sensory neuropathy from the clinical standpoint, the nerve conduction study provided evidence for a primarily demyelinating neuropathy which affected the motor nerves as well. Significantly prolonged distal latencies (i.e. more severe demyelination in the distal portion of the nerves compared to the proximal sections of the nerves) and lack of conduction blocks argue against a typical chronic inflammatory demyelinating polyneuropathy (CIDP). Kaku, et al. suggested that a disproportionate prolongation of distal latency, as indicated by a terminal distal latency (TDL) < 0.25 is predictive of demyelinating neuropathy associated anti -MAG and IgM paraproteinemia, rather than CIDP or Charcot Marie Tooth type 1A 3. Subsequently, the term DADS neuropathy was applied to these patients as part of CIDP spectrum 4. As anti-MAG related neuropathy is usually refractory to immunosuppressive treatment, such treatments are not recommended in patients with mild and slowly progressive sensory symptoms. A number of medications including intravenous immunoglobulin, plasma exchange, and immunosuppressants such as cyclophosphamide , fludarabine, and rituximab (most promising) have been tried in more severe cases (reviewed in 2).
References:
1. Kuijf ML, Eurelings M, Tio-Gillen AP, van Doorn PA, van den Berg LH, Hooijkaas H, Stork J, Notermans NC, Jacobs BC. Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonal gammopathy. Neurology 2009;73(9):688-695.
2. Dalakas MC. Pathogenesis and Treatment of Anti-MAG Neuropathy. Current treatment options in neurology 2010;12(2):71-83.
3. Kaku DA, England JD, Sumner AJ. Distal accentuation of conduction slowing in polyneuropathy associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside. Brain : a journal of neurology 1994;117 ( Pt 5):941-947.
4. Katz JS, Saperstein DS, Gronseth G, Amato AA, Barohn RJ. Distal acquired demyelinating symmetric neuropathy. Neurology 2000;54(3):615-620.