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“Ask the Doctor” Column: Anti-MAG Peripheral Neuropathy

This is a column in which leading clinicians answer your questions about neuropathy – usually one question per issue, and more when we are able. Please send your questions to “Ask the Doctor” c/o Neuropathy News, The Neuropathy Association, 60 East 42nd Street, Suite 942, New York, NY 10165.

DEAR DOCTOR: I am a 65 year-old woman, and I’ve gradually, over the past three years, developed a slight tremor in my hands, numbness in my feet and hands, and difficulty walking. I could easily fall, but I don’t because I walk with caution. My doctor tells me that my walking problems are mainly due to “numb feet” and lack of “proprioception” (or the sense of position). My doctor does not think I have muscle weakness.

My nerve conduction study shows “very prolonged distal latencies of motor nerves and absence of sensory responses,” and my blood tests show “high titers of anti-MAG antibodies.” I was diagnosed with anti-MAG peripheral neuropathy, and I am being treated with intravenous immunoglobulin (IVIg). IVIg has improved some of my symptoms (mainly intermittent shooting pains in my legs and arms), but I do not think it has, overall, helped a lot. What is anti-MAG peripheral neuropathy and how is it treated? - J.D.

DR. KSENIJA KOS ANSWERS: J.D., anti-myelin associated glycoprotein (anti-MAG) peripheral neuropathy is an immune-mediated demyelinating peripheral neuropathy wherein the body’s immune system produces antibodies that attack specific proteins, called myelin associated glycoprotein (anti-MAG), located in the neuron’s myelin sheath. Myelin associated glycoproteins are proteins produced by Schwann cells in the peripheral nervous system and are responsible for maintaining the integrity and formation of myelin. When the body’s immune system produces anti-MAG antibodies, they attack MAG and disrupt its function, consequently leading to the destruction of myelin and causing peripheral neuropathy.

The symptoms of anti-MAG neuropathy are predominantly sensory, but patients can also develop motor symptoms. Most patients present with sensory loss starting in toes and fingers, loss of vibration sense, and proprioception causing sensory ataxia (or an unsteady gait). They can also develop tremors in the hands more than the legs. As the disease progresses, the tremors can become more severe, sensory loss can progress to the hands and legs, and muscle weakness and atrophy can also develop. Ninety percent of patients are male, and most of them are in their 50s or 60s. Usually, only 10 percent of patients become severely disabled and wheelchair-bound.

The neurologist will confirm the diagnosis of anti-MAG peripheral neuropathy based on the history of symptoms, a complete neurological examination, blood tests for detection of IgM monoclonal gammopathy and anti-MAG IgM antibodies, and electrodiagnostic studies (nerve conduction study and electromyogram). Nerve and muscle biopsies are not necessary for confirming the diagnosis. Some patients may also have a coexisting disorder—Waldenström’s macroglobulinemia—characterized by enlargement of the liver and spleen, a low blood count, nose bleeding, and overproduction of an abnormal protein called monoclonal immunoglobulin M antibody (IgM).

Treatments are directed at modulating the immune system and lowering the patient’s serum IgM level. They include: plasma exchange, IVIg, corticosteroids, chlorambucil, cyclophosphamide, cladribine, fludarabine, alpha-interferon, and rituximab (either by itself or in combination with a chemotherapeutic agent). Approximately half of the patients initially experience transient improvement in symptoms when treated with the above mentioned medications, but long-term benefits are limited.

Intravenous immunoglobulin (IVIg) infusions help—to a limit—a small segment of patients in the initial phase of treatment. However, the most promising therapy for anti-MAG neuropathy to this date is rituximab, a therapeutic monoclonal antibody that reacts with and kills B cells (the producers of anti-MAG antibodies). Studies show that rituximab is effective in treating anti-MAG neuropathies, and it causes marked improvement in sensory and motor functions within the first few months of therapy. However, the effects of long-term treatment with rituximab are still unknown, and as with most immunosuppressive medications, there is a risk of infections, in particular progressive multifocal leukoencephalopathy (PML). Patients receiving rituximab should be monitored closely for—and requested to report—signs of PML (e.g., major vision changes, unusual eye movements, loss of balance or coordination, disorientation, confusion, or other neurological symptoms).

Because many patients with anti-MAG peripheral neuropathy have a favorable prognosis even over extended periods, and because current immune therapies—while temporarily effective in half of the patients—are associated with considerable side effects which limit their prolonged use and efficacy, they should probably be reserved for patients impaired in their daily life or for patients in a progressive phase of the disease.

Ksenija Kos, M.D. is a neurologist/neuromuscular specialist at St. John’s Mercy Medical Center (St. Louis, Missouri). Dr. Kos completed her neurology residency and her neuromuscular fellowship at Washington University St. Louis (Missouri).

 

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