What is Anti-MAG Peripheral Neuropathy?
Anti-MAG peripheral neuropathy is a very rare disease, constituting perhaps 5% of CIDP-like disorders. Anti-MAG occurs when the body’s own immune system develops antibodies against a key glycoprotein (myelin-associated glycoprotein, or MAG). MAG is essential to maintaining a healthy peripheral nervous system.
The disorder is predominantly characterized by distal sensory loss in the extremities (hands and feet), a tingling sensation in the affected limbs, a mild to moderate tremor, and poor balance which can lead to difficulty walking. As the disease progresses, individuals develop some muscle weakness as well. Ninety percent of patients are male, and most of them are in their 50s or 60s.
Anti-MAG differs from CIDP in that it is not an inflammatory disease, and therefore typical CIDP treatments are usually only transiently effective in these patients.
What Causes Anti-MAG?
Myelin is an important part of the peripheral nervous system. It wraps around the nerve axon (the long, wire-like part of a nerve cell) much like insulation around an electrical wire. The nerves extend from the spinal cord to the rest of the body, stimulating muscle contraction and transmitting sensory information back to the nervous system receptors in the skin and joints. This insulation (myelin) allows electrical impulses to efficiently travel along the nerve axon. When myelin is damaged or removed, these electrical impulses are slowed or lost, and messages transmitted from the brain are disrupted and may never make it to their final destination.
MAG is a special type of glycoprotein that is found within the myelin sheath and in Schwann cells, which are the cells that are responsible for creating and maintaining myelin sheaths on nerve axons. It is thought that MAG plays a role in a signaling cascade that “turns on” the Schwann cells, leading to normal myelin production and healthy peripheral nerve activity.
In anti-MAG peripheral neuropathy, the body produces serum IgM antibodies that bind to MAG, preventing MAG from signaling the Schwann cells and myelin to do their job. This results in the loss of the nerves’ normal function, leading to problems in both sensory and motor function.
It is still unclear what causes the body to create anti-MAG antibodies in the first place. In about 98% of cases, the anti-MAG antibodies are the result of an abnormal expansion (increase in numbers) of a single antibody-producing cell. This condition is called monoclonal gammopathy. Monoclonal gammopathies are the irregular proteins produced by these cells. These proteins are called immunoglobulins and there are different types; Immunoglobulin G (IgG), IgA, IgM, IgD and IgE. In anti-MAG neuropathy the monoclonal gammopathy is IgM. Most monoclonal gammopathies are not associated with neuropathies or any other disease but occasionally they can be malignant. Your neurologist may refer you to a hematologist to rule out other diseases.
How is Anti-MAG Diagnosed?
Detecting anti-MAG neuropathy starts with identifying the symptoms of the patient:
- Sensory loss starting in toes in fingers
- Loss of vibration senses
- Unsteady gait
- Tremors in hands and legs
Diagnosis proceeds with a neurological examination. If the examination indicates that the patient has a peripheral neuropathy then testing for an IgM monoclonal gammopathy and electrodiagnostic testing is done. If the blood work and/or the EMG are appropriately abnormal then blood testing for anti-MAG neuropathy is done. Other blood work will be done to exclude another cause for the patient’s condition. Some patients will have an elevated protein in their cerebral-spinal fluid, which can be obtained through a spinal tap.
How is Anti-MAG Treated?
There are many therapeutic treatments that have been used for anti-MAG neuropathy. Most of these treatments are thought to reduce the levels of anti-MAG antibodies.
- Rituximab: One of the most promising treatment options, it is itself an antibody that binds to B- cells (cells that make antibodies) and removes them from the blood, cutting off the production of anti-MAG antibodies at the source. Studies have been inconclusive but there is a suggestion that most patients experience an increase in sensory and motor abilities within the first few months of therapy. However there is a risk that other infections and diseases could occur that would normally be prevented by an intact immune system. Usually this is not prescribed unless symptoms become severe.
- Cyclophosphamide: Cyclophosphamide is a drug often used in the treatment of lymphomas. It works by killing rapidly dividing cells such as antibody-producing B-cells, which in turn decreases antibody levels. This leads to significant improvements in people with anti-MAG neuropathy in relieving sensory loss and helping to improve quality of life in a few short months. There is, however, a long-term risk of cancer with chronic use of this treatment.
- IVIg (Intravenous Immunoglobulin): IVIg infusions help only a small segment of patients in the initial phase of the disease. It is not very effective in treating anti-MAG neuropathies.
- Steriods and plasma exchange treatments are not recommended for anti-MAG.
- Other agents that target lymphocytes and particularly B cells are considered on an individual basis. This is frequently done in collaboration with a hematologist.
Current immune therapies—while temporarily effective in some patients—are associated with considerable side effects which limit their prolonged use and efficacy. They should be reserved for patients impaired in their daily activities or for patients in a progressive phase of the disease.
Living with Anti-MAG
The progression of anti-MAG is slower and less severe than CIDP, and many patients continue living relatively normal lives while managing their symptoms with simple exercises or drug therapies. Usually, only 10 percent of patients become severely disabled and wheelchair-bound.