Última actualización:
November 20, 2018
Años publicados: 2018
NORD gratefully acknowledges Dale J. Lange, MD, FAAN, FANA, Chair, Department of Neurology, Neurologist in Chief, Hospital For Special Surgery; Professor of Neurology, Weill Cornell Medicine, for assistance in the preparation of this report.
Multifocal motor neuropathy is a rare disorder characterized by slowly progressive muscle weakness, primarily of the arms and legs. The disorder is considered to be immune-mediated, which means there is inflammation resulting from abnormal functioning of the immune system and the presence of specific autoantibodies that target a specific protein in the body. Other symptoms including muscles cramps and wasting (atrophy) of muscles can also occur. The term multifocal means arising from two or more spots. The term motor refers to the motor nerves, which are those that carry nerve impulses from the brain to the muscles. The exact, underlying cause of this disorder is not fully understood. The disorder is acquired at some point during a person’s life; a person is not born with the disorder. Multifocal motor neuropathy usually responds to treatment with intravenous immunoglobulin.
Multifocal motor neuropathy is a progressive disorder, this means that the signs and symptoms tend to worsen slowly over time. The main symptom is progressive muscle weakness of the arms and legs. Unlike other neurological disorders affecting the arms and legs, there usually is not any sensory deficits. This means that feelings of tingling or numbness or pain are not associated with the disorder. Muscle weakness often begins in the hands, causing hand weakness and affected individuals may drop objects frequently or have difficulty performing tasks that require fine motor skills such as turning a key in a lock. Fine motor skills are those that require small movements involving the hands and wrists. Some individuals have trouble extending or bending their wrist upward (wrist drop). Reduced grip strength of the hands and reduced dexterity of the hands is seen. Sometimes, muscle weakness starts in the legs. There may be reduced mobility of the toes and foot drop may be early signs. Foot drop occurs when weakness of the muscles involving in lifting the food cause the foot to drop or drag when attempting to walk.
As muscle weakness progresses, severe fatigue in the affected muscles may be seen and the disorder will cause functional disability. Affected individuals may have limited endurance. The muscles on one side of the body that are affected may be different from the muscle affected on the other side of the body (asymmetrical muscle weakness).
Additional symptoms associated with multifocal motor neuropathy include cramping, involuntary muscle contractions or “twitches” (fasciculations), decreased muscle tone, and, sometimes absent deep tendon reflexes. Later in the progression of the disease, wasting (atrophy) of the affected muscles may occur.
Other muscles such as those affecting breathing are unaffected and the disorder usually does not affect life expectancy.
The exact, underlying cause of multifocal motor neuropathy is not fully understood. The disorder is believed to be caused by or related to an abnormal response of the immune system. The immune system is the body’s natural defense system against foreign or invading organisms or substances. The immune system is a complex network of cells, tissues, organs, and proteins that work together to keep the body healthy. Conduction block affecting the motor nerves is a characteristic finding of the disorder. Motor nerves are those that carry nerve impulses from the brain to the muscles. Conduction block is when a nerve impulse does not travel all the way down the nerve and are not carried along properly to the muscles. Multiple motor nerves are damaged by this disorder, although the exact reason is not fully understood. Researchers believe that conduction block in multifocal motor neuropathy is reversible.
Affected individuals have autoantibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Autoantibodies are ones that mistakenly attack healthy tissue. Many individuals (30-60%) with multifocal motor neuropathy have autoantibodies that target GM 1 ganglioside, a fatty material (lipid) found within the peripheral nerves. The peripheral nerves are the nerves found outside the central nervous system and include the nerves of the arms and legs. Researchers do not know if these autoantibodies play a role in the development of this disorder or are a byproduct of the disorder. More research is necessary to determine what role, if any, antibodies to GM 1 ganglioside play in the development of multifocal motor neuropathy.
Multifocal motor neuropathy affects both men and women, although men are more frequently affected than women by a ratio of about 2.7:1. Men also tend to be diagnosed at a younger age. The median age of onset is 40 years old, although the disorder has been reported individuals ranging from 20-80 years of age. In a handful of instances, the disorder has occurred in children (pediatric cases). Multifocal motor neuropathy is estimated to affect about 0.6 per 100,000 in the general population. Because rare disorders often go undiagnosed or misdiagnosed, determining their true frequency in the general population is difficult.
A diagnosis of multifocal motor neuropathy is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Asymmetrical muscle weakness without sensory problems (e.g. numbness, tingling, etc.) are the main signs of multifocal motor neuropathy. Diagnostic criteria for this disorder have been proposed by several groups. One set of guidelines (Van Schaik IN, 2010) is published by the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS).
Clinical Testing and Workup
A diagnosis of multifocal motor neuropathy can be supported by nerve conduction studies. Nerve conduction studies determine the ability of specific nerves in the peripheral nervous system to relay nerve impulses to the brain. During a nerve conduction study, electrodes are placed over specific nerves such as those of the shoulders and arms. The electrodes stimulate the nerves and record the conduction of the signal. This test can help to pinpoint the site of disease or injury to the nerve. These studies can show loss of myelin (demyelination) and conduction block.
Electromyography is another test that may aid in the diagnosis. During an electromyography, a tiny needle electrode is inserted through the skin into an affected muscle. The electrode records the electrical activity of the muscle. This record shows how well a muscle responds to nerve activation and can help determine whether muscle weakness is caused by the muscles themselves or by the nerves that control those muscles.
Laboratory blood tests may be done to detect antibodies to GM1 ganglioside. However, not every affected individual has these antibodies and a negative result does not exclude the disorder.
The treatment of multifocal motor neuropathy may require the coordinated efforts of a team of specialists. General internists, specialists in diagnosing and treating disorders of the central nervous system and brain (neurologists), specialists in diagnosing and treating disorders of the immune system (immunologists), specialists in diagnosing and treating disorders of the skeleton and muscles (orthopedists), and other healthcare professionals may need to systematically and comprehensively plan treatment. Physical therapy to strengthen muscles may be of benefit to some individuals.
In 2012, the U.S. Food and Drug Administration (FDA) approved Gammagard Liquid 10% for the treatment of multifocal motor neuropathy. This medication is an intravenous immunoglobulin (IVIg) and most affected individuals respond to treatment with IVIg. There is usually a rapid improvement in muscle weakness when treated is started. The effects eventually wear off and affected individuals with need to take the medication again every 2-6 weeks (maintenance therapy). Sometimes, affected individuals become less response to the medication and will require higher doses or more frequent maintenance therapy.
If affected individuals do not respond to treatment with IVIg or stop responding to this therapy, then other medications can be tried.
Various other medications have been tried to treat multifocal motor neuropathy including cyclophosphamide, which has shown some effectiveness in some reports, but also some toxicity. Rituximab, beta-interferon, mycophenolate mofetil, cyclosporine, azathioprine, and infliximab have also been tried. More research is necessary to determine the long-term safety and effectiveness of these therapies for the treatment of multifocal motor neuropathy.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOK
Schaik IN, Leger LM, Nobile-Orazio E, et al. Multifocal Motor Neuropathy. In: European Handbook of Neurological Management: Volume 1, 2nd ed., Gilhus NE, Barnes MP, Brainin M, editors. 2011;Blackwell Publishing Ltd, Oxford, UK. Pp. 343-350.
https://www.eaneurology.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Multifocal_motor_neuropathy.pdf
JOURNAL ARTICLES
Kumar A, Patwa HS, Nowak RJ. Immunoglobulin therapy in the treatment of multifocal motor neuropathy. J Neurol Sci. 2017;375:190-197. https://www.ncbi.nlm.nih.gov/pubmed/28320129
Philibert M, Grapperon AM, Delmont E, Attarian S. Monitoring the short-term effect of intravenous immunoglobulins in multifocal motor neuropathy using motor unit number index. Clin Neurophysiol. 2017;128:235-240. https://www.ncbi.nlm.nih.gov/pubmed/27988478
Tobon A. The role of immunoglobulin in the treatment of immune-mediated peripheral neuropathies. J Infus Nurs. 2017;40:375-379. https://www.ncbi.nlm.nih.gov/pubmed/29112586
Stangel R, Gold R, Pittrow D, et al. Treatment of patients with multifocal motor neuropathy with immunoglobulins in clinical practice: the SIGNS registry. Ther Adv Neurol Disord. 2016;9:165-179. https://www.ncbi.nlm.nih.gov/pubmed/27134672
Ishigaki H, Hiraide T, Miyagi Y, et al. Childhood-onset multifocal motor neuropathy with immunoglobulin M antibodies to gangliosides GM1 and GM2: a case report and review of the literature. Pediatr Neurol. 2016;62:51-57. https://www.ncbi.nlm.nih.gov/pubmed/27400822
Lawson VH, Arnold WD. Multifocal motor neuropathy: a review of pathogenesis, diagnosis, and treatment. Neuropsychiatr Dis Treat. 2014;10:567-576. https://www.ncbi.nlm.nih.gov/pubmed/24741315
Van Asseldonk JT, Franssen H, Van den Berg-Vos RM, Wokke JH, Van den Berg LH. Multifocal motor neuropathy. Lancet Neurol. 2005;4:309-319. https://www.ncbi.nlm.nih.gov/pubmed/15847844
Van den Berg-Vos RM, Franssen H, Wokke JH, Van den Berg LH. Multifocal motor neuropathy: long-term clinical and electrophysiological assessment of intravenous immunoglobulin maintenance treatment. Brain. 2002;125(pt8):1875-1886. https://www.ncbi.nlm.nih.gov/pubmed/12135977
Van den Berg LH, Franssen H, Wolke JH. The long-term effect of intravenous immunoglobulin treatment in multifocal motor neuropathy. Brain. 1998;121(Pt3):421-428. https://www.ncbi.nlm.nih.gov/pubmed/9549518
Lange DJ, Trojaborg W, Latov N, et al. Multifocal motor neuropathy with conduction block: is it a distinct clinical entity? Neurology 1992; 42: 497-505.
INTERNET
Lange D, Robinson-Papp J. Multifocal motor neuropathy. UpToDate, Inc. 2017 Jul 17. Available at: https://www.uptodate.com/contents/multifocal-motor-neuropathy Accessed April 25, 2018.
Lange D, Robinson-Papp J. Immune-mediated neuropathies. UpToDate, Inc. 2017 Jul 17. Available at: https://www.uptodate.com/contents/immune-mediated-neuropathies Accessed April 25, 2018.
National Institute of Neurological Disorders and Stroke. Multifocal motor neuropathy. March 3, 2016. Available at: https://rarediseases.info.nih.gov/diseases/11011/multifocal-motor-neuropathy Accessed April 26, 2018.
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