Last updated:
7/29/2025
Years published: 2018, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and 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 it is caused by inflammation resulting from abnormal functioning of the immune system and by the presence of specific autoantibodies that target a specific protein in the body. Other symptoms can include muscle cramps and wasting (atrophy) of muscles. 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. People with multifocal motor neuropathy usually get better when treated 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. 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 people 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 muscles affected on the other side of the body (asymmetrical muscle weakness).
Additional symptoms associated with multifocal motor neuropathy include:
Other muscles such as those affecting breathing are unaffected and the disorder usually does not affect life expectancy.
Unlike other neurological disorders affecting the arms and legs, there are usually no sensory deficits. This means that feelings of tingling or numbness or pain are not associated with the disorder.
The exact, underlying cause of multifocal motor neuropathy is not fully understood. The disorder is thought 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 is not carried along properly to the muscles. Multiple motor nerves are damaged by this disorder, although the exact reason is not fully understood. Researchers think that conduction block in multifocal motor neuropathy is reversible.
Affected people have autoantibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Autoantibodies mistakenly attack healthy tissue. Many individuals (30-80%) with multifocal motor neuropathy have autoantibodies that target GM1 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 GM1 ganglioside play in the development of multifocal motor neuropathy.
Multifocal motor neuropathy affects both males and females, although males are more frequently affected than females by a ratio of about 2.7:1. Males also tend to be diagnosed at a younger age. The median age of onset is 40 years old, although the disorder has been reported in individuals ranging from 20-80 years of age. Rarely, the disorder has been diagnosed in children. Multifocal motor neuropathy is estimated to affect about 0.6 to 2 per 100,000 people 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. The main symptoms of multifocal motor neuropathy are asymmetrical muscle weakness without sensory problems (e.g. numbness, tingling, etc.).
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. A key feature that helps distinguish multifocal motor neuropathy is the presence of conduction block in motor nerves, particularly in areas where nerves are not typically compressed.
Doctors may suspect MMN when there is a pattern of muscle weakness without significant sensory symptoms or pain, along with these specific nerve conduction abnormalities.
Electromyography is another test that may aid in 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 diagnosis of MMN is based on guidelines developed by the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS). To confirm a diagnosis of MMN, both of the following core criteria must be met:
The following signs are commonly seen in MMN and help support the diagnosis:
The following signs are not consistent with MMN and suggest a different diagnosis:
If MMN is suspected, it is recommended that the patient be referred to a neuromuscular center with expertise in diagnosing and treating rare inflammatory nerve disorders for further evaluation and care.
The treatment of multifocal motor neuropathy may require the coordinated efforts of a team of specialists. The specialists may include general internists, neurologists (experts in brain and nerve disorders), immunologists (specialists in immune system disorders), orthopedists (bone and muscle specialists) and physical or occupational therapists. A coordinated, comprehensive treatment plan is essential to managing the condition effectively.
The main treatment for MMN is intravenous immunoglobulin (IVIg). In 2012, the U.S. Food and Drug Administration (FDA) approved immune globulin infusion (Gammagard Liquid 10%) for this purpose. Most people with MMN improve with IVIg, often experiencing a noticeable and rapid improvement in muscle strength after treatment begins. However, the benefits are temporary and ongoing therapy every 2 to 6 weeks is usually required to maintain progress. Over time, some people may respond less to IVIg and may require higher doses or more frequent infusions.
For people who do not get better with IVIg or who become resistant to IVIg, treatment options are more limited.
Glucocorticoids (steroids) and plasma exchange (plasmapheresis) are generally not effective for MMN and have even been linked to worsening symptoms in some people.
In addition to these medications, supportive care plays an important role. Physical and occupational therapy can help people maintain strength and flexibility, adapt to daily tasks and maintain independence. Assistive devices like canes or braces (orthoses) improve mobility and safety. Other medications may be prescribed to ease muscle cramps or spasms.
These supportive therapies help improve quality of life and maintain function, especially when symptoms are persistent or progressive.
Several medications have been studied as possible treatments for MMN, including beta-interferon, mycophenolate mofetil, cyclosporine, azathioprine and infliximab but more research is needed to understand their long-term safety and effectiveness.
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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
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.
JOURNAL ARTICLES
Allen JA, Clarke AE, Harbo T. A Practical Guide to Identify Patients With Multifocal Motor Neuropathy, a Treatable Immune-Mediated Neuropathy. Mayo Clin Proc Innov Qual Outcomes. 2024;8(1):74-81. Published 2024 Jan 8. doi:10.1016/j.mayocpiqo.2023.12.002
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. March 07, 2024. Available at: https://www.uptodate.com/contents/multifocal-motor-neuropathy Accessed July 29, 2025.
Lange D, Robinson-Papp J. Immune-mediated neuropathies. UpToDate, Inc. Jul 11, 2023. Available at: https://www.uptodate.com/contents/immune-mediated-neuropathies Accessed July 29, 2025.
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