Polyneuropathy associated with anti-MAG IgM antibodies
The author reviews advances in the diagnosis and management of patients with anti-MAG neuropathy. Deposits of IgM antibodies can be detected in the small
Jan. 05, 2021
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What is myoclonus?
Myoclonus refers to sudden, brief involuntary twitching or jerking of a muscle or group of muscles. It describes a clinical sign and is not itself a disease. The twitching cannot be stopped or controlled by the person experiencing it.
Myoclonic twitches or jerks usually are caused by sudden muscle contractions (tightening), called positive myoclonus, or by muscle relaxation, called negative myoclonus. Myoclonic jerks may occur alone or in sequence, in a pattern of movement or without pattern. They may occur infrequently or many times per minute. Myoclonus sometimes happens in response to an external event or when a person attempts to make a movement.
In its simplest form, myoclonus consists of a quick muscle twitch followed by relaxation. Examples of this type of myoclonus are hiccups and the jerks or “sleep starts” that some people experience while drifting off to sleep. These forms of myoclonus occur in healthy people and are called physiologic myoclonus. They cause no difficulties and do not require medical treatment.
When myoclonus is more widespread, it may involve persistent, shock-like contractions in a group of muscles. In some cases, myoclonus begins in one region of the body and spreads to muscles in other areas. More severe cases of myoclonus can affect movement and severely limit a person’s ability to eat, talk, or walk. These types of myoclonus are called pathologic myoclonus and can be one of many signs indicating a wide variety of underlying disorders in the brain or nerves, secondary to certain medical conditions, or can be a reaction to certain types of medication.
The severity of myoclonus may range from mild to severe. It may begin in childhood or adulthood.
What are the causes of myoclonus?
Most myoclonus is caused by a disturbance of the brain or spinal cord (the central nervous system, or CNS). Although rare, myoclonus may be caused by an injury to the peripheral nerves (the nerves outside the central nervous system that connect to sensory organs and muscles, and relay information from/to the CNS).
Myoclonus can occur by itself or as one of several symptoms associated with a wide variety of nervous system disorders. For example, myoclonic jerks may develop in individuals with multiple sclerosis or epilepsy, and with neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, or Creutzfeldt-Jakob disease.
Myoclonus may also be seen in conjunction with infection, head or spinal cord injury, stroke, brain tumors, kidney or liver failure, chemical or drug intoxication, or metabolic disorders. Prolonged oxygen deprivation to the brain, called hypoxia, may lead to post-hypoxic myoclonus.
What are the types of myoclonus?
Classifying the many different forms of myoclonus is difficult because the causes and responses to therapy vary widely. Some of the commonly described types are:
What do scientists know about myoclonus?
Studies suggest that several locations in the brain are involved in myoclonus. The cerebral cortex is the most common origin for myoclonus. Another location is in the brain stem close to structures that are responsible for the startle response—an automatic reaction to an unexpected stimulus involving rapid muscle contraction.
The specific mechanisms underlying myoclonus are not yet fully understood. Scientists believe that some types of stimulus-sensitive myoclonus may involve overexcitability of the parts of the brain that control movement. Laboratory studies suggest that an imbalance between chemicals called neurotransmitters may bring about myoclonus, with the end result being a lack of inhibition (a decrease in the rate of chemical reaction, or its prevention) at some level. Neurotransmitters carry messages between nerve cells. They are released by one nerve cell and attach to a protein called a receptor on neighboring (receiving) cells. This attachment signals the receiving cell to act in a certain way.
Abnormalities or deficiencies in the receptors for certain neurotransmitters may contribute to some forms of myoclonus. Receptors that appear to be related to myoclonus include those for two important inhibitory neurotransmitters: serotonin and gamma-aminobutyric acid (GABA). Other receptors with links to myoclonus include those for glycine (an inhibitory neurotransmitter important for the control of motor and sensory functions in the spinal cord) and opiates. More research is needed to determine how these receptor abnormalities cause or contribute to myoclonus.
How is myoclonus diagnosed?
Following a review of the person’s medical history and physical exam, a physician may order additional tests:
How is myoclonus treated?
The first consideration is reversing or treating any underlying cause or origin of the myoclonus. However, in many cases, this may not be possible or effective, so symptomatic treatment is warranted if the myoclonus is disabling. Clonazepam is commonly used to treat some forms of myoclonus. Dosages of clonazepam usually are increased gradually until the individual improves or side effects become bothersome. Drowsiness and loss of coordination are common side effects. The beneficial effects of clonazepam may diminish over time if the individual develops a tolerance for the drug.
Many of the other drugs used for myoclonus, such as certain barbiturates, phenytoin, levetiracetam, valproate, and primidone, also are used to treat epilepsy. Each has side effects and drug interactions; however, a doctor will select the most appropriate treatment for individual patients.
Some studies have shown that doses of 5-hydroxytryptophan (5-HTP), a building block of serotonin (a chemical made in the body that transmits nerve impulses), leads to improvement in individuals with some types of action myoclonus and progressive myoclonus epilepsy. However, other studies indicate that 5-HTP therapy is not effective in all people with myoclonus, and may even worsen the condition in some individuals. These differences in the effect of 5-HTP on people with myoclonus have not yet been explained, but they may offer important clues to underlying abnormalities in serotonin receptors.
The complex origins of myoclonus may require the use of multiple medications for effective treatment. Although some medications have a limited effect when used individually, they may have a greater effect when used with others that act on different pathways or mechanisms in the brain. By combining several drugs, physicians often can achieve greater control of myoclonic symptoms. Hormonal therapy also may improve responses to antimyoclonic drugs in some people.
Botulinum toxin injections can reduce excess muscle activity by blocking the activity of a chemical that makes muscles contract at the cellular level. Botulinum toxin injection is the first line therapy for hemifacial spasm, and has also shown to effectively treat some individuals with palatal myoclonus.
What research is being done?
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NINDS is a component of the National Institutes of Health, the leading federal supporter of biomedical research in the world.
As part of its mission, the NINDS supports research on myoclonus at its laboratories in Bethesda, Maryland and through grants to major research institutions across the country.
Botulinum toxin is a treatment for a variety of movement disorders. A current NINDS study is comparing the use of ultrasound (using sound waves) and electrophysiologic guidance (using electrical stimulation and a needle) to precisely target muscles for botulinum toxin injection to treat upper limb spasticity and focal hand dystonia. Results may lead to improved treatment for movement disorders such as myoclonus.
Animal models are being used to study the mechanisms involving myoclonus. For example, NINDS-funded scientists have developed a mouse model of myoclonus-dystonia (an inherited movement disorder characterized predominantly by myoclonus of the upper body and dystonia). A striking characteristic of this disorder is that motor symptoms improve with alcohol consumption. Researchers will test the hypothesis that abnormal activity of the cerebellum (the part of the brain responsible for coordination and regulation of voluntary movement) causes myoclonus and dystonia in myoclonus-dystonia, and that by acting on targets in the cerebellum, alcohol injections will normalize cerebellar activity to relieve motor symptoms. Results may provide a better understanding of the underlying neurological cause of myoclonus and dystonia in myoclonus-dystonia, and provide targets for treatment options.
Complex movement disorders (CMDs), defined as disorders in which individuals are affected by more than one movement disorder (such as parkinsonism and dystonia, or myoclonus and tremor), are a continuing challenge for diagnosis and treatment. NINDS-funded researchers are recruiting individuals with familial and sporadic CMDs to identify genetic mutations that may cause these disorders. Findings may lead to improvements in disease diagnosis and treatment.
Glycogen is a form of sugar that is used as an energy reserve in many cells. Abnormal glycogen metabolism in nerve cells causes several illnesses, including Lafora disease. NINDS-funded scientists hope to understand what goes wrong with glycogen storage in Lafora disease, which could help provide clues to new treatments.
In addition to NINDS, other NIH institutes and centers support research on movement disorders that include myoclonus. More information is available through the NIH RePORTER (https://projectreporter.nih.gov), a searchable database of current and previously funded research, as well as research results and publications.
Many neurological disorders do not have effective treatment options. Clinical trials offer hope for many people and an opportunity to help researchers find better ways to safely detect, treat, or prevent disease. For more information about finding and participating in a clinical trial, visit Clinicaltrials.gov at https://clinicaltrials.gov. Use the search term “myoclonus” to find trials on this disorder.
Where can I get more information?
The National Institute of Neurological Disorders and Stroke conducts and support a wide range of research on neurological disorders, including myoclonus. For information on other neurological disorders or research programs funded by the NINDS, contact in the Institute’s Brain Resources and Information Network (BRAIN) at:
P.O. Box 5801
Bethesda, MD 20824
Interested individuals may wish to contact the following organizations for additional information:
Opsoclonus-Myoclonus Support Network, Inc.
2116 Casa Linda Drive
West Covina, CA 91791
National Organization for Rare Disorders (NORD)
55 Kenosia Avenue
Danbury, CT 06813-1968
800-999-6673 (voicemail only)
Publication date: September 2017. NIH Publication No. 17-NS-4793.
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892
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