Myoclonus

What is myoclonus?
Myoclonus describes a symptom and generally is not a diagnosis of a disease. It refers to sudden, involuntary jerking of a muscle or group of muscles. Myoclonic twitches or jerks usually are caused by sudden muscle contractions, called positive myoclonus, or by muscle relaxation, called negative myoclonus. Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern. They may occur infrequently or many times each minute. Myoclonus sometimes occurs in response to an external event or when a person attempts to make a movement. The twitching cannot be controlled by the person experiencing it.

In its simplest form, myoclonus consists of a muscle twitch followed by relaxation. A hiccup is an example of this type of myoclonus. Other familiar examples of myoclonus are the jerks or "sleep starts" that some people experience while drifting off to sleep. These simple forms of myoclonus occur in normal, healthy persons and cause no difficulties. When more widespread, myoclonus 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 distort movement and severely limit a person's ability to eat, talk, or walk. These types of myoclonus may indicate an underlying disorder in the brain or nerves.

What are the causes of myoclonus?
Myoclonus may develop in response to infection, head or spinal cord injury, stroke, brain tumors, kidney or liver failure, lipid storage disease, chemical or drug poisoning, or other disorders. Prolonged oxygen deprivation to the brain, called hypoxia, may result in posthypoxic myoclonus. Myoclonus can occur by itself, but most often it is one of several symptoms associated with a wide variety of nervous system disorders. For example, myoclonic jerking may develop in patients with multiple sclerosis, Parkinson's disease, Alzheimer's disease, or Creutzfeldt-Jakob disease. Myoclonic jerks commonly occur in persons with epilepsy, a disorder in which the electrical activity in the brain becomes disordered leading to seizures.

What are the types of myoclonus?
Classifying the many different forms of myoclonus is difficult because the causes, effects, and responses to therapy vary widely. Listed below are the types most commonly described.

• Action myoclonus is characterized by muscular jerking triggered or intensified by voluntary movement or even the intention to move. It may be made worse by attempts at precise, coordinated movements. Action myoclonus is the most disabling form of myoclonus and can affect the arms, legs, face, and even the voice. This type of myoclonus often is caused by brain damage that results from a lack of oxygen and blood flow to the brain when breathing or heartbeat is temporarily stopped.
• Cortical reflex myoclonus is thought to be a type of epilepsy that originates in the cerebral cortex - the outer layer, or "gray matter," of the brain, responsible for much of the information processing that takes place in the brain. In this type of myoclonus, jerks usually involve only a few muscles in one part of the body, but jerks involving many muscles also may occur. Cortical reflex myoclonus can be intensified when patients attempt to move in a certain way or perceive a particular sensation.
• Essential myoclonus occurs in the absence of epilepsy or other apparent abnormalities in the brain or nerves. It can occur randomly in people with no family history, but it also can appear among members of the same family, indicating that it sometimes may be an inherited disorder. Essential myoclonus tends to be stable without increasing in severity over time. Some scientists speculate that some forms of essential myoclonus may be a type of epilepsy with no known cause.
• Palatal myoclonus is a regular, rhythmic contraction of one or both sides of the rear of the roof of the mouth, called the soft palate. These contractions may be accompanied by myoclonus in other muscles, including those in the face, tongue, throat, and diaphragm. The contractions are very rapid, occurring as often as 150 times a minute, and may persist during sleep. The condition usually appears in adults and can last indefinitely. People with palatal myoclonus usually regard it as a minor problem, although some occasionally complain of a "clicking" sound in the ear, a noise made as the muscles in the soft palate contract.
• Progressive myoclonus epilepsy (PME) is a group of diseases characterized by myoclonus, epileptic seizures, and other serious symptoms such as trouble walking or speaking. These rare disorders often get worse over time and sometimes are fatal. Studies have identified at least three forms of PME. Lafora body disease is inherited as an autosomal recessive disorder, meaning that the disease occurs only when a child inherits two copies of a defective gene, one from each parent. Lafora body disease is characterized by myoclonus, epileptic seizures, and dementia (progressive loss of memory and other intellectual functions). A second group of PME diseases belonging to the class of cerebral storage diseases usually involves myoclonus, visual problems, dementia, and dystonia (sustained muscle contractions that cause twisting movements or abnormal postures). Another group of PME disorders in the class of system degenerations often is accompanied by action myoclonus, seizures, and problems with balance and walking. Many of these PME diseases begin in childhood or adolescence.
• Reticular reflex myoclonus is thought to be a type of generalized epilepsy that originates in the brainstem, the part of the brain that connects to the spinal cord and controls vital functions such as breathing and heartbeat. Myoclonic jerks usually affect the whole body, with muscles on both sides of the body affected simultaneously. In some people, myoclonic jerks occur in only a part of the body, such as the legs, with all the muscles in that part being involved in each jerk. Reticular reflex myoclonus can be triggered by either a voluntary movement or an external stimulus.
• Stimulus-sensitive myoclonus is triggered by a variety of external events, including noise, movement, and light. Surprise may increase the sensitivity of the patient.
• Sleep myoclonus occurs during the initial phases of sleep, especially at the moment of dropping off to sleep. Some forms appear to be stimulus-sensitive. Some persons with sleep myoclonus are rarely troubled by, or need treatment for, the condition. However, myoclonus may be a symptom in more complex and disturbing sleep disorders, such as restless legs syndrome, and may require treatment by a doctor.

What do scientists know about myoclonus?
Although some cases of myoclonus are caused by an injury to the peripheral nerves (defined as the nerves outside the brain and spinal cord, or the central nervous system), most myoclonus is caused by a disturbance of the central nervous system. Studies suggest that several locations in the brain are involved in myoclonus. One such location, for example, is in the brainstem 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. These parts are interconnected in a series of feedback loops called motor pathways. These pathways facilitate and modulate communication between the brain and muscles. Key elements of this communication are chemicals known as neurotransmitters, which carry messages from one nerve cell, or neuron, to another. Neurotransmitters are released by neurons and attach themselves to receptors on parts of neighboring cells. Some neurotransmitters may make the receiving cell more sensitive, while others tend to make the receiving cell less sensitive. Laboratory studies suggest that an imbalance between these chemicals may underlie myoclonus.

Some researchers speculate that 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, which constricts blood vessels and brings on sleep, and gamma-aminobutyric acid (GABA), which helps the brain maintain muscle control. Other receptors with links to myoclonus include those for opiates, drugs that induce sleep, and for glycine, an inhibitory neurotransmitter that is important for the control of motor and sensory functions in the spinal cord. More research is needed to determine how these receptor abnormalities cause or contribute to myoclonus.

How is myoclonus treated?
Treatment of myoclonus focuses on medications that may help reduce symptoms. The drug of first choice to treat myoclonus, especially certain types of action myoclonus, is clonazepam, a type of tranquilizer. Dosages of clonazepam usually are increased gradually until the patient improves or side effects become harmful. Drowsiness and loss of coordination are common side effects. The beneficial effects of clonazepam may diminish over time if the patient develops a tolerance for the drug.

Many of the drugs used for myoclonus, such as barbiturates, phenytoin, and primidone, are also used to treat epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin and primidone are effective antiepileptic drugs, although phenytoin can cause liver failure or have other harmful long-term effects in patients with PME. Sodium valproate is an alternative therapy for myoclonus and can be used either alone or in combination with clonazepam. Although clonazepam and/or sodium valproate are effective in the majority of patients with myoclonus, some people have adverse reactions to these drugs.

Some studies have shown that doses of 5-hydroxytryptophan (5-HTP), a building block of serotonin, leads to improvement in patients with some types of action myoclonus and PME. However, other studies indicate that 5-HTP therapy is not effective in all people with myoclonus, and, in fact, may worsen the condition in some patients. These differences in the effect of 5-HTP on patients 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 drugs for effective treatment. Although some drugs have a limited effect when used individually, they may have a greater effect when used with drugs that act on different pathways or mechanisms in the brain. By combining several of these drugs, scientists hope to achieve greater control of myoclonic symptoms. Some drugs currently being studied in different combinations include clonazepam, sodium valproate, piracetam, and primidone. Hormonal therapy also may improve responses to antimyoclonic drugs in some people.

What research is being done?
Scientists are seeking to understand the underlying biochemical basis of involuntary movements and to find the most effective treatment for myoclonus and other movement disorders. The National Institute of Neurological Disorders and Stroke (NINDS), a unit of the Federal Government's National Institutes of Health (NIH), is the agency with primary responsibility for research on the brain and nervous system.

Investigators at NINDS laboratories are evaluating the role of neurotransmitters and receptors in myoclonus. If abnormalities in neurotransmitters or receptors are found to play a causative role in myoclonus, future research can focus on determining the extent to which genetic alterations are responsible for these abnormalities and on identifying the nature of those alterations. Scientists also may be able to develop drug treatments that target specific changes in the receptors to reverse abnormalities, such as the loss of inhibition, and to enhance mechanisms that compensate for these abnormalities. Identifying receptor abnormalities also may help researchers develop diagnostic tests for myoclonus. NINDS-supported scientists at research institutions throughout the country are studying various aspects of PME, including the basic mechanisms and genes involved in this group of diseases.

Where can I get more information?
For more information on myoclonus, you may wish to contact:

Myoclonus Research Foundation
200 Old Palisade Road 17D
Fort Lee, NJ 07024
research@myoclonus.com
http://www.myoclonus.com/
Tel: 201-585-0770
Fax: 201-585-8114

Worldwide Education & Awareness for Movement Disorders (WE MOVE)
204 West 84th Street
New York, NY 10024
wemove@wemove.org
http://www.wemove.org/
Tel: 800-437-MOV2 (6682) 212-875-8312
Fax: 212-875-8389

For information on other neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

Source: National Institutes of Health; National Institute of Neurological Disorders and Stroke