Parkinson's Disease Center and Movement Disorders Clinic

Myoclonus

Myoclonus is the medical term for sudden, rapid, brief, involuntary jerking of a muscle or group of muscles. Many different neurological disorders can cause myoclonus; therefore, neurologists consider it a symptom of disease rather than a specific diagnosis. Indeed, everyone experiences myoclonus on occasion. For example, "sleep starts," the shock-like twitches that some people experience while drifting off to sleep is a form of myoclonus that occurs in normal, healthy individuals. Abnormal startle may also be a form of myoclonus. Pathological myoclonus, however, may be extremely disabling. Myoclonus may affect a small region (focal or segmental myoclonus), such as one hand, or produce violent jerks over the entire body (generalized myoclonus). Myoclonic jerks may occur alone or in sequence, either in a pattern or randomly. When patterned, they sometimes resemble more common forms of tremor. They may occur infrequently or many times each minute. Sometimes myoclonus occurs in response to a specific sensation (like being touched) or arises when a person attempts to make a movement. The brief positive muscle contractions of myoclonus are often accompanied by episodes of sudden muscle relaxation, or lapses of posture. This phenomenon, termed negative myoclonus, makes standing, walking, reaching, or grasping very difficult. All types of myoclonus are similar insofar as the movement cannot be controlled by the person who is experiencing it and, in contrast to a tic, there is no warning or premonitory sensation.

Causes

Myoclonus may develop in response to infection, head or spinal cord injury, stroke, brain tumors, kidney or liver failure, inherited metabolic diseases, chemical or drug poisoning, and other disorders such as prolonged oxygen deprivation to the brain, called hypoxia. 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.

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. Attempts at precise, coordinated movements are especially problematic. 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 heart function is temporarily impaired. It may be associated with a condition called action myoclonus renal failure syndrome.

Cortical reflex myoclonus is thought to be a forme fruste (incomplete form) of epilepsy originating in the cerebral cortex - the outer layer, or "gray matter," of the brain. In this type of myoclonus, jerks usually involve only a few muscles in one part of the body, but may involve many muscles as well. Cortical reflex myoclonus can be intensified when patients attempt to move in a certain way or perceive a particular sensation.

Essential myoclonus is a form of myoclonus that occurs in individuals without epilepsy or other neurological abnormalities. Essential myoclonus is sometimes an inherited disorder but can also arise in people with no family history of neurological disease. Essential myoclonus tends not to worsen over time. Some scientists speculate that some forms of essential myoclonus may be related to epilepsy even though these patients never develop seizures.

Palatal myoclonus, now called palatal tremor, 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. This 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 from the noise made as the tensor veli palatini muscle in the soft palate contracts. Many neurologists now classify this condition as a type of tremor rather than myoclonus.

Progressive myoclonic epilepsy (PME) is a group of diseases characterized by myoclonus, epileptic seizures, and other serious symptoms such as trouble walking or speaking. PME tends to arise during childhood or adolescence. The rare disorders that comprise PME often get worse over time and sometimes are fatal. Studies have identified several forms of PME. Lafora body disease (EPM2) 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). Another form of PME, Unverricht-Lundborg disease also called Baltic Myoclonic Epilepsy (EPM1), is also inherited as an autosomal recessive trait. Its symptoms are similar to Lafora body disease but often worsen less rapidly. A third group of PME belongs to the class of cerebral storage diseases. Examples include neuronal ceroid lipofuscinoses and sialidosis, which are disorders of lysosomes, the small compartments within cells that digest unneeded debris. The lysosomal storage diseases are also autosomal recessive and usually cause visual problems, dementia and dystonia (sustained muscle contractions that cause twisting movements or abnormal postures) in addition to myoclonus. Disorders of another cellular compartment, mitochondria, may also cause PME. Mitochondria are needed to produce energy for nerve cell growth and function. Mitochondrial diseases, such as myoclonic epilepsy with ragged-red fibers (MERRF), cause action myoclonus, seizures, muscle disease and problems with balance and walking. Some mitochondrial diseases, like MERRF, are usually inherited from one's mother because mitochondria have their own DNA that is passed unchanged from a mother to her children.

Reticular reflex myoclonus is 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 arising from this region usually affect the whole body simultaneously. 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 increases the chance of the patient having a myoclonic muscle jerk.

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. 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.

Other categories of myoclonus include familial cortical myoclonic epilepsy, myoclonus dystonia, spinal myoclonus, and asterixis.

What 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), most forms of myoclonus are caused by a disturbance of the central nervous system (the brain and spinal cord). Studies suggest that several locations in the brain are involved in myoclonus. One such location, for example, is in the brainstem region 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 over excitability 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 active, while others tend to make the receiving cell less active. Laboratory studies suggest that an imbalance between these chemicals may underlie myoclonus.

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. For example, sporadic and inherited startle disease, or hyperekplexia, are known to be caused by genetic defects in glycinergic transmission; more specifically, mutations have been found in both the alpha and beta subunits of the glycine receptor in addition to a pre-synaptic glycine transporter and postsynaptic molecules involved in glycine transmission.

The genetic bases for the common causes of progressive myoclonic epilepsy (PME) and myoclonus dystonia have also been identified. Mutations in gene coding for a lysosomal protein have been linked to both PME action myoclonus renal failure syndrome.

Diagnosis

The diagnostic approach to a patient with myoclonus has two objectives: (1) identifying what part of the nervous system is producing myoclonus and (2) establishing the cause. Clinicians are able to categorize myoclonus on the basis of its distribution over the body, its electrophysiological characteristics, and its etiology. Electrical recording techniques can often localize the source of myoclonus to the surface of the brain, deep brain structures, or the spinal cord. Laboratory testing and imaging studies (brain scans) may be helpful in determining the cause of myoclonus. In some cases, psychological or physical stress can produce psychogenic myoclonus.

Treatments

If possible, the underlying cause of myoclonus should be corrected, but this is not always possible. Treatment of myoclonus otherwise focuses on medications that help reduce symptoms.

As some forms of myoclonus are related to epileptic seizures, antiepileptic medications (seizure drugs) and other medications that reduce overactivity of neurons are sometimes effective. A commonly used drug 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 bothersome. 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.

Other useful medications include barbiturates, phenytoin, primidone and levetiracetam, which are also used to treat epilepsy. The latter has been shown to be effective in some with cortical myoclonus including severe posthypoxic myoclonus. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin and primidone are effective seizure drugs, although phenytoin can cause serious long-term side effects in some 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.

Often, a single drug is not effective by itself, and combinations of medications are frequently required. Hormonal therapy and a naturally-occurring amino acid, 5-hydroxytryptophan, which is a precursor to the neurotransmitter serotonin, also may improve the response to antimyoclonic drugs in some people.

Appendix

Brain Resources and Information Network (BRAIN)
National Institute of Neurological Disorders & Stroke
P.O. Box 5801
Bethesda,  MD  20824
Toll free: (800) 352-9424
Fax: (301) 402-2186
Email: braininfo@ninds.nih.gov

Myoclonus Research Foundation
200 Old Palisade Road, Suite 17D
Fort Lee, NJ 07024
Phone: (201) 585-0770

National Organization for Rare Disorders (NORD) 
55 Kenosia Avenue
Danbury, CT 06810
Phone: (203) 744-0100
Toll free: (800) 999-6673 
Fax: (203) 798-2291

©2011 Joseph Jankovic, M.D.

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