Myoclonus

What is 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 occur in normal, healthy persons and cause no difficulties. Abnormal startle may also be a form of myoclonus. Pathological (disease-related) 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 objects 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 tics, there is no “premonitory sensation” preceding the sudden movement.

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, 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.

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. 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.

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 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 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, by definition, never develop seizures.

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. 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, a noise made as the muscles in the soft palate contract. 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 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). Unverricht-Lundborg disease, another form of PME, 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.

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), 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 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 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. In some cases, psychological or physical stress can produce so-called “psychogenic myoclonus.”

How is myoclonus diagnosed?

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.

How is myoclonus treated?

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. 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.

Selected References

Borg M. Symptomatic myoclonus. Neurophysiol Clin. 2006;36:309-18.
Browner N, Azher SN, Jankovic J. Botulinum toxin treatment of facial myoclonus in suspected Rasmussen encephalitis. Mov Disord. 2006;21:1500-2.
Caviness JN, Brown P. Myoclonus: current concepts and recent advances. Lancet Neurol 2004;3:598-607.
DeLeon ML, Jankovic J. Clinical features and management of tardive dyskinesias, tardive myoclonus, tardive tremor, and tardive tourettism. In: Sethi K, ed. Drug Induced Movement Disorders, Marcel Dekker, Inc, New York, NY, 2004:77-109.
Fahn S, Jankovic J. Principles and Practice of Movement Disorders, Churchill Livingstone, Elsevier, Philadelphia, PA, 2007:1-652. (Accompanied by a DVD of movement disorders).
Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders, 5th edition, Lippincott Williams and Wilkins, Philadelphia, PA, 2007:1-720. (Accompanied by a CD video atlas).
Jankovic J, Shannon KM. Movement disorders. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice, 5th Edition, Butterworth-Heinemann (Elsevier), Philadelphia, PA, 2008.
Lohi H, Turnbull J, Zhao XC, et al. Genetic diagnosis in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls. Neurology 2007;68:996-1001.
Magaudda, A, Ferlazzo, E, Nguyen, VH, Genton, P. Unverricht-Lundborg disease, a condition with self-limited progression: long-term follow-up of 20 patients. Epilepsia 2006; 47:860.
Ross S, Jankovic J. Palatal myoclonus: An unusual presentation. Mov Disord. 2005;20:1200-3.
Tai KK, Bhidayasiri R, Truong DD. Post-hypoxic animal model of myoclonus. Parkinsonism Relat Disord 2007;13:377-81.
Thomas M, Jankovic J. Tics, myoclonus, stiff person syndrome, gait freezing and rigidity. In: Moore P, Naumann M, eds. Handbook of botulinum toxin treatment, 2nd Edition, Blackwell Science, London, UK, 2003:325-339.
Vercueil L. Myoclonus and movement disorders. Neurophysiol Clin. 2006;36:327-31.

Appendix

National Institute of Neurological Disorders and Stroke Brain Resources and Information Network (BRAIN)
BRAIN
P.O. Box 13050
Silver Spring, Maryland 20911
Tel: 800-352-9424
http://www.ninds.nih.gov

Myoclonus Research Foundation, Inc.
200 Old Palisade Road
Fort Lee , New Jersey 07024
Tel: 201-585-0770
http://www.myoclonus.com

National Organization for Rare Disorders (NORD)
P.O. B ox 8923
New Fairfield, Connecticut 06812-8923
Tel: 203-746-6518
Tel: 800-999-6673
http://www.rarediseases.org

For additional information visit http://www.bcm.edu/neurology/pdcmdc/