Focus on pediatric movement disorders: myoclonus. (ask the doctor).

Most people take for granted their ability to control their body movement. We will ourselves to move--walk across a room, sit in a chair or simply remain still. For millions of children, however, these simple, everyday acts are frustratingly difficult, if not impossible. These children are living with neurologic movement disorders.

The major neurologic movement disorders that may affect children include ataxia, bradykinesia, choreoathetosis, dystonia, myoclonus, spasticity, tics, and tremor. This article, the second in a series on pediatric movement disorders, offers timely information on the definition, causes, evaluation, diagnosis and treatment of myoclonus.

WHAT IS MYOCLONUS?

Myoclonus is a neurologic movement disorder characterized by sudden, quick, jerky, involuntary movements. These movements are usually extremely rapid or lightning-like. An attempted voluntary movement, a sensory stimulation or a sudden startle may trigger them, or they may occur continuously. Myoclonus may be observed as occurring rhythmically (as in myoclonic tremor) always affecting the same body parts or moving throughout the body. The condition may occur in the neck, back, face, a single limb or the entire body. If the symptoms of myoclonus are severe, children may lose their grip on objects, involuntarily throw objects, lose their balance or fall over.

There are many different causes, but in general, myoclonus occurs when a part of the brain or spinal cord is irritated or injured. Irritation may take the form of physical pressure (such as a tumor or local inflammation) or a chemical irritation because of toxins or other abnormal chemicals in the brain. While myoclonus in adults can be caused by a variety of minor and treatable problems, myoclonus in children often signals the presence of a more serious problem. For this reason, it is extremely important that children with myoclonus undergo a thorough evaluation for tumors, toxins, chemical imbalance and a variety of different diseases.

In some children, myoclonus is severely disabling, particularly when an attempted voluntary movement triggers myoclonic activity. In other children, the symptoms are relatively mild.

THERE ARE MANY DIFFERENT FORMS OF MYOCLONUS, INCLUDING:

* Sleep myoclonus is a normal and common form of mild myoclonus. It occurs frequently in both children and adults. Individuals with this form of myoclonus experience occasional brief jerking movements of an arm or a leg while falling asleep.

* Negative myoclonus, also known as asterixis, is characterized by a sudden involuntary relaxation, rather than contraction, of a muscle.

* Action myoclonus is triggered or worsened by attempts at movement.

* Polymyoclonus causes myoclonic jerks that can occur randomly throughout the body.

MYOCLONUS IS FREQUENTLY ASSOCIATED WITH EPILEPSY:

* Epilepsia partialis continua is a type of focal epilepsy that causes myoclonic tremor.

* Progressive myoclonus epilepsies; or PMEs, are a specific group of degenerative disorders in which the association of myoclonus and epilepsy is common.

The frequent association of myoclonus and seizure disorders suggests that there may be a common cause for myoclonus and certain types of epilepsy. Epilepsy, sometimes referred to as a "seizure disorder," is a neurological disorder characterized by episodes of abnormal electrical activities within the brain. These episodes typically cause seizures that affect awareness, movement or sensation.

UNDERLYING MECHANISMS IN THE CENTRAL NERVOUS SYSTEM RESPONSIBLE FOR MYOCLONUS

The precise nature of the underlying mechanism(s) responsible for the development of myoclonus is not fully understood. Myoclonus may be categorized according to the most likely source of these movements within the central nervous system. These include:

* Cortical myoclonus--originating in the outer layer of the brain or cerebral cortex;

* Subcortical myoclonus--originating within deep portions of the brain or brainstem and

* Spinal myoclonus--originating within the spinal cord.

Cortical myoclonus is possibly a result of lack of control within the brain's sensory or motor cortex; however, the reason is not known. Subcortical myoclonus is often caused by abnormalities in the brainstem. Spinal myoclonus is presumed to stem from abnormalities in certain spinal inhibitory circuits.

Another distinct group of disorders associated with myoclonic movements is known as startle syndromes. These disorders, which are characterized by explosive, jerking movement in response to environmental sounds or stimuli, typically involve excessive activity or hyperexcitability of the normal brainstem's "startle circuits." There may also be diminished control in spinal circuits.

HOW IS MYOCLONUS DIAGNOSED AND EVALUATED?

The diagnosis and evaluation of myoclonus may be challenging and is based upon:

(1) a thorough clinical assessment;

(2) evaluation of the nature of the myoclonus with specific testing of muscle activity (electrophysiologic testing);

(3) assessment of where the symptoms occur and factors that provoke or induce episodes of symptoms; and

(4) a comprehensive patient and family history.

The measurement of specific patterns of electrical activity in brain and affected muscle(s) may be necessary to assist the physician in pinpointing specific myoclonic activity. Specialized testing is often conducted, including electrical recording techniques such as:

* Electromyography (EMG): An EMG of the muscles typically shows the duration and frequency of the myoclonic bursts, and whether these bursts spread to other spinal segments (as is seen in propriospinal myoclonus). It may also be helpful in determining whether jerking movements occur simultaneously in more than one limb, or whether they flow gradually down the body.

* Electroencephalography (EEG): During an EEG, small electrodes that are placed on the head measure electrical activity within the brain. Abnormal episodes of activity are recorded and may be evidence for the presence of epilepsy.

* Reflex studies (evaluation of somatosensory evoked potential (SEP)): In cortical myoclonus, there may be an excessively large brain electrical response to electrical stimulation of the hands or feet. In some cases, it is also possible to demonstrate the myoclonic electrical signal in muscle. This is done with a "tendon tap," during which the physician literally taps on the tendon of the affected muscle and then observes the electrical response.

In any form of myoclonus, it is important to look for an underlying cause. Any medication or toxin that could produce myoclonic symptoms should be discontinued if possible. The family history needs to be investigated. Metabolic studies may be appropriate, particularly if there are other symptoms or symptoms that are progressively worsening. Metabolic tests may include screening for treatable disorders such as Wilson disease.

Since myoclonus may be a symptom of general systemic illness, including liver failure and some types of tumors, it is important to screen for general health problems. In children with opsoclonus-myoclonus syndrome (myoclonic movements with a random, dance-like jerking of the eyes in all directions), routine tests may include a CT scan or other imaging of the chest and abdomen as well as blood and urine tests. These tests look for evidence of a particular type of nervous system tumor known as a neuroblastoma tumor. A neuroblastoma may cause symptoms that are similar to those found in children with opsoclonus-myoclonus syndrome. These tests help to identify a possible neuroblastoma and enable early, appropriate treatment.

An advanced imaging technique known as magnetic resonance imaging (MRI) may be employed to help evaluate for evidence of a tumor, stroke, brain malformation, or other structural lesions near the brain's cortex, the brainstem or the cerebellum. These tests are particularly important if the myoclonus is limited to a particular area of the body or if the child is suspected of having a rare form of epilepsy known as epilepsia partialis continua. Since certain viral infections may cause myoclonus, a spinal tap is sometimes necessary in order to test for such infections.

MYOCLONUS MAY OCCUR ALONG WITH OTHER MOVEMENT DISORDERS

Myoclonus may occur along with other movement disorders. Therefore, physicians should evaluate children for evidence of dystonia, tremor, ataxia, and spasticity. Physicians may also observe for opsoclonus. This eye movement occurs in the opsoclonus-myoclonus--ataxia syndrome, which is characterized by random eye movements, myoclonic movements, and difficulty walking and maintaining balance.

To determine if symptoms improve or worsen with a voluntary activity, physicians may choose to observe children while attempting to drink from a cup. Myoclonic jerks may also be caused by unexpected, loud noises or by a gentle tap on the tip of the nose or on the forehead. Sometimes myoclonic movements have a definite rhythmic pattern and always involve the same area(s) of the body; however, in other children, the symptoms may be without rhythm and move from one part of the body to another.

To test for negative myoclonus, children are asked to extend their arms with the wrists back or to perform some other movement that requires them to hold the limb against gravity. If negative myoclonus is present, the sudden loss of muscle contraction causes the hand or the arm to fall downward.

IS TREATMENT AVAILABLE FOR CHILDREN WITH MYOCLONUS?

Some children with essential myoclonus or essential myoclonus-dystonia improve with small amounts of alcohol. A small amount of alcohol may be administered in order to assist in the diagnosis of myoclonus; however, alcohol is not helpful in long-term treatment.

When a specific cause for myoclonus is identified, such as another movement disorder or other neurologic condition, the symptoms of myoclonus are usually effectively resolved by treating the underlying disease. For example, if the identified cause of myoclonus is a tumor within the brain, surgical treatment may resolve the myoclonus.

In certain cases, the treatment of myoclonus is symptomatic and supportive. Symptomatic treatment of myoclonus usually includes the use of benzodiazepines. These belong to a specific class of drugs that act to "slow down" the activities of the central nervous system. These drugs may include clonazepam or diazepam.

OTHER TREATMENTS:

* Intravenous immunoglobulin has been used on an experimental basis to treat some children with myoclonus.

* Plasmapheresis has been investigated for use in the treatment of certain children with myoclonus. During this procedure, whole blood is removed from the body and then blood plasma (not blood cells) is replaced with saline or a plasma substitute and reinfused into the body. More studies are needed to determine the safety and effectiveness of plasmapheresis for the treatment of myoclonus.

EXAMPLES OF TREATMENT FOR SPECIFIC FORMS OF MYOCLONUS:

* Immune-mediated myoclonus, as in children with opsoclonus-myoclonus, typically requires treatment with oral steroids such as prednisone.

* Juvenile myoclonus epilepsy usually responds to valproate, and may require life-long treatment.

* Cortical myoclonus may respond to valproate, piracetam, or lamotrigine.

* Myoclonus due to an event involving hypoxia may respond to 5-hydroxy-tryptophan (5HT). There are scattered reports of this response. It is also possible the 5HT may be helpful for myoclonus that is caused by other factors.

WHAT ARE THE VARIOUS FORMS OF MYOCLONUS AND WHAT ARE THEIR UNDERLYING CAUSES? Myoclonus and its various forms include:

* Physiological myoclonus including normal sleep myoclonus and benign myoclonus of infancy;

* Essential myoclonus including familial essential myoclonus, essential myoclonus-dystonia, and stimulus-sensitive myoclonus;

* Epileptic myoclonus including juvenile myoclonic epilepsy, progressive myoclonic epilepsies (PME), epilepsia partialis continua, Rasmussen's encephalitis, early infantile myoclonic encephalopathy, infantile spasms (also known as West syndrome), Lennox-Gastaut syndrome, benign familial myoclonic epilepsy, and Angelman syndrome; and

* Symptomatic myoclonus, including:

* fixed injuries such as carbon-monoxide poisoning, hypoxic injury or near-drowning (Lance-Adams syndrome), heatstroke, trauma, stroke, or electrocution;

* storage or degenerative myoclonus such as sialidoses (cherry-red-spot-myoclonus); lipidoses; lysosomal storage diseases (e.g., Niemann-Pick type C, Tay-Sachs, Sandhoff's); other storage disorders (neuronal ceroid lipofuscinosis, neuronal brain iron accumulation type 1, Wilson's disease, Lafora body disease); Baltic myoclonus; spinocerebellar ataxias or SCAs; dentatorubropallidoluysian atrophy (DRPLA); multiple sclerosis; and certain mitochondrial disorders;

* Infectious or parainfectious myoclonus, such as new-variant Creutzfeldt-Jacob disease (nvCJD); subacute sclerosing panencephalitis (SSPE); viral encephalitis; and streptococcal infections;

* Endocrine-based myoclonus such as myoclonus associated with hyperthyroidism, hyponatremia, or hypoglycemia;

* Structural myoclonus including tumors that irritate the brain in a direct manner, tumors that release chemicals into the blood (as in abdominal or thoracic neuroblastoma, which causes the opsoclonus-myoclonus-ataxia syndrome), palatal myoclonus (with injury to the Guillain-Mollaret triangle in the brainstem and cerebellum);

* Drug- or toxin-induced myoclonus. Drugs in this category include: anti-seizure medications (e.g., valproate, carbamazepine, etc.); antidepressants (e.g., amitryptaline, nortryptaline, desipramine, fluoxetine, sertraline, lithium, etc.); stimulants (e.g., amphetamine, dexedrine, methylphenidate, some asthma inhalers, caffeine, etc.); medications that are toxic to the liver, respiratory depressants, corticosteroids, amiodarone, acyclovir, bismuth, thallium, L-dopa;

* Myoclonus associated with systemic illness such as dialysis, renal failure, liver failure, pulmonary disease or carbon dioxide intoxication.

For more information visit Kids Move, http://www.kidsmove.org, WE MOVE's new Web site devoted to pediatric movement disorders. Healthcare professionals and parents may access up-to-date information about the recognition, assessment, treatment and avenues of support available for individuals concerned with childhood movement disorders.

Terence D. Sanger, MD, PhD, is the Director of the Pediatric Movement Disorders Clinic at Lucille Packard Children's Hospital at Stanford University. He is a child neurologist and electrical engineer, and his research laboratory investigates the detailed measurement of movement disorders in children, including ataxia, dystonia, chorea, myoclonus, and spasticity.

Joy E. Bartnett, NASW, AMIA, AMWA, is a medical writer and biomedical informatics specialist for WE MOVE, a not-for-profit organization committed to increasing worldwide education and awareness for movement disorders. For more information, see WE MOVER Web site: http://www.wemove.org.

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