Definition Myoclonus is "sudden, brief, jerky, shock-like, involuntary movements" (Fahn et. al. 1986). The movements are quite rapid and may be triggered by attempts at voluntary movement, sensory stimulation, or startle. Myoclonus may cause rhythmic jerks, in which case, it is termed a "myoclonic tremor." Myoclonus is categorized based upon the likely source of movement. Such sources include cortical or subcortical areas or the spinal cord. Myoclonus may be severely disabling, particularly when it is triggered by movement. Cortical myoclonus is thought to be due to a lack of inhibition in the sensory or motor cortex. Subcortical myoclonus is often due to abnormalities in the brainstem; spinal myoclonus is presumed to be due to abnormalities in spinal inhibitory circuits. Myoclonus may be severely disabling, particularly when it is triggered by movement. In some cases, it may also be very mild. The most common example of a mild myoclonus is sleep myoclonus. In this form of myoclonus, most adults have occasional brief jerks of an arm or a leg; these "jerks" occur while the individual is falling asleep. Negative myoclonus is a sudden involuntary relaxation of a muscle, rather than a contraction; this is thought to be due to mechanisms similar to those of sleep myoclonus. Cortical reflex myoclonus is triggered by attempts to obtain a knee jerk or other tendon reflex. Epilepsia partialis continua is a type of focal epilepsy that causes myoclonic tremor. Myoclonus is often associated with epilepsy; there is a particular class of degenerative disorders called "progressive myoclonus Epilepsies (PMEs)." In this class of disorders in which the association of myoclonus and epilepsy is common. Examination As with other movement disorders, it is important to determine which parts of the body are affected by myoclonus. It may occur in a single limb, the neck, the back, or the face. In other cases, it may affect the entire body. When severe, myoclonus may cause the child to fall. It is important to determine whether symptoms improve or worsen with voluntary activity. This is often tested by observing the child while attempting to drink from a cup. In some cases, a myoclonic jerk may be caused by an unexpected, loud noise or a gentle tap on the tip of the nose or on the forehead. Myoclonus may occur along with other movement disorders. The myoclonus may be observed as rhythmic, always affects the same body parts, or move throughout the body. To test for negative myoclonus, also known as asterixis, children are asked to extend their arms with the wrists back or to perform some other movement that requires holding the limb against gravity. In this way, a sudden loss of muscle contraction causes the hand or the arm to fall in a downward direction. Since myoclonus may occur along with other movement disorders, it is important to look for evidence of dystonia, tremor, ataxia, or spasticity. It is also important to look for opsoclonus, which is a random, dance-like jerking of the eyes in all directions. This eye movement occurs in the opsoclonus-myoclonus-ataxia syndrome.

Mechanism

The mechanism of myoclonus is not well understood. Cortical myoclonus is possibly a disorder of decreased inhibition in the cortex.

There may be a common cause for myoclonus and some types of epilepsy.

The frequent association with seizure disorders suggests that there may be a common cause for myoclonus and some types of epilepsy. However, the reason for the reduced inhibition is not known. The mechanism of subcortical and spinal myoclonus is even less well understood.

A group of disorders called "startle syndromes" probably involves hyperexcitability of the normal brainstem startle circuits and decreased inhibition in spinal circuits. This is due to a mutation in the receptor for the neurotransmitter glycine

Etiology

Physiological:
Sleep myoclonus, benign myoclonus of infancy

Essential Myoclonus:
Familial essential myoclonus, essential myoclonus-dystonia, stimulus-sensitive myoclonus

Epileptic:
Juvenile myoclonic epilepsy, progressive myoclonic epilepsies, epilepsia partialis continua, Rasmussen's encephalitis, early infantile myoclonic encephalopathy, infantile spasms (West syndrome), Lennox-Gastaut syndrome, benign familial myoclonic epilepsy, Angelman syndrome

Symptomatic:
Glutaric aciduria, acyl-CoA dehydrogenase deficiency, aromatic L-amino acid decarboxylase deficiency, dopa-responsive dystonia or DRD (biopterin metabolic defect DYT5, or tyrosine hydroxylase deficiency), dopamine agonist-responsive dystonia (or ALAD: aromatic L-amino acid decarboxylase deficiency), mitochondrial disorders, Wilson's disease, homocystinuria, GM1 gangliosidosis, metachromatic leukodystrophy, Lesch-Nyhan disease, Niemann-Pick type C, methylmalonic aciduria, tyrosinemia

• Fixed injury:
  Carbon-monoxide poisoning, hypoxic injury or near-drowning (Lance-Adams syndrome), heatstroke, trauma, stroke, electrocution
  
  
• Storage/Degenerative:
  Sialidoses (cherry-red-spot-myoclonus), lipidoses, lysosomal storage disease (Niemann-Pick type C, Tay-Sachs, Sandhoff's), other storage disorders (neuronal ceroid lipofuscinosis, neuronal brain iron accumulation type 1 (NBIA-I, formerly Hallervorden-Spatz disease), Wilson's disease, Lafora body disease), baltic myoclonus, spinocerebellar ataxias (SCAs), dentatorubropallidoluysian atrophy (DRPLA), multiple sclerosis, mitochondrial disorders (e.g., myoclonic epilepsy with ragged-red fibers [MERRF], etc.)
  
  
• Infections/Para-infectious:
  New-variant Creutzfeldt-Jacob disease (nvCJD), subacute sclerosing panencephalitis (SSPE), viral encephalitis, streptococcus
  
  
• Endocrine:
  Hyperthyroidism, hyponatremia, hypoglycemia
  
  
• Structural:
  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)
  
  
• Drug-induced/toxins:
  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.), hepatotoxic medications, respiratory depressants, corticosteroids, amiodarone, acyclovir, bismuth, thallium, L-dopa
  
  
• Associated with systemic illness:
  Dialysis, renal failure, liver failure, pulmonary disease, carbon dioxide intoxication
  

Workup

Myoclonus may be tested by looking at the electrical activities in brain and affected muscle(s). Electromyography (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.

In cortical myoclonus, there may be an excessively large brain electrical response to electrical stimulation of the hands or feet. This response is tested by using somatosensory-evoked potentials (SSEPs). In some cases, it is also possible to demonstrate the myoclonic electrical signal in muscle following a tendon tap. This may be helpful in diagnosing cortical reflex myoclonus.

In any form of myoclonus, it is important to look for a cause. Any possible medication or toxin that could produce the symptoms must be removed.

Family history needs to be investigated and metabolic studies may be appropriate, particularly if there are other symptoms or symptoms become progressively worse. Metabolic tests may include screening for treatable disorders such as Wilson's 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 particular, in the opsoclonus-myoclonus syndrome, the child should have a CT of the chest and abdomen as well as blood and urine tests. These tests look for evidence of a neuroblastoma tumor. If there is a suspicion of an epilepsy syndrome, an electroencephalogram (EEG) is important to look for evidence of this.

Brain MRI is important to look for tumors, stroke, malformations, or other structural lesions near the cortex, brainstem, or cerebellum. This is particularly true if the myoclonus is focal or if the child is suspected of having the syndrome of epilepsia partialis continua. Since certain viral infections can cause myoclonus, a spinal tap is sometimes needed for this diagnosis.

Many cases of essential myoclonus or essential myoclonus-dystonia will improve with small amounts of alcohol. Although this is useful for diagnosis, it is not helpful for long-term treatment.

Treatment

If a specific cause can be found, then the myoclonus will usually resolve if treatment of the underlying disease is effective. Immune-mediated myoclonus (such as occurs in opsoclonus-myoclonus) usually requires treatment with oral steroids such as prednisone, in addition to removal of the tumor if one is found.

Carbamazepine may worsen myoclonus and should be avoided.

Intravenous immunoglobulin and plasmapheresis has also been attempted in some cases.

Juvenile myoclonus epilepsy usually responds to valproate, and may require life-long treatment. Symptomatic treatment usually includes benzodiazepines such as clonazepam or diazepam.

Cortical myoclonus may respond to valproate, piracetam, or lamotrigine. There are reports of myoclonus due to a hypoxic event responding to 5-hydroxy-tryptophan (5HT), and this may be helpful in other causes as well. Carbamazepine may worsen myoclonus and should be avoided.