What is myoclonus

Myoclonus describes a symptom and not a diagnosis of a disease. Myoclonus refers to sudden, involuntary jerking of a muscle or group of muscles ¹. 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.

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.

The symptoms associated with myoclonus vary greatly between different people. At one end of the scale myoclonus is quite a harmless condition experienced commonly by most people. For example the “jerk” that is experienced in the very early sleep stages is a type of myoclonus, as are the hiccups. At the other end of the scale, myoclonus is associated with more severe muscle contractions that are usually caused by a one of a number of neurological disorders. In other cases myoclonus is not considered a symptom associated with a disease but is considered as a disorder in itself, however this is quite rare.

Myoclonic jerking may develop in people 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 and leads to seizures. 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. It can occur by itself, but most often it is one of several symptoms associated with a wide variety of nervous system disorders.

Myoclonus types

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.

From this greatly varied expression of myoclonic symptoms it is evident that it is a difficult condition to classify. The first step the neurologist or physical therapist will take in order to classify the condition is to determine the pattern of muscles that are affected. This can be:

• Focal myoclonus: only a very small area, or muscles that are close to each other, are affected;
• Segmental myoclonus: only one or two muscles are affected which are not close to each other (for example the wrist muscles and the thigh muscles);
• Multifocal myoclonus: two or more local areas of muscles which are affected; or
• Generalized myoclonus: widespread muscle contraction.

Opsoclonus myoclonus syndrome

Opsoclonus-myoclonus syndrome (opsoclonus myoclonus) is an inflammatory neurological disorder, often identifiable as paraneoplastic. It is characterized by associated ocular, motor, behavioral, sleep, and language disturbances. The onset is usually abrupt, often severe, and it can become chronic.

Opsoclonus-myoclonus syndrome is a rare disorder affecting 1 in a million individuals worldwide. It usually affects infants and young children, although it is also known to affect adults. The peak age in children is about 18 months, with a long tail out to about 5 – 6 years. Occurrence in infants under 6 months old is quite uncommon, and opsoclonus in that age group, when isolated, is usually from another cause. Opsoclonus-myoclonus syndrome occurs in only slightly more girls than boys. It occurs in about 3% of all children with neuroblastomas.

About 95% of children with opsoclonus-myoclonus syndrome are misdiagnosed as acute cerebellar ataxia because the ataxia may appear before the eye findings. This diagnosis causes delay in recognition and treatment of opsoclonus-myoclonus syndrome. Once opsoclonus is present, however, the diagnosis cannot be acute cerebellar ataxia. Also, children with disproportionately small amounts of opsoclonus or myoclonus are harder to recognize and may carry the wrong diagnosis for years.

Myoclonus can occur in other contexts without opsoclonus and with or without ataxia. It may be epileptic or non-epileptic, rhythmical or arrhythmic, generalized or localized. Myoclonus may accompany a number of neurologic diseases, including seizure disorders, brain injuries, hereditary brain disorders, viral infections, and metabolic or toxic disorders.

Opsoclonus-myoclonus syndrome signs and symptoms

The component features of opsoclonus-myoclonus syndrome include repeated, random and rapid eye movements in both horizontal and vertical directions (opsoclonus); unsteady, gait (ataxia); brief, repeated, shock-like spasms of several muscles within the arms, legs (myoclonus). Extreme irritability, reduced and fragmented sleep (insomnia), rage attacks, difficulty articulating speech (dysarthria), or inability to speak (mutism), decreased muscle tone (hypotonia), and vomiting are common.

Opsoclonus-myoclonus syndrome causes

When opsoclonus and myoclonus occur together, the cause is a tumor until proven otherwise— not a brain tumor, but rather an occult body cavity tumor. In approximately 50 percent of affected children, a tumor of embryonic nerve cells (neuroblastoma) is responsible for the symptoms associated with opsoclonus-myoclonus syndrome. In other cases, the disorder has been designated ‘idiopathic’ or attributed to various mostly viral infections, such as Coxsackie virus B3 or St. Louis encephalitis virus, however, the high rate of spontaneous tumor regression means that the tumor may be gone before it is looked for. In adults, the tumors are most often lung and breast cancer.

Opsoclonus-myoclonus syndrome diagnosis

The diagnosis is clinical; there is no diagnostic test yet, as the antigen remains unidentified. The presence of the ‘dancing eyes’, the shock-like muscle spasms, and the stumbling gait, especially if accompanied by irritability, are highly reliable indicators of this syndrome. To detect a tumor in children, both a CT scan of the neck, chest, abdomen, and pelvis (with oral and IV contrast) as well as an MIBG scan need to be done. PET scanning is often done in adults. In addition, a spinal tap to detect neuroinflammation is necessary. Besides routine tests for infection, recommended CSF studies include oligoclonal bands (with paired serum sample), which are autoantibodies secreted by B cells in the CSF. Also, lymphocyte subset analysis using immunophenotyping reveals an increased frequency of CSF B cells, which is an invaluable biomarker of opsoclonus-myoclonus syndrome disease activity. Studies of cytokines/chemokines, which are inflammatory mediators, have identified an increase of B-cell attractants (CXCL13) and activators (BAFF) in CSF. Autoantibodies in some children with opsoclonus-myoclonus syndrome have been at detected in research laboratories, but commercial autoantibody testing is not cost-effective and best reserved for atypical cases.

Opsoclonus-myoclonus syndrome treatment

The main tenet of treatment for opsoclonus-myoclonus syndrome is early and sufficient immunotherapy with the goal of gaining a durable complete neurological remission. If a tumor is present, surgical resection is standard. The tumors are usually low stage (I or II), and tumor chemotherapy or radiation therapy are not indicated. Tumor resection does not usually provide sufficient clinical benefit for opsoclonus-myoclonus syndrome, however. opsoclonus-myoclonus syndrome treatment, which is usually continued over 1-2 years, should involve combined immunotherapies as soon as possible after diagnosis. FLAIR therapy is a three-agent protocol involving front-loaded high-dose ACTH (corticotropin), IVIg, and rituximab that was developed by the National Pediatric Myoclonus Center for pediatric opsoclonus-myoclonus syndrome, and has the best-documented outcomes for moderately severe and severe cases. Rituximab is a monoclonal antibody against B cells (anti-CD20). Almost all patients (80-90%) show improvement with this treatment. Over time, treatment with ACTH may have mostly cortisol-related adverse effects that must be monitored carefully. Pulse dose dexamethasone instead of ACTH is an option in mild and more moderate cases. The use of prednisone-type oral steroids is not recommended, because they are the least effective of the steroids for pediatric opsoclonus-myoclonus syndrome. For opsoclonus-myoclonus syndrome relapse, low-dose IV cyclophosphamide (3-6 cycles) or more rituximab (1-2 cycles) are given. Oral weekly methotrexate may be a useful steroid sparer in chronic relapse. A biomarker-guided approach, which led to the introduction of anti-B-cell monoclonal antibodies in opsoclonus-myoclonus syndrome, promises to give rise to new therapeutic targets and strategies.

Opsoclonus-myoclonus syndrome prognosis

Almost all children with neuroblastoma and opsoclonus-myoclonus syndrome survive their tumor, which usually does not behave aggressively, though some tumors may be large and pose difficulties for resection. In contrast, the tumors that afflict adults are sometimes fatal. The opsoclonus-myoclonus syndrome relapse rate in children treated with only conventional agents is 50-75%. Increased immunosuppression has improved neurodevelopmental outcomes in opsoclonus-myoclonus syndrome. With FLAIR therapy, the relapse rate appears to be much lower. opsoclonus-myoclonus syndrome onset in the first year of life is particularly damaging to expressive speech and language development, and may result in a higher incidence of cognitive impairment. The best responders appear to be those who received early combination therapy and were only of mild to moderate severity. Failure to achieve complete neurological remission and multiple relapses may result in chronic-progressive opsoclonus-myoclonus syndrome, with permanent deficits, such as ADD/ADHD, OCD, and irreversible cognitive impairment (low IQ). Children in the chronic sick role can become oppositional, depressed, and aggressive, and attention to these issues often helps to improve quality of life.

Action myoclonus

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

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 individuals attempt to move in a certain way (action myoclonus) or perceive a particular sensation.

Epileptic myoclonus

This type of myoclonus occurs as part of an epileptic disorder.

Essential myoclonus

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. In some families, there is an association of essential myoclonus, essential tremor, and even a form of dystonia, called myoclonus dystonia. Another form of essential myoclonus may be a type of epilepsy with no known cause.

Myoclonus on standing

Myoclonus on standing is myoclonus that is exhibited when the person is standing, significantly lessening when walking, sitting or lying.

Palatal myoclonus

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. Some people with palatal myoclonus 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. The disorder can cause discomfort and severe pain in some individuals.

Physiological myoclonus

Physiological myoclonus is the most a common type of myoclonus which often occurs in otherwise healthy people.

This type of myoclonus occurs in normal, healthy people and rarely needs treatment. Examples include:

• Hiccups which are caused by myoclonus of the diaphragm
• Sleep jerks
• Shakes or spasms due to anxiety or exercise
• Infant muscle twitching during sleep or after a feeding

Progressive myoclonus epilepsy

Progressive myoclonus epilepsy describes a large and varied group of progressive disorders that involve myoclonus with the main complaint of 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 many forms of progressive myoclonus epilepsy. 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 progressive myoclonus epilepsy 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 progressive myoclonus epilepsy disorders in the class of system degenerations often is accompanied by action myoclonus, seizures, and problems with balance and walking. Many of these progressive myoclonus epilepsy diseases begin in childhood or adolescence.

Juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy is a progressive myoclonus epilepsy that is a common cause of myoclonic and clonic-tonic seizures (body rigidity followed by jerking) in epilepsy. Some people with juvenile myoclonic epilepsy will experience myoclonic seizures as their only seizure type.

Reticular reflex myoclonus

Reticular reflex myoclonus is thought to be a type of generalized epilepsy that originates in the brain stem, 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.

Secondary myoclonus

Muscle jerks that occur as a result of an underlying medical condition, including:

• Head or spinal cord injury
• Infection
• Kidney or liver failure
• Lipid storage disease
• Chemical or drug poisoning
• Prolonged oxygen deprivation
• Medication reaction
• Autoimmune inflammatory conditions
• Metabolic disorders

Nervous system conditions that result in secondary myoclonus include:

• Stroke
• Brain tumor
• Huntington’s disease
• Creutzfeldt-Jakob disease
• Alzheimer’s disease
• Parkinson’s disease and Lewy body dementia
• Corticobasal degeneration
• Frontotemporal dementia
• Multiple system atrophy

Stimulus-sensitive myoclonus

Stimulus-sensitive myoclonus is triggered by a variety of external events, including noise, movement, and light. Surprise may increase the sensitivity of the individual.

Sleep myoclonus

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.

Myoclonus causes

Although rare 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. Myoclonus is thought to originate in various locations in the central nervous system such as the cerebral cortex (the part of the brain responsible for initiating voluntary movement), cerebellum (the part of the brain responsible for fine-tuning voluntary movement), brainstem (plays a key role in movement) or spinal cord (transmits signals from the brain to the body). Studies suggest that several locations in the brain are involved in myoclonus. One such location, for example, is in the brain stem close to structures that are responsible for the startle response, an automatic reaction to an unexpected stimulus involving rapid muscle contraction.

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.

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 and gamma-aminobutyric acid (GABA). Other receptors with links to myoclonus include those for opiates and glycine, the latter 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.

Myoclonus is often a symptom associated with the following neurological events and conditions:

• Spinal cord injury;
• Epilepsy;
• Multiple sclerosis;
• Alzheimer’s disease;
• Parkinson’s disease;
• Lipid storage disease;
• Brain tumor;
• Chemical or drug poisoning;
• Complex-region pain syndrome;
• After prolonged oxygen deprivation to the brain (a condition named hypoxia or anoxia);
• Stroke;
• Mitochondrial encephalopathy;
• Heart attack;
• Kidney failure; and
• Liver failure.

Myoclonus symptoms

People with myoclonus often describe their signs and symptoms as jerks, shakes or spasms that are:

• Sudden
• Brief
• Involuntary
• Shock-like
• Variable in intensity and frequency
• Localized to one part of the body or all over the body
• Sometimes severe enough to interfere with eating, speaking or walking

Myoclonus diagnosis

To diagnose myoclonus, your doctor will review your medical history and symptoms and conduct a physical examination.

To determine the cause of myoclonus and rule out other potential causes of your condition, your doctor may recommend several tests, including:

Electroencephalography (EEG)

This procedure records the electrical activity of your brain and may help determine where in your brain the myoclonus originates. In this procedure, doctors attach small electrodes to your scalp. You may be asked to breathe deeply and steadily and look at bright lights or listen to sounds, as these actions may uncover abnormal electrical activity.

Electromyography (EMG)

This test measures the electrical discharges produced in muscles and helps establish the pattern of myoclonus. In this procedure, doctors put EMG surface electrodes on multiple muscles, especially on those muscles that are involved in the jerking.

An instrument records the electrical activity from your muscle at rest and as you contract the muscle, such as by bending your arm. These signals help to determine the pattern and origin of the myoclonus.

Magnetic resonance imaging (MRI)

An MRI scan may be used to check for structural problems or tumors inside your brain or spinal cord, which may cause your myoclonus symptoms. An MRI scan uses a magnetic field and radio waves to produce detailed images of your brain, spinal cord and other areas of your body.

Laboratory tests

Your doctor may suggest genetic testing to help identify possible causes of myoclonus. He or she may also test your blood or urine to check for:

• Metabolic disorders
• Autoimmune disease
• Diabetes
• Kidney or liver disease
• Drugs or toxins

Myoclonus treatment

Treatment of myoclonus is most effective when a reversible underlying cause can be found that can be treated — such as another condition, a medication or a toxin.

Most of the time, however, the underlying cause can’t be cured or eliminated, so treatment is aimed at easing myoclonus symptoms, especially when they’re disabling. There are no drugs specifically designed to treat myoclonus, but doctors have borrowed from other disease treatment arsenals to relieve myoclonic symptoms. More than one drug may be needed to control your symptoms.

Medications

Medications that doctors commonly prescribe for myoclonus include:

• Tranquilizers. Clonazepam (Klonopin), a tranquilizer, is the most common drug used to combat myoclonus symptoms. Clonazepam may cause side effects such as loss of coordination and drowsiness.
• Anticonvulsants. Drugs used to control epileptic seizures have also proved helpful in reducing myoclonus symptoms. The most common anticonvulsants used for myoclonus are levetiracetam (Keppra), valproic acid (Depakene) and primidone (Mysoline). Valproic acid may cause side effects such as nausea. Levetiracetam may cause side effects such as fatigue and dizziness. Side effects from primidone may include sedation and nausea.

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 individual 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 individual develops a tolerance for the drug.

Many of the drugs used for myoclonus, such as barbiturates, levetiracetam,phenytoin, and primidone, are also used to treat epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin, levetiracetam, and primidone are effective antiepileptic drugs, although phenytoin can cause liver failure or have other harmful long-term effects in individuals with progressive myoclonus epilepsy. 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 people 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 people with some types of action myoclonus and progressive myoclonus epilepsy. 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 individuals. These differences in the effect of 5-HTP on individuals 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, levetiracetam, and primidone. Hormonal therapy also may improve responses to antimyoclonic drugs in some people.

Therapies

OnabotulinumtoxinA (Botox) injections may be helpful in treating various forms of myoclonus, particularly if only a single area is affected. Botulinum toxins block the release of a chemical messenger that triggers muscle contractions.

Surgery

If your myoclonus symptoms are caused by a tumor or lesion in your brain or spinal cord, surgery may be an option. People with myoclonus affecting parts of the face or ear also may benefit from surgery.

Deep brain stimulation has been tried in some people with myoclonus and other movement disorders. Researchers continue to study deep brain stimulation for myoclonus.

1. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myoclonus-Fact-Sheet[↩]