Myoclonus

Myoclonus /maɪˈÉ'klÉ™nÉ™s/ or /maɪəˈkloÊŠnÉ™s/ is a brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. These myoclonic twitches, jerks, or seizures are usually caused by sudden muscle contractions (positive myoclonus) or brief lapses of contraction (negative myoclonus). The most common circumstance under which they occur is while falling asleep (hypnic jerk), but myoclonic jerks are also a sign of a number of neurological disorders. Hiccups are also a kind of myoclonic jerk specifically affecting the diaphragm. When a spasm is caused by another person it is known as a "provoked spasm". Shuddering attacks in babies also fall in this category.

Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern. They may occur infrequently or many times each minute. Most often, myoclonus is one of several signs in a wide variety of nervous system disorders such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, subacute sclerosing panencephalitis, Creutzfeldt-Jakob disease (CJD), serotonin toxicity, some cases of Huntington's disease, some forms of epilepsy, and occasionally in intracranial hypotension. Some researchers indicate that jerks persistently may even cause early tremors.

In almost all instances in which myoclonus is caused by central nervous system disease it is preceded by other symptoms; for instance, in CJD it is generally a late-stage clinical feature that appears after the patient has already started to exhibit gross neurological deficits.

Anatomically, myoclonus may originate from lesions of the cortex, subcortex or spinal cord. The presence of myoclonus above the foramen magnum effectively excludes spinal myoclonus, but further localisation relies on further investigation with electromyography (EMG) and electroencephalography (EEG).

Symptoms

Myoclonic seizure can be described as "jumps." They are caused by rapid contraction and relaxation of the muscles. People without epilepsy can suffer small but similar jerks in the form of hiccups or brief twitches. These are perfectly normal.

In someone with epilepsy, myoclonic seizures can cause abnormal movements on both sides of the body at the same time. In reflex epilepsies, myoclonic seizures can be brought on by flashing lights or other environmental triggers (see photosensitive epilepsy).

Familiar examples of normal myoclonus include hiccups and hypnic jerks that some people experience while drifting off to sleep. Severe cases of pathologic myoclonus can distort movement and severely limit a person's ability to sleep, eat, talk, and walk. Myoclonic jerks commonly occur in individuals with epilepsy. The most common types of myoclonus include action, cortical reflex, essential, palatal, those seen in the progressive myoclonus epilepsies, reticular reflex, sleep and stimulus-sensitive.

Types

Epilepsy forms

• Cortical reflex myoclonus is thought to be a type of epilepsy that originates in the cerebral cortex â€" 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 patients attempt to move in a certain way or perceive a particular sensation.
• 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. Some scientists speculate that some forms of essential myoclonus may be a type of epilepsy with no known cause.
• Juvenile myoclonic epilepsy seizures usually involve the neck, shoulders, and upper arms. These seizures typically occur shortly after waking up. They normally begin between puberty and early adulthood. They can usually be controlled with medication but it must be taken for life.
• Lennox-Gastaut syndrome occurs in rare cases beginning in early childhood and usually involving the face, neck, shoulders, and upper arms. In these cases, the seizures tend to be strong and difficult to control.
• Progressive myoclonus epilepsy (PME) is a group of diseases characterized by myoclonus, epileptic seizures, tonic-clonic 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 at least three forms of PME. Lafora 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 disease is characterized by myoclonus, epileptic seizures, and dementia (progressive loss of memory and other intellectual functions). A second group of PME 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 PME disorders in the class of system degenerations often is accompanied by action myoclonus, seizures, and problems with balance and walking. Many of these PME diseases begin in childhood or adolescence. Treatment is not normally successful for any extended period of time.
• Reticular reflex myoclonus is thought to be 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 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.

Diaphragmatic Flutter

A very rare form includes the diaphragmatic flutter, or the Belly Dancer's Syndrome. It was first discovered by Antony van Leeuwenhoek in 1723. The condition characterizes spoken communication that sounds like a short-breathed hiccup. These muscle spasms can recur dozens of times per day. Rate of diaphragmatic contraction ranges between 35 and 480 contractions per minute, with the average rate found to be 150. Studies show that possible causes include disruptions within the central or peripheral nervous systems, anxiety, nutritional disorder, and certain pharmaceuticals. No single treatment has proven effective, but most involve the blocking or crushing of the phrenic nerve.

Only about 50 people in the world have been diagnosed with it. One notable case is Chaz Moore of Colorado Springs, Colorado, who was interviewed by CNN’s medical correspondent and respected medical expert Dr. Sanjay Gupta. He tried several medications, but only one worked: medical marijuana.

Other forms

• 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.
• 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. 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.
• Middle Ear myoclonus occurs in the muscles of the middle ear. These muscles may include the tensor tympani and stapedius muscles. It can also involve the muscles surrounding the Eustachian tube, which include the tensor veli palatini, levator veli palatini, and salpingopharyngeus. Sufferers describe it as a thumping sound or sensation in the ear.
• Spinal myoclonus is myoclonus originating in the spinal cord, including segmental and propriospinal myoclonus. The latter is usually due to a thoracic generator producing truncal flexion jerk. It is often stimulus-induced with a delay due to the slow conducting propriospinal nerve fibers.
• Stimulus-sensitive myoclonus is triggered by a variety of external events, including noise, movement, and light. Surprise may increase the sensitivity of the patient.
• 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 can also be associated with patients suffering from Tourette syndrome.

Cause

Rarely does myoclonus indicate anything other than arbitrary muscle contraction. Myoclonus may develop in response to infection, head or spinal cord injury, stroke, stress, brain tumors, kidney or liver failure, lipid storage disease, chemical or drug poisoning, as a side effect of certain drugs (such as tramadol quinolones Benzodiazepine and Gabapentin), or other disorders.

Benign myoclonic movements are commonly seen during the induction of general anesthesia with intravenous medications such as etomidate and propofol. These are postulated to result from decreased inhibitory signaling from cranial neurons. Prolonged oxygen deprivation to the brain, 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, Opsoclonus Myoclonus, Creutzfeldt-Jakob disease, Lyme Disease, or lupus. Myoclonic jerks commonly occur in persons with epilepsy, a disorder in which the electrical activity in the brain becomes disordered leading to seizures. It is also found in MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a rare mitochondrial encephalomyopathy. Myoclonus can also be a coexisting condition along with Tourette syndrome.

Jerks of muscle groups, much of the body, or a series in rapid succession, which results in the person jerking bolt upright from a more relaxed sitting position is sometimes seen in ambulatory patients being treated with high doses of morphine, hydromorphone, and similar drugs, and is possibly a sign of high and/or rapidly increasing serum levels of these drugs. Myoclonic jerks also can be caused by some unrelated drugs such as anticholinergics. Opioids which have other neurotransmitter impacts such as tramadol, pethidine, &c. can also cause jerks, but unlike the above are not completely benign.

Pathophysiology

Although some cases of myoclonus are caused by peripheral nervous system injury, most myoclonus is caused by a disturbance of the central nervous system. Studies suggest that several locations in the brain are involved in myoclonus. One such location, for example, is in the brainstem 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 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, 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 benzodiazepines, 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. More research is needed to determine how these receptor abnormalities cause or contribute to myoclonus.

Treatment

In Asia, the mineral calcium, in the form of supplements or antacids, has been widely known to dispel the commonly experienced sleep myoclonus, or hypnic jerk, and also restless leg syndrome.

Concerning more serious afflictions, 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, piracetam, and primidone. Hormonal therapy also may improve responses to antimyoclonic drugs in some people.

Some studies have shown that doses of 5-hydroxytryptophan (5-HTP) leads to improvement in patients with some types of action myoclonus and PME. These differences in the effect of 5-HTP on patients with myoclonus have not yet been explained, but they may offer important clues to underlying abnormalities in serotonin receptors.

Many of the drugs used for myoclonus, such as barbiturates, phenytoin and primidone, are also used to treat epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin and primidone are effective antiepileptics drugs, although phenytoin can cause liver failure or have other harmful long-term effects in 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.

When patients are taking multiple medications, the discontinuation of drugs suspected of causing myoclonus and treatment of metabolic derangements may resolve some cases of myoclonus. When pharmacological treatment is indicated anticonvulsants are the main line of treatment. Paradoxical reactions to treatment are notable. Drugs which most people respond to may in other individuals worsen their symptoms. Sometimes this leads to the mistake of increasing the dose, rather than decreasing or stopping the drug. Treatment of myoclonus focuses on medications that may help reduce symptoms. Drugs used include sodium valproate, clonazepam, the anticonvulsant levetiracetam, and piracetam. Dosages of clonazepam usually are increased gradually until the patient 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 patient develops a tolerance to the drug.

Prognosis

Although myoclonus is not a life-threatening condition, it may result in serious, debilitating impairments. Action myoclonus, with its positive and negative myoclonus components, is generally considered the most serious. It varies from person to person as to whether it is lifelong.