Etiologic Classification
The most commonly used classification of myoclonus is based upon the cause, or etiology, or the movements. This classification scheme includes
- Physiologic myoclonus
- Essential myoclonus
- Myoclonic epilepsy
- Secondary or symptomatic myoclonus
Physiologic Myoclonus
Physiologic myoclonus is a normal occurrence, with little or no associated disability. Examples of physiologic myoclonus include hypnic jerks, otherwise known as sleep starts, that occasionally occur at the onset of sleep. Hiccups (singultus) are actually a form of myoclonus resulting from the rhythmic contraction of the diaphragm and rarely require medical treatment. The final form of physiologic myoclonus is benign sleep myoclonus of infancy, which usually occurs during early infancy (immediately after the baby is born) and is often mistaken for epilepsy. The inappropriate treatment of this disorder with anticonvulsant drugs may lead to increased sedation and more myoclonic jerks. The key feature of benign sleep myoclonus of infancy is its relationship in time to the onset of sleep.
Essential Myoclonus
The second category of myoclonus, based on the cause, is essential myoclonus. By definition, essential myoclonus is idiopathic, meaning that it occurs for unknown reasons. It may occur spontaneously or in association with a family history of myoclonus, likely in an autosomal-dominant pattern of inheritance. When genetically transmitted, essential myoclonus usually occurs along with tremor or dystonia, with a genetic location on the long arm of chromosome 7 at 7q21-q31. The gene for chromosome 7-linked essential myoclonus is called ε-sarcoglycan (SCGE). Essential myoclonus may be nonprogressive or only minimally progressive. It typically affects many parts of the body (multifocal).
Progressive Myoclonic Epilepsy
The third category of myoclonus, based on etiology, is progressive myoclonic epilepsy or PME. PMEs include
Predominance of Myoclonus
- In some patients, myoclonic movements are quite pronounced. In others, seizures rather than myoclonus are more pronounced.
Cognitive Involvement
Myoclonic epilepsy may be categorized based on cognitive involvement. Disorders that typically involve the decline in the thought processes include Lafora disease, neuronal ceroid lipofuscinosis, MERRF, and sialidosis. Patients with Unverricht-Lundborg disease, an autosomal-recessive disorder, usually have mild dementia but little cognitive decline. Severe stimulus-sensitive myoclonus may occur along with generalized tonic-clonic seizures.
Age of Onset
Myoclonic epilepsy may also be categorized based on age of onset. In PME, myoclonic epilepsy is the defining symptom. Dementia and ataxia develop rapidly, typically beginning at age 6 to 15 years. Juvenile myoclonic epilepsy, which is characterized by myoclonic jerks upon awakening, has its onset during early adolescence, with a nondegenerative disease course. Familial adult myoclonic epilepsy has an onset of symptoms in adulthood. This disorder is not associated with a degenerative disease course. The myoclonus is typically seen as generalized jerks of the limbs and tremor of the fingers, with rare generalized tonic-clonic seizures. The genetic transmission is autosomal dominant, with the gene identified on the long arm of chromosome 8 at 8q24.
- Predominance of myoclonus
- Cognitive involvement
- Age of onset
Secondary Myoclonus
Most patients with myoclonus have secondary, also known as symptomatic, myoclonus. The list of associated conditions is lengthy and includes
- Inborn errors of metabolism
- Trauma
- Neurodegenerative diseases
- Viral or mitochondrial encephalopathies
- Metabolic problems
- Drug-induced syndromes
- Toxin exposure
- Celiac disease
Secondary myoclonus occurs in specific inherited metabolic diseases of childhood and adolescence, such as lysosomal storage diseases, including Gaucher disease (types 2 and 3), Tay-Sachs disease, Sandhoff disease, and sialidosis type II. The exact symptoms of myoclonus vary from one condition to another.
Trauma occurring at the level of the brain, spinal cord, or peripheral nervous system may result in myoclonic movements. Brain trauma may include injury, infectious agents (e.g., Creutzfeldt-Jakob disease), neoplasm (a growth of abnormal tissue, either cancerous or benign), inflammation, or hypoxia (Lance Adams syndrome). Spinal cord trauma can be the result of injury, inflammation, infection, or an area of damaged tissue (lesion).
Neurodegenerative diseases are conditions that involve the loss of the structure or function of tissue within the nervous system. Many of these types of diseases often have myoclonus as a part of the condition. These diseases include the spinocerebellar ataxias (SCAs), multiple system atrophy, corticobasal ganglionic degeneration, Huntington disease, Parkinson's disease, Lewy body dementia, subacute sclerosing panencephalitis, and Alzheimer's disease, MERRF, and a condition of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
Metabolic problems may be inherited, such as those associated with PME or progressive myoclonic ataxia. They may also be sporadic, such as those related to kidney failure, liver failure, abnormally high levels of carbon dioxide in the blood (hypercapnia), abnormally high levels of circulating glucose (hyperglycemia), and abnormally high levels of alkalinity (high pH) in the blood (metabolic alkalosis).
Drugs that are associated with myoclonic movements include
- Anesthetic agents such as etomidate and propofol
- Serotonergic drugs
- Opiates
- Anticonvulsants (carbamazepine, phenytoin, lamotrigine, vigabatrin)
- Mefloquine
- Gatifloxacin
- Tranexamic acid
- Γ-Hydroxybutyrate
- Antineoplastic agents
- Contrast agents used in x-rays or other imaging studies
- Dopamine agonists and antagonists
Exposure to a wide range of toxins—including gases, metals, organic solvents, and pesticides—may result in myoclonus. A few of the more common toxins that may cause myoclonus are lithium, bismuth, aluminum (particularly in patients with kidney failure), methyl bromide intoxication, tetanus, lead, mercury, enteropathogenic toxin (such as E. coli), acetone, toluene, strychnine, carbon monoxide, organophosphate compounds (such as insecticides, nerve gases, and herbicides), and baking soda.
Many people with celiac disease have myoclonic movements. Typically, myoclonus does not respond well to the removal of gluten from the diet.
