Myoclonus

Myoclonus is a sudden, brief, jerky muscle twitching that occurs as a result of active muscle contraction (positive myoclonus) or (rarely) a drop in postural muscle tone (negative myoclonus).

Nosological diagnostics should be preceded by an adequate syndromic description of myoclonus. The latter has several complex clinical characteristics. In particular, clinical analysis of myoclonus must necessarily take into account its features such as the degree of generalization and the nature of distribution (localization), severity, synchronicity/asynchrony, rhythmicity/arrhythmia, permanence/episodicity, dependence on provoking stimuli, dynamics in the "wakefulness-sleep" cycle.

Based on the above characteristics, myoclonic syndromes may vary significantly in individual patients. Thus, myoclonus is sometimes limited to the involvement of a single muscle, but more often it affects several or even many muscle groups up to complete generalization. Myoclonic jerks may be strictly synchronous in different muscles or asynchronous, they are mostly arrhythmic and may or may not be accompanied by movement in the joint. Their severity can vary from a barely noticeable contraction to a sharp general jerk, which can lead to the patient falling. Myoclonus may be single or repetitive, very persistent, or fluctuating, or strictly paroxysmal (for example, epileptic myoclonus). Oscillatory myoclonus is characterized by sudden ("explosive") movements lasting several seconds, they are usually caused by unexpected stimuli or active movements. There are spontaneous myoclonus (or resting myoclonus) and reflexive myoclonus, provoked by sensory stimuli of different modalities (visual, auditory or somatosensory). There are myoclonus caused by voluntary movements (action, intentional and postural myoclonus). Finally, there are myoclonus dependent and independent of the "wake-sleep" cycle (disappearing and not disappearing during sleep, appearing only during sleep).

According to distribution, focal, segmental, multifocal and generalized myoclonus are distinguished (similar to the syndromic classification of dystonia).

The above clinical characteristics of myoclonus (or, in other words, syndromic analysis) are usually supplemented by pathophysiological and etiological classification.

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Symptomatic myoclonus

Symptomatic (secondary) myoclonus develops within the framework of various neurological diseases.

Storage diseases are a series of illnesses that exhibit a characteristic set of syndromes in the form of epileptic seizures, dementia, myoclonus, and some neurological and other manifestations. Many of these diseases begin in infancy or childhood.

• Lafora disease is a rare disorder inherited in an autosomal recessive manner. The disease debuts at the age of 6-19 years. Generalized tonic-clonic epileptic seizures are typical, which are often combined with partial occipital paroxysms in the form of simple visual hallucinations, the appearance of scotomas or more complex visual disorders. Visual paroxysms are a characteristic sign of Lafora disease, in 50% of patients they occur already in the early stages of the disease. Soon, severe myoclonic syndrome develops, which often obscures the accompanying ataxia. Transient cortical blindness has been described. In the terminal stage, severe dementia develops, patients are bedridden. EEG shows epileptic activity in the form of "spike-slow wave" and "polyspike-slow wave" complexes, especially in the occipital areas. In diagnostics, great importance is attached to the detection of Lafora bodies in a skin biopsy in the forearm area (using light microscopy). A fatal outcome occurs several years after the onset of the disease.
• GM ₂ - gangliosidosis (Tay-Sachs disease) is inherited in an autosomal recessive manner and debuts in the first year of life with mental retardation; the neurological status reveals progressive generalized hypotonia, blindness, and loss of all voluntary movements. Hypotonia is replaced by spasticity and opisthotonus; epileptic generalized and partial myoclonic seizures and helolepsy develop. When examining the fundus, the "cherry pit" symptom is revealed. Patients die in the 2nd or 3rd year of life.
• Ceroid lipofuscinosis is characterized by the deposition of lipopigments in the central nervous system, hepatocytes, cardiac muscle, and retina. There are several types of ceroid lipofuscinosis: infantile, late infantile, early juvenile (or intermediate), juvenile, and adult. In all variants, the central manifestation is progressive myoclonus epilepsy. Electron microscopy of the skin and lymphocytes reveals characteristic “fingerprint” profiles.

• Sialidosis.
  • Cherry pit myoclonus is a type I sialidosis. The disease is based on neuroaminidase deficiency (inheritance type is autosomal recessive). The disease begins between 8 and 15 years of age. The main symptoms are: visual impairment, myoclonus and generalized epileptic seizures. Myoclonus is observed at rest, it intensifies with voluntary movements and when touched. Sensory stimulation provokes the development of massive bilateral myoclonus. The most typical symptom is myoclonus of the facial muscles: spontaneous, irregular, with predominant localization around the mouth. Facial myoclonus persists during sleep. Ataxia is characteristic. On the fundus - the "cherry pit" symptom, sometimes - vitreous opacity. The course is progressive. On the EEG - "spike-slow wave" complexes, coinciding with generalized myoclonus.
  • Another rare form of sialidosis is galactosialidosis. It is manifested by galactosidase deficiency (determined in lymphocytes and fibroblasts), which is manifested by mental retardation, angiokeratoma, chondrodystrophy and short stature, epileptic seizures and myoclonic hyperkinesis.
• Gaucher disease is known in 3 forms: infantile (type I), juvenile (type II) and chronic (type III). It is type III that can sometimes manifest itself as progressive myoclonus epilepsy, as well as splenomegaly, decreased intelligence, cerebellar ataxia, and pyramidal syndrome. EEG shows epileptic activity in the form of "polyspike-slow wave" complexes, and in some cases the amplitude of SSEP increases. Accumulations of glucocerebroside are found in biopsies of various organs, lymphocytes, and bone marrow.

Hereditary degenerative diseases of the cerebellum, brainstem and spinal cord (spinocerebellar degenerations).

• Unverricht-Lundborg disease is the best known form of the so-called progressive myoclonus epilepsies. Two populations of patients with this disease have been studied in detail: in Finland (this variant of myoclonus has recently been called Baltic myoclonus) and the Marseille group (Ramsay Hunt syndrome, also called Mediterranean myoclonus). Both variants have a similar clinical picture, age of onset of the disease and the type of inheritance (autosomal recessive). In about 85% of cases, the disease begins in the 1-2nd decade of life (6-15 years). The main syndromes are myoclonic and epileptic. Epileptic seizures are most often clonic-tonic-clonic in nature. Action myoclonus gradually progresses and becomes the main maladaptive factor. Myoclonus can transform into a seizure. Mild ataxia and slowly progressive intellectual impairment are also possible. Other neurological symptoms are not characteristic.
• Friedreich's ataxia, in addition to other symptoms, may also manifest itself as myoclonic syndrome. The disease begins before the end of puberty (on average 13 years), slowly progressive ataxia (sensory, cerebellar or mixed), pyramidal syndrome, dysbasia, dysarthria, nystagmus and somatic disorders (cardiomyopathy, diabetes mellitus, skeletal deformities, including Friedreich's foot) are typical.

Hereditary degenerative diseases with predominant involvement of the basal ganglia.

• Wilson-Konovalov disease often develops at a young age against the background of symptoms of liver dysfunction and is manifested by polymorphic neurological (various types of tremor, chorea, dystonia, akinetic-rigid syndrome, myoclonus), mental and somatic (hemorrhagic syndrome) disorders. The study of copper-protein metabolism and the detection of the Kayser-Fleischer ring allow us to make the correct diagnosis.
• Torsion dystonia is quite often combined with myoclonus (as well as with tremor), but this combination is especially characteristic of symptomatic myoclonic dystonia (Wilson-Konovalov disease, postencephalitic parkinsonism, lysosomal storage diseases, delayed postanoxic dystonia, etc.) and hereditary dystonia-myoclonus syndrome.
• Hallervorden-Spatz disease is a rare familial disorder that begins in childhood (before age 10) and is characterized by progressive dysbasia (foot deformity and slowly increasing rigidity in the limbs), dysarthria, and dementia. Some hyperkinesis (chorea, dystonia, myoclonus) is detected in 50% of patients. Spasticity, epileptic seizures, pigment retinitis, and optic nerve atrophy have been described in some cases. CT or MRI shows damage to the globus pallidus due to iron accumulation ("tiger's eye").
• Corticobasal degeneration is a disease in which myoclonus is considered a fairly typical symptom. Progressive akinetic-rigid syndrome in a mature patient, accompanied by involuntary movements (myoclonus, dystonia, tremor) and lateralized cortical dysfunction (limb apraxia, alien hand syndrome, complex sensitivity disorders) suggest corticobasal degeneration. The disease is based on asymmetric frontoparietal atrophy, sometimes detected on CT or MRI.

Some diseases that manifest as dementia, such as Alzheimer's disease and especially Creutzfeldt-Jakob disease, may be accompanied by myoclonus. In the first case, non-vascular dementia comes to the forefront in the clinical picture, while in the second case, dementia and myoclonus occur against the background of other progressive neurological syndromes (pyramidal, cerebellar, epileptic, etc.) and characteristic EEG changes (three- and polyphasic activity of acute form with an amplitude of up to 200 μV, occurring at a frequency of 1.5-2 Hz).

Viral encephalitides, especially encephalitis caused by the herpes simplex virus, subacute sclerosing encephalitis, Economo encephalitis and arboviral encephalitis, are often accompanied (along with other neurological manifestations) by myoclonus, which is a fairly characteristic element of their clinical picture.

Metabolic encephalopathies in diseases of the liver, pancreas, kidneys, lungs, in addition to disorders of consciousness, often manifest themselves with symptoms such as tremor, myoclonus, epileptic seizures. Negative myoclonus (asterixis) is highly characteristic of metabolic encephalopathy (see below), in these cases it is usually bilateral and sometimes occurs in all limbs (and even in the lower jaw). Asterixis can have both cortical and subcortical origin.

A special group of metabolic encephalopathies are some mitochondrial diseases accompanied by myoclonus - MERRF and MELAS syndromes.

• Myoclonus Epilepsia, Ragged Red Fibres (MERRF) is inherited by the mitochondrial type. The age of onset of the disease varies from 3 to 65 years. The most typical manifestations are progressive myoclonus epilepsy syndrome, which is accompanied by cerebellar ataxia and dementia. Otherwise, the clinical picture is characterized by polymorphism: sensorineural deafness, myopathic symptoms, optic nerve atrophy, spasticity, peripheral neuropathy, sensory impairment. The severity of the course is also extremely variable. EEG shows abnormal basic activity (80%), spike-slow wave complexes, polyspike-slow wave complexes, diffuse slow waves, photosensitivity. Giant SSEPs are detected. CT or MRI reveal diffuse cortical atrophy, white matter changes of varying severity, basal ganglia calcifications, and focal cortical lesions of low density. Skeletal muscle biopsy reveals a characteristic pathomorphological feature - "torn" red fibers. Biochemical analysis reveals elevated lactate levels.
• Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS syndrome) is caused by specific mutations in mitochondrial DNA. The first signs of the disease usually appear at the age of 6-10 years. One of the most important symptoms is intolerance to physical exertion (after which the patient feels worse, muscle weakness and sometimes myalgia appear). Migraine-like headaches with nausea and vomiting are characteristic. Another unusual and characteristic symptom is stroke-like episodes with headache, focal neurological symptoms (paresis and paralysis of the limbs and muscles innervated by the cranial nerve, comatose states), they are provoked by fever, intercurrent infections and are prone to relapse. They are caused by acute deficiency of energy resources in cells and, as a result, high sensitivity to potential toxic effects ("metabolic strokes"). Characteristic features are epileptic seizures (partial and generalized convulsive), myoclonus, ataxia. As the disease progresses, dementia develops. In general, the picture is very polymorphic and variable in individual patients. Myopathic syndrome is also variable and usually weakly expressed. Biochemical blood tests reveal lactic acidosis, and morphological examination of skeletal muscle biopsy reveals the symptom of "torn" red fibers.

Toxic encephalopathies, which manifest, in addition to other symptoms, as myoclonus, can develop as a result of poisoning (bismuth, DDT) or the use/overdose of certain medications (antidepressants, anesthetics, lithium, anticonvulsants, levodopa, MAO inhibitors, neuroleptics).

Encephalopathies caused by physical factors can also manifest as typical myoclonic syndrome.

• Posthypoxic encephalopathy (Lanz-Adams syndrome) is characterized by intentional and action myoclonus, sometimes combined with dysarthria, tremor and ataxia. In severe cases, the patient is freed from myoclonus only in a completely relaxed lying position, any attempts at movement lead to an "explosion" of generalized myoclonus, depriving any possibility of independent movement and self-care. The drug of choice is clonazepam, and a good effect from this drug is considered one of the confirmations of the diagnosis.
• Myoclonus in severe traumatic brain injury can be either its only consequence or combined with other neurological and psychopathological disorders.

Focal lesions of the central nervous system (including dentato-olivary lesions causing palatine myoclonus) of various etiologies (stroke, stereotactic intervention, tumor), in addition to myoclonus, are accompanied by distinct concomitant neurological symptoms and corresponding anamnesis data, which facilitates diagnosis.

Spinal myoclonus is characterized by local distribution, stability of manifestations, independence from exogenous and endogenous influences, and it develops with various lesions of the spinal cord.

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Pathophysiological classification of myoclonus

The pathophysiological classification of myoclonus indicates the source of its generation in the nervous system:

• cortical (somatosensory cortex);
• subcortical (between the cortex and the spinal cord);
• stem (reticular);
• spinal;
• peripheral (in case of damage to spinal roots, plexuses and nerves).

Some authors combine subcortical and brainstem myoclonus into one group.

• Cortical myoclonus is preceded by EEG changes in the form of spikes, spike-slow wave complexes, or slow waves. The latent period between EEG and EMG discharges corresponds to the time of excitation conduction along the pyramidal tract. Cortical myoclonus can be spontaneous, provoked by movement (cortical action myoclonus) or external stimuli (cortical reflex myoclonus). It can be focal, multifocal, or generalized. Cortical myoclonus is most often distal and occurs in the flexors; it is often combined with Kozhevnikov epilepsy, Jacksonian, and secondarily generalized tonic-clonic seizures. A pathological increase in the amplitude of SSEPs is noted (up to the formation of giant SSEPs). In addition, in cortical myoclonus, polysynaptic long-loop reflexes are significantly enhanced.
• In subcortical myoclonus, there is no temporal relationship between the EEG and EMG. EEG discharges may follow myoclonus or be absent altogether. Subcortical myoclonus may be generated by the thalamus and is manifested by generalized, often bilateral, myoclonus.
• Reticular myoclonus is generated in the brainstem by increased excitability of the caudal reticular formation, mainly the gigantocellular nucleus, from where impulses are transmitted caudally (to spinal motor neurons) and rostrally (to the cortex). Reticular myoclonus is often characterized by generalized axial twitching, with proximal muscles being more involved than distal ones. In some patients, it may be focal. Reticular myoclonus may be spontaneous, action, or reflex. Unlike cortical myoclonus, reticular myoclonus lacks a relationship between EEG and EMG changes and giant SSEPs. Polysynaptic reflexes are enhanced, but the cortical evoked response is not. Reticular myoclonus may resemble an enhanced startle reflex (primary hyperekplexia).
• Spinal myoclonus may occur in infarctions, inflammatory and degenerative diseases, tumors, spinal cord injuries, spinal anesthesia, etc. In typical cases, it is focal or segmental, spontaneous, rhythmic, insensitive to external stimuli and, unlike myoclonus of cerebral origin, does not disappear during sleep. In spinal myoclonus, EMG activity accompanies each muscle contraction, and EEG correlates are absent.

If we try to “tie” the pathophysiological classification to specific diseases, it will look like this.

• Cortical myoclonus: tumors, angiomas, encephalitis, metabolic encephalopathies. Among degenerative diseases, this group includes progressive moclonus epilepsies (MERRF syndrome, MELAS syndrome, lipidoses, Lafora disease, ceroid lipofuscinosis, familial cortical myoclonic tremor, Unverricht-Lundborg disease with variants of Baltic and Mediterranean myoclonus, celiac disease, Angelman syndrome, dentato-rubro-pallido-Lewis atrophy), juvenile myoclonic epilepsy, postanoxic Lance-Adams myoclonus, Alzheimer's disease, Creutzfeldt-Jakob disease, Huntington's chorea, olivopontocerebellar degeneration, corticobasal degeneration. Kozhevnikovsky epilepsy, in addition to tick-borne encephalitis, can be associated with Rasmussen's encephalitis, stroke, tumors, and, in rare cases, multiple sclerosis.
• Subcortical myoclonus: Parkinson's disease, multiple system atrophy, corticobasal degeneration. This group should include velopalatine myoclonus (idiopathic, with stroke, tumors, multiple sclerosis, traumatic brain injury, neurodegenerative diseases).
• Spinal myoclonus: inflammatory myelopathy, tumors, trauma, ischemic myelopathy, etc.
• Peripheral myoclonus: damage to peripheral nerves, plexuses and roots.

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Etiological classification of myoclonus

It should be noted that the pathophysiological mechanism of some myoclonic syndromes is still poorly known, therefore, it is probably more convenient for the physician to consider the etiological classification, which divides myoclonus into 4 groups: physiological, essential, epileptic, symptomatic (secondary).

• Physiological myoclonus.
  • Sleep myoclonus (falling asleep and waking up).
  • Myoclonus of fright.
  • Myoclonus induced by intense physical exertion.
  • Hiccups (some of its variants).
  • Benign infantile myoclonus during feeding.
• Essential myoclonus.
  • Hereditary myoclonus-dystonia syndrome (Friedreich's multiple paramyoclonus or myoclonic dystonia).
  • Nocturnal myoclonus (periodic limb movements, restless legs syndrome).
• Epileptic myoclonus.
  • Kozhevnikovsky epilepsy.
  • Myoclonic absences.
  • Infantile spasms.
  • Lennox-Gastaut syndrome.
  • Juvenile myoclonic epilepsy of Jans.
  • Progressive myoclonic epilepsy and some other epilepsies of infancy.
• Symptomatic myoclonus.
  • Storage diseases: Lafora body disease, GM gangliosidosis (Tay-Sachs disease), ceroid lipofuscinosis, sialidosis, Gaucher disease.
  • Hereditary degenerative diseases of the cerebellum, brainstem and spinal cord (spinocerebellar degenerations): Baltic myoclonus (Unverricht-Lundborg disease), Mediterranean myoclonus (Ramsay Hunt syndrome), Friedreich's ataxia, ataxia-telangiectasia.
  • Degenerative diseases with predominant damage to the basal ganglia: Wilson-Konovalov disease, torsion dystonia, Hallervorden-Spatz disease, corticobasal degeneration, progressive supranuclear palsy, Huntington's chorea, multiple system atrophy, etc.
  • Degenerative dementias: Alzheimer's disease, Creutzfeldt-Jakob disease.
  • Viral encephalitis (herpes encephalitis, subacute sclerosing panencephalitis, Economo encephalitis, arbovirus encephalitis, etc.).
  • Metabolic encephalopathies (including mitochondrial, as well as liver or kidney failure, dialysis syndrome, hyponatremia, hypoglycemia, etc.).
  • Toxic encephalopathy (intoxication with bismuth, antidepressants, anesthetics, lithium, anticonvulsants, levodopa, MAO inhibitors, neuroleptics).
  • Encephalopathies caused by exposure to physical factors (post-hypoxic Lanz-Adams syndrome, post-traumatic myoclonus, heat stroke, electric shock, decompression).
  • Focal CNS lesion (stroke, neurosurgery, tumors, TBI).
  • Spinal cord injuries.
• Psychogenic myoclonus.

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Physiological myoclonus

Physiological myoclonus may occur under certain circumstances in a healthy person. This group includes myoclonus of sleep (falling asleep and waking up); myoclonus of startle; myoclonus caused by intense physical exertion; hiccups (some of its variants) and benign myoclonus of infants during feeding.

• Sometimes natural physiological tremors when falling asleep and waking up in anxious individuals can become a cause for fear and neurotic experiences, but they are easily eliminated by rational psychotherapy.
• Myoclonus of startle can be not only physiological, but also pathological (startle syndrome, see below).
• Intense physical activity can cause isolated transient myoclonic contractions of a benign nature.
• Hiccups are a common phenomenon. This symptom is based on myoclonic contraction of the diaphragm and respiratory muscles. Myoclonus can be both physiological (for example, after overeating) and pathological (in diseases of the gastrointestinal tract or, less often, chest organs), including diseases of the nervous system (irritation of the phrenic nerve, damage to the brain stem or damage to the upper cervical segments of the spinal cord). Hiccups can be caused by toxic effects. Finally, it can also be purely psychogenic.

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Essential myoclonus

Essential myoclonus is a rather rare hereditary disease. There are both familial (autosomal dominant inheritance) and sporadic forms. The disease begins in the 1st or 2nd decade of life and is not accompanied by other neurological and mental disorders, there are no changes in the EEG. Clinical manifestations include irregular, arrhythmic and asynchronous twitching and flinching with multifocal or generalized distribution of myoclonus. The latter are aggravated by voluntary movements. SSEPs are not increased even during myoclonic movement, which indicates its subcortical origin. Until recently, this disease was called Friedreich's multiple paramyoclonus. Since it can cause dystonic symptoms (the so-called dystonic myoclonus), and the syndrome itself is sensitive to alcohol, multiple paramyoclonus and myoclonic dystonia are now considered the same disease and are called hereditary myoclonus-dystonia syndrome.

Another form of essential myoclonus is considered to be nocturnal myoclonus, known as "periodic limb movements" (a term proposed in the international classification of sleep disorders). This disorder is not a true myoclonus, although it is included in modern classifications of myoclonic syndromes. The disease is characterized by episodes of repetitive, stereotypical movements in the legs in the form of extension and flexion in the hip, knee and ankle joints, which occur during superficial (I-II) stages of sleep and are often accompanied by dyssomnia. The movements are not accompanied by changes in the EEG or awakening. Periodic movements during sleep can be combined with restless legs syndrome. The latter is characterized by sudden onset and rapidly increasing paresthesia in the legs, usually occurring before the onset of sleep and causing an irresistible need to move the legs. A short leg movement instantly eliminates the feeling of discomfort. For both syndromes, levodopa and benzodiazepine drugs (most often clonazepam) and opiates are usually effective.

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Epileptic myoclonus

In epileptic myoclonus, myoclonic seizures dominate the clinical picture, but there are no signs of encephalopathy, at least in the initial stages. Epileptic myoclonus can manifest itself in the form of isolated epileptic myoclonic twitching in epilepsia partialis continua (Kozhevnikovsky epilepsy), photosensitive epilepsy, idiopathic "stimulus-sensitive" myoclonus, myoclonic absences. This group also includes a group of childhood myoclonic epilepsies with more extensive manifestations: infantile spasms, Lennox-Gastaut syndrome, juvenile myoclonic epilepsy of Janz, progressive myoclonic epilepsy, early myoclonic encephalopathy, benign myoclonic epilepsy of infancy.

Kozhevnikovsky epilepsy (epilepsia partialis continud) was initially described as one of the variants of the chronic form of tick-borne spring-summer encephalitis, it is manifested by constant focal low-amplitude rhythmic clonic muscle contractions (cortical myoclonus), involving one part of the body. Most often, the muscles of the face and distal parts of the limbs are involved. Twitching is constant, they usually continue for many days and even years, sometimes secondary generalization into a tonic-clonic seizure is observed. A similar syndrome, but with a progressive course, is described in more diffuse hemispheric damage (chronic Rasmussen encephalitis), its nosological independence remains controversial. Kozhevnikovsky epilepsy syndrome has also been described in such diseases as abscess, granuloma, stroke, subdural hematoma, tumor, craniocerebral trauma, nonketotic hyperglycemic state (especially in the presence of hyponatremia), hepatic encephalopathy, multiple sclerosis, MELAS syndrome. Iatrogenic forms (penicillin, etc.) have also been described.

Myoclonic absences. The average age of onset of epilepsy with myoclonic absences (Tassinari syndrome) is 7 years (from 2 to 12.5 years). The sudden onset of absence is accompanied by bilateral rhythmic myoclonic jerks, which are observed in the muscles of the shoulder girdle, arms and legs, the facial muscles are involved to a lesser extent. The movements may increase in intensity and acquire a tonic character. Short jerks and tonic contractions may be symmetrical or predominate on one side, causing a turn of the head and trunk. During the attack, respiratory arrest and involuntary urination are also possible. Loss of consciousness during absence may be complete or partial. Each episode of myoclonic absence may last from 10 to 60 sec. Seizures may occur many times a day, they become more frequent in the morning hours (within 1-3 hours after awakening). In rare cases, episodes of myoclonic absence status are observed. In most cases, absences are combined with generalized convulsive seizures, which are usually characterized by low frequency (approximately once a month or less). A decrease in intelligence is often observed. Resistance to anticonvulsants is quite typical. The etiology is unknown, sometimes a genetic predisposition is noted.

Infantile spasms (West syndrome) are classified as age-dependent epilepsies. The first manifestations of the disease occur at 4-6 months. The syndrome is characterized by typical seizures, mental retardation, and hypsarrhythmia on the EEG (irregular high-voltage slow spike-wave activity), which formed the basis of the West triad. Infantile spasms are usually characterized by symmetrical, bilateral, sudden, and short contractions of typical muscle groups (flexor, extensor, and mixed spasms). Flexor spasms are most often observed, which manifest themselves as a short bow (if the abdominal muscles are involved), with the arms performing an adduction or abduction movement. Attacks of torso bending and arm adduction resemble an oriental greeting and are called "salaam attacks." The frequency of attacks varies greatly (in severe cases, they occur several hundred times a day). Most seizures are grouped into clusters, they often occur in the morning after waking up or when falling asleep. During the attack, eye deviation and nystagmoid movements are sometimes observed. Infantile spasms can be secondary (symptomatic), idiopathic and cryptogenic. Secondary forms are described in perinatal lesions, infections, cerebral malformations, tuberous sclerosis, injuries, congenital metabolic disorders, degenerative diseases. Infantile spasms should be differentiated from benign non-epileptic infantile spasms (benign myoclonus of infants), the latter is not accompanied by epileptic discharges on the EEG and independently passes in the coming years (up to 3 years). In the future, 55-60% of children with infantile spasms may develop other types of seizures (Lennox-Gastaut syndrome).

Lennox-Gastaut syndrome is characterized by typical EEG changes [spike-slow wave discharges at a lower frequency (2 Hz) than in typical absences (3 Hz)], mental retardation, and specific seizure types including myoclonic jerks, atypical absences, and astatic seizures (epileptic drop attacks, akinetic seizures).

The syndrome usually begins with sudden falls, seizures become more frequent, status epilepticus occurs, intellectual functions deteriorate, personality disorders and chronic psychoses are possible. Approximately 70% of children with this syndrome have tonic seizures. They are short, lasting several seconds and manifested by flexor movements of the head and trunk or extension movements, as well as deviation of the eyes or a fall of the patient. Seizures can be asymmetrical or predominantly unilateral. Sometimes the tonic stage is followed by automatic behavior. Most tonic seizures develop during sleep.

Atypical absences are observed in approximately one third of patients with Lennox-Gastaut syndrome. They are longer than typical absences and are accompanied by various motor phenomena (nodding, facial myoclonus, postural phenomena, etc.). In addition to atonic and tonic seizures, myoclonic and myoclonic-atonic seizures are typical, also leading to falls of the patient (epilepsy with myoclonic-astatic seizures). Other types of seizures are also possible (generalized tonic-clonic, clonic; partial seizures are observed less frequently). Consciousness usually remains clear. Etiologically, 70% of cases of Lennox-Gastaut syndrome are associated with perinatal injuries.

Juvenile myoclonic epilepsy of Janz ("impulsive petit mal") begins in the 2nd decade of life (most often at 12-24 years) and is characterized by myoclonic seizures, sometimes associated with generalized tonic-clonic seizures and/or absences. Myoclonic seizures predominate, characterized by sudden short, bilaterally symmetrical and synchronous muscle contractions. The movements mainly involve the shoulders and arms, less often the muscles of the trunk and legs. Seizures are isolated or grouped into clusters. The patient may fall to his knees during a seizure. During myoclonic seizures, consciousness remains intact, even if they occur in a series or in the picture of myoclonic epileptic status.

Generalized tonic-clonic seizures usually occur after (on average, 3 years) the onset of myoclonic seizures. Typically, the seizure begins with myoclonic jerks, increasing in intensity to generalized myoclonus, which turns into a generalized tonic-clonic seizure. This typical picture is called "myoclonic grand mal, "impulsive grand mal, "clonic-tonic-clonic seizure"). The seizures occur almost exclusively after waking up in the morning.

Absences are usually observed in an atypical form and occur in 15-30% of patients at an average age of 11.5 years. Intelligence is usually not affected.

Severe myoclonic epilepsy of infants begins in the first year of life. At first, generalized or unilateral clonic seizures occur without prodromal symptoms. Myoclonic jerks and partial seizures usually appear later. Myoclonic seizures often occur in one arm or head, and then transform into generalized ones; they usually occur several times a day. Atypical absences and complex partial seizures with atonic or adverse phenomena or automatisms may also appear. Delay in psychomotor development and the appearance of progressive neurological deficit in the form of ataxia and pyramidal syndrome are characteristic. A hereditary burden of epilepsy is revealed in 15-25% of patients. MRI does not reveal specific abnormalities.

Early myoclonic encephalopathy begins in the first month of life. It is characterized by early onset of partial myoclonic epileptic jerks, which are followed by simple partial seizures (eye deviation, apnea, etc.), then more massive or generalized myoclonus, tonic spasms (occur later) and other types of seizures. Hypotonia of the trunk muscles, bilateral pyramidal signs, and possible involvement of peripheral nerves are characteristic. Psychomotor development is impaired. The child either dies in the first 2 years of life or falls into a persistent vegetative state. The etiology is not precisely known.

Benign myoclonic epilepsy of infancy usually begins with myoclonic jerks in an otherwise normal child between 4 months and 3 years of age. Boys are more commonly affected. Myoclonic jerks may be subtle but become obvious over time. Seizures gradually generalize to involve the trunk and limbs, resulting in nodding movements of the head and raising the arms to the sides, as well as flexion of the lower limbs. Upward deviation of the eyes may be observed, and sudden falls are also possible. Myoclonic seizures are short (1-3 sec) and may occur several times a day. Consciousness is usually intact. Other types of seizures are absent.

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Other myoclonic syndromes

In conclusion of the description of myoclonus, it is appropriate to mention several more extremely unique syndromes that are rarely mentioned in Russian literature.

Palatine myoclonus (soft palate myoclonus, velopalatine myoclonus, soft palate nystagmus, soft palate tremor) is one of the manifestations of myorhythmia. It can be observed in isolation as rhythmic (2-3 per second) contractions of the soft palate or in combination with similar rhythmic myoclonus, almost indistinguishable from tremor, in the tongue, lower jaw, larynx, diaphragm and distal parts of the hands (classic myorhythmia). Myorhythmia is a rhythmic myoclonus that differs from tremor (parkinsonian) mainly by its low frequency (1-3 Hz) and characteristic distribution. Sometimes, along with velopalatine myoclonus, vertical ocular myoclonus ("swinging") is observed; this syndrome is called oculopalatine myoclonus. Myorhythmia disappears during sleep (sometimes pathological movements are noticeable during sleep). Myorhythmia without palatine myoclonus is rare. Isolated myoclonus of the soft palate can be either idiopathic or symptomatic (tumors in the cerebellum and cerebellopontine angle, stroke, encephalomyelitis, trauma). Idiopathic myoclonus often disappears during sleep, anesthesia, and in a comatose state. Symptomatic myoclonus of the soft palate is more stable in these states. The most common causes of generalized myorhythmia are vascular lesions of the brainstem and cerebellar degeneration associated with alcoholism or malabsorption syndrome.

Opsoclonus (dancing eyes syndrome) is a myoclonic hyperkinesis of the oculomotor muscles, manifested by fast jerky chaotic, predominantly horizontal movements of the eyeballs. A chaotic change of horizontal, vertical, diagonal, circular and pendulum-like movements of varying frequency and amplitude may be observed. According to some observations, opsoclonus persists during sleep, intensifying upon awakening, it is often mistaken for nystagmus, which differs from opsoclonus by the presence of 2 phases: slow and fast. Opsoclonus indicates an organic lesion of the cerebellar-stem connections and is often accompanied by generalized myoclonus, ataxia, intention tremor, hypotonia, etc. The main etiological factors are viral encephalitis, multiple sclerosis, tumors of the brainstem and cerebellum, paraneoplastic syndromes (especially in children), trauma, metabolic and toxic encephalopathies (drugs, toxins, nonketotic hyperglycemia).

Negative myoclonus ("fluttering" tremor, asterixis) looks like tremor. However, it is not based on active muscle contractions, but, on the contrary, on periodic drops in the tone of postural muscles with bioelectric "silence" at these moments. Asterixis is extremely characteristic of metabolic encephalopathy in diseases of the liver, kidneys, lungs, etc. In such cases, it is usually bilateral. Rarely, asterexis can be a sign of local brain damage (hemorrhage in the thalamus, parietal lobe, etc.), manifesting itself in such cases on one side. Asterixis is most easily detected when stretching the arms forward.

Startle syndrome unites a group of diseases characterized by an increased startle reaction (shuddering) in response to unexpected external stimuli (usually auditory and tactile).

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Psychogenic myoclonus

Psychogenic myoclonus is characterized by acute onset, variability in frequency, amplitude, and distribution of myoclonus. There are also other discrepancies with typical organic myoclonus (for example, the absence of falls and injuries despite pronounced instability and swaying of the body, etc.), spontaneous remissions, a decrease in hyperkinesis when attention is distracted, an increase and decrease in hyperkinesis under the influence of suggestion, psychotherapy, or in response to the introduction of a placebo, the presence of other psychogenic motor, mental disorders.

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Diagnosis and treatment of myoclonus

Diagnosis is clinical. Treatment begins with correction of underlying metabolic abnormalities. Clonazepam 0.5-2 mg orally 3 times a day is often prescribed. Valproate 250-500 mg orally 2 times a day may be effective; other anticonvulsants are sometimes helpful. Many forms of myoclonus respond to the serotonin precursor 5-hydroxytryptophan (initial dose 25 mg orally 4 times a day, then increased to 150-250 mg orally 4 times a day) with the decarboxylase inhibitor carbidopa (orally 50 mg in the morning and 25 mg at noon or 50 mg in the evening and 25 mg at bedtime).

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