Myoclonic epilepsy is a disease based on myoclonic epileptic paroxysms. Episodes of myoclonic seizures in patients are combined with generalized clonic-tonic seizures, absences. Concomitant neurological symptoms depend on the form of epilepsy. Diagnostics includes anamnesis collection, assessment of neurological and mental status, electroencephalography, genealogical analysis, biochemical studies, neuroimaging. Treatment is carried out with anticonvulsants, with resistance — a combination of antiepileptic drugs.
General information
Myoclonic seizures (myoclonia) are involuntary contractions of a single muscle/muscle group. Accordingly, epilepsy with a predominance of myoclonia in the clinical picture was called myoclonic. The concept of “myoclonic epilepsy” (ME) includes a number of diseases that are heterogeneous in etiopathogenesis, age of onset, and features of symptoms. In the vast majority of cases, they are characterized by a combination of myoclonia and generalized tonic-clonic convulsive seizures, have genetic conditioning. The occurrence of ME varies, some nosological forms are so rare that no more than 100 clinical cases are described in the literature on neurology.
Causes
Usually the genetic factor is the leading one. Clear autosomal dominant inheritance can be traced in Dravet syndrome, autosomal recessive – in some cases of early myoclonic encephalopathy. Some diseases have polygenic inheritance. Localization of genetic defects has not been established for all hereditary forms, research in this direction continues. The genetically determined pathologies also include symptomatic ME, which occurs as a result of dysmetabolic processes caused by the presence of defective genes. The formation of spontaneous mutations in the genome is facilitated by:
- Intrauterine infections. The infectious process adversely affects the development of the fetus. Viral infections are especially dangerous, since viruses can provoke abnormal rearrangement of individual genes.
- Chronic diseases of a pregnant woman. Diabetes mellitus, heart failure, chronic lung diseases, endocrine pathology of the mother lead to hypoxia, metabolic disorders in the early stages of embryo development. As a result, there are failures in the formation of the central nervous system, individual metabolic mechanisms.
- Increased radioactive background. Radiation has a mutagenic effect on living organisms. The developing fetus is most susceptible to such effects. The consequence is the occurrence of structural, dysmetabolic, functional anomalies, entailing increased epileptic activity.
- Taking teratogenic medications. Self-medication, ignorance about your pregnancy in the early period, the medical need for pharmacotherapy lead to the intake of dangerous medications for the fetus. Chemicals have a damaging effect on individual genes, make changes to existing metabolic mechanisms.
- Toxic effects on the fetus. Alcoholism, drug addiction, smoking of a woman during pregnancy are accompanied by the penetration of toxic substances into the fetus. Like teratogenic pharmaceuticals, they can damage a separate locus of the genome, resulting in myoclonic epilepsy.
Pathogenesis
Idiopathic variants of ME develop due to genetically determined increased excitability of cerebral neurons, leading to epileptogenic brain activity. Symptomatic myoclonic epilepsy is formed as a result of metabolic disorders, accumulation of pathological compounds in nerve cells (polysaccharide inclusions, prion proteins).
In Lafora’s disease, myoclonic encephalopathy of infants, increased epiactivity is caused by dysmetabolism of neurons in conditions of proliferation of glial elements (with neuronal death, violation of astrocyte apoptosis). Neuronal hyperexcitability causes the occurrence of pathological nerve impulses going to the muscle fibers. The result is individual muscle contractions (myoclonia), tonic, clonic convulsions. The different localization of myoclonia reflects the local excitation of different areas of the cerebral cortex. With the diffuse spread of hyperexcitation, a clonic-tonic paroxysm occurs with total involvement of muscle groups.
Classification
The etiological principle underlies the grouping of individual types of ME. According to the International Classification of Epilepsy in 1989 , there are 3 main groups:
- Idiopathic — hereditary forms. The manifestation of symptoms in childhood / adolescence is characteristic. Idiopathic are benign myoclonic epilepsy of infancy (BMEI), juvenile myoclonic epilepsy (JME), Unferricht-Lundborg disease, Dravet syndrome.
- Cryptogenic — not having an established etiology. They are characterized by pronounced resistance to pharmacotherapy, the presence of concomitant focal symptoms, intellectual deficiency. Cryptogenic ones include epilepsy with myoclonic-astatic seizures, epilepsy with myoclonic absences.
- Symptomatic — arising against the background of pathological processes occurring in the body. In most cases, they are caused by metabolic disorders. Early myoclonic encephalopathy, Lafora’s disease, myoclonic paroxysms with subacute sclerosing panencephalitis, Creutzfeldt-Jakob disease are considered symptomatic.
Subsequently, genetic aspects of the occurrence of cryptogenic forms of ME were identified. Taking into account the research results, the International Society of Neurologists proposed to classify previously considered cryptogenic types of ME as idiopathic.
Symptoms
The basic symptom is myoclonic paroxysms affecting various muscle groups of the extremities, less often — the face, even less often — the trunk. Myoclonia look like muscle twitching, with the involvement of muscles of one group, contractions lead to involuntary motor acts resembling hyperkinesis. Myoclonic epileptic paroxysm occurs with preserved consciousness, can occur with the movement of contractions through various muscles. Myoclonic epilepsy is characterized by a combination of myoclonia with clonic-tonic seizures and/or absences. Depending on the nosological form, mental retardation, ataxia, pyramidal insufficiency, disorders of muscle tone, visual disturbances are observed.
BMEI debuts in the age period from 6 months to 3 years. Seizures capture the upper extremities, face, neck, can simulate a tilt of the head, blinking, nodding of the head. The disease is rarely accompanied by intellectual decline. Myoclonic epilepsy of adolescence (manifestation at the age of 12-18 years) it is distinguished by the addition of tonic-clonic episodes, the absence of neurological deficit. Dravet syndrome is clinically manifested in the first year of life, accompanied by oligophrenia, behavioral disorders, pyramidal deficiency. Unferricht-Lundborg familial myoclonia begins at the age of 5-16, is combined with tremor, ataxia, dysarthria, and mental disorders.
Myoclonic-astatic paroxysms are distinguished by the loss of stability that occurs against the background of myoclonia. Patients describe the attack as a “kick under the knees”, “buckling of the legs”, forcing them to kneel, fall. Myoclonic absences are episodes of short-term disconnection of consciousness with myoclonic contractions of the shoulder girdle, limb muscles, and the periorbital region. The disease occurs in children 2-12 years old.
Myoclonic epilepsy of a symptomatic nature is characterized by the progression of symptoms, pronounced cognitive deficits, other neurological disorders, the presence of manifestations of the underlying disease, clinical and laboratory signs of metabolic disorders.
Complications
Clonic-tonic, astatic attacks are complicated by injury to the patient due to a fall. Generalized convulsions with loss of consciousness are dangerous by tongue entanglement, airway obstruction and asphyxia. Aspiration of saliva, vomit leads to the subsequent development of pneumonia. Prolonged myoclonic paroxysm, continuously following cluster contractions develop into myoclonic epistatus. In the epileptic status, serious respiratory disorders, cardiac arrest, and the development of cerebral edema are possible.
Diagnostics
Myoclonic symptoms are included in the clinic of many diseases, epileptic syndromes. The diagnosis of “myoclonic epilepsy” is established only when myoclonic seizures prevail over other clinical manifestations. Diagnostics is aimed at verifying the nosological form of epilepsy, while identifying the secondary nature of myoclonia — to search for the underlying pathology. The main diagnostic stages are:
- Collection of anamnestic data. Of great importance is the age of the debut, the nature of the beginning, the order of development of symptoms.
- Neurological examination. It is carried out by a neurologist, aimed at identifying myoclonic contractions, focal deficiency, determining the level of mental development, the degree of cognitive disorders, and assessing mental status.
- Electroencephalography. Diffuse interictal symmetrical epileptogenic discharges, ictal high-amplitude adhesions are registered in most patients. In some cases, daily EEG video monitoring, provocative tests (EEG with flashes of light, hyperventilation, sharp sound signals) are required to detect epiactivity. The results of the studies are evaluated by a neurophysiologist, an epileptologist.
- Neuroimaging. Before the closure of the fontanelles is carried out by neurosonography, in children older than one year — with the help of MRI of the brain. MSCT can be performed for adults. Morphological changes in cerebral tissues are characteristic of symptomatic ME.
- Laboratory tests. They are produced when there is a suspicion of the presence of metabolic disorders. They include biochemical analysis of blood and urine, specific tests.
- Consultation of a geneticist. Collecting a family history, compiling a family tree allows you to determine the hereditary nature of epilepsy, establish the type of inheritance.
Differential diagnosis is carried out with non-epileptic myoclonus, a distinctive feature of which is the focal character of myoclonia, the absence of a reaction to provocation, and a normal EEG picture. Differentiation of ME is also necessary with convulsive syndrome of infectious etiology, febrile convulsions, Lennox-Gastaut syndrome, Hunt’s cerebellar myoclonic dissinergia.
Treatment
Therapy is based on anticonvulsants. The selection of the pharmaceutical product and dosage is carried out individually. The drugs of choice are valproic acid derivatives that have an antiepileptic effect equally with respect to myoclonic, clonic-tonic, absentee paroxysms. In pharmacoresistant cases, combined treatment with valproates, benzodiazepines, ethosuximide, barbiturates, anticonvulsants of a new generation (topiramate, levetiracetam) is indicated. An important point is the exclusion of factors provoking seizures: sharp sounds, flashes of light, emotional outbursts, physical overload, overheating.
Prognosis and prevention
Early myoclonic encephalopathy is the most prognostically unfavorable, mortality is half of the cases of the disease, the rest of the children are deeply disabled. Myoclonic epilepsy in Lafora, Creutzfeldt-Jakob disease does not respond well to antiepileptic therapy, accompanied by progressive intellectual decay. BMEI and JME are characterized by a benign course, rarely lead to cognitive deficits. More than 50% of cases of BMEI end in spontaneous recovery.
ME has no specific preventive measures. Measures that can prevent the birth of a sick child include pregnancy planning, early registration, exclusion of adverse effects on the fetus. Pregnancy management should include explanatory conversations with a woman about the need for a protective regime, the teratogenic danger of medicines, the harmful effects of bad habits on the unborn child.
