Progressive myoclonus-epilepsy

Progressive myoclonus-epilepsy refers to polyethological syndromes. Currently, about 15 nosological forms have been isolated, combined with progressive myoclonus-epilepsy. Progressive myoclonus-epilepsy is a complex syndrome, including a combination of myoclonus, epilepsy, cognitive disorders and various other neurological disorders (most often cerebellar ataxia) with a progressive course.

Diagnostic triad of progressive myoclonus-epilepsy:

1. Myoclonic seizures.
2. Tonic-clonic seizures.
3. Progressive neurological disorders (usually ataxia and dementia).

[1], [2], [3], [4], [5], [6]

Diseases in which progressing myoclonus-epilepsy occurs

Progressive myoclonus-epilepsy occurs in the following diseases:

1. Unferricht-Lundborg disease:
   • 1. "Baltic myoclonus";
   • 2. "Mediterranean myoclonus."
2. Lafor's disease.
3. Dento-rubro-pallid-Lewis atrophy.
4. Cereal lipofuscinosis:
   • 1. Late infantile;
   • 2. Intermediate;
   • 3. The juvenile;
   • 4. Adults.
5. Gaucher disease, type 3.
6. Cialis, type 1.
7. Salidosis, type 2, galactosialidosis.
8. MERRF syndrome.
9. Gangliosidosis GM2, (type III).

Diseases bordering on progressive myoclonus-epilepsy (a combination of epilepsy and myoclonus):

1. Combination of primary epilepsy and familial myoclonus (rare)
2. Disease of Tay-Sachs (Tay-Sachs)
3. Phenylketonuria
4. Lipofuscinosis of newborns (Santavuori-Haltia syndrome)
5. Subacute sclerosing panencephalitis
6. Wilson-Konovalov's disease
7. Creutzfeldt-Jakob disease

Acute conditions in which the occurrence of myoclonus-epilepsy is possible:

1. Intoxication with methyl bromide, bismuth, strychnine.
2. Viral encephalitis.

[7], [8], [9]

Unferricht-Lundborg disease

This disease is described in two subgroups of patients. One form was discovered for the first time in Finland and was later called the Baltic myoclonus. The other is in the south of France (Marseilles) and is now called the Mediterranean myoclonus.

Diagnostic criteria for Unferricht-Lundborg disease include:

• The onset of the disease is between the ages of 6 and 15 (in 86% of cases between 9 and 13 years).
• Tonic-clonic epileptic seizures.
• Myoclonus.
• EEG: paroxysms of spikes or polyspike-wave complexes with a frequency of 3-5 per second.
• Progressing course with the addition of coarse cerebellar ataxia and dementia.

Myoclonus with Unferricht-Lundborg disease, as with all progressive myoclonus-epilepsies, refers to the cortical myoclonus. It can be both spontaneous and observed at rest, and associated with movements (action myoclonus or myoclonus of action) and thereby significantly hinder the daily activity of the patient. Myoclonic twitching is also provoked by sensory stimuli (stimulus-sensitive or reflex myoclonus) such as touch, light, sound, etc. Myoclonus can have different body distributions and varies in intensity even in the same patient. Usually it is asynchronous, it can predominate in one limb or in one half of the body, with amplification it can spread to other parts of the body and sometimes proceeds as a generalized myoclonic attack without or with a minimal disturbance of consciousness. In most patients, myoclonus has a progressive course.

Epilepsy with progressive myferonus epilepsy of Unferricht-Lundberg often occurs in the form of generalized clonic-tonic-clonic seizures of short duration, also called the "myoclonic cascade." In the terminal stage of progressive myoclonus-epilepsy, a clonic epileptic status is often observed.

Most patients develop severe cerebellar ataxia and dementia.

In patients with Mediterranean myoclonus (what was formerly called Ramsay Hunt syndrome) epileptic seizures and dementia are very weak and in some cases may even be absent. The responsible gene with Unferricht-Lundberg disease is located on 21 chromosomes, which was confirmed in patients with a Mediterranean variant of the disease.

Laforg's disease

The disease is inherited by autosomal recessive type and begins at the age of 6-19 years. Manifest manifestation are generalized tonic-clonic epileptic seizures. The latter are often combined with partial occipital paroxysms in the form of simple hallucinations, cattle or more complex visual disorders. Spotting paroxysms - a characteristic sign of Lafor's disease, observed in 50% of patients already in the early stages of the disease. Following epileptic attacks, usually a heavy resting myoclonus and action develops. Ataxia is often masked by severe myoclonus. Disturbances of cognitive functions can appear already in the debut of the disease. Greater mental disorders are characteristic of the advanced stage of the disease. Perhaps a transient cortical blindness. In the terminal stage, patients are bedridden, they have dementia. The lethal outcome occurs in 2-10 years from the onset of the disease.

In the EEG at the initial stages of the disease, separate "spike-wave" or "polyspike-wave" complexes are identified. The phenomenon of photosensitivity is typical. As the disease progresses, the main activity slows down, the number of the above paroxysmal discharges increases, focal anomalies appear, especially in the occipital regions, the physiological patterns of night sleep are grossly violated. On the EMG, myoclonus of rest is detected.

Diagnosis. With light microscopy, Lafor's bodies are found in the cerebral cortex, liver tissue and skeletal muscles. The most informative and accessible method is the study of skin biopsies, especially in the area of the forearm.

Dento-rubro-pallid-Lewis atrophy

This is a rare disease that is inherited in an autosomal dominant type and is characterized by degeneration of the dento-riblular and pallid-Lewis systems. The pathogenesis is based on the presence of CAG-triplets. Characterization is anticipated in subsequent generations and variable clinical expressiveness of the hereditary defect. The age of the debut varies from 6 to 69 years. Characterized by cerebellar ataxia, combined with dystonia, choreoathetosis, and sometimes - parkinsonism. In 50% of cases, progressive myoclonus-epilepsy and rapidly progressive dementia are observed. The main diagnostic problem is to delimit this disease from Huntington's chorea. In the EEG, slow wave bursts and generalized "spike waves".

[10]

Ceroid lipofuscinosis

Cereal lipofuscinosis (cerebro-retinal degeneration) refers to lipidosis and is characterized by the deposition of autofluorescent lipopigments in the central nervous system, hepatocytes, cardiac muscle, retina. The primary biochemical defect underlying the disease is unknown. Cereal lipofuscinosis is one of the causes of progressive myoclonus-epilepsy. There are several types of ceroid lipofuscinosis: infantile, late infantile, early juvenile or intermediate, juvenile, adult form.

Infantile type of Santavuori-Chaltia manifests after 6-8 months. And in the strict sense does not apply to progressive myoclonus-epilepsies.

[11], [12], [13], [14], [15]

The late infantile type Jansky-Bilshov

Jansky-strongielschowsky begins at the age of 1 to 4 years with locomotor disorders, ataxia, speech disorders. Characteristic lag in mental development. Develop epileptic seizures and myoclonus. By the age of 5, atrophy of the optic nerves is usually formed. The course is rapidly progressive. On EEG, epileptic activity in the form of spikes and complexes "polyspike-wave." Electron microscopy reveals granular lysosomal inclusions in biopsies of the skin, peripheral nerves and rectal mucosa.

Juvenile type of Spilmeier-Vogt-Szegrena

Spielme-yer-Vogt-Sjogren is common in the Scandinavian countries. The disease begins at the age of 4 to 14 years (in 70% of cases - from 6 to 10 years) with reduced visual acuity (retinitis pigmentosa) and gradually progressing mental disorders. After 2-3 years, extrapyramidal symptoms (slowed movements, a tremor similar to Parkinsonian ones), cerebellar ataxia, myoclonus, pyramidal insufficiency, absences or generalized tonic-clonic seizures join. Myoclonus is vividly represented in mimic muscles. The sequence of the appearance of symptoms can vary. In the terminal stage of the disease, myoclonic seizures become almost constant and clonic epileptic status often develops. The lethal outcome usually occurs at the age of about 20 years. Ultrastructure study of the skin and lymphocytes reveals vacuolized lymphocytes of peripheral blood and characteristic profiles of intracellular (intralisosomal) inclusions in the form of "fingerprints".

Adult form of Kufsa

Kufs refers to rare diseases. The age of the disease debut varies from 11 to 50 years. Gradually develops dementia, cerebellar ataxia, dyskinesia. Epileptic seizures and myoclonus are observed in the terminal stage. There are no visual impairments. The lethal outcome occurs approximately 10 years after the onset of the disease. In the brain biopsies, typical pathomorphological changes are revealed: intracellular inclusions in the form of "fingerprints" and osmophilic granular groups. In the study of other organs, the diagnosis is more difficult to establish.

[16], [17]

Gaucher's disease

Gaucher's disease is known in three forms: infantile (type I), juvenile (type II) and chronic (type III). The last type of Gaucher disease can be manifested by progressive myoclonus-epilepsy. The disease is due to the insufficiency of beta-glucocerebrosidase and is characterized by the accumulation of glucocerebroside in various tissues of the body.

The debut of the disease varies from childhood to adult. The disease is manifested by splenomegaly, anemia and neurologic symptoms in the form of supranuclear paralysis of eyes and (or) strabismus, generalized tonic-clonic or partial seizures. In the early stages, there is also ataxia and a moderate decline in intelligence. As the disease progresses, myoclonic paroxysms develop. The course is progressive. In the EEG multifocal complexes "polyspike-wave". In biopsies of various organs, circulating lymphocytes and bone marrow, as well as in the rectal mucosa, accumulations of glucocerebroside are found. The prognosis of the disease is marked by considerable variability.

Cialis, type I

At the heart of the disease is the lack of neuraminidase. Type of inheritance: autosomal recessive. The disease begins between the ages of 8 and 15 years. The first symptoms are often visual disturbances (night blindness), myoclonus, and generalized epileptic seizures. Intellect usually does not suffer. Myoclonus is observed at rest, amplified with arbitrary movements and with a touch. Sensory stimulation provokes the development of massive bilateral myoclonias. The most typical symptom is myoclonus of mimic muscles - spontaneous, irregular, with predominant localization in the perioral region. Unlike myoclonias in the extremities, the facial myoclonus is preserved during sleep. Often there is ataxia and paresthesia in the limbs. On the fundus there is a characteristic symptom of the "cherry bones", sometimes - the opacity of the vitreous. The course is progressive. Myoclonus is combined with generalized "spike-wave" complexes on EEG. In the culture of lymphocytes and fibroblasts, neuraminidase deficiency is detected. In most cases (with rare exception) myoclonus progresses rapidly and leads to disability of patients.

[18]

Cialis, type II

Cialidosis, type II, (galactosialidosis) is due to the deficiency of beta-galactosidase and is described primarily in Japanese. It is manifested by mental retardation, angiokeratoma, chondrodystrophy, hepatosplenomegaly and short stature. A symptom of the "cherry bones" on the fundus is revealed . Possible development of the syndrome of progressive myoclonus-epilepsy.

[19], [20], [21]

MERRF Syndrome

MERRF syndrome or "myoclonus epilepsy with torn red fibers" refers to mitochondrial encephalomyopathies (mitochondrial cytopathies). The disease is inherited by the mitochondrial type and transmitted through the maternal line. The age of debut syndrome MERRF varies from 3 to 65 years. In addition to myoclonus and generalized convulsive seizures, there are progressive dementia, cerebellar ataxia, spasticity; rarely observed: atrophy of the optic nerves, sensorineural hearing loss, myopathic symptoms, clinical and EMG signs of peripheral neuropathy. The sequence of symptoms in the MERRF syndrome is variable from case to case: neurological, sensory and mental disorders can occur several years before epileptic seizures, myoclonus and ataxia occur. Clinical expressiveness is characterized by considerable variability and polymorphism, even within the same family. The severity of the MERRF syndrome is also extremely variable. In EEG, abnormal background activity is recorded in 80% of cases; in 73% - "spike-wave" complexes. In all cases, giant evoked potentials are noted. Neuroimaging (CT, MRI) reveals diffuse atrophy of the cortex, damage to white matter of different sizes, basal ganglia calcifications and focal cortical foci of reduced density. In the biopsy specimen of skeletal muscles, a characteristic pathomorphological trait is revealed - ruptured red fibers (ragged-red fibres). In some cases, mitochondrial anomalies are revealed when examining the skin.

Gangliosidosis GM2, type III

The disease is inherited by autosomal recessive type. At the heart of the disease is the insufficiency of the enzyme hexosaminidase type A (as in the case of the Tay-Sachs disease, but not so pronounced and not so extensive). The disease begins to manifest itself in childhood or adolescence. Cerebellar ataxia, dysarthria develops, then dementia, spasticity, dysphagia, dystonia, epileptic seizures, and myoclonus progress. In some patients, there is an atypical phenomenon of the "cherry bones" on the fundus. The disease progresses slowly over many years. Some patients live up to 40 years.