Progressive myoclonus epilepsy.

Progressive myoclonus epilepsy is a polyetiological syndrome. Currently, about 15 nosological forms have been identified that are combined with progressive myoclonus epilepsy. Progressive myoclonus epilepsy is a complex syndrome that includes a combination of myoclonus, epilepsy, cognitive impairment, 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).

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Diseases in which progressive myoclonus epilepsy occurs

Progressive myoclonus epilepsy occurs in the following diseases:

1. Unverricht-Lundborg disease:
   • 1. "Baltic myoclonus";
   • 2. "Mediterranean myoclonus".
2. Lafora disease.
3. Dento-rubro-pallido-Lewis atrophy.
4. Ceroid lipofuscinosis:
   • 1. Late infantile;
   • 2. Intermediate;
   • 3. Juvenile;
   • 4. Adults.
5. Gaucher disease type 3.
6. Sialidosis, type 1.
7. Salidosis, type 2, galactosialidosis.
8. MERRF syndrome.
9. GM2 gangliosidosis (type III).

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

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

Acute conditions in which myoclonus epilepsy may occur:

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

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Unverricht-Lundborg disease

This disease is described in two subgroups of patients. One form was first identified in Finland and was subsequently called Baltic myoclonus. The other - in the south of France (Marseille) and is currently called Mediterranean myoclonus.

Diagnostic criteria for Unverricht-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.
• Progressive course with the addition of severe cerebellar ataxia and dementia.

Myoclonus in Unverricht-Lundborg disease, as in all progressive myoclonus epilepsies, refers to cortical myoclonus. It can be either spontaneous and observed at rest, or associated with movements (action myoclonus or myoclonus of action) and thus significantly impede the patient's daily activities. Myoclonic twitching is also provoked by sensory stimuli (stimulus-sensitive or reflex myoclonus) such as touch, light, sound, etc. Myoclonus can have different distribution over the body and varies in intensity even in the same patient. It is usually asynchronous, can predominate in one limb or one half of the body, with intensification it can spread to other parts of the body and sometimes occurs as a generalized myoclonic seizure with or without minimal impairment of consciousness. In most patients, myoclonus has a progressive course.

Epilepsy in Unverricht-Lundberg progressive myoclonus epilepsy most 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, clonic epileptic status is often observed.

Most patients develop severe cerebellar ataxia and dementia.

In patients with Mediterranean myoclonus (formerly known as Ramsay Hunt syndrome), epileptic seizures and dementia are very weakly expressed and in some cases may even be absent. The gene responsible for Unverricht-Lundberg disease is located on chromosome 21, which has been confirmed in patients with the Mediterranean variant of the disease.

Lafora disease

The disease is inherited in an autosomal recessive manner and begins at the age of 6-19 years. The manifest manifestation is generalized tonic-clonic epileptic seizures. The latter are often combined with partial occipital paroxysms in the form of simple hallucinations, scotomas or more complex visual disorders. Visual paroxysms are a characteristic sign of Lafora disease, observed in 50% of patients already in the early stages of the disease. Following epileptic seizures, severe myoclonus of rest and action usually develops. Ataxia is often masked by severe myoclonus. Cognitive impairment may manifest itself already at the onset of the disease. More severe mental disorders are characteristic of the advanced stage of the disease. Transient cortical blindness is possible. In the terminal stage, patients are bedridden and have dementia. Death occurs 2-10 years after the onset of the disease.

In the EEG at the initial stages of the disease, individual spike-wave or polyspike-wave complexes are detected. The phenomenon of photosensitivity is characteristic. As the disease progresses, the main activity slows down, the number of the above-mentioned paroxysmal discharges increases, focal anomalies appear, especially in the occipital regions, and physiological patterns of night sleep are grossly disrupted. Resting myoclonus is detected on the EMG.

Diagnosis. Light microscopy reveals Lafora bodies in the cerebral cortex, liver tissue, and skeletal muscles. The most informative and accessible method is the examination of skin biopsies, especially in the forearm area.

Dento-rubro-pallido-Lewis atrophy

This is a rare disease inherited in an autosomal dominant pattern and characterized by degeneration of the dento-rubral and pallido-Lewis systems. The pathogenesis is based on the presence of CAG triplets. Anticipation in subsequent generations and variable clinical expressivity of the hereditary defect are characteristic. The age of onset varies from 6 to 69 years. Cerebellar ataxia is characteristic, combined with dystonia, choreoathetosis, and sometimes parkinsonism. Progressive myoclonus epilepsy and rapidly progressive dementia are observed in 50% of cases. The main diagnostic problem is to distinguish this disease from Huntington's chorea. The EEG shows bursts of slow waves and generalized "spike waves".

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Ceroid lipofuscinosis

Ceroid lipofuscinosis (cerebroretinal degeneration) is a lipidoses characterized by the deposition of autofluorescent lipopigments in the central nervous system, hepatocytes, cardiac muscle, and retina. The primary biochemical defect underlying the disease is unknown. Ceroid 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, and adult form.

The infantile type of Santavuori-Haltia manifests after 6-8 months and in the strict sense does not belong to progressive myoclonus epilepsies.

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Late infantile type of Jansky-Bilshovsky

Jansky-strongielschowsky begins at the age of 1 to 4 years with movement disorders, ataxia, speech disorders. Mental retardation is typical. Epileptic seizures and myoclonus develop. By the age of 5, optic nerve atrophy usually develops. The course is rapidly progressive. EEG shows epileptic activity in the form of spikes and "polyspike-wave" complexes. Electron microscopy reveals granular lysosomal inclusions in biopsies of the skin, peripheral nerves and rectal mucosa.

Juvenile Spielmeyer-Vogt-Sjogren type

Spielme-yer-Vogt-Sjogren is common in Scandinavian countries. The disease begins at the age of 4 to 14 years (in 70% of cases - from 6 to 10 years) with a decrease in visual acuity (retinitis pigmentosa) and gradually progressing mental disorders. After 2-3 years, extrapyramidal symptoms (slowness of movement, tremor similar to Parkinson's), cerebellar ataxia, myoclonus, pyramidal insufficiency, absences or generalized tonic-clonic seizures join in. Myoclonus is clearly represented in the facial muscles. The sequence of symptoms may vary. In the terminal stage of the disease, myoclonic seizures become almost constant and clonic epileptic status often develops. Death usually occurs at about 20 years of age. Ultrastructural examination of the skin and lymphocytes reveals vacuolated peripheral blood lymphocytes and characteristic profiles of intracellular (intralysosomal) inclusions in the form of “fingerprints”.

Adult form of Kufsa

Kufs is a rare disease. The age of onset of the disease varies from 11 to 50 years. Dementia, cerebellar ataxia, and dyskinesia gradually develop. Epileptic seizures and myoclonus are observed in the terminal stage. There are no visual impairments. Lethal outcome occurs approximately 10 years after the onset of the disease. Typical pathomorphological changes are found in brain biopsies: intracellular inclusions in the form of "fingerprints" and osmophilic granular groups. When examining other organs, the diagnosis is more difficult to establish.

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Gaucher disease

Gaucher disease is known in three forms: infantile (type I), juvenile (type II) and chronic (type III). The last type of Gaucher disease can manifest itself as progressive myoclonus epilepsy. The disease is caused by a deficiency of beta-glucocerebrosidase and is characterized by the accumulation of glucocerebroside in various tissues of the body.

The onset of the disease varies from childhood to adulthood. The disease manifests itself as splenomegaly, anemia, and neurological symptoms in the form of supranuclear gaze palsy and/or strabismus, generalized tonic-clonic or partial seizures. Ataxia and moderate intellectual disability are also noted in the early stages. As the disease progresses, myoclonic paroxysms develop. The course is progressive. In the EEG, multifocal "polyspike-wave" complexes are found. Accumulations of glucocerebroside are found in biopsies of various organs, circulating lymphocytes and bone marrow, as well as in the rectal mucosa. The prognosis of the disease is characterized by significant variability.

Sialidosis, type I

The disease is based on neuroaminidase deficiency. The type of inheritance is autosomal recessive. The disease begins between the ages of 8 and 15. The first symptoms are often visual impairment (night blindness), myoclonus and generalized epileptic seizures. Intelligence is usually not affected. Myoclonus is observed at rest, increases 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 in the perioral area. Unlike myoclonus in the limbs, facial myoclonus persists during sleep. Ataxia and paresthesia in the limbs are often observed. A characteristic "cherry pit" symptom is found on the fundus, sometimes - clouding of the vitreous body. The course is progressive. Myoclonus is associated with generalized spike-wave complexes on the EEG. Neuroamidase deficiency is detected in lymphocyte and fibroblast cultures. In most cases (with rare exceptions), myoclonus progresses rapidly and leads to patient disability.

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Sialidosis, type II

Sialidosis type II (galactosialidosis) is caused by beta-galactosidase deficiency and has been described primarily in Japanese. It presents with mental retardation, angiokeratoma, chondrodystrophy, hepatosplenomegaly, and short stature. A cherry pit sign is seen in the fundus. Progressive myoclonus-epilepsy syndrome may develop.

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MERRF syndrome

MERRF syndrome or "myoclonus-epilepsy with ragged red fibers" refers to mitochondrial encephalomyopathies (mitochondrial cytopathies). The disease is inherited by the mitochondrial type and is transmitted through the maternal line. The age of onset of MERRF syndrome varies from 3 to 65 years. In addition to myoclonus and generalized seizures, progressive dementia, cerebellar ataxia, and spasticity are observed; less common are: optic nerve atrophy, sensorineural hearing loss, myopathic symptoms, clinical and EMG signs of peripheral neuropathy. The sequence of symptom onset in MERRF syndrome varies from case to case: neurological, sensory, and mental disorders may occur several years before the onset of epileptic seizures, myoclonus, and ataxia. Clinical expressivity is highly variable and polymorphic even within a family. The severity of MERRF syndrome is also highly variable. EEG shows abnormal background activity in 80% of cases; spike-wave complexes in 73%. Giant evoked potentials are observed in all cases. Neuroimaging (CT, MRI) reveals diffuse cortical atrophy, white matter lesions of varying size, basal ganglia calcifications, and focal cortical lesions of low density. Skeletal muscle biopsy reveals a characteristic pathomorphological feature - ragged-red fibres. In some cases, mitochondrial abnormalities are detected during skin examination.

GM2 gangliosidosis type III

The disease is inherited in an autosomal recessive manner. The disease is based on a deficiency of the enzyme hexosaminidase type A (as in Tay-Sachs disease, but not as pronounced and not as extensive). The disease begins to manifest itself in childhood or adolescence. Cerebellar ataxia, dysarthria develop, then dementia, spasticity, dysphagia, dystonia, epileptic seizures, and myoclonus progress. Some patients have an atypical "cherry pit" phenomenon in the fundus. The disease progresses slowly over many years. Some patients live up to 40 years.