Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes of melas. Rare diseases Debut of melas syndrome in adulthood observation

22.07.2023 Thrush

Keywords

MELAS SYNDROME / MELAS SYNDROME / EPILEPSY / EPILEPSY / CLINICAL / CLINICAL PICTURE / DIAGNOSTICS / TREATMENT / TREATMENT

annotation scientific article on clinical medicine, author of the scientific work - Mukhin K.Yu., Mironov M.B., Nikiforova N.V., Mikhailova S.V., Chadayev V.A.

MELAS syndrome is a genetically determined disease from the group of mitochondrial diseases, defined as mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes. All organs and tissues are involved in the pathological process, but the muscular and nervous systems suffer to a greater extent. The disease most often develops between the ages of 6 and 10 years. The course of the disease is progressive. In most cases, the disease manifests itself with epileptic seizures, recurrent headaches, vomiting, and anorexia. Epilepsy is an important clinical manifestation of MELAS syndrome. Epileptic seizures are the first recognizable symptom in mitochondrial encephalopathies (ME) in 53% of cases. In MELAS, occipital epilepsy is most common. As the disease progresses, epilepsy becomes resistant to therapy, often with a status course. Cases of transformation into Kozhevnikov epilepsy have been described. We present the medical history of a patient with a diagnosis of MELAS syndrome verified during his lifetime.

EPILEPSY IN MELAS SYNDROME

MELAS syndrome is a genetically determined disease of the mitochondrial group, defined as mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes. The pathological process involves all organs and tissues, but it is mostly adversive for the muscular and nervous systems. The disease is most frequent in children aged 6 to 10. The clinical course is progressive. In most cases the disease is manifested by epileptic seizures, relapsing headaches, vomiting, anorexia. The important clinical presentation of MELAS syndrome is epilepsy. Epileptic seizures are the initial diagnosed symptom of mitochondrial encephalopathies (ME) in 53% of cases. Occipital epilepsy is most frequent in MELAS syndrome. As the disease progresses, resistance of epilepsy to treatment is observed, often with occurrence of status epilepticus. Some cases of transformation into Kozhevnikov's epilepsy are described. A history of a patient with a verified while alive diagnosis of MELAS syndrome is given.

Text of scientific work on the topic “Epilepsy in melas syndrome”

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EPILEPSY WITH MELAS SYNDROME

K.Yu. Mukhin1, M.B. Mironov1, N.V. Nikiforova1, S.B. Mikhailova2, VA. Chadayev1, A.A. Alikhanov1-2, B.N. Ryzhkov1, A.S. Petrukhin1

EPILEPSY IN MELAS SYNDROME

KYu. Mukhin1, M.B. Mironov1, N.V. Nikiforova1, S.V. Mikhailova2, U.A. Chadaev1, A.A. Alikhanov1-2, B.N. Ryzkov1, A.S. Petrukhin1

1 - Department of Neurology and Neurosurgery, Pediatric Faculty, State Educational Institution of Higher Professional Education, Russian State Medical University of Roszdrav

2 - Russian Children's Clinical Hospital

MELAS syndrome is a genetically determined disease from the group of mitochondrial diseases, defined as mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes. All organs and tissues are involved in the pathological process, but the muscular and nervous systems suffer to a greater extent. The disease most often develops between the ages of 6 and 10 years. The course of the disease is progressive. In most cases, the disease manifests itself with epileptic seizures, recurrent headaches, vomiting, and anorexia. Epilepsy is an important clinical manifestation of MELAs syndrome. Epileptic seizures are the first recognizable symptom in mitochondrial encephalopathies (ME) in 53% of cases. In MELAS, occipital epilepsy is most common. As the disease progresses, epilepsy becomes resistant to therapy, often with a status course. Cases of transformation into Kozhevnikov epilepsy have been described. We present the medical history of a patient with a diagnosis of MELAS syndrome verified during his lifetime.

Key words: MELAS syndrome, epilepsy, clinical picture, diagnosis, treatment.

Key words: MELAS syndrome, epilepsy, clinical picture, diagnostics, treatment.

MELAS syndrome is a genetically determined disease from the group of mitochondrial diseases, defined as mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes.

MELAS syndrome was first identified as an independent nosological form by S. Pavlakis et al. in 1984. However, a number of authors suggest that the disease was described earlier under the name “familial polyodystrophy, mitochondrial myopathy, lactic acidemia.”

Prevalence in the population has not been established. By 2000, more than 120 observations of MELAS syndrome had been published, including in the domestic press.

MELAS syndrome in 25% of cases is inherited on the maternal line with a high risk, but in 56-75% of patients there is no family history. The disease is associated with mutations in mitochondrial DNA genes encoding subunits of the respiratory chain complexes and transfer RNA genes (MT-ND1, MT-ND5, MT-TH, MT-TL1 and MT-TV). In 80-90% of cases of MELAS syndrome, the disease is based on a point mutation in the MT-TL1 gene, which encodes leucine transfer RNA. With this mutation, the nucleotide adenine is replaced by guanine at position 3243 (A3243G), which disrupts the synthesis of all proteins in mitochondria.

All organs and tissues are involved in the pathological process, but the muscular and nervous systems suffer to a greater extent.

Mukhin K.Yu., Mironov M.B., Nikiforova N.V., Mikhailova S.B., Chadayev V.A., Alikhanov A.A., Ryzhkov B.N., Petrukhin A.S.

Epilepsy in MELAS syndrome Rus. zhur. det. neuro.: vol. IV, issue. 3, 2009.

ORIGINAL ARTICLES

topics as the most energy-dependent. The severity of clinical manifestations depends on the threshold effect (age, tissue energy needs), on the control of nuclear genes over the synthesis of the respiratory chain, heteroplasmy (different content of mutant mtDNA molecules in tissues). It has been shown that in patients with MELAS syndrome, the content of mutant mtDNA in various tissues is 93-96%. In family members of probands, mutant mtDNA is also detected in the tissues, but its content is significantly lower: 62-89% in the erased form of the disease, from 28 to 89% in the absence of clinical signs of the syndrome.

The disease most often develops between the ages of 6 and 10 years, but there are cases of earlier (up to two years) or later onset - from 21 to 40 years. Before the onset of the disease, 90-100% of patients develop normally. The course of the disease is progressive, more malignant with early onset.

In most cases, the disease manifests itself with epileptic seizures, recurrent headaches, vomiting, and anorexia. You should also pay attention to exercise intolerance in the form of deterioration in well-being and the appearance of muscle weakness. The myopathic symptom complex is manifested by exercise intolerance, muscle weakness, fatigue, and sometimes muscle hypotrophy.

As the disease progresses, dementia usually develops. Symptoms such as cerebellar ataxia, sensorineural deafness, and peripheral polyneuropathy are less common.

Stroke-like episodes are characteristic, which can manifest as recurrent attacks of headache, dizziness, development of focal neurological symptoms (paresis, hemianopsia), coma. Such acute episodes are often precipitated by fever or intercurrent infections. These manifestations can have a fairly rapid regression (from several hours to several weeks), as well as a tendency to recur.

Epilepsy is an important clinical manifestation often occurring early in MELAS syndrome. This

often the most obvious neurological manifestation, especially in atypical mitochondrial encephalopathies (ME). Epileptic seizures are the first recognizable symptom in mitochondrial encephalopathies (ME) in 53% of cases.

In MELAS, occipital epilepsy (OE) is the most common disorder. Characteristic are focal seizures emanating from the occipital lobes. Seizures are often associated with transient or persistent neurological symptoms such as visual field loss.

Seizures emanating from the occipital cortex are divided according to their manifestations into subjective sensations (aura) and into clinically detectable symptoms, usually with a motor component. Epileptic auras emanating from the occipital lobe include simple and complex visual hallucinations and amaurosis. The most typical attacks characteristic of SE are simple visual hallucinations, which can manifest as positive (flashes, spots of light) and negative symptoms (scotoma, hemianopsia). The most common visual hallucinations are described as a spot or spots of light, either constant or flashing. As a rule, the spot is white with a greenish tint. Hallucinations can also be multi-colored or monochromatic. Hallucinations usually appear in visual fields contralateral to the focus of excitation in the occipital cortex and subsequently spread. However, it should be noted that visual aura is not often detected in patient complaints.

Complex visual hallucinations are observed when epileptic excitation spreads to the occipito-temporal or occipito-parietal sections. Complex visual hallucinations can appear in the form of people, animal objects or scenes, be familiar or unfamiliar, pleasant or frightening, frightening, simple or grotesque, can be static or move horizontally and disappear. As a rule, they are a terminal symptom before the development of a motor attack; may be the first ictal symptom, but more often occurs after

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elementary hallucinations.

A special, extremely difficult to diagnose type of seizures emanating from the occipital cortex is ictal ama. According to many authors, this is as common a symptom of irritation of the occipital lobe as visual hallucinations, but often remains unrecognized. Typically, patients do not identify this symptom separately in the structure of the attack. Vision loss occurs bilaterally with loss of the lateral fields. Possible homonymous hemianopia contralateral to the source of the attack. The patients describe the sensations as darkening in the eyes, “white darkness,” and impaired color perception. A status course with the formation of the so-called status epilepticus amauroticus is possible.

Occipital seizures may present with autonomic symptoms. These include migraine headaches, dizziness, nausea, and vomiting. A common symptom is post-attack migraine-like headache.

Clinical manifestations of seizures that occur limited to the occipital cortex are characterized by deviation of the eyes to the side. Deviation of the eyes can be observed together with deviation of the head to the side. In most cases, there is a deviation of the eyes in the direction contralateral to the lesion. However, cases have been described when eye deviation is observed towards the lesion. Also, one of the features of “occipital” attacks is the instantaneous spread of the discharge to the anterior parts of the brain, while the clinical picture, as a rule, is dominated by a pronounced motor component. Tonic, tonic-clonic (both hemiconvulsive and secondary generalized), automotor seizures are possible. In this regard, it is important to identify the initial clinical symptoms - an unmotivated and sudden stop of gaze, looking at non-existent objects, an unreasonable smile, vegetative manifestations and necessarily documentary confirmation of the primary ictogenic zone using the VEM method.

As the disease progresses, epilepsy becomes resistant to therapy, often with a status course. Cases of transformation into Kozhevnikov epilepsy have been described. A number of cars

dat describes the possibility of status epilepticus as the first symptom in patients with MELAS without a history of previous seizures. Ribacoba R. et al. describe in their publication 4 cases of the development of epilepsia partialis continua with focal motor attacks, which were preceded by a history of episodes of migraine headache. Miyazaki M. et al. showed the possibility of continued focal myoclonus as part of epilepsia partialis continua in patients with MELAS. Araki T. et al. We observed a patient aged 37 years with status epilepticus of focal seizures in the form of fluctuations of consciousness, homonymous hemianopia in combination with paroxysmal episodes of eye deviation to the side. Continuous EEG patterns of seizures localized in the occipital region were recorded on the EEG. In adult patients with MELAS, there is a predominance of focal motor seizures, but the EEG shows a predominance of multiregional epileptiform activity in the occipital regions.

Epileptiform activity is recorded in 71% of cases after the onset of seizures. An electroencephalographic study of patients with MELAS syndrome is characterized by epileptiform activity in the occipital regions. A number of authors associate the appearance of regional epileptiform disorders with strokes. According to a study by Fujimoto S., in the acute period (i.e., within 5 days after a stroke-like episode), the majority of examined patients with MELAS syndrome had regional high-amplitude delta waves in combination with polyspikes. The authors propose to consider this pattern as pathognomonic for stroke-like episodes. In addition to the occipital regions, epileptiform activity can spread to the temporal regions, bifrontally, and also bilaterally to the posterior regions with diffuse distribution. A photoparoxysmal response may occur during rhythmic photostimulation.

The leading laboratory sign is an increase in the level of lactate in the blood

ORIGINAL ARTICLES

vi above 2.0 mmol/l, which leads to the development of lactic acidosis.

MRI of the brain in the early stages of the disease may be unremarkable, even when epilepsy occurs. Neuroimaging methods reveal infarct zones in the cerebral hemispheres (80%), less often in the cerebellum and basal ganglia. Calcification of the basal ganglia and atrophy of the cerebral cortex may also be observed. In a photon emission study, the accumulation of the isotope is detected 3-16 days before the appearance of the infarction zone (decrease in the isotope signal) on a computed tomogram of the brain. MRI of the brain demonstrates areas of lesions predominantly located in the occipital lobes, which may be transient. The occipital cortex is predominantly affected, the white matter is damaged to a lesser extent. On T2-weighted images, brain lesions in MELA appear as areas of increased signal intensity. A number of authors associate transient hyperintense areas with reversible vascular edema.

Angiography usually does not reveal vascular abnormalities. Diffusion-weighted MRI demonstrates changes associated with vasogenic edema.

Histopathology: When examining a muscle biopsy, fibers with ragged “red edges” are identified. Brain autopsy is characterized by a combination of old and new foci of infarction, as well as cortical atrophy with focal foci of necrosis.

Currently, therapy is supportive. The main direction of treatment is to improve the energy balance of mitochondria and the respiratory chain. Coenzyme p10 (80-300 mg/day), vitamins K1 and K3 (25 mg/day), succinic acid (up to 6 g/day), vitamin C (2-4 g/day), riboflavin (100 mg/day) are used. and nicotinamide (up to 1 g/day). Due to developing secondary carnitine deficiency, patients are prescribed L-carnitine (up to 100 mg/kg/day). Vitamin E (300-500 mg/day) and vitamin C (2-4 mg/day) are used as antioxidant therapy.

There are no generally accepted antiepileptic treatment regimens for MEDIA. A number of authors suggest excluding drugs that can inhibit energy metabolism (barbiturates, valproic acid drugs; as well as some drugs from other groups, for example, chloramphenicol). The literature describes several isolated cases of aggravation of convulsive attacks when using valproic acid in MELA syndrome with the A3243C mutation. The main AEDs in the treatment of epilepsy in MELAYA syndrome are considered to be Tegretol (or Trileptal), Topamax, Keppra in medium therapeutic doses. Properly selected therapy leads to a significant reduction in the frequency of secondary generalized seizures. However, attacks with impaired autonomic-visceral and visual functions are usually resistant to treatment. In the terminal stage of the disease, the frequency of epileptic seizures may decrease.

We present the medical history of a patient with a verified diagnosis of MELAYA syndrome during his lifetime.

Patient Ch.A., 11 years old, was observed at the Center for Pediatric Neurology and Epilepsy. Upon admission, there were complaints of a gradual loss of speech skills, severe gait disturbance with refusal to walk, significant decrease in vision, moodiness, and negative behavior; daily serial attacks in the form of twitching of the facial muscles, muscles of the upper and lower extremities, as well as short-term episodes of vision loss.

The onset of the disease was noted at 5 years 9 months. For the first time, against the background of complete health, when falling asleep, a severe headache, simple visual hallucinations (“yellow ray”) appeared, followed by a forced turning of the eyes and head to the side and the development of a generalized tonic-clonic convulsive attack, after which vomiting was noted. After 9 months attacks with the same symptoms recurred and quickly became serial. After prescribing Tegretol at a dose of 400 mg per day, the frequency of attacks decreased to 1 time per month. Tegretol was replaced by Depakine Chrono at a dose of 900 mg/day, against which clinical remission was observed for 6 months. Considering the clinical symp-

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tomatism, the timing of the attacks during the period of falling asleep, the patient’s normal intelligence, a positive reaction to valproate, idiopathic occipital epilepsy was diagnosed.

At the age of 7, focal versive seizures resumed with secondary generalization upon falling asleep with the same frequency of 1 time per month. Increasing the dose of depakin to 1500 mg/day did not lead to a decrease in the frequency of attacks. With the addition of Lamictal at a dose of 75 mg/day, the attacks stopped for 4 months, then resumed with the same frequency. At the age of 8, attacks with short-term loss of vision began. From 8 years 8 months. before falling asleep, atypical absences began to occur: rapid blinking with closing of the eyelids and moving the eyeballs upward; consciousness fluctuates.

At the age of 9, multiple serial attacks appeared, lasting for several days, with simple visual hallucinations in the form of a “ray” flashing before the eyes, with the eyes and head turning to the right. Before falling asleep, such attacks sometimes turned into focal hemiclonic ones, which were manifested by contraction of the facial

muscles on the right, twitching of the head to the right, cloning of the right limbs (more than an arm). Sometimes after an attack there was a severe headache and vomiting. At the same age, inhibitory attacks appeared: an aura in the form of a sensation of pins and needles in the big toe of the right foot, followed by short-term weakness of the right leg and awkwardness of the right hand. Topamax was introduced into the treatment regimen at a dose of 100 mg/day - there were no epileptic seizures for 1 year.

Also, at the age of 9, paroxysmal conditions first appeared, accompanied by severe headache, vomiting and the development of right-sided hemiparesis. In some cases, such conditions were accompanied by amaurosis lasting from several minutes to several days.

At the age of 10.5 years, attacks reappeared in the form of turning the head to the left, jerky movements of the eyeballs to the left, lasting up to 5 seconds, with a frequency of up to 3 times per hour, daily, even during sleep. The dose of Topamax was increased to 150 mg/day without significant effect. At 10 years 10 months. after an intense headache, alterna-

Rice. 1. Patient Ch.A. 10 years. Diagnosis: MEAE syndrome. Symptomatic focal epilepsy.

Video-EEG monitoring (2004): against the background of diffuse slowing of the main brain activity, continued epileptiform activity is recorded in the left occipital region. Subclinical EEG patterns of a seizure were also recorded in the left occipital region, spreading to the left posterior temporal region.

Center for Pediatric Neurology and Epilepsy

under the guidance of Professor K.Yu. Mukhina is engaged in the diagnosis and treatment of diseases of the nervous system in Aetey, specializing in Aetian forms of epilepsy.

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Epilepsy in children and adolescents

Headache

Sleep disorders in children

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Examination of children in the first ^ months of life.

Examinations in our center:

Diagnosis and treatment of diseases of the nervous system in children

Full diagnostics (including presurgical) and treatment of epilepsy

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Consultation with a pediatrician (frequently ill children, gastroenterology, etc.)

Consultation with a psychiatrist and psychologist.

Consultation with a geneticist with testing (including karyotyping)

Video-EEG monitoring (in specially equipped rooms of the Center or visiting the patient’s home)

Computer (digital) electroencephalography

Ultrasound Dopplerography (Doppler ultrasound) of the vessels of the head and neck

Echoencephalography (ECHO EG)

On our website you can subscribe to the journal “Russian Journal of Child Neurology” via the Internet.

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Address: St. Borisovskie Ponds, 13, bldg. 2. Internet: www.epileptologist.ru E-mail: [email protected](for detailed directions, see the website)

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raging focal hemclonic and secondary generalized seizures, which became serial and lasted 48 hours. Frisium was added to Topamax at a dose of 10 mg/day with a temporary positive effect.

From the age of 8, difficulties with mastering school material began to be noted; memory has decreased. Increased fatigue, exhaustion, and inhibition of mental activity appeared. The boy became moody, irritable, and negative; the background mood has decreased. From the age of 9 years, an increase in these symptoms was noted.

From the life history it is known that the child was born from a second normal pregnancy, a second term birth, birth weight 2800 g, length 53 cm. Early psychomotor and speech development was fully consistent with age. Previous illnesses: chickenpox at the age of 6, frequent ARVI (up to 4 times a year) from the age of 6. Heredity for epilepsy and other neurological diseases is not burdened.

At the time of examination (11 years old), the child’s condition was serious; reacts negatively to inspection. Conscious, oriented in pro-

travel and time. He is extremely reluctant to make contact and refuses to follow instructions. Spontaneous nystagmus to the left, the head is tilted to the left shoulder with a turn to the right. The tongue is in the midline, the pharyngeal reflex is reduced; Dysphagia and dysarthria are noted. Vision is reduced.

Moderate diffuse muscle hypotonia is determined. Tendon reflexes are uniformly reduced. There was a slight decrease in muscle strength in the right extremities. No pathological foot reflexes were detected. There is no objective evidence for sensory impairment. There is no Romberg in the sample. Refuses to walk. When he tries to get him to his feet, he cries and sits down on the floor. Missing when performing a finger-index test. Speaks slowly, in separate words, reluctantly.

Additional examination methods. Video-EEG monitoring (2004). Significant slowdown in core background recording activity. During the study, continued epileptiform activity was recorded in the left occipital region, spreading to the left posterior temporal region and with the periodic formation of an EEG pattern.

Born 1993 16/12/05

Rice. 2. Patient Ch.A. 11 years. Diagnosis: MELAS syndrome. Symptomatic focal epilepsy.

Video-EEG monitoring was carried out over time after 1 year (2005): a significant slowdown in background brain activity. During sleep recording, continued regional slowing is recorded in the right fronto-central region, the structure of which reveals peak-wave activity in the right fronto-central region.

ORIGINAL ARTICLES

stupa (Fig. 1). Continued regional slowing is also detected in the right frontal-central region with the inclusion of single sharp waves.

Video-EEG monitoring in dynamics (2005): Significant slowdown of background brain activity. During the study, continued regional slowing was recorded in the right frontocentral region. In the structure of regional slowing in the right frontal-central region, peak-wave activity is detected (Fig. 2).

MRI of the brain. The first MRI (6 years) revealed a single hyperintense signal in T2 mode in the left hemisphere of the cerebellum. MRI study over time (10.5 years): a significant deterioration of the primary lesion was revealed with the spread of the pathological process widely to the left and right occipital-parietal regions of both hemispheres of the brain (Professor A.A. Alikhanov).

Visual evoked potentials: significant morphofunctional changes in the visual afferent system at the level of the optic nerve and the cortical part of the visual analyzer, more pronounced on the left.

Consultation with an ophthalmologist: partial atrophy of the optic nerves. Elements of cortical agnosia.

Electrocardiogram: ectopic rhythm with acceleration up to 100 beats per minute.

Vertical position of the electrical axis of the heart. Changes in repolarization processes, which are more pronounced in orthostasis.

Electroneuromyography: a primary muscular type of lesion was revealed. Conduction velocities along peripheral nerves are not reduced.

Study of blood lactate level: blood lactate level is 3.0 mmol/l (normal is up to 1.8).

Considering the presence of epileptic seizures emanating from the occipital parts of the cerebral cortex, resistant to therapy, stroke-like episodes, periods of amaurosis, decreased cognitive functions, the presence of hyperintense signals on MRI in the cerebellum and posterior parts of the cerebral cortex, increased levels of lactate in the blood, the patient had A diagnosis of MELAS syndrome was suggested. During a genetic examination, the A3243G mutation in the heteroplasmic state was detected in blood cells (diagnosis was carried out at the Moscow State Research Center of the Russian Academy of Medical Sciences), and the diagnosis was verified.

Follow-up observation showed rapid progression of disorders of higher mental functions, development of cortical blindness, complete immobility of the patient, followed by death at the age of 12 years 10 months. (7 years after the onset of the disease).

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29. Williamson P.D., Thadani V.M., Darcey T.M., Spencer D.D., Spencer S.S., Mattson R.H. Occipital lobe epilepsy: clinical characteristics, seizure spread patterns, and results of surgery // Ann Neurol. - 1992. - V. 31. - P. 3-13.

30. Yi-Min Chen, Chih-Ming Lin, Peterus Thajeb. Paradoxical effect of sodium valproate that aggravates epilepsy of MELAS in a patient with A3243G mutation of the mitochondrial DNA // Central European Journal of Medicine. - 2007. - V. 2(1). - P.103-107.

31. Yoneda M., Maeda M., Kimura H., Fujii A., Katayama K., Kuriyama M. Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging. Neurology. - 1999. - V. 53. - P. 2182-2184.

MELAS syndrome is a mitochondrial disease characterized by muscle and central nervous system damage.

MELAS (eng. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - “mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes”) is a progressive neurodegenerative disease characterized by the manifestations listed in the name and is accompanied by polymorphic symptoms - stroke, diabetes, seizures, decreased hearing, heart disease, short stature, endocrinopathies, exercise intolerance and neuropsychiatric disorders.

Story.
MELAS syndrome was first described in 1984 by Pavlakis and colleagues; ten years later, Pavlakis and Mizio Hirano published a review of 110 cases.

Inheritance type:

maternal

Epidemiology:

The exact incidence of the disease is not known. There is limited data on the incidence of the disease in the literature. In northern Finland, the frequency of the A3243G mutation is 16.3:100,000.

Pathogenesis:

Mutations of mitochondrial DNA, which control the respiratory chain of mitochondria, are accompanied by disruption of oxidative phosphorylation processes, the most important source of energy for metabolic processes in the cell.

Clinical manifestations

Under the age of 40, patients with MELAS are admitted with a transient ischemic attack, as well as epilepsy, repeated vomiting, headache, and muscle weakness. These patients are often clinically diagnosed with dementia.
Young age and the absence of risk factors characteristic of stroke helps to think about MELAS.
Laboratory data
Lactate acidosis is an increase in lactate and pyruvate levels.

Visualization data
The changes in the brain are similar to those caused by a stroke.
Differences from stroke
1) the affected areas do not coincide with the boundaries of the arterial vascular territories.
2) with repeated attacks, the lesions are visualized in a different location.
+ clinical data (young age, absence of risk factors for stroke).

CT
Multiple hypodense areas that do not correspond to the vascular territory.
Calcification of the basal ganglia (most common in older patients).

Atrophy occurs against a background of regression and clinical improvement.

MRI
Acute myocardial infarction
To differentiate from stroke, ADC and DWI are used (with strokes, diffusion is limited (cytotoxic edema), and with MELAS, diffusion is limited slightly or without changes (vasogenic edema).
Involvement of the subcortical white matter of the brain in the pathological process.
Deterioration in the visualization of the clarity of the contours of the gyri and an increase in the signal from them on T2-weighted images.

Chronic heart attack
Changes can be symmetrical or asymmetrical.
Focal atrophy occurs against a background of regression and clinical improvement.
The parietal, occipital and temporal lobes of the brain are most often affected.

MR spectroscopy
Increased lactate levels.

The materials are intended for neurologists, therapists, and general practitioners.

Sergey Likhachev, head, doctor of medicine. sciences, professor;

Inessa Pleshko, leading researcher, candidate of medical sciences. Sciences, neurological department of the Republican Scientific and Practical Center of Neurology and Neurosurgery.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive autosomal dominant disease whose clinical manifestations include recurrent subcortical ischemic strokes, migraine, subcortical dementia and affective disorders. Current prevalence - 1 case
per 100,000 population.

The Republican Scientific and Practical Center for Neurology and Neurosurgery is observing 7 patients (including 4 women) with CADASIL; age - from 32 to 68 years. They were examined by neurological and molecular genetic methods. There were characteristic symptoms; history of migraine, recurrent lacunar strokes and affective disorders. MRI of the brain revealed subcortical infarcts and leukoencephalopathy characteristic of CADASIL.

In 2 people, molecular genetic diagnostics revealed a heterozygous mutation in the Notch3 gene on chromosome 19, which causes CADASIL. Notch genes encode transmembrane receptors involved in cell ontogenesis. With CADASIL, in most cases, missense mutations are determined, due to which the structure of the transmembrane protein changes and its functions are disrupted.

The pathogenesis of CADASIL is not completely clear. It is believed that the main factor is arteriopathy with progressive occlusion of small perforating vessels of the white matter of the brain (leading to chronic hypoperfusion). In this case, characteristic granular osmiophilic inclusions are found, causing proliferation of the components of the basement membrane, thickening of the tunica media and mechanical compression of small arteries. As a result, the blood-brain barrier is damaged and edema develops.

An additional pathological factor is the activation of astrocytes near the vascular wall. They release endothelium-1, causing vasoconstriction and impaired blood flow.

The composition of granular osmiophilic inclusions is unknown. It is assumed that the Notch3 protein is one of their components. In skin biopsies of patients with a Notch3 mutation, osmiophil granules and smooth muscle cell degeneration can be detected before age 20.

Clinical diagnosis of CADASIL:

family history;
development of the first symptoms of the disease before age 50;
the presence of two of the following symptoms - migraine, recurrent strokes, mood disorders, subcortical dementia.

Vascular risk factors etiologically associated with neurological symptoms should be excluded. MRI shows lesions of the white matter of the cerebral hemispheres and the absence of cortical infarcts.

A reliable diagnosis of CADASIL is confirmed by a positive result of molecular genetic diagnostics or the detection of arteriopathy with characteristic granular osmiophilic inclusions during a skin or muscle biopsy.

The most common symptoms of CADASIL are transient ischemic attacks and ischemic strokes, observed in almost 85% of patients.

They are characterized by a recurrent course, manifesting themselves as classic lacunar stroke syndromes and complete clinical remission after a few days or weeks.

The second most common are cognitive impairments (noted in 60% of patients). They can begin at the age of 35, sometimes even before ischemic episodes. Approximately 75% of cases with CADASIL develop dementia. The first symptom is usually a migraine; often occurs before age 20 and usually precedes strokes.

Data on the involvement of the heart in the pathological process in CADASIL are contradictory. L. Oberstein et al. (2003) found that 25% of patients diagnosed with CADASIL had a history of acute myocardial infarction or Q-wave abnormality on the electrocardiogram. In another study, Cumurciuc et al. (2006) found no positive cardiac history in 23 people with a mutation in the Notch3 gene.

The clinical manifestations of CADASIL and cerebral microangiopathy of other etiologies are similar - differential diagnosis is required.

To promptly identify CADASIL in patients and their family members, it is necessary to resort to molecular genetic methods and/or histological studies.

MELAS syndrome

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare hereditary disease caused by pathology of the mitochondrial genome, disruption of energy metabolism and the functioning of the most energy-dependent organs and tissues (CNS, cardiac and skeletal muscles, eyes, kidneys, liver, bone marrow, endocrine system). The wide variability of clinical manifestations of MELAS syndrome and its rare occurrence predetermine difficulties in diagnosis for a practicing physician.

The Republican Scientific and Practical Center for Neurology and Neurosurgery is observing 3 patients (a 46-year-old woman and her sons, 24 and 23 years old) diagnosed with MELAS syndrome. They underwent a clinical neurological examination, molecular genetic diagnostics, and MRI of the brain.

Everyone is short; history of symptoms of mitochondrial pathology: sensorineural hearing loss, migraine-like headaches, poor exercise tolerance. The onset of the disease is generalized convulsive seizures. In 2 patients, the first symptoms appeared before age 20; there were epileptic seizures following one after another, episodes of visual impairment with the presence of foci on neuroimaging in the occipital and temporal regions, increased lactate levels in the blood and cerebrospinal fluid. One person showed a moderate decline in cognitive function; according to cardiac ultrasound - hypertrophic cardiomyopathy; diabetes.

A molecular genetic study revealed multisystem lesions typical of MELAS, wide variability and varying degrees of severity of clinical manifestations, corresponding to the number of mutant copies of A3243G in the tRNALeu(UUR) gene.

MELAS is characterized by a maternal type of inheritance, the presence of sporadic cases when a de novo mutation occurs; accumulation in cells - both normal and mutant types - of mitochondrial DNA (heteroplasmy) and random distribution during division between daughter cells (mitotic segregation). At the genetic level, the cause of MELAS syndrome is the heteroplasmic rearrangement 3243A>G in the tRNALeu(UUR) gene (detected in 80% of cases).

The pathogenesis of the disease has not yet been studied. There are 2 main theories - “mitochondrial angiopathy” and “mitochondrial cytopathy”. It is known that stroke-like lesions do not correspond to vascular zones and spread to surrounding areas due to concomitant vasogenic edema caused by prolonged epileptic activity. Stroke-like episodes are thought to be caused by neural hyperexcitability in a localized area of the brain. It arises from mitochondrial dysfunction in capillary endothelial cells, or neurons, or astrocytes; depolarizes adjacent neurons, leading to the spread of epileptic activity.

In addition, in the intervals between stroke-like episodes, single photon emission computed tomography (SPECT) has shown that patients with MELAS have hypoperfusion of the posterior cingulate cortex, indicating a disorder of cerebral hemodynamics.

Impaired oxidative phosphorylation and disruption of the mitochondrial respiratory chain contribute to the predominance of catabolic metabolism and changes from the Krebs cycle to anaerobic glycosis with lactate accumulation. High levels of the latter in the central nervous system usually correlate with periods of neurological symptoms.

The main clinical signs of MELAS are stroke-like episodes, lactic acidosis, and the presence of “ragged red fibers” in muscle biopsies. Additional manifestations may be dementia, psychosis, epileptic paroxysms, migraine-like headaches, ataxia, myopathy, calcification of the basal ganglia according to neuroimaging, optical atrophy, retinopathy, deafness, diabetes, intestinal pseudo-obstruction, cardiomyopathy.

The early age of onset of MELAS is from 5 to 20 years, but there are observations of a late onset - in the 5th–6th decades of life. There are cases when the syndrome started after cardiac disorders.

The multisystem nature of the lesion in MELAS complicates clinical diagnosis.

The hereditary nature of the disease requires molecular genetic research to be carried out to make an accurate diagnosis.
and identify other patients from among the patient’s relatives.

The materials are intended for neurologists, therapists, and general practitioners.

1 of 24

Presentation on the topic: MELAS syndrome

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MELAS syndrome (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - “mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes”) is a progressive neurodegenerative disease characterized by the manifestations listed in the name and is accompanied by polymorphic symptoms - diabetes, seizures, hearing loss , heart disease, short stature, endocrinopathies, exercise intolerance and neuropsychiatric disorders.

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History MELAS syndrome was first identified as a nosologically independent form by S. Pavlakis et al. in 1984. However, there is reason to believe that the disease was described earlier under the name “familial polyodystrophy, mitochondrial myopathy, lactic acidemia.” By 1994, 110 observations of MELAS syndrome had been published in the literature.

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Etiology, pathogenesis MELAS refers to mitochondrial diseases. The syndrome develops as a result of point mutations in mitochondrial DNA. The localization of 3 point mutations with which MELAS syndrome is associated was revealed: two in transfer RNA and one in cytochrome c oxidase.

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Pathomorphological changes A characteristic pathomorphological sign of MELAS syndrome, as well as a number of other mitochondrial encephalomyopathies (Kearns-Sayre syndromes, MERRF, etc.), are “ragged” red fibers (RRF), which appear in muscle tissue with a modified Gomori trichrome stain. They are a morphological substrate of mitochondrial DNA damage and are formed due to the proliferation of abnormal mitochondria. Red “torn” fibers are the result of mutations that damage transfer RNA genes and lead to disruption of intramitochondrial protein synthesis. It has been shown that such morphological characteristics of muscle tissue, such as the presence of vessels with high succinate dehydrogenase activity and a significant number of cytochrome c-oxidase-positive muscle fibers, are a characteristic feature of MELAS syndrome, which allow it to be differentiated from Kearns-Sayre and MERRF syndromes. One of the specific signs of brain damage in this disease is the presence of old and new foci of infarction.

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ragged red fibers (RRF)

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Clinical picture The first signs most often appear at the age of 6-10 years, although both an earlier onset of the disease (up to 2 years) and a later one (21-40 years) are possible. Before the first signs of the disease appear, most patients develop normally. Initial clinical manifestations: convulsions, recurrent headaches, vomiting, anorexia, exercise intolerance, mental disorders, neurological symptoms (paresis, ataxia, etc.).

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Clinical picture Intolerance to physical activity, after which the state of health worsens, muscle weakness appears, and sometimes myalgia. Stroke-like episodes are manifested by recurrent attacks of headache, dizziness, development of focal neurological symptoms (paresis, paralysis of the limbs, cranial nerves), coma. Convulsions in MELAS syndrome are very variable - focal paroxysms, generalized tonic-clonic, myoclonus. Convulsions are poorly responsive to anticonvulsant therapy.

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Clinical picture Dementia usually develops along with the progression of the disease, but relatively rarely it acts as a manifest symptom. Myopathic symptom complex (muscle weakness, fatigue, sometimes malnutrition). With the early onset of the disease, its course is more malignant. Thus, when MELAS debuts before age 20, the mortality rate is 30%.

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Main diagnostic criteria: exercise intolerance; onset of the disease before 40 years of age (usually before 20 years of age); stroke-like episodes; seizures; “torn” red fibers in skeletal muscle biopsies; lactic acidosis; progressive dementia; myopathic syndrome; short stature; deafness.

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Additional diagnostic criteria: calcification of the basal ganglia on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain; ataxia; comatose states; optic nerve atrophy; retinitis pigmentosa; Wolff-Parkinson-White syndrome; heart failure; progressive external ophthalmoplegia; cardiac conduction disorders; diabetes mellitus.

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Data from laboratory and functional studies: A characteristic sign of the disease is the detection of lactic acidosis in the blood and cerebrospinal fluid. In half of the patients, an increase in lactate and protein levels is detected in the cerebrospinal fluid. The study of respiratory chain enzymes is of great importance; changes in the activity of enzymes of complex I are more often detected. ECG: cardiac conduction disorders, Wolff-Parkinson-White syndrome may be detected. CT scan of the brain: zones of infarction are more often in the hemisphere, less often in the cerebellum, basal ganglia. Calcification of the basal ganglia and atrophy of the cerebral cortex may be observed. Cerebral angiography: increase in the caliber of blood vessels (arteries, veins, capillaries).

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MRI of the brain of patient A., T2-weighted images. a, b – 1f study: symmetrical foci of increased signal intensity in the projection of the parietal lobes of both hemispheres. c, d – 2nd study: in the projection of the temporal and parietal lobes of the right hemisphere, an expansion of the zone of the altered MR signal is noted. In the left hemisphere in the projection of the parietal lobe, the size of the pathological focus noticeably decreased.

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CT scan of the brain: in the temporal lobe of the left hemisphere with partial extension to the parietal lobe, a focus of slightly reduced density is detected (arrow). In both hemispheres, in the area of the lenticular nuclei and visual thalamus, foci of increased density (calcifications) are detected.

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Study of cerebral perfusion using SPECT in patient A. a–c – study November 12, 2003 – zone of low perfusion (blue and green) in the temporal region of the right hemisphere (a) and high perfusion (red) in the occipital lobes (b) and the temporal lobe of the left hemisphere (c). d–f – study 02/18/2004 – decrease in perfusion in the left temporal lobe (f) compared to the previous study.

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Treatment Symptomatic. To correct biochemical defects, coenzyme Q10 (80 - 300 mg / day), vitamins K1, K3 - phylloquinone (25 mg / day) and menadione (up to 75 mg / day), succinic acid (up to 6 mg / day) are used. , vitamin C (2-4 g/day) and other vitamins (riboflavin, thiamine, nicotinamide). It is known that coenzyme Q10, under physiological conditions, transfers electrons from complexes I and II to complex III and thereby contributes to the stabilization of the respiratory chain, reducing the level of lactate and pyruvate. Vitamins K1 and K3 are obviously capable of performing the function of electron transport at the level of complexes I and III. Succinic acid ensures the transfer of electrons to complex II. Vitamin C is considered an electron donor of complex IV, as well as an important antioxidant. In addition to ascorbic acid, vitamin E (300 - 500 mg / day) is prescribed to prevent oxygen-radical damage to mitochondrial membranes.

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Treatment In order to stimulate ATP synthesis, it is proposed to use idebenone (90 - 180 mg / day), which has the property of enhancing energy metabolism in brain tissue. The introduction of the vitamins riboflavin (100 mg/day) and nicotinamide (up to 1 g/day) - precursors of the coenzymes NAD and FAD, which are actively involved in oxidative processes, also helps improve the energy production of mitochondria. Due to secondary carnitine deficiency, patients are prescribed L-carnitine (up to 100 mg/day). In order to reduce the level of lactate in the blood and cerebrospinal fluid, sodium dichloroacetate (25-100 mcg / kg) is used. Using laboratory tests, you need to check for possible dysfunctions of the endocrine system (diabetes mellitus, hypoparathyroidism) and the cardiovascular system (blockade). If violations are detected, they are corrected with medication.

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ASIUV Bulletin, special issue, 2013. udk 616.8-007: 616.853.3

debut of melas syndrome with febrile convulsions

(case from practice)

That. Musabekova, A. I. Khamzina

Kyrgyz-Russian Slavic University, Department of Neurology and Neurosurgery, Bishkek, Kyrgyzstan

Febrile seizures (FS) have been known since antiquity. Hippocrates also wrote that FS most often occurs in children in the first 7 years of life and much less often in older children and adults. But for the first time the term “febrile convulsions” was used in 1904 by B. Hochsinge to refer to convulsive paroxysms that develop in childhood against the background of fever. Currently, it is preferable to talk about febrile seizures (AF) rather than FS, since in the clinical picture of this condition not only convulsive, but also non-convulsive paroxysms can be observed 2]. The 1993 ILAE definition defines AF as attacks occurring in children over 1 month of age associated with a febrile illness not caused by a CNS infection; without previous neonatal seizures or unprovoked seizures, and not meeting criteria for other acute symptomatic seizures. According to the 2001 draft classification, AF is classified as a condition that does not require a mandatory diagnosis of epilepsy. Thus, AF is defined as an episode of epileptic seizures that occurs in children aged 6 months or older. up to 5 years when the temperature rises during a viral or bacterial disease not associated with neuroinfection and metabolic disorders. True AF should be distinguished from febrile-provoked seizures, which can be part of the structure of a number of forms of epilepsy, for example, in Dravet syndrome. In rare cases, AF may be the first symptom of mitochondrial disease in children.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) was first identified as a separate nosological form by S. Pavlakis et al. only in 1984. The disease belongs to the group of mitochondrial diseases associated with point mutations in mitochondrial DNA, which result in disruption of energy production in the mitochondrial respiratory chain. It is known that point mutations can occur in many genes (MTTL1, MTTQ, MTTH, MTTK, MTTS1, MTND1, MTND5, MTND6, MTTS2) and are inherited on the maternal line. The prevalence of MELAS syndrome is difficult to estimate due to the variety of presentations and the associated difficulty of diagnosis. by 2000, more than 120 observations of the disease had been published. The cardinal symptoms of MELAS syndrome are: exercise intolerance, stroke-like episodes, seizures, “ragged red” fibers in muscle tissue biopsies, lactic acidosis and the onset of the disease before the age of 40 years. MELAS syndrome should be differentiated from other mitochondrial diseases: Kearns-Sayer syndrome and MERRF.

Below is our own observation of patient P., born in 2003, living in the city of Bishkek. A child came to us at the MEBI LTD clinic center in Bishkek in the spring of 2013 with complaints of tonic-clonic convulsions in the legs and arms lasting up to 2 minutes, occurring with loss of consciousness and developing

only against the background of an increase in body temperature above 37 C°, as well as difficulty in mastering school material, memory loss, increased fatigue and muscle weakness, awkwardness when walking.

The onset of the disease in the girl was noted at the age of 6 months with a generalized tonic-clonic seizure lasting up to 1 minute against the background of an increase in body temperature to 38 C°, after which she was hospitalized in the Republican Infectious Diseases Hospital of Bishkek, where a neuroinfection was ruled out. Subsequently, AF occurred every time the body temperature increased above 37 C°. At the age of 1 year, upon contacting the National Center of Pediatrics and Pediatric Surgery of the Kyrgyz Republic, an MRI of the brain was performed, an EEG, where no pathology was detected, depakine was prescribed at a dose of 20 mg/kg/day. However, AF continued while taking the anticonvulsant drug. At the age of 5 years, we independently went to the Republican Children's Clinical Hospital (RDCH) in Moscow, where an MRI of the brain and video EEG monitoring (VEM) of daytime sleep were repeated, where again no pathology was detected. Doctors at the Russian Children's Clinical Hospital diagnosed cryptogenic epilepsy and recommended increasing the dose of depakine to 25 mg/kg/day. I finished the first three classes at a comprehensive school with grades of “4” and “5”. From the age of 9, the mother began to notice a gradual increase in the child’s rapid fatigue after physical exertion, the emergence of difficulties in mastering school material, and the question arose about transferring the child to a specialized school institution for children with mental retardation. AF continued to bother the child even after 7 years of age while taking Depakine Chrono at a dose of 25 mg/kg/day.

From the life history: a child from the first pregnancy, which occurred against the background of mild toxicosis in the first trimester, had an episode of acute respiratory viral infection without fever at 5 months. Delivery was on time, independent in cephalic presentation, Apgar score 7/8 points, GPR - 3340 g, height - 52 cm. The early development of the child corresponded to the age norm.

At the time of examination at the clinic at the age of 10 years, from the side of the cranial nerves there is a slight deviation of the tongue to the right, myopathic syndrome in the arms and legs in the form of hypotension, mild hypotrophy of the proximal parts of the arms and legs with a decrease in muscle strength to 4 points, a decrease tendon reflexes, as well as slight staggering in the Romberg position and awkwardness when performing finger-nose and knee-heel tests, decreased short-term memory and attention.

Additional examinations: HB 112 g/l, red blood cells 3.5 * 10"12/l, liver tests, total protein, sugar, creatinine within normal limits.

The continuation of AF after 5 years with the development of resistance to valproate, the addition of myopathic syndrome and a decrease in cognitive functions made it possible to suggest that the patient may have mitochondrial pathology, namely MELAS syndrome, which requires

It was necessary to conduct a number of additional studies. Electroneuromyography performed in the NCP and DH revealed a primary muscular type of lesion in the form of a decrease in the duration of the motor unit potential by 30-35% and a decrease in their amplitude with normal conduction speed along the peripheral nerves. Repeated VEM revealed no pathology. At the SVS laboratory named after V.M. Savinov in Almaty, the concentration of depakine in the blood was determined before taking the drug - 86.98 ng/ml and 2 hours after taking the drug - 113.61 ng/ml with a norm of 50-100 ng/ml. At the Privat Clinic in Almaty, the level of lactic acid on an empty stomach was determined to be 3.1 mmol/l, with a normal level of up to 1.7 mmol/l. A preliminary diagnosis of MELAS syndrome was made, depakine was replaced with keppra, coenzyme Q10, carnitine, B vitamins, vitamin E were introduced, a diet with limited carbohydrate intake was recommended, and genetic testing was recommended.

Thus, in the clinical case we presented, the child had simple AF, for the preventive treatment of which Depakine was prescribed with long-term use for several years despite the presence of pharmacoresistance. Taking into account the lack of clear evidence of the effectiveness of the prophylactic use of anticonvulsants in children with AF, the prescription of Depakine in this case was inappropriate. Thus, according to the literature, long-term use of depakine and barbiturates significantly aggravates the course of mitochondrial diseases, sometimes leading to progression of the pathological process, which is what happened in our clinical case.

bibliography:

1. Guzeva V.I. Special syndromes (situation-related attacks) / V.I. Guzeva // Epilepsy and non-epileptic paroxysmal states in children.-M.: MIA, 2007.- P. 443-457

2. Mukhin K.Yu. Febrile convulsions / A.S. Petrukhin

// Neurology of childhood. - M.: Medicine, 2004.-P.664-668.

3. Nikanorova M.Yu., Temin P.A., Kobrinsky B.A. Febrile convulsions / P.A. Temina, M.Yu. Nikanorova // Epilepsy and convulsive syndromes in children. - M.: Medicine, 1999. - P. 169-195.

4. Basic methods of treating children suffering from mitochondrial diseases: Methodological. instructions.-M., 2001.

5. Temin P.A. and others //Nevrol. zhurn.- 1998. No. 2.- P. 43.

6. Yakhno N.N. and others //Nevrol. magazine 1998.- No. 5.- P. 14.

7. Ban S. et al. //Acta Pathol. Jpn.- 1992. -Vol. 42. -P. 818.

8. Hirano M., Pavlakis S.G. // J. Clin. Neurol. -1994.-Vol. 9. -P. 4.

9. ILAE Commission report: glossary of descriptive terminology for ictal semiology: report of the ILAE Task Force on Classification and Terminology /Epilepsia.- 2001.- Vol. 42. -P.1212-1218.

10. ILAE. Guidelines for epidemiologic studies on epilepsy /Epilepsia.- 1993.- Vol.34.- P. 592-596.

11. Pavlakis S.G. et al. //Ann. Neurol.-1984. -Vol. 16.-P. 481.

12. Sciacco M. et al. // J. Neurol. -2001. -V 248. -P. 778.

Febrile seizures can often be the first symptom of mitochondrial diseases in children, which significantly complicates the timely diagnosis and initiation of pathogenetic treatment of the disease, and sometimes leads to the use of drugs that worsen the course and prognosis of the disease.

Key words: seizures, therapy.

Febrile seizures can often be the first symptom of mitochondrial disease in children, which greatly complicates the timely diagnosis and early treatment, and sometimes causes the use of drugs worsen the course and prognosis of the disease.

Keywords: convulsions, therapy.

udk 616.831-005.4

CASES OF ISCHEMIC STROKE AS A MANIFESTATION OF MITOCHONDRIAL ENCEPHALOPATHY IN A YOUNG PATIENT

AGE

Karbozova K.Z., Lutsenko I.L.

Department of Neurology with a course in medical genetics, Kyrgyz State Medical Academy named after I.K. Akhunbaeva,

Bishkek, Kyrgyzstan

The prevalence of stroke at a young age (up to 45 years) ranges from 2.5 to 10% of all cases of cerebrovascular accidents and continues to increase. In young patients, the most common causes of the development of ischemic vascular disorders are: anomalies of the cerebrovascular system, dissection, cardiac pathology, migraine, coagulation defects, AFLS,.

Over the past 5 months, 608 patients received treatment in the neurology department No. 1 of the National Hospital under the Ministry of Health of the Kyrgyz Republic (NMMHKR). An analysis was made of 46 (7.5) case histories of patients who suffered an ischemic stroke, of which 4 (8.7%) were young (up to 45 years according to WHO). Table 1 shows the subtypes of ischemic stroke.

We present the medical history of a patient hospitalized with an initial diagnosis of acute cerebrovascular accident (ACI), in whom the true nature of the disease could only be established through dynamic observation and special additional examination.

Table 1.

Stroke subtype Number of patients in %

Atherothrombotic 32 69.5

Lacunarny 6 13.04

Hemorheological 3 6.5

Cardio embolic 3 6.5

Mitochondrial 1 2.2

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Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes of melas. Rare diseases Debut of melas syndrome in adulthood observation

annotation scientific article on clinical medicine, author of the scientific work - Mukhin K.Yu., Mironov M.B., Nikiforova N.V., Mikhailova S.V., Chadayev V.A.

Related topics scientific works on clinical medicine, author of the scientific work - Mukhin K.Yu., Mironov M.B., Nikiforova N.V., Mikhailova S.V., Chadayev V.A.

EPILEPSY IN MELAS SYNDROME

Text of scientific work on the topic “Epilepsy in melas syndrome”

Presentation on the topic: MELAS syndrome

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