Melas syndrome is a progressive neurodegenerative disease characterized by the manifestations listed in the name. Rare diseases Molasses syndrome

Description:

MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes, mitochondrial, lactic acidosis, stroke-like episodes) is a disease caused by point mutations in mitochondrial DNA.

Causes of MELAS syndrome:

The syndrome is associated with mutations in many genes: MTTL1, MTTQ, MTTH, MTTK, MTTS1, MTND1, MTND5, MTND6, MTTS2. Mutations may occur for the first time in a particular patient, or may be inherited through the maternal line. A total of 23 missense point mutations and 4 mtDNA deletions leading to MELAS have been identified by 2009, but reports continue of new patients presenting with symptoms of the disorder in the absence of known mutations.

Symptoms of MELAS syndrome:

The age at which the disease manifests varies widely from infancy to adulthood, but most often the first symptoms appear between 5 and 15 years. The onset of the disease is often characterized by stroke-like episodes, malignant migraines, or psychomotor retardation. Strokes are most often localized in the temporal, parietal or occipital regions of the brain, are accompanied by hemiparesis and tend to recover quickly. They are caused by mitochondrial angiopathy, characterized by excessive proliferation of mitochondria in the walls of arterioles and capillaries of brain vessels. As the disease progresses, neurological symptoms increase against the background of repeated strokes. Muscle weakness and sensorineural hearing loss are also present. Sometimes endocrine disorders develop (diabetes mellitus, pituitary dwarfism).

MELAS syndrome is accompanied by polymorphic symptoms - diabetes, seizures, hearing loss, heart disease, short stature, endocrinopathies, intolerance physical activity and neuropsychiatric disorders.

Diagnostics:

The examination includes biochemical, morphological and molecular genetic studies. The most common mutation is the replacement of A with G at position 3243. As a result, the transcription terminator located inside the tRNA gene is inactivated. Consequently, as a result of a single-nucleotide substitution, a change in the transcriptional ratio of rRNA and mRNA occurs and a decrease in translation efficiency. In second place in frequency is the T to C mutation at position 3271 of mtDNA, leading to the development of MELAS syndrome.

Treatment of MELAS syndrome:

Treatment for the syndrome is not yet known; it often worsens, ultimately leading to the death of the patient. Efforts are being made to slow it down. L-arginine is being studied to reduce brain damage during stroke-like episodes, with researchers reporting that before taking the drug, patients' blood arginine levels were significantly reduced during episodes. Preliminary results are encouraging, but more research is needed. L-arginine provokes the release of NO gas, which has both a positive effect - vasodilation, and a negative one: excess can be toxic. It is known, for example, that L-arginine initially showed positive results in heart attack, but larger and longer studies did not confirm the earlier findings and also revealed increased mortality among those who took this drug.

Coenzyme Q has also been used in the absence of adequate clinical studies; such studies have begun but have not yet been completed as of the end of 2009.

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 mitochondrial respiratory chain, 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.

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 fluctuation 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 early stages the disease may be without features, 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 muscles of the face, muscles of the upper and lower limbs, 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 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 diagnoses and bakes diseases nervous system in Aetei, specializes in Aetean forms of epilepsy.

Main directions

activities:

Epilepsy in children and adolescents

Headache

Sleep disorders in children

Tics, enuresis

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

Consultation with neurologists and epileptologists

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.

Detailed information about the work of the Center from 10:00 to 19:00 by phone:

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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 completely age appropriate. 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 others neurological diseases 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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8. Canafoglia L., Franceschetti S., Antozzi C., Carrara F., Farina L., Granata T., Lamantea E., Savoiardo M., Uziel G., Villani F., Zeviani M., Avanzini G. Epileptic phenotypes associated with mitochondrial disorders // Neurology. - 2001. - V. 56(10). - P. 1340-6.

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Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes

Basal ganglia calcification, cerebellar atrophy, increased lactate; CT image of a person diagnosed with MELAS
Speciality	neurology

genetics

Muscle biopsy of a person diagnosed with MELAS, but not carrying a known mutation. (a) Modified Gomori tricolor dye shows several ragged red fibers (arrows). (b) Cytochrome c oxidase stain showing lightly stained type-1 and type II fibers, dark fibers, and a few fibers with abnormal mitochondrial collections (arrows). Note, cytochrome c oxidase negative fibers are typically seen in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). (c) Succinate dehydrogenase staining shows several ragged blue fibers and intense staining in the mitochondria of blood vessels (arrow). (d) Electron microscopy shows an abnormal collection of mitochondria with paracrystalline inclusions (arrows), osmiophilic inclusions (large arrows), and mitochondrial vacuoles (small arrows).

MELAS is caused by mutations in genes in mitochondrial DNA.

NADH dehydrogenases

Mutations in MT-TL1 cause more than 80 percent of all MELAS cases. They reduce the ability of mitochondria to make proteins, use oxygen and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to study the effects of mitochondrial gene mutations in various tissues, especially the brain.

inheritance

This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance and heteroplasmy. This pattern of inheritance refers to genes contained in mitochondrial DNA. Of the eggs, but not the sperm, contribute mitochondria to the developing embryo; only females undergo mitochondrial conditions for their children. Mitochondrial disorders can appear in every generation of a family and can affect both men and women, but fathers do not pass on mitochondrial traits to their children. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in the mitochondrial gene and occurs in people who do not have a family history of MELAS.