[Early infantile epileptic encephalopathy type 14: three cases of epilepsy in infancy with migrating focal seizures due to KCNT1 mutations]. / Rannyaya mladencheskaya epilepticheskaya entsefalopatiya 14-go tipa: tri sluchaya epilepsii mladenchestva s migriruyushchimi fokal'nymi pristupami, obuslovlennymi mutatsiyami gena KCNT1.

OBJECTIVE: To study clinical and neurophysiological data of early infantile epileptic encephalopathy type 14 caused by KCNT1 mutations. MATERIAL AND METHODS: For the period 2017 to 2019, 3 non-relative girls with clinical characteristics of epilepsy of infancy with migrating focal seizures (EIMFS) and mutations in the KCNT1 gene are identified and studied. DNA sequencing was performed using the Hereditary epilepsy panel (Next Generation Sequencing on platform IlluminaNextSeq 500, USA). Dynamical video-EEG monitoring was done with "Encephalan-Video" RM-19/26 ("Medicom MTD", Russia). RESULTS AND CONCLUSION: De novo KCNT1 mutations are identified and studied in three unrelated Russian girls: M.V., 3 years and 3 month old, T.V., 9 month old and M.A., 5 month old. M.V. has the previously unknown mutation in exon 12 (chr9:138656907C>T) with amino acid substitution Arg356Trp. T.V. has the previously described mutation in chromosome 9: 138651532G>A with amino acid substitution Gly288Ser (OMIM: 608167.0010). M.U. has the previously unknown mutation in exon 15 (chr9:138660712A>G) with amino acid substitution Asp480Gly. M.V. has seizure onset at the age of 4 month with behavioral arrest seizures and tonic versive seizures. T.V. developed seizures at 4,5 month in the manner of behavior arrest and ophthalmo-clonic seizures with hyperemia of face. M.U. has neonatal seizures with bilateral tonic-clonic seizures, cyanosis and further development of status epilepticus of alternating hemiconvulsive seizures. Further all the girls develop polymorphic seizures of multiregional genesis up to migrating status epilepticus with typical electro-clinical pattern of EIMFS. Therefore, KCNT1 is likely to be a major gene causing this rare and severe epileptic syndrome.

[Peptidergic nootropic therapy in cerebral palsy associated with epilepsy]. / Peptidergicheskaia nootropnaia terapiia pri detskom tserebral'nom paraliche v sochetanii s épilepsiei.

AIM: To assess the efficacy and safety of сortexin in the treatment of children with cerebral palsy (CP) combined with epilepsy. MATERIAL AND METHODS: Eighty-four patients (55 boys and 29 girls), aged from 1 to 11 years, with CP combined with epilepsy received cortexin together with antiepileptic drugs (AEDs). Cortexin was administered in doses of 5-10 mg depending on the patient's age and body weight intramuscularly during hospitalization. RESULTS AND CONCLUSION: Cortexin as add-on to AEDs reduced for more than two times the number of seizures, along with improvement of motor function, in 31 (36.9%) patients. The improvement of motor function, but without a significant decrease in epileptic seizures, was achieved in 15 (17.8%) of the patients. Reduction of epileptic seizures frequency (>2 times), but without a significant effect on motor function, was observed in 14 cases (16.7%). Twenty-three patients (27.4%) did not respond the therapy. The aggravation of epileptic seizures during cortexin therapy was observed in only 1 girl with West syndrome (1.2%), and this was significantly lower than the probability of seizures aggravation on AED. Polypeptide nootropic medication cortexin demonstrated efficacy and safety as adjunctive therapy in children with CP combined with epilepsy.

[Treatment of epilepsy in children with brain tumors]. / Lechenie epilepsii u detei s opukholyami golovnogo mozga.

AIM: Symptomatic focal epilepsy is frequently caused by supratentorial brain tumors that may be surgically removed. The authors studied outcomes of surgical treatment depending on the use of electrocorticography c (ECoG). MATERIAL AND METHODS: Seventy-five children, aged 5-7 years, with supratentorial brain tumors were examined. Symptomatic epilepsy was found in 52 (69.3%) patients. Dysembryoplastic neuroepithelial tumors (DNET) and fibrillary astrocytomas were the most epileptogenic tumors. RESULTS AND CONCLUSION: The outcomes on the Engel scale were as follows: in 27 patients with surgical intervention without ECoG: class I - 9 patients, class II - 7 patients, class III - 5 patients, class IV - 6 patients and in 25 patients operated with ECoG: class I - 19 patients, class II - 4 patients and class III - 2 patients. The significant difference (p<0.01) between I+II Engel classes in comparison with III+IV Engel classes in operated patients demonstrated the necessity of ECoG during surgery in the resection of supratentorial brain tumors in patients with symptomatic epilepsy.

[ETACISIN-INDUCED BRUGADA SYNDROME IN A PATIENT WITH LONG-STANDING SUPRAVENTRICULAR EXTRASYSTOLE].

Brugada syndrome is a commonest cause of malignant disorders of cardiac rhythm associated with sudden death. It is diagnosed based on characteristic ECG signs and ventricular arrhythmia. This paper reports a 49 year-old patient with long-standing latent BS manifest as supraventricular and transient blockade of the right branch of the His bundle. The ECG pattern of BS became apparent in association with a 7 day treatment with class IC antiarrhythmic agent etacisin. Diagnostic difficulties account for the fact that the disease was initially described as myocardial infarction. Diagnosis of BS was confirmed by an electrophysiological study in which stable ventricular tachycardia and fibrillation were induced by etacisin. A cardioverter defibrillator was implanted to the patient.

[Efficacy and safety of topiramate depending on patient's age and forms of epilepsy].

Seven hundreds and twenty-two epileptic patients receiving topiramate (374 males, 348 females), aged from 3 month to 57 years, were followed with video-EEG control during the period of 2002-2012. Topiramate was effective in 465 (64.4%) patients, and among them the efficacy of monotherapy (72.2%) was higher compared to combined therapy (61.9%). The low efficacy was seen in 198 (27.4%) patients. The aggravation effect was noted in 59 (8.2%) of patients. Drug compliance (for >1 year) was 60.7%. In the group <1 year, the high efficacy was observed in 55.2%, low efficacy - in 34.5%, aggravation - in 10.3%. In the group 1-3 years, these indicators were 54.8%, 31.8% and 13.4%, respectively. In the pediatric population (>3 years), they were 67.3%, 26.2% and 6.5% as well as in the adult population (>18 years) - 82.1%, 16.6% and 1.3%, respectively. Thus, topiramate is a highly effective medication in the therapy of idiopathic generalized epilepsies without absences and in symptomatic/cryptogenic focal forms of epilepsy. The efficacy of topiramate raised with increasing of age while the aggravation risk decreased significantly.

[Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics].

Syndrome Leigh (SL) or subacute necrotizing encephalomyelopathy - is a rare hereditary genetically heterogeneous disease from the group of mitochondrial encephalomyopathies. Twenty-seven children with SL were examined using clinical, laboratory (measuring lactate levels), MRI and molecular-genetic (polymerase chain reaction genotyping of 9 exons of the SURF1 gene) studies. The mean age of manifestation was 11,6 months. The main manifestations of SL were: delay of psychomotor development, diffuse muscle hypertonic, cerebellar syndrome, ophthalmoparesis, hypertrichosis. The disease had a progressive course with the loss of acquired skills. The blood lactate concentration was increased on average up to 3,1 mM/ml (from 1,9 to 5,1 mM/ml) compared to normal values (1,8 mM/ml). Brain MRI revealed the subcortical and cortical atrophy (80% of cases), symmetrical distinctly delineated hyperintense lesions on T2-weighted images (demyelization) in the basal ganglia and the brain stem (50%), as well as in the cerebellum (25%). Genotyping identified 7 different mutations. The most frequent (64,8%) was the deletion of 2 nucleotides (845delCT) in exon 8 that was in line with early data of Polish researchers thus indicating the Slavic origin of this mutation. Other mutations (574-575insCTGT, 311-321del10insAT and IVS8-1G>) were also frequent in the Russian population.

[West syndrome: clinico-electro-anatomical characteristics and a differential therapeutical approach].

One hundred and thirty children with West syndrome, aged 1.5 months-2 years, were studied. The symptomatic form of West syndrome was diagnosed in 95.4% of cases. The prenatal etiological factors were observed in 57% of patients. Different variants of hypsarrhythmia at EEG were revealed in 87%. The percentage of cases with typical and modified hypsarrhythmia was 13.3% and 86.7%, respectively. The choice of treatment was based on the revealed disturbances on EEG and MRI that was useful for increasing the effectiveness of treatment of West syndrome resulting not only in the reduction of seizures and improvement of EEG but also in the stabilization of intellectual disintegration and recovery of functions. The basic drugs in the treatment were valproates used both as mono- and polytherapy.

[Clinical polymorphism of malignant epilepsy of infancy with migrating multifocal seizures (8 cases)].

Malignant migrating partial seizures in infancy are rare epilepsy syndrome that begins in the first 6 months of life and characterized by multiple continuous electroencephalographic and electroclinical focal ictal patterns which involved different independent areas of both hemispheres with arrest of psychomotor development. The present detailed review is based on the personal observation of 8 patients newly diagnosed at the Russian Children Clinical hospital, Moscow, Russia. At least three ictal patterns recorded from different independent areas of both hemispheres were fixed by video-EEG-monitoring in all patients. The high polymorphism and very frequent seizures (not less than five types at every child) were observed. The cases were pharmacoresistant, with the absence of reaction to antiepileptic therapy and progressive deterioration in 4 (50%) patients. Decreasing of seizure frequency by 50% was achieved in 3 (37.5%) patients treated with the combination of valproates, benzodiazepines and barbiturates and by 75% in 1 (12.5%) patient case treated with valproates, benzodiazepines and levetyracetam (keppra). The authors proposed a definition of this epileptic syndrome as: "malignant epilepsy of infancy with migrating multifocal seizures".

Clinical-psychological characteristics of children with dysgenesis of the cerebellar vermis.

This report addresses behavioral abnormalities in children with cerebellar anomalies demonstrated on MRI scans. Published data are presented showing an interaction between cerebellar pathology and early childhood autism. The cerebellum is involved not only in movement coordination, but also in social adaptation and verbal communication. The genes expressed in the cerebellum during childhood are identical to those expressed in the hippocampus. We have observed 20 children with MRI-identified agenesis of the cerebellar vermis and behavioral abnormalities; children were aged 3-15 (mean 7.05) years and there were 12 males and eight females. A variety of autistic characteristics were identified in these children.

[Glutaric aciduria type 1: clinical presentations, diagnostics and treatment.].

Glutaric aciduria type I is a rare autosomic recessive neurometabolic disease, which develops in the first year of life and is characterized by progressive extrapyramidal disorders as a result of the basal ganglia damage. We describe first cases of this disease in Russian population. The clinical observations are compared to the literature data. The disease usually develops after infections and features by seizures, vomiting, metabolic acidosis and deprivation of consciousness up to coma. These crises lead to the development of necroses of the basal ganglia that results in dystonias, dyskinesias and choreoatethosis. The secondary complications of the disease are difficulties with feeding, speech delay, chronic aspiration syndrome and severe delay of movement development. Diagnostics of the disease is based on urine and blood tests using methods of tandem mass spectrometry and gas chromatography. Treatment is based on dietary lysine or protein restriction and supplementation with carnitine. The data on the treatment of this disease are presented.

[Opsoclonus-myoclonus syndrome in children].

To study clinical peculiarities of parainfectious opsoclonus-myoclonus syndrome (OMS) in children and to elaborate approaches to its pharmacotherapeutic correction, 20 children, including 12 girls and 8 boys, have been examined using neurological, neurophysiological, immunological and virological methods along with magnetic resonance tomography (MRT). Age-at-disease-onset was from 8 months to 3 years old. The development of neurological symptoms was related to a virus infection (55% of cases) or vaccination (15%). Marked disease seasonality (autumn, spring) was observed. In some cases, a possible role of infectious factor in the disease development was confirmed by virological and immunological studies. OMS was featured by the absence of specific brain MRT changes and low frequency of significant abnormalities of cerebrospinal fluid. A positive experience of the use of hormonal therapy and immunomodulators is presented.

[Clinical and psychological features of children with agenesis of the vermis cerebelli].

The article considers behavioral disturbances in children with anomalies of the cerebellum found by MRI studies. Presented are literature data on the relations between pathology of the cerebellum and early autism in children. The cerebellum is involved not only in movement coordination but also in social adaptation and speech communication. Cerebellum-specific genes expressed in early age are similar to those of hippocampus. Our own study of children with agenesis of the vermis cerebelli detected by MRI and behavioral disturbances included 20 children aged 3-15 years (mean age 7,05 years, 12 male, 8 female). Some autistic features have been found.

[Electroencephalographic characteristics of West syndrome]. / Elektroéntsefalograficheskie kharakteristiki sindroma Vesta.

The study aimed at interictal electroencephalographic characteristics investigation in the patients with West syndrome. It has been carried out in 48 children, aged 3 months--2 years, the inpatients of Psychoneurology and Epilepsy Department, Russian Clinical Children Hospital No. 2, from March 1999 to march 2001. The following EEG awakeness types were detected: typical hypsarrithmia--8 (16.7%) patients; different variants of modified hypsarrithmia--35 (72.9%); a presence of focal epileptiform discharges, but not in the form of modified hypsarrithmia with focal component--3 (6.2%); an absence of epileptiform discharges--2 (4.2%). Typical and modified hypsarrithmia cases ratio was estimated as 18.6%:81.4%. Among the patients with modified hypsarrithmia, the following variants have been detected: synchronized variant of modified hypsarrithmia--35.3% of the cases with modified hypsarrithmia; asymmetric regional or unilateral hypsarrithmia--42.9%; hypsarrithmia with partial component--45.7%; hypsarrithmia with persisting "suppressive-burst" pattern--20% of the cases. Correct evaluation of clinical, electrophysiological and neurovisual data (clinico-electro-anatomical approach) facilitated the rational differential choice of antiepileptic therapy. The approach allows the early prognosis of disease course and its transformation to other epilepsy types.

[Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation]. / Nedostatochnost' tripeptidil peptidazy 1 pri neironal'nom tseroidnom lipofuktsinoze. Novaia mutatsiia.

The data on biochemical and molecular-genetic diagnostics of a hereditary lisosomal storage disease, late infantile neuronal ceroid lipofuscinosis (CLN2) are presented. The disease is associated with a hereditary deficiency of pepstatin-unsensitive peptidase--tripeptidylpeptidase 1 (TPP1)--caused by mutations in the TPP1-coding gene CLN2. Among the 30 patients with clinical manifestations of CLN, six patients with a pronounced decrease in TPP1 activity were revealed; these data were interpreted as indicating the presence of CLN2 in these patients. The analysis of the isolated DNA indicated the availability of the most widespread mutation g3670 C > T(R208X) leading to the untimely termination of TPP1 synthesis. It was shown that in 5 patients this mutation is present in homozygous state and in one patient, in the heterozygous state. In this patient a hitherto unknown mutation, g3665G > A (R206H), was revealed. The pathogenetic significance of this mutation and the importance of molecular-genetic diagnosis of CLN are discussed with regard to medico-genetic consulting and prenatal diagnosis of this disease.

[The neuroradiological aspects of infantile spasms]. / Neiroradiologicheskie aspekty infantil'nykh spazmov.

The observation of 38 children with early form of children epilepsy that is with syndrome of infantile spasms (IS) was performed by means of computed tomography of the brain. The structural alterations of the brain were revealed in 89.5% of cases. They varied from rough developmental anomalies and pronounced destructive phenomena to microdysgenesias and moderate cortical atrophies. These changes were systematized according to the time of the beginning of some alteration on the definite stage of neuro-ontogenesis. There were embryofetal disturbances (23.6%), peri- and postnatal alterations (50%) and combined ones (15.7%). The definite correlation was established between neuroradiological damages, clinical pattern of IS, differentiated policy of the treatment and the prognosis of neuropsychic development of a child.