[A case of a pathological variant of the PRRT2 gene in twins with paroxysmal kinesiogenic dyskinesia]. / Sluchai patologicheskogo varianta gena PRRT2 u bliznetsov s paroksizmal'noi kineziogennoi diskineziei.

Paroxysmal dyskinesia is a clinically and etiologically polymorphic group of diseases, the main clinical manifestation of which is transient attacks of extrapyramidal movements, with different conditions of occurrence. Paroxysmal kinesigenic dyskinesia belongs to the group of primary dyskinesias, which also includes paroxysmal non-kinesigenic dyskinesia and exercise-induced paroxysmal dyskinesia. The most common cause of paroxysmal kinesiogenic dyskinesia is mutations in the PRRT2 gene; in cases of non-kinesiogenic dyskinesia, a mutation in the MR1 gene is detected. The diagnosis of primary dyskinesias causes significant difficulty for clinicians due to the rarity of occurrence, as well as the large spectrum of conditions occurring with paroxysmal motor disorders in childhood. The article describes the clinical observation of 16-year-old twin brothers with transient attacks of dystonic, choreic and ballistic hyperkinesis that suddenly arose during movement. Patients were treated for tics and epilepsy for 12 years. Taking into account the clinical picture - transient attacks of hyperkinesis, their connection with movement, as well as data from video-electroencephalographic monitoring, a diagnosis of paroxysmal kinesiogenic dyskinesia was established, which in a further diagnostic search was confirmed by targeted sequencing of the pathological variant of the PRRT2 gene previously described in patients with kinesiogenic dyskinesia. The administration of carbamazepine, which is the drug of choice in the treatment of this category of patients, has achieved significant control over hyperkinesis in twins. Thus, molecular genetic diagnosis helps confirm the diagnosis of paroxysmal dyskinesias, but careful analysis of the clinical picture, considering the provoking factor, remains the basis of diagnosis.

[A longitudinal study of pediatric-onset multiple sclerosis in the Voronezh region]. / Prospektivnyi analiz klinicheskogo techeniya rasseyannogo skleroza s debyutom v detskom i podrostkovom vozraste v Voronezhskoi oblasti.

OBJECTIVE: To study the clinical course, the rate of progression and the results of the disease modifying treatment (DMT) in pediatric-onset multiple sclerosis (POMS) patients in the Voronezh region. MATERIAL AND METHODS: The clinical characteristics of the course of relapsing-remitting multiple sclerosis (MS) were analyzed among 51 POMS patients and 51 patients with the adult-onset MS (AOMS). The clinical course was assessed based on the Expanded Disability Status Scale (EDSS) score, the average annual frequency of exacerbations and the rate of disease progression before and during DMT. RESULTS: There were no statistically significant differences in EDSS scores 11 years after the onset of MS between the groups: POMS patients achieved moderate disability by the age of 25, and AOMS patients showed stabilization of their condition during DMT by the age of 36. During changing first-line drugs in patients with POMS, there was again an increase in disability with the transition of 25% of patients to the group with secondary progression of MS on average after 8 years of DMT. CONCLUSION: The onset of the disease in children and adolescents leads to a significant decrease in their quality of life and the deterioration of all activities throughout their lives. To prevent the progression of the disease it seems appropriate to transfer patients with POMS immediately to second-line DMT when signs of a suboptimal response to first line DMT appear, and in the case of a rapidly progressive course to start therapy with second-line drugs.

[P.S. Babkin (To the 100th anniversary)]. / Petr Semenovich Babkin (K 100-letiyu so dnya rozhdeniya).

There was the 100th anniversary of the birth of Peter Semenovich Babkin, a front-line soldier, famous neurologist, clinician, scientist and educator, Professor, Doctor of Medical Sciences, the founder of the theory of intrapartum fetal hibernation and maternal autoanalgesia.

[Improvement of the efficacy and safety of treatment of epilepsy using new forms of controlled release antiepileptic drugs]. / Povyshenie éffektivnosti i bezopasnosti terapii épilepsii s ispol'zovaniem novykh form protivoépilepticheskikh preparatov s kontroliruemym vysvobozhdeniem.

The paper summarizes the results of the studies on the efficacy and safety of a new form of controlled release levetiracetam XR (Lev XR) compared to standard tablet immediate release form in treatment of resistant partial seizures. The authors present the data on the bioequivalence and absorption of LevXR related to the meal and therapeutic doses in the range between 1000 to 3000 mg/day. It has been concluded that LevXR has high efficacy and safety due to its stable plasma concentration during the day. The results meet FDA bioequivalence criteria and, in authors opinion, can be recommended as drug of choice in additional treatment of partial seizures in patients above 12 years of age.

[Comorbidity of epilepsy and chronic disorders in children and adolescents with the assessment of the effectiveness of therapy]. / Komorbidnost' épilepsii i khronicheskikh tikoznykh rasstroistv u detei i podrostkov s otsenkoi éffektivnosti terapii.

AIM: To determine the comorbidity of epilepsy and chronic tic disorders (HTR) in children and adolescents based on the results of video-EEG monitoring and treatment efficacy. MATERIAL AND METHODS: One hundred and sixteen patients diagnosed with HTR, 83 boys and 33 girls, aged from 3 to 15 years, were studied. Clinical psychoneurological examination, psychological testing and video-EEG monitoring were performed at the first stage of the study. An effect of treatment was assessed at the second stage. RESULTS AND CONCLUSION: The high prevalence of epileptiform activity was observed in 46.6% of patients with HTR, comorbidity of epilepsy and chronic tic disorders in 16.4%. Antiepileptic drugs, in particular extended release valproate (depakine chronosphere), are most effective for both epilepsy and tic disorders.

Loss of Heterozygosity in BRCA1 and BRCA2 Genes in Patients with Ovarian Cancer and Probability of Its Use for Clinical Classification of Variations.

Changes (or variants) in BRCA1 and BRCA2 gene sequences can have different lengths and clinical significance: from single nucleotide variants (SNV) and short insertions/deletions (<50 bp) to extended deletions and duplications (so-called copy number variations, or CNV). According to their clinical significance, all variants can be divided into pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign. Moreover, variants can be germinal (i.e. inherited from parents) and somatic (arising in the process of development of the organism). A specific somatic event is loss of heterozygosity (LOH), i.e. transition of one or many point and short variants from heterozygous to homozygous state. Such an event can be the key to the development of carcinogenesis for cells carrying a pathogenic variant, if we consider it within the framework of the Knudson's two-hit carcinogenesis theory. We studied the prevalence and nature of LOH in of ovarian cancer samples carrying or not carrying a pathogenic variant. To this end, a full coding sequence of BRCA1/2 genes was determined in 30 pairs of DNA samples isolated from blood cells and paraffinized histological blocks of patients on a MiSeq Illumina instrument. Analyss of the obtained reads revealed 9 pathogenic point and short variants (30% patients): 6 germinal (20%) and 3 somatic (10%), and 8 somatic CNV (3 deletions and 5 duplications of several or all exons of the BRCA1 gene). LOH was detected in 70% patients; among the carriers of pathogenic variants - in 83%. For pathogenic variants, the percentage of reads with the alternative allele increased more often than for benign variants located in another gene, or detected in other patients (67% vs. 44%). However, the difference was statistically insignificant, which can be due to insufficient number of patients. Only in 3 of 21 cases of LOH (14%), it can be attributed to CNV. In other cases, LOH is most likely determined by gene conversion, but further research is needed.

[Exalief as a newer antiepileptic drug for adjunctive therapy of refractory partial-onset seizures].

Results of a multicenter international study on the efficacy of exalief (eslicarbazepine acetate (ESL)), a newer blocker of voltage-gated sodium channels and T-type voltage gated calcium channels, for adjunctive therapy of refractory partial-onset seizures are presented. A clinical program included phase II (BIA-2093-201) followed by three phase Ill studies (BIA-2093-301, -302 and-303), each of which was accompanied by an additional open one-year study (301 E, 302E, 303E). In three parallel phase Ill studies patients were randomized to receive ESL in single doses 400, 800, 1200 mg or placebo together with 1 - 3 antiepileptic drugs used in stable doses, with the exception of felbamate and oxcarbazepine. The design of the study included 8-week initial period, double-blind phase (2-week titration period, 12-week maintenance period), 4-week dose reduction period. The results of clinical phase II trials demonstrated the high efficacy and best tolerability profile for single dose titration regimen. Median changes in the frequency of partial-onset seizures were greater (p<0,0001) in patients receiving 800 and 1200 mg ESL (35 and 39%)compared to placebo (15%). The proportion of treatment responders was significantly higher in the groups treated with ESL indoses 800 mg (36%) and 1200 mg (44%) compared to the placebo group (22%). The aversive effects of the drug were of mild or moderate severity. Treatment retention was higher in patients receiving ESL (84,9% of patients completed the 6-month treatment period and 76,6% completed the one-year period). The use of ESL leads to the reduction in partial seizure frequency and the increase in the proportion of treatment responders. The drug has a good tolerability profile.

[Focal features of idiopathic generalized epilepsy].

Idiopathic generalized epilepsies (IGE), in some cases, have focal features in the kinematic of seizures and in the EEG. The aim of the paper was to study these clinical phenomena using video-EEG monitoring. We studied 180 patients (80 men and 100 women) with different forms of IGE with epileptic seizures recorded with this method. The effect of the "superposition" of focal electro-clinical features on the kinematic matrix and EEG pattern of the generalized myo- (clonic)-tonic-clonic seizures was noted. The authors suggest to discuss the definition of the "phenomenon of secondary focalization". This is the clinical/electroencephalographic phenomenon developed in IGE and presented by the appearance of secondary focal features (clinical and electroencephalographic) in the structure of the generalized epileptic seizure. The evidence for the secondary generalization of the seizure with the presence of the regional cortical ictogenic source as well as the diagnosis of focal epilepsy are the exclusion criteria for the phenomenon of secondary focalization.

[Focal characteristics in the clinical examination and EEG in children with idiopathic generalized epilepsy].

The aim of the study was to determine the prevalence of focal characteristics in the clinical symptoms of seizures and in EEG in children with different clinical variants of generalized idiopathic epilepsy. We studied 71 patients, 29 boys and 42 girls, aged from 2 to 18 years. Video-EEG-monitoring and MRI were performed in all cases. The results provided further evidence fort the continuum between focal and generalized epilepsy supported by the presence of focal characteristics in the semiology of seizures and in EEG as well.

[Epilepsies with electric status epilepticus in sleep: peculiarities of clinical course and rational approaches to treatment].

We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.

[Idiopathic focal epilepsies of infancy and childhood].

We studied 1036 children with epileptic seizures, aged from 1 to 18 years, during 2004-2008. One hundred and six patients were diagnosed with idiopathic focal epilepsy (IFE). The following forms of IFE were singled out: benign seizures of infancy (familial and non-familial) - Watanabe--Vigevano syndrome - 5,7%, occipital epilepsy of childhood with early manifestation (Panayiotopoulos syndrome) -26,4%, occipital epilepsy of childhood with late manifestation (Gastaut syndrome) - 12,3%, benign epilepsy of childhood with central-temporal spikes (rolandic epilepsy) - 51%, benign focal epilepsy with affective symptoms - 4,7%. The efficacy of the first monotherapy was significantly worse in rolandic epilepsy compared to the other IFE forms. Prescription of valproate or the combination of valproate, ethosuximidum and levetiracetam, in case of resistant course, as a starting therapy was found optimal.

[Transitory cognitive dysfunction in rolandic epilepsy].

Forty-four patients with rolandic epilepsy (32 boys, 12 girls), aged from 5 to 14 years, were examined in the prospective study during 5 years. Before the antiepileptic treatment, most of patients had transitory cognitive disturbances. There were the impairment of verbal functions, especially verbal intellect, while non-verbal intellect remained intact; dyspraxia, impairment of auditory-speech memory, disturbances of arbitrary regulation and optical-motor coordination. The cognitive impairment was not severe and did not impact on learning of school program. No significant correlations were found between the lateralization of regional EEG changes and the character of cognitive dysfunction though the age-related lateralization of the focal epileptiform activity was shown: the right-side localization of central-temporal EEG spikes predominated in children at the age of 6.29 +/- 0.9 years, the left-side localization - in children at the age of 8.4 +/- 1.4 years. The clinical remission was achieved 4-5 years earlier than the recovery of cognitive functions. Valproates used as monotherapy or in the combination with ethosuximidum and levetiracetam were drugs of choice.

[Diagnostic algorithm of biliary tract diseases in children].

Biliary tract (BT) diseases occupy one of the first places among the gastrointestinal diseases in children. The term "biliary tract" includes the gallbladder and intra-and extrahepatic bile ducts. The structure of biliary tract diseases had a significant increase in metabolic and inflammatory diseases, functional disorders. According to this, purpose of this study was to propose algorithms for children examination with biliary tract diseases in outpatient and hospital phases. In this article, based on their own experience was described the features and significance of laboratory and instrumental methods in the diagnosis of biliary tract disease in children. It was shown that the diagnostic significance of intrascope research methods in the identification of bile-excreting system diseases in children.

[Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of the Altai region of the Russian Federation].

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

[Epilepsy with prolonged epileptiform activity during sleep in children and adolescents].

Benign epileptic discharges of childhood (BEDC) are typical age-related EEG patterns associated with idiopathic benign focal epilepsy (BFE). The study of BFE revealed the symptomatic phenocopies in patients with structural brain lesions in infantile cerebral paralysis and malformations. The authors discuss the question of "benignity" of BEDC that may lead to various disturbances of cognitive functions and behavior, i.e. to signs of epileptic encephalopathy. Based on the examination of 1862 children, including 840 patients with epileptic seizures and 1022 neurologic patients, clinical and neurophysiological features of epileptic syndromes associated with prolonged epileptiform EEG activity in children were found. The most rational antiepileptic therapy was determined.

[Efficacy and safety of the monotherapy with trileptal (oxcarbazepine) in children and adolescents].

A prospective non-randomized non-controlled multicenter trial has been conducted. The trial included 254 children, aged from 11 months to 18 years (mean age 9.3 +/- 4.5 years), with predominantly focal forms of epilepsy treated with trileptal (oxcarbazepine). The observation period was 31 weeks. Efficacy and safety of therapy was assessed in 3 visits: screening and assignment to therapy (visit 1), the end of titration and achievement of maintenance dose (visit 2), assessment of maintenance therapy (visit 3). The percentage of patients with a positive response to the trileptal therapy (the decrease of seizure frequency by 50% and more) was 91.1%. The complete reduction of seizures was achieved in 59.4% of patients. Most of patients (95.3%) continued to receive trileptal until the end of the trial. The significant decrease (p < 0.001) of seizure frequency from visit 1 to visit 3, the reduction of epileptiform activity (p < 0.05) on the awake EEG in visit 3 were found. The mean effective dose of trileptal was 902.4 +/- 442.7 mg/day, i.e. was less than 30 mg/kg/day, daily doses did not exceed 600 mg. Adverse effects were observed in 11.2% of patients but in 40% of cases they seemed not be related to the drug. The adverse effects were from mild to moderate extent. In conclusion, trileptal as the monotherapy is effective and well-tolerated in the treatment of focal epilepsies in the age groups studied.

[Clinical-psychological analysis of the development of movement, perceptual, intellectual and speech functions in children with cerebral palsy]. / Kliniko-psikhologicheskii analiz razvitiia dvigatelnykh, pertseptiv- nykh, intellektual'nykh i rechevykh funktsii u detei s tserebral'nymi paralichami.

105 children with cerebral paralysis at the age under 3 years were examined. CNS damages in children of early age with disneuroontogenesis may be divided into 4 degrees of severity. This enables to estimate objectively both the patients' state and the results of their therapy in the groups with the same degree of severity of CNS damage. High efficiency of the complex method of metameric stimulation of the development of static-motor and psychospeech functions allows to recommend this method for treatment of children with cerebral paralysis. Application of this method in children of early age with disorders of neurologic development in some cases prevents neurologic disability.

[The motor adaptation syndrome in the human fetus and its dynamics in newborns]. / O sindrome dvigatel'noi adaptatsii u ploda cheloveka i ego dinamike u novorozhdennykh.

The authors describe a new syndrome characteristic of neonates born in the breech presentation. The syndrome, most evident upon the delivery, was observed in 30 infants, followed up in 20 of them. The neonates have specific lower limb position (maximally flexed thighs, extended, legs, slightly bent in the soles feet), spontaneous movements of the legs and feet are restrained, muscular tonicity reduced in the leg flexors and sole muscles is high in femoral flexors, the Achilles reflex is inhibited, motor response to plantar stimulation is weak or absent. Within day 3-7 of life the syndrome usually undergoes involution. The observed syndrome develops in the fetus as adaptation to abnormal lower limb position and hypokinesia.