[Epilepsy and other phenotypic features of X-linked intellectual disability caused by the mutations in the KIAA2022 gene]. / Epilepsiya i drugie fenotipicheskie osobennosti X-stseplennoi intellektual'noi nedostatochnosti, obuslovlennoi mutatsiyami gena KIAA2022.

OBJECTIVE: To study the literature data and a series of our cases regarding the epilepsy clinic, electroencephalographic changes and other phenotypic features in X-linked intellectual disability (ID) caused by KIAA2022 mutations. MATERIAL AND METHODS: We analyzed the anamnesis of the disease, using medical records from different Russian medical organizations, as well as the results of the genealogical anamnesis, clinical, genetic, electroencephalographic (EEG) and neuroimaging (brain MRI ) examinations of 7 patients (5 girls and 2 boys aged 5 to 13 years) with a confirmed diagnosis of X-linked ID caused by KIAA2022 mutations, in whom the clinical picture of the underlying disease was combined with epilepsy. RESULTS: The main common phenotypic features of patients with X-linked ID caused by the KIAA2022 mutations are mental retardation, lack of phrasal speech, motor developmental delay, and dysmorphism. The prominent epilepsy characteristics are myoclonic, atonic seizures with nods, flinches, body propulsions, atypical absences, and diffuse discharges «spike-polyspike-slow wave¼ on the EEG. No pathognomonic brain changes were found on MRI. In many cases, the absence of the effect of antiepileptic therapy was noted. CONCLUSION: The described cases of X-linked ID in combination with epilepsy show that this disease can be seen in males as well as in females, epilepsy is rather characterized by generalized seizures, and it is pharmacoresistant in many cases. There is a need for further research on this rare genetic syndrome.

[Psychometric validation of the Russian version of the Central Sensitization Inventory in adolescents (14-17 years old)]. / Psikhometricheskaya validatsiya russkoyazychnoi versii Oprosnika tsentral'noi sensitizatsii dlya podrostkov 14­17 let.

OBJECTIVE: To validate a Russian version of the Central Sensitization Inventory (CSI) in adolescents (14-17 years old). MATERIAL AND METHODS: The study included adolescents aged 14-17 years. Group 1 (n=69) - frequent episodic and chronic tension type headache; group 2 (n=63) - chronic myogenic neck pain; group 3 (n=61) - infrequent episodic tension type headache; group 4 (n=67) - adolescents without pain during the last 6 months. The first stage was linguistic validation of the statements (symptoms) in CSI (100 randomly selected adolescents). Psychometric validation was performed by comparing the indicators of CSI, Pediatric Anxiety Rating Scale (PARS), and M. Kovacs' Children's Depression Inventory. RESULTS: A strong correlation between CSI scores with the PARS indicators (number of symptoms, severity scale, clinical examination scale) and M.Kovacs' Children's Depression Inventory was shown. CONCLUSION: CSI can be used in adolescents from the age of 14, and it is an informative and useful clinical tool for identifying and assessing the severity of central sensitization in pediatrics.

[Genetics of epilepsy: successes, problems and development prospects]. / Genetika epilepsii: uspekhi, problemy i perspektivy razvitiya.

The authors present a detailed review of current advances in the field of genetics of epilepsy. Separately, new views on the etiology and pathogenesis of genetic epileptic encephalopathies, focal epilepsy and idiopathic generalized epilepsies are examined. The authors emphasize the importance of genetic discoveries for the clinical practice, including the prospects in the development of patients' personalized treatment. A comparative analysis of the value of various methods of genetic research in the diagnosis of epilepsy, methods of integrating molecular genetic analyses into everyday practical medicine is presented.

[Central Sensitization Inventory - a Russian version]. / Oprosnik tsentral'noi sensitizatsii ­ russkoyazychnaya versiya.

OBJECTIVE: To develop and validate a Russian version of The Central Sensitization Inventory (CSI-R). MATERIAL AND METHODS: The study included 3 stages: 1) direct and reverse translation, linguistic validation of the questionnaire; 2) assessment of internal consistency, reliability and sensitivity (n=50); 3) psychometric validation in the samples of patients with fibromyalgia syndrome (n=40), chronic widespread pain (n=40), regional chronic low back pain without other specific pain complaints (n=40), and in the control sample of informants with no pain complaints (n=40). RESULTS AND CONCLUSION: The Russian version of CSI-R is valid, reliable and can be used in clinical practice as a diagnostic tool for revealing central sensitization. The study of the sensitivity of the questionnaire in patients during drug therapy proved its effectiveness in assessing the dynamics of the disease and the effect of therapy.

[Modern achievements in genetic studies of idiopathic generalized epilepsies]. / Sovremennye dostizheniia v oblasti geneticheskikh issledovanii idiopaticheskikh generalizovannykh épilepsii.

The review presents modern data on the genetics of idiopathic generalized epilepsies. Identified genes encode different structures of neurons, including voltage-dependent channels, receptors of neurotransmitters, protein-associated ion channels and synaptic proteins. The authors describe already identified genes, which are a causative factor of idiopathic generalized epilepsies and discuss further prospects of using molecular genetic studies.

Timing of treatment initiation in West's syndrome.

BACKGROUND: Infantile spasms (called the West's Syndrome) represent a severe epileptic syndrome which is characterized by a peculiar type of epileptic seizures, spasms, and by electroencephalographic (EEG) abnormalities often called hypsarrhythmia [1]. Infantile spasms are usually resistant to conventional antiepileptic drugs (AEDs) and adrenocorticotrophic hormone (the synthetic analog - tetracosactide) has been the preferred treatment since 1958. The evidence for other antiepileptic drugs is extremely limited compared with vigabatrin. Most recent studies deal only with short-term drug effects and fail to use clinically meaningful outcome measures. Furthermore, attention needs to be given to dropout rates in the studies, because some studies include a majority of patients with primarily favourable outcome [2]. Effective treatment is now defined as complete cessation of the spasms plus abolition of hypsarrhythmia ('all-or-none response') [3]. So far there has been no consensus on dosage or duration of therapy, influence of early initiation of treatment on the outcomes of West syndrome therapy. OBJECTIVE: To assess if the timing of treatment initiation (early or late) influences the outcomes of West syndrome therapy. METHODS: We conducted a retrospective observational study at the Kazan Municipal children's hospital № 8 among children with West syndrome. When treatment with tetracosactide (synacthen depot) or antiepileptic drugs was initiated within 1 month after the onset of seizures we defined it as "early treatment initiation". If this therapy was started after 1 month of the onset of seizures, we defined it as "late treatment initiation". We used was the number of seizure-free patients after 2 months, 6 months and 1 year from the start of the treatment as the favorable outcome measure. We calculated risk ratios (RR) for favorable outcomes and their confidence intervals (CI) using RevMan 5.3 Software, comparing outcomes of early and late treatments. RESULTS: We analyzed medical records of 150 children with infantile spasms. The diagnosis of West syndrome was confirmed by video-EEG-monitoring findings and by clinical examinations. Gender distribution of patients with West syndrome was with some predominance of boys: 93 boys (62%) and 57 girls (38%), which corresponded to the published literature data. The duration of follow-up was at least 3.5 years. The mean age of patients at the time of analysis was 6 years, from 4 years (min) to 14 years 5 months (max). We divided all of the children into four groups:Group IA - early treatment initiation - included children who were started on tetracosactide within 1 month from the onset of seizures (30 patients).Group IB - late treatment initiation - included children who were started on tetracosactide after 1 month of the onset of seizures (60 patients).Group IIA - early treatment initiation - included children who were started on antiepileptic drugs as mono- or polytherapy within 1 month from the onset of seizures (22 patients).Group IIB - late treatment initiation - included children who were started on antiepileptic drugs after 1 month of the onset of seizures (38 patients).Children in all groups were similar with respect to age, sex, severity of the disease. Effectiveness of tetracosactide in the group IA and in the group IB at 2 months, 6 months and 1 year of follow up (from the beginning of treatment) was comparable: RR = 1.00; 95% CI [0.79, 1.27]; P = 1,00; RR = 0.96; 95% CI [0.74, 1.24]; P = 0,74; RR = 1.00; 95% CI [0.75, 1.33]; P = 1,00; respectivelyComparative analysis of the effectiveness of treatment with antiepileptic drugs (without tetracosactide) at 2 months, 6 months and 1 year of follow up (from the initiation of treatment) demonstrated that the number of patients achieving clinical remission was higher in the group IIA, in which the therapy was started within 1 month of the onset of the disease versus the "late treatment initiation" group IIB: RR = 2.76; 95% CI [1.03, 7.41]; P = 0,04; RR = 1.62; 95% CI [1.01, 2.59]; P = 0,04; RR = 1.37; 95% CI [1.02, 1.84]; P = 0,04; respectively. CONCLUSIONS: The timing of initiation of tetracosactide therapy did not influence the outcomes of West syndrome therapy. The early initiation of treatment with antiepileptic drugs (but without tetracosactide) resulted in a greater number of patients achieving remission, compared with late treatment initiation.

[Pharmacoepidemiology of epilepsy].

The lecture presents the history of the pharmacotherapy of epilepsy and analyzes the current situation at the pharmaceutical market related to the appearance of new, high-cost antiepileptic drugs in recent decades. The lecture substantiates the need of pharmacoepidemiology studies for the objective assessment of efficacy, safety and economical impact of new antiepileptics, especially in children, taking into account limited randomized preclinical trials in this group of patients. The lecture describes the role of pharmacoepidemiology in supplementing the findings of randomized controlled trials with new real-life evidence, in quantitative evaluation of adverse reactions, and in discovery of new adverse effects, as well as in the development of cost-effective strategies for rational antiepileptic therapy of children and in the overall improvement of public health economics.

[Pharmacoepidemiology of antiepileptic drugs in children: comparative analysis of drug effectiveness and safety].

Pharmacoepidemiological analysis of the effectiveness and safety (tolerance) of antiepileptic drugs belonging to various classes has been carried out using data for a group of patients registered at municipal children epilepsy services, including 548 children in 2005 and 718 in 2007, aged between 2 months and 18 years. Remission lasting for at least 1 year or longer than 3 years was used as primary effectiveness criterion and the total number of adverse effects as the safety (tolerance) criterion. No advantages of new anticonvulsants over the older antiepileptic drugs in terms of efficacy and safety have been found.