Cytogenic testing is routinely applied in most neurological centres for severe paediatric epilepsies. However, which characteristics of copy number variants (CNVs) confer most epilepsy risk and which epilepsy subtypes carry the most CNV burden, have not been explored on a genome-wide scale. Here, we present the largest CNV investigation in epilepsy to date with 10 712 European epilepsy cases and 6746 ancestry-matched controls. Patients with genetic generalized epilepsy, lesional focal epilepsy, non-acquired focal epilepsy, and developmental and epileptic encephalopathy were included. All samples were processed with the same technology and analysis pipeline. All investigated epilepsy types, including lesional focal epilepsy patients, showed an increase in CNV burden in at least one tested category compared to controls. However, we observed striking differences in CNV burden across epilepsy types and investigated CNV categories. Genetic generalized epilepsy patients have the highest CNV burden in all categories tested, followed by developmental and epileptic encephalopathy patients. Both epilepsy types also show association for deletions covering genes intolerant for truncating variants. Genome-wide CNV breakpoint association showed not only significant loci for genetic generalized and developmental and epileptic encephalopathy patients but also for lesional focal epilepsy patients. With a 34-fold risk for developing genetic generalized epilepsy, we show for the first time that the established epilepsy-associated 15q13.3 deletion represents the strongest risk CNV for genetic generalized epilepsy across the whole genome. Using the human interactome, we examined the largest connected component of the genes overlapped by CNVs in the four epilepsy types. We observed that genetic generalized epilepsy and non-acquired focal epilepsy formed disease modules. In summary, we show that in all common epilepsy types, 1.5–3% of patients carry epilepsy-associated CNVs. The characteristics of risk CNVs vary tremendously across and within epilepsy types. Thus, we advocate genome-wide genomic testing to identify all disease-associated types of CNVs.

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AIMS-The purpose of this study is to analyse the use of cognitive enhancers among medical students in Lithuania, determine the reasons for usage and evaluate the contributing factors such as socio-demographic characteristics, stress levels, sleep quality and knowing somebody who has used a neuro-enhancing drug. DESIGN-A cross-sectional survey study was performed by analysing a convenience sample of n=579 in the two universities offering medical education in Lithuania, Vilnius University and the Lithuanian University of Health Sciences. In 2014, students were asked to fill in anonymous paper questionnaires consisting of 13 items on prevalence of substance use to enhance cognitive performance, and on reasons and correlates (response rate 95%) during lecture time. RESULTS-Of the respondents, 8.1% indicated that they had used cognitive enhancers. Among those who had used these drugs, nootropics were the most frequently mentioned (59.6%), while psychostimulants, such as modafinil, methylphenidate and amphetaminederived drugs were mentioned less frequently (38.3%). Other substances were indicated by 23.4% of the respondents. Improvement of concentration and increased studying time were predominant purposes (55.3% and 48.9% of users, respectively). Male students reported three times higher prevalence rates than females (14.6% vs. 5.1%, p<0.05). Prevalence was also higher in students who knew someone using these substances than among those who did not know such persons (17.3% vs. 5.1%, p< 0.05). This was the most associated factor with cognitive-enhancing drug-taking behaviour. No correlation between cognitive enhancement usage and sleep quality or stress levels was found, nor between usage and belonging to a student organisation or having a job. CONCLUSIONS In Lithuania, 1 of 12 medical students admits to having used neuro-enhancing drugs. Our study results provide an overview of the actual situation on correlates and reasons for taking performance-enhancing substances.

Evidence exists indicating that sodium valproate (VPA) increases diuresis in rats. The chloriuretic and natriuretic effect of VPA has not previously been investigated, so the aim of the present study was to define the peculiarities of 24-hour urinary sodium (Na) and chloride (Cl) excretion in young adult Wistar rats of both genders, and to evaluate the effects of VPA. 24-Hour urinary Na, Cl, creatinine and pH levels were measured in 28 control intact Wistar rats and 26 Wistar rats after a single intragastric administration of 300 mg/kg VPA. After VPA administration, 24-hour diuresis and 24-hour diuresis per 100 g of body weight were significantly higher in VPA rats of both genders. 24-Hour urine Na and Cl excretion were significantly higher in VPA male and VPA female rats than in gender-matched controls. The 24-hour urinary Cl excretion was found to be significantly higher in VPA male than in VPA female rats. The study data show that VPA, alongside the diuretic effect, enhances Na and Cl excretion with urine. The 24-hour chloriuretic response to VPA in male rats was significantly higher than in female rats. The mechanism of such a gender-related effect is not yet clear.

The aim of this study was to investigate behavioral problems in two groups of children with benign childhood epilepsy with centrotemporal spikes (BECTS), i.e., those treated with antiepileptic drugs and those not treated in order to identify the factors associated with behavioral problems. Material and Methods. In total, 20 newly diagnosed untreated, 23 treated patients with BECTS, and 20 patients with acute/subacute peripheral nervous system disorders as a comparison group (aged 6–11 years) were examined. The evaluation was performed using the Lithuanian version of the Child Behavior Checklist (CBCL). Schooling parameters, clinical parameters, EEG parameters, and their relation to the results of the CBCL were also investigated. Results. The treated patients with BECTS had significantly higher scores in the subscales of Social Problems, Anxious/Depressed, Aggressive Behavior, and Attention Problems compared with the scores of the patients with peripheral nervous system disorders. A significant relationship was established between the scores of native language grades and Attention Problems; grades in mathematics and treatment duration; and age when the first seizure occurred and Delinquent Behavior in the group of treated patients. The duration of epilepsy was positively correlated with the scores in the subscales of Withdrawn and Delinquent Behavior. The presence of additional extrarolandic focus and spread of focal specific discharges to the centrofrontotemporal and centroparietotemporal areas were related to higher scores in Social Problems, Attention Problems, and Delinquent Behavior in the group of the treated patients with BECTS. Conclusions. Children with BECTS, especially those treated and with a longer epilepsy course, were found to be at risk of behavioral problems. Lower grades were associated with a longer disease course and medications. The presence of extrarolandic discharges was related to higher CBCL scores in the group of the treated patients with BECTS.