Novel SCN1A variants in Dravet syndrome and evaluating a wide approach of patient selection.

Voltage-gated sodium channels are essential for generation and propagation of the action potential mainly in nerve and muscle cells. Causative variants in SCN1A gene which codes the main, pore-forming subunit of the channel expressed in central nervous system are associated predominantly with Dravet syndrome (DS), as well as with generalized epilepsy with febrile seizures plus (GEFS+) making it one of the most significant epilepsy gene. Our goal was to determine whether SCN1A screening is relevant in patients with a broad range of epileptic syndromes. 52 patients diagnosed with DS, generalized epilepsy with GEFS+ or similar types of epileptic syndromes were included. Sequencing of the protein coding parts of the gene complemented with MLPA analysis was carried out. One already described nonsense variant, four novel protein truncating variants and a deletion encompassing the whole SCN1A gene were revealed, all in heterozygous state. All identified variants were found in DS patients with 85.7% sensitivity, thus supporting the role of profound SCN1A gene variants in etiology of DS phenotype. No causative variants were identified in any of non-DS epileptic patients in our cohort, suggesting a minor, but not irrelevant role for SCN1A in patients with other types of childhood epilepsy.

Methylenetetrahydrofolate reductase gene polymorphisms and neural tube defects epidemiology in the Slovak population.

BACKGROUND: Folate deficiency is a known factor contributing to the formation of neural tube defects (NTDs). Many folate metabolism gene variants have been investigated, but only a few substantial associations have been established, the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene being one of the most significant. METHODS: We determine the MTHFR C677T and A1298C genotypes in 93 Slovak NTD patients and 290 control newborns with respect to sex and ethnicity. Furthermore, we summarize current data on the incidence and types of NTDs in Slovakia. RESULTS: The Slovak population frequencies of T allele and TT genotype of the C677T MTHFR gene polymorphism were 0.25 and 6.9%, respectively; similarly, those of the C allele and CC genotype of the A1298C polymorphism were 0.35 and 13.8%, respectively. No differences between the sexes and within ethnic groups were observed. In NTD patients, genotype analysis of the C677T polymorphism revealed 0.29 and 9.8% for T allele and TT genotype frequencies, respectively (p = 0.26; OR, 1.23; 95% CI, 0.84-1.81; resp. p = 0.36; OR, 1.46; 95% CI, 0.56-3.52) compared to the controls. The frequencies of C allele and CC genotype of A1298C polymorphism were 0.34 and 6.5%, respectively (p = 0.81; OR, 0.96; 95% CI, 0.66-1.38; resp. p = 0.06; OR, 0.44; 95% CI, 0.15-1.09). There were also no sex-related differences in genotypes distribution in NTD patients. CONCLUSIONS: No significant associations between the C677T and A1298C MTHFR gene polymorphisms and NTDs and no differences between the two main ethnic groups (white-Caucasians, Roma) were found in Slovakia. The total incidence of NTDs in Slovakia is, according to the official sources, 0.53/1000, and the incidence among liveborn newborns is 0.28/1000.

Current status of epilepsy health care for adult patients from central and eastern European Union countries--a survey of members of the Central Europe Epilepsy Experts Working Group.

PURPOSE: The aim of this survey was to review and compare the current approaches to epilepsy management in central and eastern EU (CEEU) countries. METHOD: The questionnaire was sent to ten invited experts from Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. It focused on the treatment of adults. RESULTS: The number of neurologists and epilepsy reference centers is highly variable in CEEU countries. None of the analyzed states has a formal specialization in epileptology. No universal state-approved criteria for reference centers exist in Czech Republic, Estonia, Hungary, Latvia, and Slovenia. Generally, the protocols for epilepsy treatment in CEEU countries, including drug-resistant epilepsy, are in accordance with international guidelines; however, most countries have their own national standards of care and some have local clinical guidelines. Also, the reimbursement systems for antiepileptic drugs in CEEU countries are highly variable. Seven countries have epilepsy surgery centers. The costs of epilepsy surgeries are fully reimbursed, procedures performed abroad may also be covered. The length of time spent on waiting lists for surgery following the completion of preoperative investigations varies from two weeks to three years. The fraction of patients who qualified and were operated on within 12 months ranges from 20% to 100%. CONCLUSION: The lack of unified procedures pertaining to the evaluation and therapy of epilepsy is reflected by marked differences in access to treatment modalities for patients from CEEU countries.