Evolução da epilepsia de lobo temporal mesial familiar

OBJECTIVE: To analyze seizure outcome in individuals with familial mesial temporal lobe epilepsy (FMTLE). METHOD: We followed prospectively 64 individuals with FMTLE and 37 asymptomatic individuals belonging to 28 families. RESULTS: Patients with FMTLE had a mean follow up was 93.4 ± 15.8 months. At baseline they were divided in benign (n = 29), remission (n = 28) and refractory (n = 7). At last follow up visit 41.4% patients with benign FMTLE remained classified as benign, 20.7% became refractory and 37.9% were in remission. In the subgroup of FMTLE in remission 21 75% remained without seizures; 21.4% were classified as benign FMTLE, and one died (3.6%) from cause unrelated to epilepsy. All refractory patients remained refractory. From the asymptomatic group, 10.8% became symptomatic (FMTLE). The mean follow up was 76.0 ± 21.2 months. CONCLUSION: Prospective follow up of more than 7 years in patients with FMTLE revealed that it is unlikely to achieve seizure control in those with refractory seizures. Patients with diagnose of more benign forms of FMTLE for more than one year are likely to either remit or remain under well controlled seizures. The majority of patients who had achieved seizure remission remained seizure-free and none became refractory. Asymptomatic individuals had a greater probability to have seizures compared to the general population in a 6 year period of follow up.OBJETIVOS: Analisar a evolução de famílias com epilepsia de lobo temporal mesial familiar (ELTMF). METODOLOGIA: Seguimento prospectivo de 64 pacientes com ELTMF e 37 membros assintomáticos pertencente a 28 famílias. RESULTADOS: A média de seguimento dos pacientes com ELTMF foi de 93,4 ± 15,8 meses. Na avaliação inicial os pacientes foram divididos em benignos (n = 29), remissão (n = 28) e refratários (n = 7). Na última visita disponível, 41,4% dos pacientes com ELTMF benigna permaneceram classificados como benignos, 20,7% tornaram-se refratários e 37,9% entraram em remissão. No grupo em remissão, 75% permaneceram livres de crise, 21,4% foram classificados como benignos e um faleceu (3,6%) de causa não relacionada à epilepsia. Todos pacientes refratários permaneceram refratários. Em relação aos assintomáticos 10,8% evoluíram com crises. A média de seguimento dos assintomáticos foi de 76,0 ± 21,2 meses. CONCLUSÃO: O seguimento prospectivo de mais de 7 anos de pacientes com ELTMF revelou que é improvável ocorrer controle de crises no grupo refratário. No grupo benigno é muito provável que estes indivíduos entrem em remissão ou permaneçam com evolução benigna. A maioria dos pacientes do grupo em remissão permaneceu em remissão e nenhum se tornou refratário. Em relação aos assintomáticos a probabilidade de apresentar uma crise no decorrer de aproximadamente 6 anos foi maior que o observado na população geral.111113Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Expression Profile of Genes Potentially Associated with Adequate Glycemic Control in Patients with Type 2 Diabetes Mellitus

Despite increasing research in type 2 diabetes mellitus (T2D), there are few studies showing the impact of the poor glycemic control on biological processes occurring in T2D. In order to identify potential genes related to poorly/well-controlled patients with T2D, our strategy of investigation included a primary screen by microarray (Human Genome U133) in a small group of individuals followed by an independent validation in a greater group using RT-qPCR. Ninety patients were divided as follows: poorly controlled T2D (G1), well-controlled T2D (G2), and normoglycemic individuals (G3). After using affy package in R, differentially expressed genes (DEGs) were prospected as candidate genes potentially relevant for the glycemic control in T2D patients. After validation by RT-qPCR, the obtained DEGs were as follows—G1 + G2 versus G3: HLA-DQA1, SOS1, and BRCA2; G2 versus G1: ENO2, VAMP2, CCND3, CEBPD, LGALS12, AGBL5, MAP2K5, and PPAP2B; G2 versus G3: HLA-DQB1, MCM4, and SEC13; and G1 versus G3: PPIC. This demonstrated a systemic exacerbation of the gene expression related to immune response in T2D patients. Moreover, genes related to lipid metabolisms and DNA replication/repair were influenced by the glycemic control. In conclusion, this study pointed out candidate genes potentially associated with adequate glycemic control in T2D patients, contributing to the knowledge of how the glycemic control could systemically influence gene expression

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

<div><p>Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in <i>ABCB1</i>, <i>ABCC2</i>, <i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP1B1</i>, <i>CYP2C9</i>, <i>CYP2C19</i>, <i>CYP2D6</i>, <i>CYP2E1</i>, <i>CYP3A4</i>, and <i>CYP3A5</i> genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner.</p></div

Percentage that each AED appears in monotherapy or polytherapy in the responsive and refractory patients.

<p>Percentage that each AED appears in monotherapy or polytherapy in the responsive and refractory patients.</p

<i>ABCC2</i> mRNA relative quantification.

<p>The boxplots include dots for each sample, showing the relative quantification of ABCC2 mRNA, in terms of 2^-ΔΔCT (y-axis), between hippocampal tissue from refractory MTLE patients and control autopsies.</p

Descriptive statistics of the two groups of patients with MTLE.

<p>Descriptive statistics of the two groups of patients with MTLE.</p

Variable importance plot.

<p>Each point represents the mean decreased accuracy estimate (y-axis), for each clinical variable and SNP genotype selected by the model (x-axis). Letter codes (AB and BB), after SNP name, indicate heterozygote and the alternative homozygote allele for each SNP, respectively.</p

Chromosome location of candidate genes and SNPtag map.

<p>a) genes are indicated by the grey vertical bars and distribution of SNPs used in the population structure are indicated by the red vertical bars; b) linkage disequilibrium estimates are presented in terms of pairwise r² values. Values of r² > 80 indicate linkage disequilibrium.</p

Fst values from the sample for all five chromosomes combined and separated.

<p>The table also includes the percentage of genetic variation between and within groups.</p