Clinical Features And Cognitive Function In The Children With Benign Childhood Epilepsy With Centro-temporal Spikes And GRIN2A Mutation Screening

BackgroundBenign epilepsy with centro-temporal spikes(BECTS) is the most common idiopathic partial epilepsy in childhood. The EEG is characterized by sharp and waves in unilateral or bilateral centrotemporal region(CTS). The discharges can be either isolated or bursting, either unilateral(left or right side) or bilateral with synchronous or asynchronous discharges; discharges increase significantly especially in sleep. Currently, there is no unified view on the preferred drug for the treatment of BECTS patients, and it is necessary to comparatively analyze the efficacy of different drugs. It was believed in the past that BECTS was benign childhood epilepsy, and the International League Against Epilepsy(ILAE) once Regarded no cognitive impairment as a diagnostic indicator. In recent years, however, different studies have reported different cognitive dysfunctions that may occur in BECTS patients. It is thus necessary to re-explore what cognitive dysfunctions BECTS patients may have. So far, the specific pathogenesis of BECTS remains unknown, and more studies tend to suggest the participation of genetic factors. Recently, foreign studies have found the presence of de novo mutations of GRIN2 A gene in epileptic children with CTS of EEG associated with language disorders. Genetic studies on this gene have only been found in Europe and American populations, while the relevant study in Chinese people remains blank. Given the existence of racial differences in genetics, it is necessary to conduct GRIN2 A mutation screening in Chinese BECTS patients. ObjectiveTo summarize the clinical, prognosis and EEG characteristics of BECTS patients; evaluate the cognitive function of BECTS patients; conduct GRIN2 A mutation screening in some BECTS patients. MethodsThrough telephone or outpatient follow-up, the clinical data of 108 BECTS patients were retrospectively analyzed, including their EEG, medication compliance, episodes and other conditions; the Revised Chinese Version of Wechsler Intelligence Scale and the Revised Chinese Version of Wechsler Memory Scale were employed for intelligence and memory tests in some new treatment-seeking BECTS patients. Test results in the normal group were used as control; the peripheral blood of some new treatment-seeking BECTS patients was collected for GRIN2 A mutation screening by using polymerase chain reaction and the first-generation gene sequencing technology; spss 20.0 statistical software was employed for statistical data analysis with test level α = 0.05. Results1. Review of clinical data of BECTS patients(1) Demographic data: in the 108 BECTS patients, there were 61 males and 47 females; the minimum age of onset was 3 years, the maximum age of onset was 12.92 years, and the average age of onset was 7.38 ± 1.80 years;(2)frequency of sezures:before treatment, the frequency of episode was once every 6 months in 33 cases(32.04%) and twice and more every 6 months in 70 cases(67.96%); After treament, remission rate of different time period was 66.02%(in 6 months after treament), 72.82%(half to one year after treament),73.63%(one to two years after treament),74.19%(two Years Later after treament) respectively;(3)Characteristics of initial EEG examination: 108 patients all had discharges in sleep, and the sites of discharges sequenced by the probability of discharges occurrence were central region, temporal region, parietal region, posterior temporal region, frontal region, anterior temporal region and occipital region in order;(4)Characteristics of EEG re-examination : 44 patients underwent video-EEGs re-examination, 7 cases were reviewed after half to one year, 7 cases were reviewed after one to two years, 30 cases were reviewed after two years. Their EEGs showed a variety of evolution processes, which can be characterized by the changes of sites of unilateral or bilateral discharges, also can be characterized by the changes of side of discharges. there were 10 cases’ VEEGs returned to normal, and the minimum time cost for EEG to return to normal was 2 years, mean recovery time was 3.93±1.63 years;(5) Comparison of efficacy of monotherapy: monotherapy was the first choice for medication for half a year and 1 year, and there was no statistical difference in remission rate of oxcarbazepine(OXC), valproate(VPA), levetiracetam(LEV) and lamotrigine(LTG); after 2 years of medication, there was no statistical significance in the proportion of electroencephalogram returned to normal.2. Evaluation of cognitive function of BECTS patients(1) Comparison of Wechsler intelligence test between BECTS patient group and control group: the scores of knowledge, calculation, vocabulary and comprehension of patient group in VIQ, FIQ and Verbal Scale tests were lower than the control group, which have statistical difference; but no statistical differencewas seen in PIQ;(2) Comparison of Wechsler memory test between BECTS patient group and control group: the Memory Quotient(MQ) and the scores of 1â†'100,100â†'1,accumulation and comprehension in verbal memory subtest in the patient group were all lower than the control group, and there were statistical differences; there was no statistical difference in various sub-items of spatial image memory;(3) Comparison of test results of BECTS patients whose recent EEG shows unilateral and bilateral discharges:in Wechsler intelligence test, only the score of item Information in Verbal Category Fluency Test of patients with unilateral discharges was lower than that of patients with bilateral discharges, and there was statistical difference; in Wechsler memory test, only the score of item Comprehension of patients with unilateral discharges was lower than that of patients with bilateral discharges, and there was statistical difference;3. GRIN2 A mutation screening: in 29 BECTS patients, three missense mutations of GRIN2 A were found in 2 patients:c.4322C>A/p.T1441 N,C.205G>T/ p.V69 L, with a detection rate of 6.9%. Conclusion1. BECTS patients responded well to medications, epileptic seizures of most patients can be controled with single drug treatment. After treatment, remission rate of seizures increased gradually in unit time.2. The differences in remission rate and EEG normalization proportion of OXC, VPA, LEV and LTG monotherapy are not significant; the seizure frequency in BECTS patients is not high and drug reactions are good, so individualized treatment should be implemented;3. Although seizures are easy to control, EEG discharges may also exist for a long term; it takes a long time for EEG to return to normal, and re-examination of EEG in a short time is of little significance; during the course of disease, there are changeful forms of EEG discharges;4. BECTS generates certain negative effects on cognitive function, particularly affecting language function, but no significant difference between unilateral and bilateral discharges;5. Some BECTS patients have GRIN2 A mutations, which may be related to their pathogenesis.