Novel familial IQSEC2 pathogenic sequence variant associated with neurodevelopmental disorders and epilepsy.

Pathogenic sequence variants in the IQ motif- and Sec7 domain-containing protein 2 (IQSEC2) gene have been confirmed as causative in the aetiopathogenesis of neurodevelopmental disorders (intellectual disability, autism) and epilepsy. We report on a case of a family with three sons; two of them manifest delayed psychomotor development and epilepsy. Initially proband A was examined using a multistep molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, both with negative results. Therefore, probands A and B and their unaffected parents were enrolled for an analysis using targeted "next-generation" sequencing (NGS) with a gene panel ClearSeq Inherited DiseaseXT (Agilent Technologies) and verification analysis by Sanger sequencing. A novel frameshift variant in the X-linked IQSEC2 gene NM_001111125.2:c.1813_1814del, p.(Asp605Profs*3) on protein level, was identified in both affected probands and their asymptomatic mother, having skewed X chromosome inactivation (XCI) (100:0). As the IQSEC2 gene is a known gene escaping from XCI in humans, we expect the existence of mechanisms maintaining the normal or enough level of the IQSEC2 protein in the asymptomatic mother. Further analyses may help to the characterization of the presented novel frameshift variant in the IQSEC2 gene as well as to elucidate the mechanisms leading to the rare asymptomatic phenotypes in females.

Long-term approach to patients with postsurgical seizures.

OBJECTIVE: The main purpose of the study was to analyze the long-term outcomes and therapeutic approaches for patients with seizures within the first year after surgery. The secondary aim of the study was to evaluate the relationship between 1-year outcome and long-term outcome and choice of therapy. METHODS: Our study was a retrospective investigation of the long-term outcomes of 95 patients (33.5% of all surgically treated patients) with seizure recurrence in the first year after surgery. The patients had follow-up visits for >5 years. RESULTS: At the 5-year follow-up visit (FU5), 28 (29.5%) of the 95 patients were completely seizure-free (International League Against Epilepsy (ILAE) class 1), 17 (17.9%) had auras only (ILAE class 2), and 21 (22.1%) were unimproved (ILAE classes 5 and 6). Statistically significant factors for these long-term outcomes were the focus localization of the epilepsy, preoperative MRI findings, and postoperative follow-up results in the first year. The patients with <3 seizure days in the first postoperative year (ILAE 3) represented 53.6% of the seizure-free patients at FU5; the patients with auras in the first year constituted 64.7% of the patients with only auras at FU5; and the patients unimproved in the first year represented 76.2% of the unimproved patients at FU5. SIGNIFICANCE: Postoperative outcome depends to a certain extent on the outcome achieved in the first postoperative year. More than one third of the patients with postoperative seizures reached a long-term seizure-free outcome, and more than half of them did not experience disabling seizures in the last outcome year. The most therapeutic options were used in patients who were minimally influenced by the operation; the majority of patients with considerable improvement because of the operation do not use any other add-on antiepileptic drugs or other kinds of therapy.

Long-term outcomes in patients after epilepsy surgery failure.

PURPOSE: The primary aim of this study was to analyze the long-term outcomes of patients who were classified as Engel IV one year after resective epilepsy surgery. The secondary objectives were to evaluate the effectiveness of different treatment options and to examine the reasons that the patients did not undergo resective reoperation. METHODS: Our study was designed as a retrospective open-label investigation of the long-term outcomes of 34 patients (12% of all surgically treated patients) who were classified as Engel IV one year after epilepsy surgery. RESULTS: At the last follow-up visit (average of 7.6 ± 4.2 years after surgery), 12 of the 34 examined patients (35.3%) were still classified as Engel IV; 22 of the 34 patients (64.7%) were improved (Engel I-III). Of the 34 patients, 8 (23.5%) achieved an excellent outcome, classified as Engel I, 3 patients (8.8%) were classified as Engel II, and 11 patients (32.4%) as Engel III. The seizure outcome in the patients classified as Engel I was achieved by resective reoperation in 4; by a change in antiepileptic medication in 3 patients; and by vagus nerve stimulation (VNS) in 1 patient. The seizure outcome of Engel II was achieved by a change in antiepileptic medication in all 3 patients. Of the 34 patients, a total of 6 (17.6%) underwent resective reoperation only. The major reasons for this were the absence of a plausible hypothesis for invasive re-evaluation, the risk of postoperative deficit, and multifocal epilepsy in the rest of patients. CONCLUSION: Although the reoperation rate was relatively low in our series, we can achieve better or even excellent seizure outcomes using other procedures in patients for whom resective surgery initially failed.

Effect of chronic vagal nerve stimulation on interictal epileptiform discharges.

We evaluated the effect of vagus nerve stimulation (VNS) on interictal epileptiform discharges (IEDs) in 32 epileptic patients (18 females; 14 males) with an average age of 42.2+/-11.4 years, all of whom had been suffering from epilepsy for an average of 29.2+/-14.5 years. All of the patients had received VNS for 5 years. The first EEG was performed prior to the initiation of stimulation; the second EEG was performed at the 5-year follow-up visit. The duration of each EEG was 30 min. We compared these two EEGs in terms of the number of IEDs present in each patient and correlated them to other variables. The average total number of IEDs during EEG and the total number of seconds in which IEDs were present decreased significantly after 5 years of stimulation from 97.3+/-106.9 resp. 80.6+/-86.1 to 49.4+/-94.0 resp. 37.8+/-65.0. Although there was no positive correlation between the reduction of IEDs and the percent of seizure reduction, we found a greater decrease of IEDs in patients who responded to VNS in comparison to those who did not. The decrease of IEDs was more pronounced in patients suffering from temporal lobe epilepsy than in patients suffering from extratemporal epilepsy. No other significant correlations were found. VNS reduced IEDs in patients chronically simulated for epilepsy. The reduction of IEDs was greater in patients who responded to VNS and in patients suffering from temporal lobe epilepsy.