Effectiveness and Safety of Epilepsy Surgery for Pediatric Patients with Intractable Epilepsy: A Clinical Retrospective Study from a Single-Center Experience.

INTRODUCTION: Pediatric epilepsy surgery is an effective treatment modality for patients with drug-resistant epilepsy (DRE). Early pediatric surgery yields favorable results for DRE in terms of seizure control and neurophysiological outcome. In this study, pediatric patients were categorized based on their age (above 3 years old and below 3 years old) to demonstrate the effectiveness and safety of surgical procedures. METHODS: In this retrospective, single-center study, 60 pediatric patients who underwent epilepsy surgery at Istanbul Faculty of Medicine between 2002 and 2018 were evaluated. Overall morbidity and mortality rates, as well as seizure outcomes of the patients, were assessed and compared based on two age groups: those aged 3 years old or younger and those older than 3 years old. The effectiveness of invasive monitoring was also evaluated in relation to pathological results. The postoperative seizure outcome rates were evaluated using Engel's classification, with an average follow-up period of 8.7 years. RESULTS: Out of the total number of patients, 47 (78.4%) underwent resective surgery, while 13 (21.6%) had palliative surgery. Ten patients (16.6%) had invasive monitoring. Among all patients, 34 were classified as Engel I and II (56.6%), while 26 were classified as Engel III and IV (43.4%) postoperatively. 47% of patients who were under 3 years old, 60.4% of patients who were over 3 years old, and 50% of patients who underwent invasive monitoring had a favorable seizure outcome (Engel I-II). Postoperative morbidity and mortality rates were 35% (n = 21) and 1.6% (n = 1), respectively. CONCLUSION: Pediatric epilepsy surgery is an important treatment modality for preserving cognitive abilities and providing effective treatment for pediatric DRE. In our study, we claim that both invasive monitoring and epilepsy surgery lead to favorable seizure outcomes for all age groups. Further clinical studies should be conducted to provide more reliable data on the safety and effectiveness of the surgery, particularly in patients under the age of three.

Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

BEND4 as a Candidate Gene for an Infection-Induced Acute Encephalopathy Characterized by a Cyst and Calcification of the Pons and Cerebellar Atrophy.

Three siblings born to Turkish parents from the same village had normal brain development until acute neurological deterioration between 12 months and 8 years of age. Consequent loss of all acquired motor, social, and language functions following infections was associated with a pontine cyst, calcification, and cerebellar atrophy. Exome sequencing revealed a homozygous c.1297G>A (p.Gly433Ser) alteration in BEND4, which was predicted to be deleterious in in silico analysis tools and segregated in multiple affected individuals in the family. BEND4 has not been associated with any existing disease. Immunofluorescence microscopy analysis of wild-type and mutant BEND4 expressing Vero cells showed nuclear and cytoplasmic localization. Wild-type BEND4 displayed a network-like distribution, whereas mutant BEND4 showed a juxtanuclear distribution pattern. Differential proteome analysis of Vero cells expressing BEND4 revealed that mutant BEND4 expression caused selective increase in reticulocalbin-1 and endoplasmic reticulum resident protein-29. Both proteins are associated with the endoplasmic reticulum and are primarily involved in protein processing and folding pathways. Any defect or stress in protein folding creates stress on cells and may cause chronic damage. This is the first study showing that pathogenic BEND4 variants may lead to an infection-induced acute necrotizing encephalopathy as demonstrated in characteristic neuroimaging findings.