Outcomes of resective surgery in pediatric patients with drug-resistant epilepsy: A single-center study from the Eastern Mediterranean Region.

OBJECTIVE: Epilepsy surgery is widely accepted as an effective therapeutic option for carefully selected patients with drug-resistant epilepsy (DRE). There is limited data on the outcome of epilepsy surgery, especially in pediatric patients from the Eastern Mediterranean region. Hence, we performed a retrospective study examining the outcomes of resective surgery in 53 pediatric patients with focal DRE. METHODS: Patients with focal DRE who had undergone epilepsy surgery were included in the present study. All patients underwent a comprehensive presurgical evaluation. Postoperative seizure outcomes were classified using the Engel Epilepsy Surgery Outcome Scale. RESULTS: After surgery, 33 patients (62.2%) were Class I according to the Engel classification of surgical outcomes; eight patients (15.0%) were Class II, 11 (20.7%) were Class III, and one (1.8%) was Class IV. The relationships of presurgical, surgical, and postsurgical clinical variables to seizure outcomes were compared. Older age at seizure onset, older age at the time of surgery, the presence of focal to bilateral tonic-clonic seizures, seizure duration over 2 minutes, unsuccessful treatment with three or fewer antiseizure medications, lesions confined to one lobe (as demonstrated via magnetic resonance imaging [MRI]), surgical site in the temporal lobe, and histopathology including developmental tumors were significantly linked to an Engel Class I outcome. A univariate analysis of excellent surgical outcomes showed that lateralized semiology, localized interictal and ictal electroencephalogram (EEG) discharges, lateralized single-photon emission computed tomography and positron emission tomography findings, and temporal lobe resections were significantly related to excellent seizure outcomes. SIGNIFICANCE: The results of our study are encouraging and similar to those found in other centers around the world. Epilepsy surgery remains an underutilized treatment for children with DRE and should be offered early.

Continuous Spikes and Waves During Sleep (CSWS), Severe Epileptic Encephalopathy, and Choreoathetosis due to Mutations in FRRS1L.

Background. Biallelic pathogenic variants in the FRRS1L gene are now known to cause developmental and epileptic encephalopathy-37 (DEE37). It can also be associated with chorea and continuous spikes and waves during sleep (CSWS). CSWS is a rare age-related epileptic encephalopathy syndrome of childhood that is characterized by seizures, neurocognitive regression and electrical status epilepticus during sleep (ESES) on electroencephalogram (EEG) that evolves in four stages. Seizures start during the prodromal phase but the ESES on EEG appears only during acute stage and this is the stage when the diagnosis of CSWS can be made. Methods. We present two patients with FRRS1L mutation causing DEE37 with CSWS. We also review twenty-nine cases of DEE37 described in the literature before and discuss its association with CSWS in the total cohort of thirty-one cases. Results. Developmental regression was found in 80% of the patients, mean age of seizure onset was 18 months, ESES or slow spike and wave on the EEG were reported mostly in the older patients (median age of 11 years) and hypsarrhythmia was reported in younger patients (median age of 4 years). This could suggest that if the younger patients were followed longer their EEG would have evolved into ESES during the acute stage of this syndrome and a diagnosis of CSWS could be made. Conclusion. Recognizing ESES and the natural evolution of CSWS is important in diagnosis and proper management of these patients. More detailed report of EEG findings and the evolution of epilepsy and development are needed to further characterize this syndrome.

SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.

The uptake and efflux of solutes across a plasma membrane is controlled by transporters. There are two main superfamilies of transporters, adenosine 5'-triphosphate (ATP) binding cassettes (ABCs) and solute carriers (SLCs). In the brain, SLC transporters are involved in transporting various solutes across the blood-brain barrier, blood-cerebrospinal fluid barrier, astrocytes, neurons, and other brain cell types including oligodendrocytes and microglial cells. SLCs play an important role in maintaining normal brain function. Hence, mutations in the genes that encode SLC transporters can cause a variety of neurological disorders. We identified the following SLC gene variants in 25 patients in our cohort: SLC1A2, SLC2A1, SLC5A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SLC12A6, SLC13A5, SLC16A1, SLC17A5, SLC19A3, SLC25A12, SLC25A15, SLC27A4, SLC45A1, SLC46A1, and SLC52A3. Eight patients harbored pathogenic or likely pathogenic mutations (SLC5A1, SLC9A6, SLC12A6, SLC16A1, SLC19A3, and SLC52A3), and 12 patients were found to have variants of unknown clinical significance (VOUS); these variants occurred in 11 genes (SLC1A2, SLC2A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SLC13A5, SLC25A12, SLC27A4, and SLC45A1). Five patients were excluded as they were carriers. In the remaining 20 patients with SLC gene variants, we identified 16 possible distinct neurological disorders. Based on the clinical presentation, we categorized them into genes causing intellectual delay (ID) or autism spectrum disorder (ASD), those causing epilepsy, those causing vitamin-related disorders, and those causing other neurological diseases. Several variants were detected that indicated possible personalized therapies: SLC2A1 led to dystonia or epilepsy, which can be treated with a ketogenic diet; SLC6A3 led to infantile parkinsonism-dystonia 1, which can be treated with levodopa; SLC6A5 led to hyperekplexia 3, for which unnecessary treatment with antiepileptic drugs should be avoided; SLC6A8 led to creatine deficiency syndrome type 1, which can be treated with creatine monohydrate; SLC16A1 led to monocarboxylate transporter 1 deficiency, which causes seizures that should not be treated with a ketogenic diet; SLC19A3 led to biotin-thiamine-responsive basal ganglia disease, which can be treated with biotin and thiamine; and SLC52A3 led to Brown-Vialetto-Van-Laere syndrome 1, which can be treated with riboflavin. The present study examines the prevalence of SLC gene mutations in our cohort of children with epilepsy and other neurological disorders. It highlights the diverse phenotypes associated with mutations in this large family of SLC transporter proteins, and an opportunity for personalized genomics and personalized therapeutics.