Altered S100 Calcium-Binding Protein B and Matrix Metallopeptidase 9 as Biomarkers of Mesial Temporal Lobe Epilepsy with Hippocampus Sclerosis.

Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) is the most common form of partial epilepsy. The aim of the present study is to highlight possible and suitable biomarkers that can help in the diagnosis and prognosis of this intractable form of epilepsy. The study was carried out on 30 epileptic patients of both sexes with complex partial seizures, having an age ranging from 4 to 30 years and were selected from the outpatient epilepsy clinic at the Kasr El-Aini Hospital in Cairo, Egypt. Thirty healthy children and young adults, age- and sex-matched to the patients, were included in the study as controls. Patients with epilepsy and healthy controls were subjected to a set of laboratory analyses including S100 calcium-binding protein B (S100B), matrix metallopeptidase 9 (MMP9), C-reactive protein (CRP), and prolactin (PRL), in addition to neurophysiological, radiological, and psychometric assessments, on the basis of the recent evidence of the field. The results of this study showed a marked increase in the investigated biomarkers in patients with epilepsy compared to controls. The performance of the epileptic patients in psychometric assessments was below the average threshold, with the MRI analysis showing specific findings of mesial temporal sclerosis (MTS) and EEG showing anterior temporal spikes. A significant negative correlation was found between MMP9 and psychometric test. On the other hand, a significant positive correlation was observed between seizure severity and the indicated biomarker. The present study suggests that S100B and MMP9 could be used as biomarkers for neuronal injury and helps in the prognosis of MTLE.

Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy.

Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.