Genetic determinism of epilepsy refractoriness in patients with congenital cerebral p

Abstract

Background. In the phenotype of cerebral palsy, motor and mental disorders are often accompanied by epilepsy. Congenital epilepsy has been intensively researched in recent years. Special attention is drawn to epilepsy caused by congenital disturbance of the excitability of the neuronal membrane due to canalopathies.Aim. To analyze a large number of genes associated with the development of the cerebral palsy phenotype and distribute them according to determinable traits.Materials and methods. The results of clinical and genetic analysis of 136 cases of cerebral palsy with epilepsy are presented. The patients were divided into groups according to the syndromes according to the classification of cerebral palsy. Epileptic syndromes were divided into three groups: focal childhood epilepsy with structural brain changes and benign epileptiform discharges in electroencephalogram – 41 (30.1 %) cases, structural focal epilepsy – 37 (27.2 %) cases, epileptic encephalopathies – 58 (42.7 %) cases. Pathogenic variants in genes were confirmed by next generation sequencing Sanger methods of venous blood.Results. The performed risk analysis showed that in the presence of disorders in genes attributed to the group of regulation of the formation and functioning of the cytoskeleton, the risk of lack of remission is significantly lower than in other dominants, while abnormalities in genes attributed to the group of regulation of the function of the mitochondrial apparatus significantly increase the risks of failure to achieve remission and need in polytherapy.Conclusion. Probably, the violation of energy metabolism in the cell neutralizes the stabilization of the neuronal membrane under the action of anticonvulsants. The determinant of the formation and functioning of the cytoskeleton, according to our preliminary data, is largely associated with the formation of malformations of the brain. In this case, the refractoriness of epilepsy may be secondary and determined by the severity of structural changes in the brain

Keywords

• perinatal brain lesion
• cerebral palsy
• epilepsy
• genetics
• pharmacogenetics
• antiepileptic drugs
• anticonvulsants