EC Neurology

Case Study Volume 15 Issue 5 - 2023

Genetic Determinism of Epilepsy Refractoriness in Patients with Congenital Cerebral Palsy

Pavel L Sokolov1*, Natalia V Chebanenko2 and Diana M Mednaya3

1St. Luka´s Clinical Research Center for Children, Moscow, Russia
2Federal State Budgetary Educational Institution of Further Professional Education “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian Federation, Moscow, Russia
3Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University Named After N.I. Pirogov” Ministry of Health of Russia, Moscow, Russia

*Corresponding Author: Pavel L Sokolov, St. Luka´s Clinical Research Center for Children, Moscow, Russia.
Received: March 26, 2023; Published: April 10, 2023

Background: Epilepsy often accompanies congenital cerebral palsy (CP). Channelopathies can be the cause of congenital epilepsy. The aim of the study is to determine the influence of various determinants on the course of epilepsy.

Materials and Methods: The results of clinical and genetic analysis of 136 cases of cerebral palsy (CP) with epilepsy are presented. The patients were divided into groups according to the syndromes according to the classification of CP (Panteliadis and R. Korinthenberg, 2005). Epileptic syndromes were divided into three groups: focal childhood epilepsy with structural brain changes and benign epileptiform discharges (BEDC) in EEG - 41 children (30.1%), structural focal epilepsy - 37 children (27.2%), epileptic encephalopathies 58 children (42.7%). Pathogenic variants in genes were confirmed by next generation sequencing (NGS) Sanger methods of venous blood.

Results: Remission was more difficult to achieve in patients with determinants of regulation of general aspects of cellular metabolism, mitochondrial function, cytoskeleton formation and function, and transport across the outer membrane. The need for polypharmacy was in the groups that regulate the function of mitochondria, the formation and functioning of the cytoskeleton, and the regulation of membrane excitability.

Conclusion: Determinant analysis provides a better understanding of the mechanisms of patient responsiveness to anticonvulsant therapy. The determinant of mitochondrial function most significantly affects its effectiveness. Probably, the violation of energy metabolism in the cell neutralizes the stabilization of the neuronal membrane under the influence of anticonvulsants. The determinant of the formation and functioning of the cytoskeleton, according to our preliminary data, is associated with the formation of malformations of the brain. In this case, the refractoriness of epilepsy can be secondary and determined by the severity of structural changes in the brain.

Keywords: Perinatal Brain Lesion; Cerebral Palsy; Epilepsy; Genetics; Pharmacogenetics; Anti-Epileptic Drugs; Anticonvulsants

  1. Goto A., et al. “Characteristics of KCNQ2 variants causing either benign neonatal epilepsy or developmental and epileptic encephalopathy”. Epilepsia9 (2019): 1870-1880.
  2. Zhang S., et al. “SCN9A Epileptic Encephalopathy Mutations Display a Gain-of-function Phenotype and Distinct Sensitivity to Oxcarbazepine”. Journal of Neuroscience Bulletin 1 (2020): 11-24.
  3. Patino GA., et al. “A functional null mutation of SCN1B in a patient with Dravet syndrome”. The Journal of Neuroscience 34 (2009): 10764-10778.
  4. Michael C Fahey., et al. “The genetic basis of cerebral palsy”. Developmental Medicine and Child Neurology 5 (2017): 462-469.
  5. McMichael G., et al. “Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy”. Molecular Psychiatry 2 (2015): 176-182.
  6. Sokolov PL., et al. “Congenital cerebral palsy: genetic cause and nosological integrity”. Russian Journal of Child Neurology 3-4 (2020): 65-77.
  7. Banerjee A., et al. “ADSL Deficiency - The Lesser-Known Metabolic Epilepsy in Infancy”. Indian Journal of Pediatrics 3 (2021): 263-265.
  8. Kolc K., et al. “PCDH19 Pathogenic Variants in Males: Expanding the Phenotypic Spectrum”. Advances in Experimental Medicine and Biology 1298 (2020): 177-187.
  9. Parsamanesh N., et al. “Identification and In Silico Characterization of a Novel Point Mutation within the Phosphatidylinositol Glycan Anchor Biosynthesis Class G Gene in an Iranian Family with Intellectual Disability”. Journal of Molecular Neuroscience 4 (2019): 538-545.
  10. Mitta N., et al. “Genotype-phenotype correlates of infantile-onset developmental and epileptic encephalopathy syndromes in South India: A single centre experience”. Epilepsy Research 166 (2020): 106398.
  11. Terrone G., et al. “Intrafamilial variability in SPTAN1-related disorder: From benign convulsions with mild gastroenteritis to developmental encephalopathy”. The European Journal of Paediatric Neurology 28 (2020): 237-239.

Pavel L Sokolov., et al. “Genetic Determinism of Epilepsy Refractoriness in Patients with Congenital Cerebral Palsy”. EC Neurology  15.5 (2023): 19-25.