Epilepsy and Cerebral Palsy: Clinical Syndromology, Outcomes and Prognosis

Objective of the Review: To analyze modern scientific research on clinical syndromology, genetic factors of epilepsy and cerebral palsy (CP), therapeutic tactics and outcomes.

Key points. Multiple genetic factors contribute to the emergence of CP. With CP, low birth weight, neonatal seizures, epileptic seizures during the first year of life, a burdened family history of epilepsy, the severity of CP and the presence of changes in neuroimaging are associated with the risk of developing epilepsy. Children with CP may have Otahar, West, Lennox — Gastaut, syndromes-focal epilepsy of childhood with structural brain changes and benign epileptiform discharges in EEG — FECSB-BEDC. The selection of antiepileptic drugs in patients with epilepsy and CP is determined by the epileptic syndrome, cognitive, motor manifestations and side effects of the drug. Most of the failures of remission occur within the first year after discontinuation of therapy. Failure of remission is associated with a greater likelihood of subsequent development of pharmacoresistant epilepsy.

Conclusion. Video EEG monitoring and spectral analysis of bioelectric activity of the brain can be of great importance for optimizing the management of patients with CP and epilepsy. In addition, the search for EEG criteria for the withdrawal of antiepileptic drugs in patients with a combination of CP and epilepsy, as well as predictors of failure of remission, remains relevant.

1. Bobylova M.Yu., Mukhin K.Yu. Epilepsy in children with cerebral palsy. Child and Adolescent Rehabilitation. 2019; 4(40): 15. (in Russian)

2. Pavone P., Gulizia C., Le Pira A., Greco F. et al. Cerebral palsy and epilepsy in children: clinical perspectives on a common comorbidity. Children (Basel). 2020; 8(1): 16. DOI: 10.3390/children8010016

3. Chiang K.-L., Kuo F.-C., Cheng C.-Y., Chang K.-P. Prevalence and demographic characteristics of comorbid epilepsy in children and adolescents with cerebral palsy: a nationwide population-based study. Childs Nerv. Syst. 2019; 35(1): 149–56. DOI: 10.1007/s00381-018-3920-9

4. Sadowska M., Sarecka-Hujar B., Kopyta I. Cerebral palsy: current opinions on definition, epidemiology, risk factors, classification and treatment options. Neuropsychiatr. Dis. Treat. 2020; 16: 1505–18. DOI: 10.2147/NDT.S235165

5. Moreno-De-Luca A., Millan F., Pesacreta D.R., Elloumi H.Z. et al. Molecular diagnostic yield of exome sequencing in patients with cerebral palsy. JAMA. 2021; 325(5): 467–75. DOI: 10.1001/jama.2020.26148

6. Van Naarden Braun K., Doernberg N., Schieve L., Christensen D. et al. Birth prevalence of cerebral palsy: a population-based study. Pediatrics. 2016; 137(1): 1–9. DOI: 10.1542/peds.2015-2872

7. Peljto A.L., Barker-Cummings C., Vasoli V.M., Leibson C.L. et al. Familial risk of epilepsy: a population-based study. Brain. 2014; 137(pt3): 795–805. DOI: 10.1093/brain/awt368

8. Koko M., Motelow J.E., Stanley K.E., Bobbili D.R. et al. Association of ultra-rare coding variants with genetic generalized epilepsy: a case control whole exome sequencing study. Epilepsia. 2022; 63(3): 723–35. DOI: 10.1111/epi.17166

9. Abdel Maksoud Y.H., Suliman H.A., Elsayed Abdulsamea S., Mohamed Kamal N. et al. Risk factors of intractable epilepsy in children with cerebral palsy. Iran. J. Child Neurol. 2021; 15(4): 75–87. DOI: 10.22037/ijcn.v15i3.31556

10. Karatoprak E., Sözen G., Saltık S. Risk factors associated with epilepsy development in children with cerebral palsy. Childs Nerv. Syst. 2019; 35(7): 1181–7. DOI: 10.1007/s00381-019-04152-w

11. Pisani F., Prezioso G., Spagnoli C. Neonatal seizures in preterm infants: a systematic review of mortality risk and neurological outcomes from studies in the 2000's. Seizure. 2020; 75: 7–17. DOI: 10.1016/j.seizure.2019.12.005

12. Hanci F., Türay S., Dilek M., Kabakus N. et al. Epilepsy and drug resistant epilepsy in children with cerebral palsy: a retrospective observational study. Epilepsy Behav. 2020; 112: 107357. DOI: 10.1016/j.yebeh.2020.107357

13. Sadowska M., Sarecka-Hujar B., Kopyta I. Evaluation of risk factors for epilepsy in pediatric patients with cerebral palsy. Brain Sci. 2020; 10(8): 481. DOI: 10.3390/brainsci10080481

14. Tsubouchi Y., Tanabe A., Saito Y., Noma H. et al. Long-term prognosis of epilepsy in patients with cerebral palsy. Dev. Med. Child Neurol. 2019; 61(9): 1067–73. DOI: 10.1111/dmcn.14188

15. 15 Baumgartner C., Pirker S. Video-EEG. Hand. Clin. Neurol. 2019; 160: 171–83. DOI: 10.1016/B978-0-444-64032-1.00011-4

16. Pavone P., Corsello G., Ruggieri M. Benign and severe early-life seizures: a round in the first year of life. Italian J. Pediatr. 2018; 44(1): 1–11. DOI: 10.1186/s13052-018-0491-z

17. Pavone P.A., Polizzi S.D. West syndrome: a comprehensive review. Neurol. Sci. 2020; 41(12): 3547–62. DOI: 10.1007/s10072-020 04600-5

18. Gehlawat V.K., Arya H., Bhardwaj М., Vaswani N.D. et al. Clinical profile of children with West syndrome: a retrospective chart review. J. Family Med. Prim. Care. 2021; 10(1): 350–3. DOI: 10.4103/jfmpc.jfmpc_1405_20

19. Mukhin K.Yu., Mironov M.B. Epileptic spasms. Russian Journal of Child Neurology. 2014; 9(4): 20–9. (in Russian). DOI: 10.17650/2073-8803-20149-4-20-29

20. Fusco L., Serino D., Santarone M.E. Three different scenarios for epileptic spasms. Epilepsy Behav. 2020; 113: 107531. DOI: 10.1016/j.yebeh.2020.107531

21. Ostendorf A.P., Ng Y.-T. Treatment-resistant Lennox — Gastaut syndrome: therapeutic trends, challenges and future directions. Neuropsychiatr. Dis. Treat. 2017; 13: 1131–40. DOI: 10.2147/NDT. S115996

22. Strzelczyk A., Schubert-Bast S. Expanding the treatment landscape for Lennox — Gastaut syndrome: current and future strategies. CNS drugs. 2021; 35(1): 61–83. DOI: 10.1007/s40263-020-00784-8

23. Mukhin K.Yu., Mironov M.B., Borovikov K.S., Petrukhin A.S. Focal epilepsy of childhood with structural brain changes and benign epileptiform discharges in EEG, FECSBC-BEDC (preliminary results). Russian Journal of Child Neurology. 2010; 5(1): 3–18. (in Russian)

24. Mironov M.B., Chebanenko N.V., Bychenko V.G., Rubleva Yu.V. et al. Comorbidity of infantile cerebral palsy and benign epileptiform EEG discharges of childhood in dizygotic twins. Epilepsy and Paroxysmal Conditions. 2018; 10(3): 52–62. (in Russian). DOI: 10.17749/20778333.2018.10.3.052-062

25. Tantawi N.T., Abd Elmegid D.S., Atef E. Seizure outcome and epilepsy patterns in patients with cerebral palsy. Seizure. 2019; 65: 166–71. DOI: 10.1016/j.seizure.2019.01.003

26. Tokatly Latzer I., Bluovich A., Sagi L. et al. Prediction of drug-resistant epilepsy in children with cerebral palsy. Journal of Child Neurology. 2020; 35(3): 187–94. DOI: 10.1177/0883073819883157

27. Badalyan O.L., Trepilets V.M., Trepilets S.V. Clinical experience of using zonisamide in structural focal epilepsy in children with cerebral palsy. S.S. Korsakov Journal of Neurology and Psychiatry. Special issues. 2018; 118(10–2): 90–7. (in Russian). DOI: 10.17116/jnevro201811810290

28. Zenkov L.R. Clinical electroencephalography with elements of epileptology. M.: Medpress-inform; 2017. 360 p. (in Russian)

29. Sivakova N.A., Korsakova E.A., Lipatova L.V. Pathomorphosis of focal epilepsy and its neurophysiological correlates. Epilepsy and Paroxysmal Conditions. 2018; 10(1): 6–13. (in Russian). DOI: 10.17749/2077-8333.2018.10.1.006-013

30. Baumgartner C., Koren J.P., Britto-Arias M., Zoce L. et al. Presurgical epilepsy evaluation and epilepsy surgery. F1000Research. 2019; 8: F1000. DOI: 10.12688/f1000research.17714.1

31. Vázquez-Sánchez F., García-López B., Gómez-Menéndez A., Martín Santidrián A. et al. Long-term V-EEG in epilepsy: chronological distribution of recorded events focused on the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures. J. Clin. Med. 2021; 10(10): 2080. DOI: 10.3390/jcm10102080

32. Sagi V., Shoup J., Chilukuri R., Steven Evans M. Latency to first event is shorter in psychogenic non-epileptic seizures than in epileptic seizures in an epilepsy monitoring unit. Innov. Clin. Neurosci. 2020; 17(7–9): 26–9.

33. Cho Y.W., Motamedi G.K., Kim K.T. The clinical utility of non-invasive video-electroencephalographic monitoring has been diversifying. Neurol. Sci. 2019; 40(12): 2625–31. DOI: 10.1007/s10072-019 04022-y

34. Nguyen-Michel V.H., Dinkelacker V., Solano O., Levy P.-P. et al. 4h versus 1h-nap-video-EEG monitoring in an Epileptology Unit. Clin. Neurophysiol. 2016; 127(9): 3135–9. DOI: 10.1016/j.clinph.2016.06.008

35. Abouelleil M., Deshpande N., Ali R. Emerging trends in neuromodulation for treatment of drug-resistant epilepsy. Front. Pain Res. (Lausanne). 2022; 3: 839463. DOI: 10.3389/fpain.2022.839463

36. Pillai S. Postencephalitic epilepsy and drug-resistant epilepsy after infectious and antibody-associated encephalitis in childhood. Clinical and etiologic risk factors. Epilepsia. 2016; 57(1): 7–11. DOI: 10.1111/epi.13253

37. Belousova E.D., Zavadenko N.N., Kholin A.A., Sharkov A.A. New classifications of epilepsies and seizure types created by the International League against Epilepsy (2017). S.S. Korsakov Journal of Neurology and Psychiatry. 2017; 117(7): 99–106. (in Russian). DOI: 10.17116/jnevro20171177199-106

38. Mukhin K.Yu. Basic definitions in epileptology and classification of epileptic seizures in 2017. Bulletin of Epileptology. 2019; 1: 3–10. (in Russian)

39. Moavero R., Pisani L.R., Pisani F., Curatolo P. Safety and tolerability profile of new antiepileptic drug treatment in children with epilepsy. Expert Opin. Drug Saf. 2018; 17(10): 1015–28. DOI: 10.1080/14740338.2018.1518427

40. Kartal A. Can high-dose levetiracetam be safe? A case report of prolonged accidental high-dose levetiracetam administration and review of the literature. Clin. Neuropharmacol. 2017; 40(5): 217 18. DOI: 10.1097/WNF.0000000000000229

41. Qiao M.Y., Cui H.T., Zhao L.Z. Efficacy and safety of levetiracetam vs. phenobarbital for neonatal seizures: a systematic review and meta-analysis. Front. Neurology. 2021; 12: 747745. DOI: 10.3389/fneur.2021.747745

42. Mukhin K.Yu., Kuzmich G.V., Mironov M.B. Epilepsy with cerebral palsy in children: electro-clinical features and prognosis. Bulletin of the Russian State Medical University. 2011; 5: 37–41. (in Russian)

43. Kipnis P.A., Kadam S.D. Concepts for the role of chloride cotransporters in refractory seizures. Aging Dis. 2021; 12(4): 1056 69. DOI: 10.14336/AD.2021.0129

44. Depositario-Cabacar D.F., Zelleke T.G. Treatment of epilepsy in children with developmental disabilities. Develop. Disabil. Res. Rev. 2010; 16(3): 239–47. DOI: 10.1002/ddrr.116

45. Kotov A.S. Remissions and relapses in epilepsy. S.S. Korsakov Journal of Neurology and Psychiatry. 2020; 120(3): 23–8. (in Russian). DOI: 10.17116/jnevro20201200312310

46. Feng L., Wang J., Li X., Hu Y. et al. Prospective control study of efficacy and influencing factors of a ketogenic diet on refractory epilepsy in children. Transl. Pediatr. 2022; 11(1): 138–48. DOI: 10.21037/tp-21-595

47. Mironov M.B., Andreeva N.I., Fomchenkova D.S., Chebanenko N.V. et al. Epilepsy in de Vivo syndrome: a literature review and a clinical case. Еpilepsy and Paroxysmal Conditions. 2019; 11(3): 270–7. (in Russian). DOI: 10.17749/2077-8333.2019.11.3.270-277

48. Hernán F.J., Yengo-Kahn A., Englot D. Vagus nerve stimulation for the treatment of epilepsy. neurosurgery clinics of North America. 2019; 30(2): 219–30. DOI: 10.1016/j.nec.2018.12.005