Risk factors for developing epilepsy after neonatal seizures

Neonatal seizures are the most frequent neurological disorder in the neonatal period. The incidence is reported to be higher than at any other period in life. Because of the unique nature of neonatal brain anatomy, connections and the paradoxical nature of neurotransmitters, seizures in this age group vary in semiology from those in older children. They may cause irreversible changes to the synapses in the immature brain and progress to epilepsy. 

The aim of the study was to analyse laboratory, clinical, neurophysiological and neuroimaging risk factors for epilepsy in a group of children who experienced seizures in the neonatal period.

A retrospective study of 176 newborns admitted to the Department of Neonatology, University Children’s Hospital Ljubljana, due to seizures, was performed. Metabolic disorders and hypoxic-ischaemic encephalopathy were the most frequent aeti-ological factors associated with seizures. Epilepsy rate in the group was 18%. Pathological cardiotocography, reanimation after delivery, myoclonic type of seizures, more than one type of seizures, severely abnormal electroencephalography, abnormal neurological examination and neuroimaging, treatment with more than one antiepileptic drug and duration of treatment more than one month constituted statistically significant independent predictive factors for epilepsy (p< 0.05). The results of our study further elucidate risk factors for epilepsy after neonatal seizures.

newborns, seizures, epi-lepsy, risk factors

1. Volpe JJ. Neonatal seizures. In: Neurology of the newborn. 5th ed. Philadelphia. WB  Saunders; 2001. p. 203-44.

2. Clancy RR. Summary proceeding from the Neurology Group on neonatal seizures. Pediatrics 2006;117:S23-7.

3. Isaeva E, Isaev D, Savrasova A, Khazipov R, Holmes GL. Recurrent neonatal seizures result in long-term increases in neuronal network excitability in the rat neocortex. Eur J Neurosci 2010;31:1446–55.

4. Holmes GL. Effects of seizures on brain development: Lessons from laboratory. Pediatr Neurol 2005;33:1-11.

5. Holden KR, Mellits D, Freeman JM. Neonatal seizures I: correlation of prenatal and perinatal events with outcome. Pediatrics 1982;70:165-76.

6. Ronen GM, Buckley D, Penney S, Streiner DL. Long-term prognosis in children with neonatal seizures: a population based study. Neurology 2007;69:1816-22.

7. Garfinkle J, Shevell MI. Cerebral palsy, developmental delay, and epilepsy after neonatal seizures. Pediatr Neurol 2011; 44: 88-96.

8. Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology 1987;37:1837-44.

9. Tekgul H, Gauvreau K, Soul J. Murphy L, Robertson R, Stewart J, et al. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics 2006;117:1270–80.

10. Clancy RR, Legido A. Postnatal epilepsy after EEG-confirmed neonatal seizures. Epilepsia 1991;32:69-76.

11. Holmes GL, Lombroso CT. Prognostic value of background patterns in the neonatal EEG. J Clin Neurophysiol 1993;10(3):323-52.

12. Clancy RR, Legido A. Postnatal epilepsy after EEG-confirmed neonatal seizures. Epilepsia 1991;32:69–76.

13. Almubarak S, Wong PK. Long-term clinical outcome of neonatal EEG findings. J Clin Neurophysiol 2011;28(2):185-9.

14. Ronen GM, Buckley D, Penney S, Streiner DL. Long-term prognosis in children with neonatal seizures: a population-based study. Neuro-logy 2007;69:1816–22.

15. Guillet R, Kwon J. Seizure recurrence and developmental disabilities after neonatal seizures: outcomes are unrelated to use of phenobar-bital prophylaxis. J Child Neurol 2007;22:389–95.

16. Biagioni E, Ferrari F, Boldrini A, Roversi MF, Cioni G. Prediction of outcome based on clinical seizure type in newborn infants. J Pediatr 2002;140:707–12.

17. Glass HC, Glidden D, Jeremy RJ, Barkovich AJ, Ferriero DM, Miller SP. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury. J Pediat. 2009;155:318–23.

18. Miller SP, Weiss J, Barnwell A, Ferriero DM, Latal-Hajnal B, Ferrer-Rogers A, et al. Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology 2002;52:542-8.

19. Garfinkle J, Shevell MI. Prognostic factors and development of a scoring system for outcome of neonatal seizures in term infants. EJP Neurology 2011;15:222-9.

20. Dudek FE, Ekstrand JJ, Staley KJ. Is neuronal death necessary for acquired epileptogenesis in the immature brain? Epilepsy Curr 2010;10:95-9.

21. Amiel-Tison C. Update of the Amiel-Tison neurologic assessment for the term neonate or at 40 weeks corrected age. Pediatr Neurol 2002;15:196–212.

22. Paro-Panjan D, Neubauer D, Kodric J, Bratanic B. Amiel-Tison Neurological assessment at term age clinical application, correlation with other methods, and outcome at 12 to15 months. Dev Med Child Neurol 2005 Jan;47(1):19-26.

23. Khan PL, Nunes ML, Gardas de Silva LF, Costa de Costa J. Predictive value of sequential electroencephalogram in neonates with seizures and its relation to neurological outcome. J Child Neurol 2008;23:144-50.

24. Shewmon DA. What is neonatal seizure? Problems in definition and quantification for investigative and clinical purposes. J Clin Neurophy-siol 1990;7:315-68.

25. Paro-Panjan D, Neubauer D, Kodric J, Bratanic B. Electroclinical correlation in neonatal seizures. Eur J Paediatr Neurol 1998;2:117-25.

26. Aicardi J, Goutrieres F. Encephalopathie myoclonique neonatal. Rev Electroencephalogr Neurophysiol Clin 1978;8:99-101.

27. Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics 2008;122(1):65-74.