Challenges in diagnosis and treatment refractory neonatal seizures in immature brain

Authors

  • Ilija G. Palic Neonatal Intensive Care Unit, Institute of Neonatology, Belgrade, Serbia https://orcid.org/0000-0002-9284-3173
  • Olgica P. Rakic Department for Admission and Specialized Transport of Neonates, Institute of Neonatology, Belgrade, Serbia

DOI:

https://doi.org/10.18203/2320-6012.ijrms20252037

Keywords:

Anti-seizure medication, Electroencephalography, Neuromonitoring, Neonatal seizures, Preterm new-born

Abstract

Seizures are the most common clinical signs of neurologic dysfunction in neonates. The risk for seizures is inversely related to gestational age and birth weight. Several factors contribute to excessive excitation in the immature brain, such as depolarizing action of γ-aminobutyric acid, change of the subunit composition of the glutamate receptors and incomplete glial clearance of glutamate and potassium. Continuous EEG is the gold standard for diagnosing neonatal seizures. However, video EEG recording has several limitation, especially in preterm neonates. In recent years, amplitude-integrated EEG has been used to detect electrographic seizures. In accordance with the current recommendations, if neonatal seizures do not stop to phenobarbitone, levetiracetam or phenytoin may be used as a second-line anti-seizure medications, as well as midazolam or lidocaine. Midazolam is recommended in the treatment for refractory seizures in neonates requiring mechanical ventilation. In this report, we present a diagnostic and treatment dilemmas of refractory seizures in extremely preterm neonate.

Metrics

Metrics Loading ...

References

Spagnoli C, Pisani F. Acute symptomatic seizures in newborns: a narrative review. Acta epileptol. 2024;6:5. DOI: https://doi.org/10.1186/s42494-024-00151-w

Pisani F, Spagnoli C, Falsaperla R, Nagarajan L, Ramantani G. Seizures in the neonate: A review of etiologies and outcomes. Seizure. 2021;85:48-56. DOI: https://doi.org/10.1016/j.seizure.2020.12.023

Nardou R, Ferrari DC, Ben-Ari Y. Mechanisms and effects of seizures in the immature brain. Semin Fetal Neonatal Med. 2013;18(4):175-84. DOI: https://doi.org/10.1016/j.siny.2013.02.003

Carrasco M, Stafstrom CE. How early can a seizure happen? pathophysiological considerations of extremely premature infant brain development. Dev Neurosci. 2018;40(5-6):417-36. DOI: https://doi.org/10.1159/000497471

Rao LM, Marcuccilli CJ. Seizures in the Preterm Neonate. Neoreviews. 2017;18(1):52–9. DOI: https://doi.org/10.1542/neo.18-1-e52

Spagnoli C, Falsaperla R, Deolmi M, Corsello G, Pisani F. Symptomatic seizures in preterm newborns: a review on clinical features and prognosis. Ital J Pediatr. 2018;44(1):115. DOI: https://doi.org/10.1186/s13052-018-0573-y

Vučetić Tadić B, Kravljanac R, Sretenović V, Martić J, Vukomanović V. The features of neonatal seizures as predictors of drug-resistant epilepsy in children. Epilepsy Behav. 2020;106:107004. DOI: https://doi.org/10.1016/j.yebeh.2020.107004

Pressler RM, Cilio MR, Mizrahi EM, Moshé SL, Nunes ML, Plouin P, et al. The ILAE classification of seizures and the epilepsies: modification for seizures in the neonate. position paper by the ilea task force on neonatal seizures. Epilepsia. 2021;62(3):615-28. DOI: https://doi.org/10.1111/epi.16815

Ziobro J, Pilon B, Wusthoff CJ, Benedetti GM, Massey SL, Yozawitz E, et al. Neonatal seizures: new evidence, classification and guidelines. Epilepsy Curr. 2024:152. DOI: https://doi.org/10.1177/15357597241253382

Jacobs J, Spelbrink EM. Seizures in preterm infants. J Clin Neurophysiol. 2016;33(5):382-93. DOI: https://doi.org/10.1097/WNP.0000000000000310

Kim EH, Shin J, Lee BK. Neonatal seizures: diagnostic updates based on new definition and classification. Clin Exp Pediatr. 2022;65(8):387-97. DOI: https://doi.org/10.3345/cep.2021.01361

Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999;341(7):485-9. DOI: https://doi.org/10.1056/NEJM199908123410704

Pressler RM, Abend NS, Auvin S, Boylan G, Brigo F, Cilio MR, et al. Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-special report from the ILAE task force on neonatal seizures. Epilepsia. 2023;64(10):2550-70. DOI: https://doi.org/10.1111/epi.17745

Neubauer D, Soltirovska-Salamon A, Osredkar D, Paro-Panjan D. Management of refractory neonatal seizures. Res Rep Neonatol. 2014;4:17-29. DOI: https://doi.org/10.2147/RRN.S39714

Abiramalatha T, Thanigainathan S, Ramaswamy VV, Pressler R, Brigo F, Hartmann H. Antiseizure medications for neonates with seizures. Cochrane Database Syst Rev. 2022;2022(3):14967. DOI: https://doi.org/10.1002/14651858.CD014967

Zeller B, Giebe J. Pharmacologic Management of Neonatal Seizures. Neonatal Netw. 2015;34(4):239-44. DOI: https://doi.org/10.1891/0730-0832.34.4.239

Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur J Paediatr Neurol. 2011;15(1):1-7. DOI: https://doi.org/10.1016/j.ejpn.2010.10.003

Komur M, Okuyaz C, Celik Y, Resitoglu B, Polat A, Balci S, et al. Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats. Childs Nerv Syst. 2014;30(6):1001-9. DOI: https://doi.org/10.1007/s00381-014-2375-x

Talos DM, Chang M, Kosaras B, Fitzgerald E, Murphy A, Folkerth RD, et al. Antiepileptic effects of levetiracetam in a rodent neonatal seizure model. Pediatr Res. 2013;73(1):24-30. DOI: https://doi.org/10.1038/pr.2012.151

El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med. 2017;22(5):321-27. DOI: https://doi.org/10.1016/j.siny.2017.07.008

Pacifici GM. Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics. Curr Pediatr Rev. 2016;12(1):48-54. DOI: https://doi.org/10.2174/1573397111666151026223914

Agrawal A, Banergee A. A review on pharmacokinetics of levetiracetam in neonates. Curr Drug Metab. 2017;16;18(8):727-34. DOI: https://doi.org/10.2174/1389200218666170607100054

Tulloch JK, Carr RR, Ensom MH. A systematic review of the pharmacokinetics of antiepileptic drugs in neonates with refractory seizures. J Pediatr Pharmacol Ther. 2012;17(1):31-44. DOI: https://doi.org/10.5863/1551-6776-17.1.31

Pacifici GM. Clinical pharmacology of midazolam in neonates and children: effect of disease-a review. Int J Pediatr. 2014;2014:309342. DOI: https://doi.org/10.1155/2014/309342

Downloads

Published

2025-06-27

How to Cite

Palic, I. G., & Rakic, O. P. (2025). Challenges in diagnosis and treatment refractory neonatal seizures in immature brain. International Journal of Research in Medical Sciences, 13(7), 2993–2996. https://doi.org/10.18203/2320-6012.ijrms20252037

Issue

Section

Case Reports