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November 18, 2020
Accepted
January 2, 2022
Published
February 13, 2022
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Abstract
Neonatal seizures are the most common manifestation of neurological illness in the newborn, yet their accurate diagnosis and management remain challenging. This is particularly true in resource-limited settings. In this symposium, members of two International League Against Epilepsy (ILAE) task forces on classification, diagnosis and treatment of neonatal seizures presented a novel, evidence-based framework for the diagnosis and classification of neonatal seizures that integrates clinical signs and electroencephalographic findings to specify varying levels of diagnostic certainty. The wide spectrum of neonatal seizures are illustrated, as well as common management challenges, and practical evidence-based management strategies that can be tailored to a wide range of practice settings.
Keywords
infant
newborn
neonate
seizure
hypoxic-ischemic encephalopathy
electroencephalography
anticonvulsants
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
How to Cite
Sandoval Karamian, A., Pressler, R., Hahn, C., Hartmann, H., Wilmshurst, J., & Wusthoff, C. (2022). Neonatal Seizures: Practical Approaches to Classification, Diagnosis and Management. Journal of the International Child Neurology Association, 1(1). https://doi.org/10.17724/jicna.2022.218
References
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1. Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology. 1987 Dec;37(12):1837–44.
2. Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009 Sep;50(9):2097–101.
3. Boylan GB, Rennie JM, Chorley G, Pressler RM, Fox GF, Farrer K, et al. Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study. Neurology. 2004 Feb 10;62(3):486–8.
4. Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, et al. Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study. J Pediatr. 2016 Jul;174:98-103.e1.
5. Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004218.
6. Guidelines on Neonatal Seizures [Internet]. Geneva: World Health Organization; 2011 [cited 2019 Feb 27]. (WHO Guidelines Approved by the Guidelines Review Committee). Available from: http://www.ncbi.nlm.nih.gov/books/NBK304092/
7. Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, et al. Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial. Pediatrics. 2020 May 8;
8. Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005 Apr;46(4):470–2.
9. Tsuchida TN, Wusthoff CJ, Shellhaas RA, Abend NS, Hahn CD, Sullivan JE, et al. American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society critical care monitoring committee. J Clin Neurophysiol. 2013 Apr;30(2):161–73.
10. Nagarajan L, Palumbo L, Ghosh S. Brief electroencephalography rhythmic discharges (BERDs) in the neonate with seizures: their significance and prognostic implications. J Child Neurol. 2011 Dec;26(12):1529–33.
11. Oliveira AJ, Nunes ML, Haertel LM, Reis FM, da Costa JC. Duration of rhythmic EEG patterns in neonates: new evidence for clinical and prognostic significance of brief rhythmic discharges. Clin Neurophysiol. 2000 Sep;111(9):1646–53.
12. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015 Oct;56(10):1515–23.
13. Volpe J. Neonatal Seizures. N Engl J Med. 1973 Aug 23;289(8):413–6.
14. Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2008 May;93(3):F187-191.
15. Shellhaas RA, Clancy RR. Characterization of neonatal seizures by conventional EEG and single-channel EEG. Clin Neurophysiol. 2007 Oct;118(10):2156–61.
16. Shellhaas RA, Chang T, Tsuchida T, Scher MS, Riviello JJ, Abend NS, et al. The American Clinical Neurophysiology Society’s Guideline on Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol. 2011 Dec;28(6):611–7.
17. Glass HC, Wusthoff CJ, Shellhaas RA, Tsuchida TN, Bonifacio SL, Cordeiro M, et al. Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology. 2014 Apr 8;82(14):1239–44.
18. Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci. 2003 May;993:103–14; discussion 123-124.
19. Donovan MD, Griffin BT, Kharoshankaya L, Cryan JF, Boylan GB. Pharmacotherapy for Neonatal Seizures: Current Knowledge and Future Perspectives. Drugs. 2016 Apr;76(6):647–61.
20. McHugh DC, Lancaster S, Manganas LN. A Systematic Review of the Efficacy of Levetiracetam in Neonatal Seizures. Neuropediatrics. 2018;49(1):12–7.
21. 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 Aug 12;341(7):485–9.
22. Nash KB, Bonifacio SL, Glass HC, Sullivan JE, Barkovich AJ, Ferriero DM, et al. Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. Neurology. 2011 Feb 8;76(6):556–62.
23. Scher MS, Alvin J, Gaus L, Minnigh B, Painter MJ. Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use. Pediatr Neurol. 2003 Apr;28(4):277–80.
24. Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, et al. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 10;37(52):7596–609.
25. Hingray C, El-Hage W, Duncan R, Gigineishvili D, Kanemoto K, LaFrance WC, et al. Access to diagnostic and therapeutic facilities for psychogenic nonepileptic seizures: An international survey by the ILAE PNES Task Force. Epilepsia. 2018;59(1):203–14.
26. Enweronu-Laryea CC, Nsiah-Boateng E, Andoh HD, Frimpong-Barfi A, Asenso-Boadi FM, Aikins M. Evaluating services for perinatal asphyxia and low birth weight at two hospitals in Ghana: a micro-costing analysis. Ghana Med J. 2019 Dec;53(4):256–66.
27. Co JPT, Elia M, Engel J, Guerrini R, Mizrahi EM, Moshé SL, et al. Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries. Epilepsia. 2007 Jun;48(6):1158–64.
28. Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil S. Cooling in a low-resource environment: lost in translation. Semin Fetal Neonatal Med. 2015 Apr;20(2):72–9.
29. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One. 2013;8(3):e58834.
References
1. Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology. 1987 Dec;37(12):1837–44.
2. Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009 Sep;50(9):2097–101.
3. Boylan GB, Rennie JM, Chorley G, Pressler RM, Fox GF, Farrer K, et al. Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study. Neurology. 2004 Feb 10;62(3):486–8.
4. Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, et al. Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study. J Pediatr. 2016 Jul;174:98-103.e1.
5. Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004218.
6. Guidelines on Neonatal Seizures [Internet]. Geneva: World Health Organization; 2011 [cited 2019 Feb 27]. (WHO Guidelines Approved by the Guidelines Review Committee). Available from: http://www.ncbi.nlm.nih.gov/books/NBK304092/
7. Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, et al. Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial. Pediatrics. 2020 May 8;
8. Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005 Apr;46(4):470–2.
9. Tsuchida TN, Wusthoff CJ, Shellhaas RA, Abend NS, Hahn CD, Sullivan JE, et al. American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society critical care monitoring committee. J Clin Neurophysiol. 2013 Apr;30(2):161–73.
10. Nagarajan L, Palumbo L, Ghosh S. Brief electroencephalography rhythmic discharges (BERDs) in the neonate with seizures: their significance and prognostic implications. J Child Neurol. 2011 Dec;26(12):1529–33.
11. Oliveira AJ, Nunes ML, Haertel LM, Reis FM, da Costa JC. Duration of rhythmic EEG patterns in neonates: new evidence for clinical and prognostic significance of brief rhythmic discharges. Clin Neurophysiol. 2000 Sep;111(9):1646–53.
12. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015 Oct;56(10):1515–23.
13. Volpe J. Neonatal Seizures. N Engl J Med. 1973 Aug 23;289(8):413–6.
14. Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2008 May;93(3):F187-191.
15. Shellhaas RA, Clancy RR. Characterization of neonatal seizures by conventional EEG and single-channel EEG. Clin Neurophysiol. 2007 Oct;118(10):2156–61.
16. Shellhaas RA, Chang T, Tsuchida T, Scher MS, Riviello JJ, Abend NS, et al. The American Clinical Neurophysiology Society’s Guideline on Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol. 2011 Dec;28(6):611–7.
17. Glass HC, Wusthoff CJ, Shellhaas RA, Tsuchida TN, Bonifacio SL, Cordeiro M, et al. Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology. 2014 Apr 8;82(14):1239–44.
18. Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci. 2003 May;993:103–14; discussion 123-124.
19. Donovan MD, Griffin BT, Kharoshankaya L, Cryan JF, Boylan GB. Pharmacotherapy for Neonatal Seizures: Current Knowledge and Future Perspectives. Drugs. 2016 Apr;76(6):647–61.
20. McHugh DC, Lancaster S, Manganas LN. A Systematic Review of the Efficacy of Levetiracetam in Neonatal Seizures. Neuropediatrics. 2018;49(1):12–7.
21. 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 Aug 12;341(7):485–9.
22. Nash KB, Bonifacio SL, Glass HC, Sullivan JE, Barkovich AJ, Ferriero DM, et al. Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. Neurology. 2011 Feb 8;76(6):556–62.
23. Scher MS, Alvin J, Gaus L, Minnigh B, Painter MJ. Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use. Pediatr Neurol. 2003 Apr;28(4):277–80.
24. Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, et al. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 10;37(52):7596–609.
25. Hingray C, El-Hage W, Duncan R, Gigineishvili D, Kanemoto K, LaFrance WC, et al. Access to diagnostic and therapeutic facilities for psychogenic nonepileptic seizures: An international survey by the ILAE PNES Task Force. Epilepsia. 2018;59(1):203–14.
26. Enweronu-Laryea CC, Nsiah-Boateng E, Andoh HD, Frimpong-Barfi A, Asenso-Boadi FM, Aikins M. Evaluating services for perinatal asphyxia and low birth weight at two hospitals in Ghana: a micro-costing analysis. Ghana Med J. 2019 Dec;53(4):256–66.
27. Co JPT, Elia M, Engel J, Guerrini R, Mizrahi EM, Moshé SL, et al. Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries. Epilepsia. 2007 Jun;48(6):1158–64.
28. Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil S. Cooling in a low-resource environment: lost in translation. Semin Fetal Neonatal Med. 2015 Apr;20(2):72–9.
29. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One. 2013;8(3):e58834.
2. Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009 Sep;50(9):2097–101.
3. Boylan GB, Rennie JM, Chorley G, Pressler RM, Fox GF, Farrer K, et al. Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study. Neurology. 2004 Feb 10;62(3):486–8.
4. Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, et al. Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study. J Pediatr. 2016 Jul;174:98-103.e1.
5. Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004218.
6. Guidelines on Neonatal Seizures [Internet]. Geneva: World Health Organization; 2011 [cited 2019 Feb 27]. (WHO Guidelines Approved by the Guidelines Review Committee). Available from: http://www.ncbi.nlm.nih.gov/books/NBK304092/
7. Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, et al. Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial. Pediatrics. 2020 May 8;
8. Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005 Apr;46(4):470–2.
9. Tsuchida TN, Wusthoff CJ, Shellhaas RA, Abend NS, Hahn CD, Sullivan JE, et al. American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society critical care monitoring committee. J Clin Neurophysiol. 2013 Apr;30(2):161–73.
10. Nagarajan L, Palumbo L, Ghosh S. Brief electroencephalography rhythmic discharges (BERDs) in the neonate with seizures: their significance and prognostic implications. J Child Neurol. 2011 Dec;26(12):1529–33.
11. Oliveira AJ, Nunes ML, Haertel LM, Reis FM, da Costa JC. Duration of rhythmic EEG patterns in neonates: new evidence for clinical and prognostic significance of brief rhythmic discharges. Clin Neurophysiol. 2000 Sep;111(9):1646–53.
12. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015 Oct;56(10):1515–23.
13. Volpe J. Neonatal Seizures. N Engl J Med. 1973 Aug 23;289(8):413–6.
14. Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2008 May;93(3):F187-191.
15. Shellhaas RA, Clancy RR. Characterization of neonatal seizures by conventional EEG and single-channel EEG. Clin Neurophysiol. 2007 Oct;118(10):2156–61.
16. Shellhaas RA, Chang T, Tsuchida T, Scher MS, Riviello JJ, Abend NS, et al. The American Clinical Neurophysiology Society’s Guideline on Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol. 2011 Dec;28(6):611–7.
17. Glass HC, Wusthoff CJ, Shellhaas RA, Tsuchida TN, Bonifacio SL, Cordeiro M, et al. Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology. 2014 Apr 8;82(14):1239–44.
18. Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci. 2003 May;993:103–14; discussion 123-124.
19. Donovan MD, Griffin BT, Kharoshankaya L, Cryan JF, Boylan GB. Pharmacotherapy for Neonatal Seizures: Current Knowledge and Future Perspectives. Drugs. 2016 Apr;76(6):647–61.
20. McHugh DC, Lancaster S, Manganas LN. A Systematic Review of the Efficacy of Levetiracetam in Neonatal Seizures. Neuropediatrics. 2018;49(1):12–7.
21. 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 Aug 12;341(7):485–9.
22. Nash KB, Bonifacio SL, Glass HC, Sullivan JE, Barkovich AJ, Ferriero DM, et al. Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. Neurology. 2011 Feb 8;76(6):556–62.
23. Scher MS, Alvin J, Gaus L, Minnigh B, Painter MJ. Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use. Pediatr Neurol. 2003 Apr;28(4):277–80.
24. Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, et al. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 10;37(52):7596–609.
25. Hingray C, El-Hage W, Duncan R, Gigineishvili D, Kanemoto K, LaFrance WC, et al. Access to diagnostic and therapeutic facilities for psychogenic nonepileptic seizures: An international survey by the ILAE PNES Task Force. Epilepsia. 2018;59(1):203–14.
26. Enweronu-Laryea CC, Nsiah-Boateng E, Andoh HD, Frimpong-Barfi A, Asenso-Boadi FM, Aikins M. Evaluating services for perinatal asphyxia and low birth weight at two hospitals in Ghana: a micro-costing analysis. Ghana Med J. 2019 Dec;53(4):256–66.
27. Co JPT, Elia M, Engel J, Guerrini R, Mizrahi EM, Moshé SL, et al. Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries. Epilepsia. 2007 Jun;48(6):1158–64.
28. Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil S. Cooling in a low-resource environment: lost in translation. Semin Fetal Neonatal Med. 2015 Apr;20(2):72–9.
29. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One. 2013;8(3):e58834.