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DOI: 10.1055/s-0040-1702943
Neonatal Seizures: Diagnosis, Etiologies, and Management
Publication History
Publication Date:
06 March 2020 (online)
Abstract
Neonates are exquisitely susceptible to seizures due to several physiologic factors and combination of risks that are uniquely associated with gestation, delivery, and the immediate postnatal period. Neonatal seizures can be challenging to identify; therefore, it is imperative that clinicians have a high degree of suspicion for seizures based on the clinical history or the presence of encephalopathy with or without paroxysmal abnormal movements. Acute symptomatic neonatal seizures are due to an acute brain injury, whereas neonatal-onset epilepsy may be related to underlying structural, metabolic, or genetic disorders. Though initial, acute treatment is similar, long-term treatment and prognosis varies greatly based on underlying seizure etiology. Early identification and treatment are likely important for long-term outcomes in acute symptomatic seizures, though additional studies are needed to understand optimal seizure control metrics and the ideal duration of treatment. Advances in genetic medicine are increasingly expanding our understanding of neonatal-onset epilepsies and will continue to open doors for personalized medicine to optimize outcomes in this fragile population.
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References
- 1 Vasudevan C, Levene M. Epidemiology and aetiology of neonatal seizures. Semin Fetal Neonatal Med 2013; 18 (04) 185-191
- 2 Shellhaas RA, Wusthoff CJ, Tsuchida TN. , et al; Neonatal Seizure Registry. Profile of neonatal epilepsies: characteristics of a prospective US cohort. Neurology 2017; 89 (09) 893-899
- 3 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 Pediatr 2009; 155 (03) 318-323
- 4 Uria-Avellanal C, Marlow N, Rennie JM. Outcome following neonatal seizures. Semin Fetal Neonatal Med 2013; 18 (04) 224-232
- 5 McCabe BK, Silveira DC, Cilio MR. , et al. Reduced neurogenesis after neonatal seizures. J Neurosci 2001; 21 (06) 2094-2103
- 6 Stafstrom CE, Thompson JL, Holmes GL. Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures. Brain Res Dev Brain Res 1992; 65 (02) 227-236
- 7 Dzhala VI, Talos DM, Sdrulla DA. , et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med 2005; 11 (11) 1205-1213
- 8 Rivera C, Voipio J, Payne JA. , et al. The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 1999; 397 (6716): 251-255
- 9 Carrasco M, Stafstrom CE. How early can a seizure happen? Pathophysiological considerations of extremely premature infant brain development. Dev Neurosci 2018; 40 (5–6): 417-436
- 10 Nardou R, Ferrari DC, Ben-Ari Y. Mechanisms and effects of seizures in the immature brain. Semin Fetal Neonatal Med 2013; 18 (04) 175-184
- 11 Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994; 12 (03) 529-540
- 12 Miller SM, Goasdoue K, Björkman ST. Neonatal seizures and disruption to neurotransmitter systems. Neural Regen Res 2017; 12 (02) 216-217
- 13 Glass HC. Neonatal seizures: advances in mechanisms and management. Clin Perinatol 2014; 41 (01) 177-190
- 14 Boylan GB, Kharoshankaya L, Wusthoff CJ. Seizures and hypothermia: importance of electroencephalographic monitoring and considerations for treatment. Semin Fetal Neonatal Med 2015; 20 (02) 103-108
- 15 Shah DK, Wusthoff CJ, Clarke P. , et al. Electrographic seizures are associated with brain injury in newborns undergoing therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed 2014; 99 (03) F219-F224
- 16 Wirrell EC, Armstrong EA, Osman LD, Yager JY. Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage. Pediatr Res 2001; 50 (04) 445-454
- 17 Glass HC, Wusthoff CJ, Shellhaas RA. , et al. Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology 2014; 82 (14) 1239-1244
- 18 Kirton A, Armstrong-Wells J, Chang T. , et al; International Pediatric Stroke Study Investigators. Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study. Pediatrics 2011; 128 (06) e1402-e1410
- 19 Soul JS. Acute symptomatic seizures in term neonates: etiologies and treatments. Semin Fetal Neonatal Med 2018; 23 (03) 183-190
- 20 Bruno CJ, Beslow LA, Witmer CM. , et al. Haemorrhagic stroke in term and late preterm neonates. Arch Dis Child Fetal Neonatal Ed 2014; 99 (01) F48-F53
- 21 Glass HC, Shellhaas RA, Tsuchida TN. , et al; Neonatal Seizure Registry study group. Seizures in preterm neonates: a multicenter observational cohort study. Pediatr Neurol 2017; 72: 19-24
- 22 Wong DST, Poskitt KJ, Chau V. , et al. Brain injury patterns in hypoglycemia in neonatal encephalopathy. AJNR Am J Neuroradiol 2013; 34 (07) 1456-1461
- 23 Cornet MC, Sands TT, Cilio MR. Neonatal epilepsies: clinical management. Semin Fetal Neonatal Med 2018; 23 (03) 204-212
- 24 Pearl PL. Epilepsy syndromes in childhood. Continuum (Minneap Minn) 2018; 24 ( 1, Child Neurology) 186-209
- 25 North KN, Storey GNB, Henderson-Smart DJ. Fifth day fits in the newborn. Aust Paediatr J 1989; 25 (05) 284-287
- 26 Yamamoto H, Okumura A, Fukuda M. Epilepsies and epileptic syndromes starting in the neonatal period. Brain Dev 2011; 33 (03) 213-220
- 27 Hart AR, Pilling EL, Alix JJP. Neonatal seizures-part 2: aetiology of acute symptomatic seizures, treatments and the neonatal epilepsy syndromes. Arch Dis Child Educ Pract Ed 2015; 100 (05) 226-232
- 28 Plouin P, Kaminska A. Neonatal seizures. In: Dulac O, Lassonde M, Sarnat H. , eds. Handbook of Clinical Neurology. Vol 111. (3rd series). Amsterdam: Elsevier B.V.; 2013: 467-476
- 29 Grinton BE, Heron SE, Pelekanos JT. , et al. Familial neonatal seizures in 36 families: clinical and genetic features correlate with outcome. Epilepsia 2015; 56 (07) 1071-1080
- 30 Axeen EJT, Olson HE. Neonatal epilepsy genetics. Semin Fetal Neonatal Med 2018; 23 (03) 197-203
- 31 Allen NM, Mannion M, Conroy J. , et al. The variable phenotypes of KCNQ-related epilepsy. Epilepsia 2014; 55 (09) e99-e105
- 32 Beal JC, Cherian K, Moshe SL. Early-onset epileptic encephalopathies: Ohtahara syndrome and early myoclonic encephalopathy. Pediatr Neurol 2012; 47 (05) 317-323
- 33 Pearl PL. Amenable treatable severe pediatric epilepsies. Semin Pediatr Neurol 2016; 23 (02) 158-166
- 34 Johannesen K, Marini C, Pfeffer S. , et al. Phenotypic spectrum of GABRA1: from generalized epilepsies to severe epileptic encephalopathies. Neurology 2016; 87 (11) 1140-1151
- 35 Ohtahara S, Yamatogi Y. Epileptic encephalopathies in early infancy with suppression-burst. J Clin Neurophysiol 2003; 20 (06) 398-407
- 36 Barcia G, Fleming MR, Deligniere A. , et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012; 44 (11) 1255-1259
- 37 McTague A, Appleton R, Avula S. , et al. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum. Brain 2013; 136 (Pt 5): 1578-1591
- 38 Poduri A, Chopra SS, Neilan EG. , et al. Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy. Epilepsia 2012; 53 (08) e146-e150
- 39 Mikati MA, Jiang YH, Carboni M. , et al. Quinidine in the treatment of KCNT1-positive epilepsies. Ann Neurol 2015; 78 (06) 995-999
- 40 Ficicioglu C, Bearden D. Isolated neonatal seizures: when to suspect inborn errors of metabolism. Pediatr Neurol 2011; 45 (05) 283-291
- 41 Mills PB, Footitt EJ, Mills KA. , et al. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 2010; 133 (Pt 7): 2148-2159
- 42 Van Hove J, Coughlin II C, Scharer G. Glycine Encephalopathy. 2002 [Updated July 11, 2013]. In: Adam MP, Ardinger HH, Pagon RA. , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1357/ . Accessed April 5, 2019
- 43 Suzuki Y, Kure S, Oota M, Hino H, Fukuda M. Nonketotic hyperglycinemia: proposal of a diagnostic and treatment strategy. Pediatr Neurol 2010; 43 (03) 221-224
- 44 Schwahn BC, Van Spronsen FJ, Belaidi AA. , et al. Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study. Lancet 2015; 386 (10007): 1955-1963
- 45 Almannai M, El-Hattab AW. Inborn errors of metabolism with seizures: defects of glycine and serine metabolism and cofactor-related disorders. Pediatr Clin North Am 2018; 65 (02) 279-299
- 46 Clancy RR, Legido A, Lewis D. Occult neonatal seizures. Epilepsia 1988; 29 (03) 256-261
- 47 Scher MS, Alvin J, Gaus L, Minnigh B, Painter MJ. Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use. Pediatr Neurol 2003; 28 (04) 277-280
- 48 Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia 2009; 50 (09) 2097-2101
- 49 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; 93 (03) F187-F191
- 50 Shellhaas RA, Chang T, Tsuchida T. , et al. The American Clinical Neurophysiology Society's guideline on continuous electroencephalography monitoring in neonates. J Clin Neurophysiol 2011; 28 (06) 611-617
- 51 Shellhaas RA. Continuous long-term electroencephalography: the gold standard for neonatal seizure diagnosis. Semin Fetal Neonatal Med 2015; 20 (03) 149-153
- 52 Hellström-Westas L, Boylan G, Ågren J. Systematic review of neonatal seizure management strategies provides guidance on anti-epileptic treatment. Acta Paediatr 2015; 104 (02) 123-129
- 53 Glass HC, Shellhaas RA, Wusthoff CJ. , et al; Neonatal Seizure Registry Study Group. Contemporary profile of seizures in neonates: a prospective cohort study. J Pediatr 2016; 174: 98-103.e1
- 54 Painter MJ, Scher MS, Stein AD. , et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med 1999; 341 (07) 485-489
- 55 Glass HC, Soul JS, Chu CJ. , et al; Neonatal Seizure Registry Study Group. Response to antiseizure medications in neonates with acute symptomatic seizures. Epilepsia 2019; 60 (03) e20-e24
- 56 Dwivedi D, Lin N, Venkatesan C, Kline-Fath B, Holland K, Schapiro M. Clinical, neuroimaging, and electrographic predictors of phenobarbital failure in newborns with hypoxic ischemic encephalopathy and seizures. J Child Neurol 2019; 34 (08) 458-463
- 57 Merhar SL, Schibler KR, Sherwin CM. , et al. Pharmacokinetics of levetiracetam in neonates with seizures. J Pediatr 2011; 159 (01) 152-154.e3
- 58 Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci 2003; 993: 103-114 , discussion 123–124
- 59 Chhun S, Troude P, Villeneuve N. , et al. A prospective open-labeled trial with levetiracetam in pediatric epilepsy syndromes: continuous spikes and waves during sleep is definitely a target. Seizure 2011; 20 (04) 320-325
- 60 Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res 2012; 72 (01) 43-49
- 61 Rao LM, Hussain SA, Zaki T. , et al. A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic-ischemic encephalopathy. Epilepsy Behav 2018; 88: 212-217
- 62 Haas RH, Nespeca M, Rismanchi N. , et al. Efficacy of intravenous levetiracetam in neonatal seizures: NEOLEV2 - a multicenter, randomized, blinded, controlled phase IIb trial of the optimal dose, efficacy and safety of levetiracetam compared with phenobarbital in the first-line treatment of neonatal seizures. Abstract presented at: Pediatric Academic Societies Meeting, May 2, 2019 ; Baltimore, MD
- 63 Weeke LC, Schalkwijk S, Toet MC, van Rooij LG, de Vries LS, van den Broek MP. Lidocaine-associated cardiac events in newborns with seizures: incidence, symptoms and contributing factors. Neonatology 2015; 108 (02) 130-136
- 64 Low E, Boylan GB, Mathieson SR. , et al. Cooling and seizure burden in term neonates: an observational study. Arch Dis Child Fetal Neonatal Ed 2012; 97 (04) F267-F272
- 65 Lynch NE, Stevenson NJ, Livingstone V, Murphy BP, Rennie JM, Boylan GB. The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy. Epilepsia 2012; 53 (03) 549-557
- 66 Shellhaas RA, Chang T, Wusthoff CJ. , et al; Neonatal Seizure Registry Study Group. Treatment duration after acute symptomatic seizures in neonates: a multicenter cohort study. J Pediatr 2017; 181: 298-301.e1
- 67 Grinspan ZM, Shellhaas RA, Coryell J. , et al. Comparative effectiveness of levetiracetam vs phenobarbital for infantile epilepsy. JAMA Pediatr 2018; 172 (04) 352-360
- 68 van Rooij LGM, van den Broek MPH, Rademaker CMA, de Vries LS. Clinical management of seizures in newborns: diagnosis and treatment. Paediatr Drugs 2013; 15 (01) 9-18
- 69 Sands TT, Balestri M, Bellini G. , et al. Rapid and safe response to low-dose carbamazepine in neonatal epilepsy. Epilepsia 2016; 57 (12) 2019-2030
- 70 El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med 2017; 22 (05) 321-327
- 71 O'Leary H, Bernard PB, Castano AM, Benke TA. Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure. Neurobiol Dis 2016; 87: 134-144
- 72 Lippman-Bell JJ, Zhou C, Sun H, Feske JS, Jensen FE. Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity. Mol Cell Neurosci 2016; 76: 11-20
- 73 Casanova JR, Nishimura M, Swann JW. The effects of early-life seizures on hippocampal dendrite development and later-life learning and memory. Brain Res Bull 2014; 103: 39-48
- 74 Holmes GL, Gairsa JL, Chevassus-Au-Louis N, Ben-Ari Y. Consequences of neonatal seizures in the rat: morphological and behavioral effects. Ann Neurol 1998; 44 (06) 845-857
- 75 Holmes GL. The long-term effects of neonatal seizures. Clin Perinatol 2009; 36 (04) 901-914 , vii–viii
- 76 McBride MC, Laroia N, Guillet R. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology 2000; 55 (04) 506-513
- 77 Perucca P, Perucca E. Identifying mutations in epilepsy genes: Impact on treatment selection. Epilepsy Res 2019; 152: 18-30