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Incidence and predictors of epilepsy in children with congenital heart disease

Part of: Surgery

Published online by Cambridge University Press:  09 August 2021

Carlos Castillo-Pinto*
Affiliation:
Department of Neurology, Children’s National Hospital, Washington, DC, USA
Jessica L. Carpenter
Affiliation:
Department of Neurology, Children’s National Hospital, Washington, DC, USA
Mary T. Donofrio
Affiliation:
Division of Pediatric Cardiology, Children’s National Hospital, Washington, DC, USA
Anqing Zhang
Affiliation:
Division of Biostatistics and Study Methodology, Children’s National Hospital, Washington, DC, USA
Gil Wernovsky
Affiliation:
Division of Pediatric Cardiology, Children’s National Hospital, Washington, DC, USA Division of Cardiac Critical Care, Children’s National Hospital, Washington, DC, USA
Pranava Sinha
Affiliation:
Division of Cardiovascular Surgery, Children’s National Hospital, Washington, DC, USA
Dana Harrar
Affiliation:
Department of Neurology, Children’s National Hospital, Washington, DC, USA
*
Author for correspondence: C. Castillo-Pinto, MD, Department of Neurology, Division of Clinical Neurophysiology, Nicklaus Children’s Hospital, 3100 SW 62nd Ave, Miami, FL33155, USA. Tel: +1 7866242891; Fax: +1 3056696531. E-mail: [email protected]

Abstract

Objective:

Children with CHD may be at increased risk for epilepsy. While the incidence of perioperative seizures after surgical repair of CHD has been well-described, the incidence of epilepsy is less well-defined. We aim to determine the incidence and predictors of epilepsy in patients with CHD.

Methods:

Retrospective cohort study of patients with CHD who underwent cardiopulmonary bypass at <2 years of age between January, 2012 and December, 2013 and had at least 2 years of follow-up. Clinical variables were extracted from a cardiac surgery database and hospital records. Seizures were defined as acute if they occurred within 7 days after an inciting event. Epilepsy was defined based on the International League Against Epilepsy criteria.

Results:

Two-hundred and twenty-one patients were identified, 157 of whom were included in our analysis. Five patients (3.2%) developed epilepsy. Acute seizures occurred in 12 (7.7%) patients, only one of whom developed epilepsy. Predictors of epilepsy included an earlier gestational age, a lower birth weight, a greater number of cardiac surgeries, a need for extracorporeal membrane oxygenation or a left ventricular assist device, arterial ischaemic stroke, and a longer hospital length of stay.

Conclusions:

Epilepsy in children with CHD is rare. The mechanism of epileptogenesis in these patients may be the result of a complex interaction of patient-specific factors, some of which may be present even before surgery. Larger long-term follow-up studies are needed to identify risk factors associated with epilepsy in these patients.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Hoffman, JI, Kaplan, S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39: 18901900.10.1016/S0735-1097(02)01886-7CrossRefGoogle ScholarPubMed
Marino, BS, Lipkin, PH, Newburger, JW, et al. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 2012; 126: 11431172.10.1161/CIR.0b013e318265ee8aCrossRefGoogle ScholarPubMed
Clancy, RR, McGaurn, SA, Wernovsky, G, et al. Risk of seizures in survivors of newborn heart surgery using deep hypothermic circulatory arrest. Pediatrics 2003; 111: 592601.10.1542/peds.111.3.592CrossRefGoogle ScholarPubMed
Clancy, RR, Sharif, U, Ichord, R, et al. Electrographic neonatal seizures after infant heart surgery. Epilepsia 2005; 46: 8490.10.1111/j.0013-9580.2005.22504.xCrossRefGoogle ScholarPubMed
Gaynor, JW, Nicolson, SC, Jarvik, GP, et al. Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures. J Thorac Cardiovasc Surg 2005; 130: 12781286.10.1016/j.jtcvs.2005.02.065CrossRefGoogle ScholarPubMed
Ghosh, S, Philip, J, Patel, N, et al. Risk factors for seizures and epilepsy in children with congenital heart disease. J Child Neurol 2020; 35: 442447.10.1177/0883073820904912CrossRefGoogle ScholarPubMed
Gunn, JK, Beca, J, Hunt, RW, Olischar, M, Shekerdemian, LS. Perioperative amplitude-integrated EEG and neurodevelopment in infants with congenital heart disease. Intensive Care Med 2012; 38: 15391547.10.1007/s00134-012-2608-yCrossRefGoogle ScholarPubMed
Helmers, S, Wypij, D, Constantinou, J, et al. Perioperative electroencephalographic seizures in infants undergoing repair of complex congenital cardiac defects. Electroencephalogr Clin Neurophysiol 1997; 102: 2736.10.1016/S0013-4694(96)95079-8CrossRefGoogle ScholarPubMed
Karl, TR, Hall, S, Ford, G, et al. Arterial switch with full-flow cardiopulmonary bypass and limited circulatory arrest: neurodevelopmental outcome. J Thorac Cardiovasc Surg 2004; 127: 213222.10.1016/j.jtcvs.2003.06.001CrossRefGoogle ScholarPubMed
Desnous, B, Lenoir, M, Doussau, A, et al. Epilepsy and seizures in children with congenital heart disease: a prospective study. Seizure 2019; 64: 5053.10.1016/j.seizure.2018.11.011CrossRefGoogle ScholarPubMed
Wang, C, Weng, W, Chang, L, et al. Increased prevalence of inattention-related symptoms in a large cohort of patients with congenital heart disease. Eur Child Adolesc Psychiatry 2021; 30: 647655.10.1007/s00787-020-01547-yCrossRefGoogle Scholar
Hansen, E, Poole, TA, Nguyen, V, et al. Prevalence of ADHD symptoms in patients with congenital heart disease. Pediatr Int 2012; 54: 838843.10.1111/j.1442-200X.2012.03711.xCrossRefGoogle ScholarPubMed
Rappaport, LA, Wypij, D, Bellinger, DC, et al. Relation of seizures after cardiac surgery in early infancy to neurodevelopmental outcome. Circulation 1998; 97: 773779.10.1161/01.CIR.97.8.773CrossRefGoogle ScholarPubMed
Sigmon, ER, Kelleman, M, Susi, A, Nylund, CM, Oster, ME. Congenital heart disease and autism: a case-control study. Pediatrics 2019; 144: e20184114.10.1542/peds.2018-4114CrossRefGoogle Scholar
Leisner, MZ, Madsen, NL, Ostergaard, JR, Woo, JG, Marino, BS, Olsen, MS. Congenital heart defects and risk of epilepsy: a population-based cohort study. Circulation 2016; 134: 16891691.10.1161/CIRCULATIONAHA.116.024538CrossRefGoogle ScholarPubMed
Massin, MM, Astadicko, I, Dessy, H. Noncardiac comorbidities of congenital heart disease in children. Acta paediatr 2007; 96: 753755.10.1111/j.1651-2227.2007.00275.xCrossRefGoogle ScholarPubMed
Fisher, RS, Acevedo, C, Arzimanoglou, A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55: 475482.10.1111/epi.12550CrossRefGoogle ScholarPubMed
Jacobs, ML, Mayer, JE Jr. Congenital heart surgery nomenclature and database project: single ventricle. Ann Thorac Surg 2000; 69: 197204.10.1016/S0003-4975(99)01245-XCrossRefGoogle ScholarPubMed
O'Brien, SM, Clarke, DR, Jacobs, JP, et al. An empirically based tool for analyzing mortality associated with congenital heart surgery. J Thorac Cardiovasc Surg 2009; 138: 11391153.10.1016/j.jtcvs.2009.03.071CrossRefGoogle ScholarPubMed
Chong, DJ, Hirsch, LJ. Which EEG patterns warrant treatment in the critically ill? reviewing the evidence for treatment of periodic epileptiform discharges and related patterns. J Clin Neurophysiol 2005; 22: 7991.10.1097/01.WNP.0000158699.78529.AFCrossRefGoogle ScholarPubMed
Payne, ET, Zhao, XY, Frndova, H, et al. Seizure burden is independently associated with short term outcome in critically ill children. Brain 2014; 137: 14291438.10.1093/brain/awu042CrossRefGoogle ScholarPubMed
Topjian, AA, Gutierrez-Colina, AM, Sanchez, SM, et al. Electrographic status epilepticus is associated with mortality and worse short-term outcome in critically ill children. Crit Care Med 2013; 41: 215223.10.1097/CCM.0b013e3182668035CrossRefGoogle ScholarPubMed
Abend, NS, Arndt, DH, Carpenter, JL, et al. Electrographic seizures in pediatric ICU patients: cohort study of risk factors and mortality. Neurology 2013; 81: 383391.10.1212/WNL.0b013e31829c5cfeCrossRefGoogle ScholarPubMed
Pisani, F, Cerminara, C, Fusco, C, Sisti, L. Neonatal status epilepticus vs recurrent neonatal seizures: clinical findings and outcome. Neurology 2007; 69: 21772185.10.1212/01.wnl.0000295674.34193.9eCrossRefGoogle ScholarPubMed
Billinghurst, LL, Beslow, LA, Abend, NS, et al. Incidence and predictors of epilepsy after pediatric arterial ischemic stroke. Neurology 2017; 88: 630637.10.1212/WNL.0000000000003603CrossRefGoogle ScholarPubMed
Beghi, E, Carpio, A, Forsgren, L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia 2010; 51: 671675.10.1111/j.1528-1167.2009.02285.xCrossRefGoogle ScholarPubMed
Glass, HC, Hong, KJ, Rogers, EE, et al. Risk factors for epilepsy in children with neonatal encephalopathy. Pediatr Res 2011; 70: 535540.10.1203/PDR.0b013e31822f24c7CrossRefGoogle ScholarPubMed
Harris, PA, Taylor, R, Thielke, R, Payne, J, Gonzalez, N, Conde, JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377381.10.1016/j.jbi.2008.08.010CrossRefGoogle ScholarPubMed
Billett, J, Cowie, MR, Gatzoulis, MA, Vonder Muhll, IF, Majeed, A. Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional, population-based study with case-control analysis. Heart 2008; 94: 11941199.10.1136/hrt.2007.122671CrossRefGoogle ScholarPubMed
Newburger, JW, Jonas, RA, Wernovsky, G, et al. A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med 1993; 329: 10571064.10.1056/NEJM199310073291501CrossRefGoogle ScholarPubMed
Naim, MY, Gaynor, JW, Chen, J, et al. Subclinical seizures identified by postoperative electroencephalographic monitoring are common after neonatal cardiac surgery. J Thorac Cardiovasc Surg 2015; 150: 169180.10.1016/j.jtcvs.2015.03.045CrossRefGoogle ScholarPubMed
Frey, LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia 2003; 44: 1117.10.1046/j.1528-1157.44.s10.4.xCrossRefGoogle ScholarPubMed
Beslow, LA, Abend, NS, Gindville, MC, et al. Pediatric intracerebral hemorrhage: acute symptomatic seizures and epilepsy. JAMA Neurol 2013; 70: 448454.10.1001/jamaneurol.2013.1033CrossRefGoogle ScholarPubMed
Zhen, J, Wang, W, Zhou, J, et al. Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced seizures and associated hippocampal neurodegeneration. Brain Res 2014; 1563: 122130.10.1016/j.brainres.2014.03.032CrossRefGoogle ScholarPubMed
Xie, Y, Qin, S, Zhang, R, et al. The effects of high-altitude environment on brain function in a seizure model of young-aged rats. Front Pediatr 2020; 8: 561.10.3389/fped.2020.00561CrossRefGoogle Scholar
Bellinger, DC, Jonas, RA, Rappaport, LA, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 1995; 332: 549555.10.1056/NEJM199503023320901CrossRefGoogle ScholarPubMed
Xiong, T, Gonzalez, F, Mu, D. An overview of risk factors for poor neurodevelopmental outcome associated with prematurity. World J Pediatr 2012; 8: 293300.10.1007/s12519-012-0372-2CrossRefGoogle ScholarPubMed
Clancy, RR, McGaurn, SA, Wernovsky, G, et al. Preoperative risk-of-death prediction model in heart surgery with deep hypothermic circulatory arrest in the neonate. J Thorac Cardiovasc Surg 2000; 119: 347357.10.1016/S0022-5223(00)70191-7CrossRefGoogle ScholarPubMed
Kornilov, IA, Sinelnikov, YS, Soinov, IA, et al. Outcomes after aortic arch reconstruction for infants: deep hypothermic circulatory arrest versus moderate hypothermia with selective antegrade cerebral perfusion. Eur J Cardiothorac Surg 2015; 48: e45e50.10.1093/ejcts/ezv235CrossRefGoogle ScholarPubMed
Donofrio, MT, Massaro, AN. Impact of congenital heart disease on brain development and neurodevelopmental outcome. Int J Pediatr 2010; 2010: 113.10.1155/2010/359390CrossRefGoogle ScholarPubMed
Peer, SM, d'Udekem, Y. Commentary: Will fetal brain magnetic resonance imaging guide our timing of surgery for hypoplastic left heart syndrome and transposition of the great arteries? J Thorac Cardiovasc Surg 2020;S0022-5223(20)32999-8. doi: 10.1016/j.jtcvs.2020.10.109.CrossRefGoogle Scholar
Wernovsky, G, Licht, DJ. Neurodevelopmental outcomes in children with congenital heart disease-what can we impact? Pediatr Crit Care Med 2016; 17: S232S242.10.1097/PCC.0000000000000800CrossRefGoogle ScholarPubMed
Hirvonen, M, Ojala, R, Korhonen, P, et al. The incidence and risk factors of epilepsy in children born preterm: a nationwide register study. Epilepsy Res 2017; 138: 3238.10.1016/j.eplepsyres.2017.10.005CrossRefGoogle ScholarPubMed
Li, W, Peng, A, Deng, S, et al. Do premature and postterm birth increase the risk of epilepsy? An updated meta-analysis. Epilepsy Behav 2019; 97: 8391.10.1016/j.yebeh.2019.05.016CrossRefGoogle ScholarPubMed
Glauser, TA, Rorke, LB, Weinberg, PM, Clancy, RR. Congenital brain anomalies associated with the hypoplastic left heart syndrome. Pediatrics 1990; 85: 984990.10.1542/peds.85.6.984CrossRefGoogle ScholarPubMed
Jones, M. Anomalies of the brain and congenital heart disease: a study of 52 necropsy cases. Pediatr Pathol 1991; 11: 721736.10.3109/15513819109065468CrossRefGoogle ScholarPubMed
Golomb, MR, Garg, BP, Carvalho, KS, Johnson, CS, Williams, LS. Perinatal stroke and the risk of developing childhood epilepsy. J Pediatr 2007; 151: 409413.e2.10.1016/j.jpeds.2007.03.058CrossRefGoogle ScholarPubMed
Laugesaar, R, Vaher, U, Lõo, S, et al. Epilepsy after perinatal stroke with different vascular subtypes. Epilepsia Open 2018; 3: 193202.10.1002/epi4.12104CrossRefGoogle ScholarPubMed
Pierpont, ME, Brueckner, M, Chung, WK, et al. Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association. Circulation 2018; 138: e653e711.10.1161/CIR.0000000000000606CrossRefGoogle ScholarPubMed
Towbin, J, Roberts, R. Cardiovascular diseases due to genetic abnormalities, The Heart Arteries and Veins, 8th edn. McGraw-Hill, New York, 1994, p. 17251759.Google Scholar
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: 611617.10.1097/WNP.0b013e31823e96d7CrossRefGoogle ScholarPubMed
Gaynor, JW, Stopp, C, Wypij, D, et al. Neurodevelopmental outcomes after cardiac surgery in infancy. Pediatrics 2015; 135: 816825.10.1542/peds.2014-3825CrossRefGoogle ScholarPubMed
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