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Seizure Severity and Treatment Response in Newborn Infants with Seizures Attributed to Intracranial Hemorrhage

Published:November 12, 2021DOI:https://doi.org/10.1016/j.jpeds.2021.11.012

      Objective

      We sought to characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born term and preterm. For infants born term, we sought to compare seizure severity and treatment response for multisite vs single-site ICH and hypoxic–ischemic encephalopathy (HIE) with vs without ICH.

      Study design

      We studied 112 newborn infants with seizures attributed to ICH and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multisite vs single-site ICH and HIE with vs without ICH.

      Results

      ICH was a more common seizure etiology in infants born preterm vs term (27% vs 10%, P < .001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multisite ICH was associated with more subclinical seizures than single-site ICH (93% vs 66%, P = .05) and an incomplete response to the initial ASM (100% vs 66%, P = .02). Status epilepticus was more common in HIE with ICH vs HIE alone (38% vs 17%, P = .05).

      Conclusions

      Seizure severity was greater and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multistep treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.

      Keywords

      Abbreviations:

      aEEG (Amplitude-integrated electroencephalogram), ASM (Antiseizure medication), cvEEG (Continuous video electroencephalogram), EEG (Electroencephalogram), HIE (Hypoxic–ischemic encephalopathy), ICH (Intracranial hemorrhage), IVH (Intraventricular hemorrhage), NSR (Neonatal Seizure Registry), PVHI (Periventricular hemorrhagic infarction)
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      References

        • Glass H.C.
        • Shellhaas R.A.
        • Wusthoff C.J.
        • Chang T.
        • Abend N.S.
        • Chu C.J.
        • et al.
        Contemporary profile of seizures in neonates: a prospective cohort study.
        J Pediatr. 2016; 174: 98-103.e1
        • Yıldız E.P.
        • Tatlı B.
        • Ekici B.
        • Eraslan E.
        • Aydınlı N.
        • Çalışkan M.
        • et al.
        Evaluation of etiologic and prognostic factors in neonatal convulsions.
        Pediatr Neurol. 2012; 47: 186-192
        • Loman A.M.W.
        • ter Horst H.J.
        • Lambrechtsen F.A.C.P.
        • Lunsing R.J.
        Neonatal seizures: aetiology by means of a standardized work-up.
        Eur J Paediatr Neurol. 2014; 18: 360-367
        • Heljic S.
        • Uzicanin S.
        • Catibusic F.
        • Zubcevic S.
        Predictors of mortality in neonates with seizures; a prospective cohort study.
        Med Arch. 2016; 70: 182-185
        • Glass H.C.
        • Shellhaas R.A.
        • Tsuchida T.N.
        • Chang T.
        • Wusthoff C.J.
        • Chu C.J.
        • et al.
        Seizures in preterm neonates: a multicenter observational cohort study.
        Pediatr Neurol. 2017; 72: 19-24
        • Pisani F.
        • Facini C.
        • Pelosi A.
        • Mazzotta S.
        • Spagnoli C.
        • Pavlidis E.
        Neonatal seizures in preterm newborns: a predictive model for outcome.
        Eur J Paediatr Neurol. 2016; 20: 243-251
        • Sirgiovanni I.
        • Avignone S.
        • Groppo M.
        • Bassi L.
        • Passera S.
        • Schiavolin P.
        • et al.
        Intracranial haemorrhage: an incidental finding at magnetic resonance imaging in a cohort of late preterm and term infants.
        Pediatr Radiol. 2014; 44: 289-296
        • Volpe J.J.
        • Inder T.E.
        • Darras B.T.
        • de Vries L.S.
        • du Plessis A.J.
        • Neil J.J.
        • et al.
        Volpe’s neurology of the newborn.
        (6th ed. New York: Elsevier; 2017.)
        • Soul J.S.
        Acute symptomatic seizures in term neonates: etiologies and treatments.
        Semin Fetal Neonatal Med. 2018; 23: 183-190
        • 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: 115
        • Shellhaas R.A.
        • Chang T.
        • Tsuchida T.
        • Scher M.S.
        • Riviello J.J.
        • Abend N.S.
        • et al.
        The American Clinical Neurophysiology Society’s guideline on continuous electroencephalography monitoring in neonates.
        J Clin Neurophysiol. 2011; 28: 611-617
        • Harris P.A.
        • Taylor R.
        • Thielke R.
        • Payne J.
        • Gonzalez N.
        • Conde J.G.
        Research Electronic Data Capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.
        J Biomed Inform. 2009; 42: 377-381
        • Harris P.A.
        • Taylor R.
        • Minor B.L.
        • Elliott V.
        • Fernandez M.
        • O’Neal L.
        • et al.
        The REDCap consortium: building an international community of software platform partners.
        J Biomed Inform. 2019; 95: 103208
        • Shellhaas R.A.
        • Wusthoff C.J.
        • Tsuchida T.N.
        • Glass H.C.
        • Chu C.J.
        • Massey S.L.
        • et al.
        Profile of neonatal epilepsies.
        Neurology. 2017; 89: 893-899
        • Glass H.C.
        • Soul J.S.
        • Chu C.J.
        • Massey S.L.
        • Wusthoff C.J.
        • Chang T.
        • et al.
        Response to antiseizure medications in neonates with acute symptomatic seizures.
        Epilepsia. 2019; 60: e20-e24
        • Hanigan W.C.
        • Powell F.C.
        • Miller T.C.
        • Wright R.M.
        Symptomatic intracranial hemorrhage in full-term infants.
        Childs Nerv Syst. 1995; 11: 698-707
        • Brouwer A.J.
        • Groenendaal F.
        • Koopman C.
        • Nievelstein R.-J.A.
        • Han S.K.
        • de Vries L.S.
        Intracranial hemorrhage in full-term newborns: a hospital-based cohort study.
        Neuroradiology. 2010; 52: 567-576
        • Bashir R.A.
        • Vayalthrikkovil S.
        • Espinoza L.
        • Irvine L.
        • Scott J.
        • Mohammad K.
        Prevalence and characteristics of intracranial hemorrhages in neonates with hypoxic ischemic encephalopathy.
        Am J Perinatol. 2018; 35: 676-681
        • Hong H.S.
        • Lee J.Y.
        Intracranial hemorrhage in term neonates.
        Childs Nerv Syst. 2018; 34: 1135-1143
        • Beslow L.A.
        • Abend N.S.
        • Gindville M.C.
        • Bastian R.A.
        • Licht D.J.
        • Smith S.E.
        • et al.
        Pediatric intracerebral hemorrhage: acute symptomatic seizures and epilepsy.
        JAMA Neurol. 2013; 70: 448-454
        • Sheth R.D.
        • Hobbs G.R.
        • Mullett M.
        Neonatal seizures: incidence, onset, and etiology by gestational age.
        J Perinatol. 1999; 19: 40-43
        • Lloyd R.O.
        • O’Toole J.M.
        • Pavlidis E.
        • Filan P.M.
        • Boylan G.B.
        Electrographic seizures during the early postnatal period in preterm infants.
        J Pediatr. 2017; 187: 18-25.e2
        • Vesoulis Z.A.
        • Inder T.E.
        • Woodward L.J.
        • Buse B.
        • Vavasseur C.
        • Mathur A.M.
        Early electrographic seizures, brain injury, and neurodevelopmental risk in the very preterm infant.
        Pediatr Res. 2014; 75: 564-569
        • Buraniqi E.
        • Sansevere A.J.
        • Kapur K.
        • Bergin A.M.
        • Pearl P.L.
        • Loddenkemper T.
        Electrographic seizures in preterm neonates in the neonatal intensive care unit.
        J Child Neurol. 2017; 32: 880-885
        • Shah D.K.
        • Zempel J.
        • Barton T.
        • Lukas K.
        • Inder T.E.
        Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury.
        Pediatr Res. 2010; 67: 102-106
        • Kharoshankaya L.
        • Stevenson N.J.
        • Livingstone V.
        • Murray D.M.
        • Murphy B.P.
        • Ahearne C.E.
        • et al.
        Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy.
        Dev Med Child Neurol. 2016; 58: 1242-1248
        • Miller S.P.
        • Weiss J.
        • Barnwell A.
        • Ferriero D.M.
        • Latal-Hajnal B.
        • Ferrer-Rogers A.
        • et al.
        Seizure-associated brain injury in term newborns with perinatal asphyxia.
        Neurology. 2002; 58: 542-548
        • Glass H.C.
        • Glidden D.
        • Jeremy R.J.
        • Barkovich A.J.
        • Ferriero D.M.
        • Miller S.P.
        Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury.
        J Pediatr. 2009; 155: 318-323
        • Pisani F.
        • Copioli C.
        • Di Gioia C.
        • Turco E.
        • Sisti L.
        Neonatal seizures: relation of ictal video-electroencephalography (EEG) findings with neurodevelopmental outcome.
        J Child Neurol. 2008; 23: 394-398
        • Wusthoff C.J.
        • Sundaram V.
        • Abend N.S.
        • Massey S.L.
        • Lemmon M.E.
        • Thomas C.
        • et al.
        Seizure control in neonates undergoing screening vs confirmatory EEG monitoring.
        Neurology. 2021; 97: e587-e596https://doi.org/10.1212/WNL.0000000000012293
        • Reynolds M.L.
        • Evans C.A.N.
        • Reynolds E.O.R.
        • Saunders N.R.
        • Durbin G.M.
        • Wigglesworth J.S.
        Intracranial haemorrhage in the preterm sheep fetus.
        Early Hum Dev. 1979; 3: 163-185
        • Roland E.H.
        • Flodmark O.
        • Hill A.
        Thalamic hemorrhage with intraventricular hemorrhage in the full-term newborn.
        Pediatrics. 1990; 85: 737-742
        • Huang A.H.
        • Robertson R.L.
        Spontaneous superficial parenchymal and leptomeningeal hemorrhage in term neonates.
        AJNR Am J Neuroradiol. 2004; 25: 469-475
        • Srinivasakumar P.
        • Zempel J.
        • Trivedi S.
        • Wallendorf M.
        • Rao R.
        • Smith B.
        • et al.
        Treating EEG seizures in hypoxic ischemic encephalopathy: a randomized controlled trial.
        Pediatrics. 2015; 136: e1302-e1309