I have no relevant financial relationships with the manufacturers of any commercial products or provider of commercial CME services discussed in this

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1 Neonatal Seizures Dennis J. Dlugos, MD Pediatric Regional Epilepsy Program The Children s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania

2 I have no relevant financial relationships with the manufacturers of any commercial products or provider of commercial CME services discussed in this CME activity.

3 Road map Etiologies Identifying neonatal seizures Streamlined seizure detection techniques Challenges in clinical practice

4 Learning Objectives Know major etiologies for neonatal seizures Be skilled at clinical and EEG identification of neonatal seizures List pros and cons of streamlined EEG seizure detection methods Identify challenges and solutions to integrating EEG monitoring into clinical practice

5 Seizures in per 1000 term births Glass HC, Wirrell E.,J Child Neuro, Etiologies (also risk factors) Hypoxic ischemic encephalopathy (HIE) Infection Malformations of cortical development Trauma Stroke Metabolic (glucose, Ca, Mg) Inborn Errors of Metabolism Early onset epilepsy of unknown cause

6 HIE & Therapeutic Hypothermia N=41, ceeg, Electrographic sz in 34% including status epilepticus (SE) in 10%, subclinical in 43%. Nash KB, Neurology, N=26, ceeg, Electrographic sz in 65% including SE in 23%, subclinical in 47%. Wusthoff CW, J Child Neuro, Cardiac Surgery Peri-operative convulsions: 6-18%. Clancy RR, Pediatrics, 2003; Helmers SL, EEG Clin Neurophys, Peri-operative NCS: 6-20%. Chock VY, J Perinat, 2006; Clancy RR, Epilepsia, 2005; Helmers SL, EEG Clin Neurophys, 1997; Gaynor JW, J Thorac Cardiovasc Surg, 2005; Schmitt B, Ped Res, HIE, Stroke. Mahle WT, Circulation, 2002; Galli KK, J Thorac Cardivasc Surg, 2004; Licht DJ et al., J Thorac Cardiovasc Surg, Extracorporeal Membrane Oxygenation (ECMO) Clinical seizures: 5-10%. Haines NM, ASAIO J, NCS: 11-30%. Campbell LR, J Ped, 1991; Hahn JS, Neuroped, 1993; Horan A, Early Hum Dev, Seizures possible risk factor for adverse outcome. Streletz LJ, Ped Neuro, 1992; Hahn JS, Neuroped, 1993; Parish AP, J Child Neuro, 2004; Bennett CC, J Perinat Med, 2002; Campbell LR, J Ped, 1991.

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8 Road map Etiologies Identifying neonatal seizures Streamlined seizure detection techniques Challenges in clinical practice

9 Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Arch. Dis. Child. Fetal Neo Ed Clancy RR, Legido A, Lewis D. Epilepsia, 1988.

10 Role for Clinical Diagnosis Seizures (n) Patients (n) Ictal EEG correlate (%) No EEG correlate (%) Focal clonic % 0 Focal tonic % 0 Myoclonic % 63% Gen tonic % Subtle % Mizrahi and Kellaway. Neurology 1987;37:

11 Identify the seizure 3 babies, 1 is having seizures Which one? A B C

12 Seizures hard to predict based on clinical data (Sarnat encephalopathy score, Apgar score, ph). Murray DM, Ryan CA, Boylan GB, Fitzgerald AP, Connolly S. Pediatrics, Clinical seizure diagnosis difficult. Average correct identification = 50% Poor inter-rater agreement (kappa 0.2) Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Epilepsia 2009 Electroclinical uncoupling/dissociation 58% after Phenytoin or Phenobarbital Scher MS, Alvin J, Gaus L, Minnigh B, Painter MJ. Ped Neuro, % after Phenobarbital Connell J, Oozeer R, devries L, Dubowitz LM, Dubowitz V. Arch Dis Child 1989

13 Sudden Stand out from background Rhythmic and Repetitive At least 10 seconds in duration Evolve In amplitude, frequency, morphology and/or spatial distribution Distinct beginning, middle and end Recurrent and Stereotyped Shellhaas et al. J Clin Neurophys 2011;28:

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33 Artifact or seizure? Artifacts are usually monomorphic Do not evolve in frequency, morphology and/or amplitude Technologist comments are critical

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37 Almost all have focal or multi-focal onset About 50% of seizures are < 1 minute Very rare to have a single seizure Status Epilepticus in about one-third Single seizure > 30 minutes Multiple seizures totaling 50% seizure burden ( ictal fraction ) EEG background a useful predictor of seizures Unlikely if normal or immature background Likely if severely abnormal EEG background Background better assessed with 1-4 hour EEGs Shellhaas et al. J Clin Neurophys 2011;28:

38 Electrographic Seizures Electroclinical Seizures Clinical Spells

39 Road map Etiologies Identifying neonatal seizures Streamlined seizure detection techniques Challenges in clinical practice

40 Raw EEG Al Naqeeb 1999 Hellstrom-Westas 2006 Bandpass Filter Rectification Smooth Data Time Compression Continuous, Sleep-Wake Cycling Inactive-Flat El-Dib M, Chang T, Tsuchida TN, Clancy RR. Ped Neurology, 2009.

41 El-Dib M, Chang T, Tsuchida TN, Clancy RR. Ped Neurology, Wusthoff C, Shellhaas RA, Clancy RR. Perinatology, 2009 Identification N C3-C4 FP3- FP4 N (%) EEG Records with at least 1 Seizure Identified 125 records 113 (90.4%) 82 (65.6%) N (%) of Seizures Identified 350 seizures 242 (73%) 153 (46.4%)

42 International survey N=201, 63% neonatology Access to EEG Monitoring = 90% EEG 27%, aeeg 22%, Both 51% Confident in interpretation = 28% Boylan GB, Burgoyne L, Moore C, O Flaherty B, Rennie JM. Acta Pediatrica, 2010.

43 Neo HIE. Randomized to clinical sz management vs. aeeg based management. SEIZURE DURATION MRI INJURY aeeg No aeeg van Rooj LG, Toet MC, van Huffelen AC, Groenendaal F, Laan W, Zecic A, de Haan T, van Straaten IL, Vrancken S, van Wezel G, van der Sluijs J, Ter Host H, Gavilanes D, Laroche S, Naulaers G, de Vries LS. Pediatrics, 2010

44 Density Spectral Array (DSA)

45 DSA

46 Road map Etiologies Identifying neonatal seizures Streamlined seizure detection techniques Challenges in clinical practice

47 aeeg application and interpretation Conventional EEG application and interpretation Communication and Collaboration Between nursing, EEG technologists, Neonatalogists, Neurophsyiologists and Neurologists

48 Practice Changes to Consider Know that clinical diagnosis of neonatal seizures is fundamentally flawed Develop a clinical pathway for the diagnosis, etiologic work-up, monitoring, treatment, and outcome assessment of neonatal seizures If conventional EEG is used, review lines of communication between Neonatalogy, EEG and Neurology If aeeg or DSA is used, assess accuracy of interpretation

49 Neonatal seizures are common Any and all causes of neonatal encephalopathy are risk factors for seizures Most seizures are subclinical Seizures may independently worsen outcome Conventional EEG optimal, not always practical aeeg imperfect, but useful Better treatments needed Collaboration and teamwork essential

50 Nicholas Abend, MD Robert Clancy, MD Sudha Kessler, MD Maureen Donnelly, REEGT, CLTM CHOP Clinical Neurophysiology CHOP Pediatric Regional Epilepsy Program CHOP Neuro-ICU Consultation Service CHOP Division of Neonatology CHOP Department of Critical Care Medicine

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