Clinical Predictors of Drug Resistant Epilepsy in Children with Cerebral Palsy: A Hospital Based Cohort Study
Abstract number :
2.12
Submission category :
4. Clinical Epilepsy / 4D. Prognosis
Year :
2021
Submission ID :
1825684
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Nimra Feroz, BAMSc - The University of Sydney; Katarina Ostojic, B Sc – Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Russell Dale, MRCPCH, PhD. – The Children’s Hospital at Westmead Clinical School, The University of Sydney, Sydney, NSW, Australia; Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, NSW, Australia; Sarah McIntyre, PhD – 2. Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Elizabeth Barnes, Statistics – Department of Statistics, University of Sydney, The Children's Hospital at Westmead, Sydney, NSW, Australia; Iona Novak, PhD – Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Nadia Badawi, FRACP,PhD – Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Simon Paget, FAFRM – Kids Rehab, The Children's Hospital at Westmead, Sydney, NSW, Australia; Mary-Clare Waugh, FAFRM – Kids Rehab, The Children's Hospital at Westmead, Sydney, NSW, Australia; Deepak Gill, FRACP – Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, NSW, Australia; Kavitha Kothur, FRACP,PhD – Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, NSW, Australia
Rationale: Epilepsy is seen in 15 to 60% of children with cerebral palsy (CP), of whom a significant proportion have drug-resistant epilepsy. However, the factors associated with drug resistance are not well characterised. We aim to investigate the clinical characteristics of epilepsy and the predictors of drug-resistant epilepsy in children with cerebral palsy.
Methods: We have selected a cohort of children diagnosed with CP and epilepsy born between 2003 to 2015 (inclusive) identified from the NSW/ACT CP Register who attended the Children’s Hospital at Westmead (n=230). Data on perinatal/CP characteristics (Apgar scores, neonatal seizures, neonatal encephalopathy, gestational age, birth weight, etiology, CP comorbidities, type of CP, MRI classification) and detailed epilepsy phenotyping (types of seizures/epilepsy, age of onset of seizures, family history, EEG (electroencephalography), treatment modalities and drug resistance) were collected from medical records and compared children between drug-resistant (failed > two appropriate anti-epileptic drugs) and responsive groups.
Results: The median age of onset of epilepsy was nine months (4-24 Mo). The median duration of epilepsy was 9.5 yrs (SD 6.3-13 yrs), and 190 children (86%) were on the anti-epileptic drug, at last follow up. Neonatal seizures were present in 77 (43%). A high proportion of children had multiple seizure types (73%), grey matter injury (43%), and 147 (64%) children had drug resistance either previously or at last follow up. Seven of 12 patients remained seizure-free after epilepsy surgery. Hypoxic-ischemic encephalopathy (21%), infarct (15%), genetic (14%) and structural causes (24%) accounted for the majority of the cases, whereas prematurity was seen in 11%. Children in the drug-resistant group were more likely to have a younger age of onset of seizures (0.5 vs 1.5 Mo; p< .0001), severe impairment GMFCS (IV-V) (64% vs 40%; p=0.02), moderate to severe intellectual disability (56% vs 39%; p=0.0004), non-verbal communication (55% vs 35%; p=0.0005) microcephaly (57% vs 30%; p=0.0005), generalised seizures (myoclonic, tonic and spasms) (p < .0001) and multifocal interictal epileptic discharges (42% vs 20%;p=0.0009) compared to drug-responsive group. Children in the drug-responsive group had focal epilepsy (49% vs 23%; p< .0001) or generalised epilepsy (20% vs 2% p< .0001) alone and had normal EEG (19% vs 9%; p=.02) compared to the drug-resistant group. On multivariate analysis, type of epilepsy (OR 9.9, 95%CI 3-29), and microcephaly (OR 0.2, 95%CI 0.1-0.5) remained as independent predictors of drug resistant epilepsy.
Conclusions: Children with CP have active epilepsy needing polypharmacy and are less likely to be seizure-free. The current study highlights important clinical associations of drug resistance in children with CP, which will help identify different prognostic groups for surveillance and optimal treatment. The contribution of genetic findings is an important avenue for future research and treatments.
Fig 1: The clinical associations for the presence of drug-resistant epilepsy using a hospital-based cohort study: Younger age of onset of seizures, severe motor impairment GMFCS (IV-V), microcephaly, generalised seizures (myoclonic, tonic and spasms), and multifocal interictal epileptic discharges at onset/evolution were associated with drug-resistant epilepsy in CP.
Abbreviations: GMFCS (Gross Motor Function Classification System)
Funding: Please list any funding that was received in support of this abstract.: Cerebral Palsy Alliance.
Clinical Epilepsy