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Seizures in Children with Cerebral Palsy and White Matter Injury Monica S Seizures in Children With Cerebral Palsy and White Matter Injury Monica S. Cooper, MBBS, BMedSc, a, b, c Mark T. Mackay, MBBS, PhD,a, b, c Michael Fahey, MBBS, PhD, d Dinah Reddihough, MD, a, b, c Susan M. Reid, PhD, a, b, c Katrina Williams, MBBS, PhD, a, b, c A. Simon Harvey, MDa, b, c OBJECTIVE: The goal of this study was to describe the prevalence, syndromes, and evolution of abstract seizure disorders in children with cerebral palsy (CP) due to white matter injury (WMI). METHODS: For this population-based cohort study, brain MRI scans and medical records were reviewed in children in the Victorian Cerebral Palsy Register born between 1999 and 2006 recorded as having WMI. Children were excluded if they had features of an undiagnosed syndrome, associated cortical malformation or injury, or no medical contact in the preceding year. Included were 166 children with CP and isolated WMI due to presumed vascular insufficiency or hemorrhage; 87 were born preterm. Seizure and CP details were obtained from medical records and interviews, and EEG recordings were reviewed. RESULTS: Forty-one children (25%) had seizures beyond the neonatal period. Four children had West syndrome, which resolved with treatment. Thirteen children had febrile seizures that they outgrew. Thirty children had focal epilepsy with seizure manifestations and EEG discharges typical of early-onset childhood occipital epilepsy or childhood epilepsy with centrotemporal spikes; 23 have outgrown these seizures. Two children had idiopathic generalized epilepsy; it was ongoing in 1 child. Fourteen children had evolution from 1 epileptic syndrome to another. At last follow-up (median age, 12.7 years; minimum age, 9.7 years), 80% had not had a seizure for >2 years. CONCLUSIONS: The electroclinical features of seizure disorders associated with CP and WMI are those of the age-limited, epileptic syndromes of childhood, with favorable outcome in the majority. The findings have important implications for counseling and drug treatment. WHAT’S KNOWN ON THIS SUBJECT: Seizures occur a The Royal Children’s Hospital, Melbourne, Victoria, Australia; bDepartment of Paediatrics, The University of Melbourne, Victoria, Australia; cMurdoch Childrens Research Institute, Melbourne, Victoria, Australia; and more frequently in children with cerebral palsy dDepartment of Paediatrics, Monash University, Melbourne, Victoria, Australia (CP) than in typically developing children. Few studies address the heterogeneity of epilepsies in Dr Cooper designed the data collection instruments, coordinated and supervised data collection CP. Seizures are often attributed to the underlying at 2 sites, conceptualized and designed the study, and drafted the initial manuscript. Drs Mackay brain abnormality, with expected poor prognosis for and Harvey conceptualized, supervised data collection, designed the study, and drafted the initial manuscript; Dr Mackay reviewed all available MRIs, and Dr Harvey reviewed all available EEGs. Drs seizure remission. Reddihough, Reid, and Williams conceptualized and designed the study and critically reviewed the WHAT THIS STUDY ADDS: One in 5 children with manuscript; and Dr Fahey critically reviewed the manuscript and supervised data collection at 1 CP due to white matter injury develops seizures. site. All authors approved the fi nal manuscript as submitted. Seizures occur in the context of age-limited, epileptic DOI: 10.1542/peds.2016-2975 syndromes of childhood, with a favorable outcome Accepted for publication Dec 19, 2016 in the majority. This has implications for counseling and antiepileptic drug treatment. Address correspondence to A. Simon Harvey, MD, Neurology Department, Royal Children’s Hospital, 50 Flemington Rd, Parkville, Victoria 3052, Australia. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2017 by the American Academy of Pediatrics To cite: Cooper MS, Mackay MT, Fahey M, et al. Seizures FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant in Children With Cerebral Palsy and White Matter Injury. to this article to disclose. Pediatrics. 2017;139(3):e20162975 Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 139 , number 3 , March 2017 :e 20162975 ARTICLE Cerebral palsy (CP), a group of gestation, to confirm and characterize Data were analyzed by using nonprogressive disorders of the WMI and to exclude those with Stata version 14.1 (StataCorp, movement and posture, occurs in ∼2 associated cortical involvement, such College Station, TX). The strength per 1000 live births. 1 The pathologic as focal encephalomalacia, cortical of associations between seizure substrates and etiologies of CP are gliosis, or hippocampal sclerosis. status and categorical variables varied, the most common being white (demographic, clinical, EEG, and Medical records from the 2 pediatric matter injury (WMI) complicating imaging data) were tested by using χ2 hospitals in Victoria were screened cerebral ischemia or hemorrhage in or Fisher’s exact tests, and numerical for information about the children’s preterm and term infants. 2 Reported data were compared by using a CP and its etiology. Children rates of seizures and epilepsy Mann-Whitney U test. A Kaplan-Meier were excluded if pathologic copy in CP vary widely depending on plot was produced for time from number variants or underlying patient ascertainment, underlying onset of epilepsy until 2 years after genetic syndromes were identified; pathology, and etiology. 3 – 7 Studies the last seizure. conditions such as autosomal of epilepsy in CP should ideally be recessive primary microcephaly, The study was approved by the population based, address specific Wolf-Hirschhorn syndrome, or Human Research and Ethics CP subtypes and etiologies, and Waardenburg syndrome were Committees of the Royal Children’s analyze electroclinical features identified. Hospital and Monash Children’s beyond just the presence of seizures. Hospital, Melbourne. However, few studies address the Information about potential seizures heterogeneity of epilepsy in children was obtained from medical records. with CP, overlooking important In addition, parents/guardians were RESULTS aspects of seizure semiology and invited by mail to participate in a specific EEG patterns. 8 – 11 In children telephone interview to determine Search of the Victorian Cerebral with CP, the presumption is that they whether their child ever had an Palsy Register returned data on have a “structural” or “symptomatic” epileptic seizure. Children were 256 children with a categorization epilepsy, the seizures will likely excluded if their parents or carers of "WMI." Review of MRIs excluded continue into later life, and the could not be interviewed and their 53 children with associated cortical childhood epileptic syndromes are medical record contained no clinical abnormalities or WMI suggestive not relevant. 12 information during the previous of a genetic syndrome. Screening 12 months because the presence of of medical records excluded 23 We previously described the seizures and the current status of children with genetic or syndromic epileptology of hemiplegic CP any seizures could therefore not be diagnoses. Fourteen children were secondary to perinatal arterial reliably determined. excluded because clinical information ischemic stroke, noting that the for the preceding 12 months was majority of children had common Information was obtained about unavailable, including 2 deceased epileptic syndromes with favorable family history of seizures, age and children ( Fig 1). Three of these outcome. 13 The present article circumstances of seizures, seizure children had a history of seizures or describes the epileptic syndromes descriptions, seizure outcome, possible seizures; 1 child had West associated with CP and WMI due treatment details, Gross Motor syndrome followed by a tonic-clonic to presumed cerebral ischemia or Function Classification System 17 seizure, 1 child had a focal seizure, hemorrhage. level, and the presence of intellectual and 1 child died with minimal disability and behavioral problems. information available about the EEG recordings were reviewed by a reported episodes. METHODS pediatric neurologist (ASH) for the A total of 166 children with CP and presence of interictal epileptiform The Victorian Cerebral Palsy Register, isolated WMI were included in the discharges (IEDs); 3 of the total 79 which was established in 1986, 14, 15 study; their perinatal, CP, and MRI EEG recordings were not available, was searched for children with findings are summarized in Table and the reports were used. prenatally or perinatally acquired CP 1. Eighty-seven children were born between 1999 and 2006 who Epilepsy was defined as ≥2 born preterm (<37 weeks). Eighty- had an MRI after age 6 months and afebrile seizures occurring beyond seven families were interviewed by were classified as having “WMI.” 16 the neonatal period. 18 Epileptic telephone, and information about MRIs were reviewed by a pediatric syndrome diagnoses were made in possible seizures was gleaned from neurologist (MTM in all cases accordance with the International medical records in the remainder. and ASH in cases of uncertainty), League Against Epilepsy classification The median age at last telephone or blinded to the children’s history and scheme. 19 hospital contact was 13.7 years. Of Downloaded from www.aappublications.org/news by guest on September 29, 2021 2 COOPER et al FIGURE 1 Diagram
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