Neonatal seizures triple the risk of a remote seizure after perinatal ischemic stroke

Abstract

Objectives: To determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke. Methods:We retrospectively identified a population-based cohort of children with perinatal arterial ischemic stroke (presenting acutely or in a delayed fashion) from a large Northern Californian integrated health care system. We determined incidence and predictors of a remote seizure (unprovoked seizure after neonatal period, defined as 28 days of life) by survival analyses, and measured epilepsy severity in those with active epilepsy ($1 remote seizure and maintenance anticonvulsant treatment) at last follow-up.Results: Among 87 children with perinatal stroke, 40 (46%) had a seizure in the neonatal period.During a median follow-up of 7.1 years (interquartile range 3.2-10.5), 37 children had $1 remote seizure. Remote seizure risk was highest during the first year of life, with a 20% (95% confidence interval [CI] 13%-30%) cumulative incidence by 1 year of age, 46% (CI 35%-58%) by 5 years, and 54% (CI 41%-67%) by 10 years. Neonatal seizures increased the risk of a remote seizure (hazard ratio 2.8, CI 1.3-5.8). Children with neonatal seizures had a 69% (CI 48%-87%) cumulative incidence of remote seizure by age 10 years. Among the 24 children with active epilepsy at last follow-up, 8 (33%) were having monthly seizures despite an anticonvulsant and 7 (29%) were on more than one anticonvulsant.Conclusions: Remote seizures and epilepsy, including medically refractory epilepsy, are common after perinatal stroke. Neonatal seizures are associated with nearly 3-fold increased remote seizure risk. Neurology ® 2016;86:2179-2186 GLOSSARY AIS 5 arterial ischemic stroke; CI 5 confidence interval; HR 5 hazard ratio; ICD-9 5 International Classification of Diseases-9; IQR 5 interquartile range; KPNC 5 Kaiser Permanente Northern California; PPIS 5 presumed perinatal ischemic stroke.Perinatal arterial ischemic stroke (AIS) occurs in 1 in 4,000 term births and is an important cause of childhood epilepsy.1 In some newborns, an ischemic brain injury is initially unrecognized and only diagnosed later during development when a hemiparesis becomes clinically apparent or a remote symptomatic seizure occurs. This subset often receives a diagnosis of presumed perinatal ischemic stroke (PPIS), which refers to a stroke presumed to have occurred in the perinatal period because of a chronic focal infarction on neuroimaging.2 Stroke that is clinically apparent in the neonatal period may differ from PPIS. Seizures during the neonatal period are perhaps the most notable factor differentiating these groups, and are reported in about 75%-90% of infants diagnosed with stroke during the perinatal period.3-5 Neonatal seizures of any cause may confer a long-term risk of postnatal epilepsy. An estimated 10%-20% of neonates with seizures from any cause will go on to have further seizures in childhood. 6 Our objective was to measure the incidence rate and risk factors for a first remote seizure after perinatal AIS utilizing a previo...

Epilepsy after perinatal stroke with different vascular subtypes

“…Rates of epilepsy after perinatal stroke vary largely due to different inclusion criteria and various periods of observation. Previous studies have shown that epilepsy develops in 21–67% of children with neonatal AIS, in 3% of children with neonatal AHS, in 17–41% of children with neonatal CSVT, in 13–41% of children with presumed AIS, and in 23% of children with presumed PVI . Some studies have not found any predictive factors for epilepsy after perinatal stroke, but others have shown that cortical lesions, large stroke size, involvement of the right middle cerebral artery or multiple territories, and neonatal seizures may predict remote seizures.…”

A 15-year epileptogenic period after perinatal brain injury

“…It is also reported that up to 55% of hemiplegic patients with perinatal stroke can be expected to develop epilepsy by 10 years of age (Wanigasinghe et al, 2010). Furthermore, a recent study highlighted that, among children with a history of perinatal stroke and NSs, the 10-year cumulative incidence of a first remote seizure was 69% (CI 48-87%) and of active epilepsy 54% (CI 32-79%) (Fox et al, 2016). Nevertheless, a seizure-free period lasting as long as 15 years, as in our patient, has not previously been described.…”

“…Most children with NSs experience early spontaneous recurrent epileptic seizures. Almost 3/4 of seizures occurred within the first year of life (Ellenberg et al, 1984;Fox et al, 2016) and the others usually before the age of 5 (Pisani et al, 2012). We report the case of a young boy with onset of epilepsy at the age of 15 years, found to be related to an ischemic lesion due to a perinatal stroke with seizures in the neonatal period.…”

Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk

“…Our higher incidence rates may be explained by age differences between the stroke cohorts; our cohort included neonates with stroke. Among neonates in the Kaiser Pediatric Stroke Study, the cumulative incidence of an unprovoked remote seizure was similar to our cohort, at 20% by 1 year of age . Another reason for our higher incidence rate could be that our cohort, enrolled at pediatric stroke centers that are generally regional tertiary care facilities, may have preferentially included children with more severe strokes or greater medical illness, who were then more likely to go on to develop epilepsy.…”

“…Convulsions at stroke presentation are more likely in young children . Although determinants of epilepsy after pediatric AIS are poorly understood, emerging data suggest early seizures may be associated . Therefore, the high incidence of acute seizures after pediatric AIS is worrisome.…”