Acute Seizures and Epilepsy Risk in Pediatric Intracerebral Hemorrhage
Acute Seizures and Epilepsy Risk in Pediatric Intracerebral Hemorrhage
Abstract & Commentary
By Sotirios Keros, MD, PhD, Instructor, Department of Pediatrics, Division of Pediatric Neurology, Weill Cornell Medical College. Dr. Keros reports no financial relationships relevant to this field of study.
Synopsis: Children with intracerebral hemorrhage are at increased risk for seizures and epilepsy compared to adults, particularly those who develop elevated intracranial pressures.
Source: Beslow LA, et al. Pediatric intracerebral hemorrhage: Acute symptomatic seizures and epilepsy. JAMA Neurol 2013;70:448-454.
Spontaneous intracranial hemmorhage (ICH) is a known risk factor for acute seizures as well as the subsequent development of epilepsy. The association between seizures and ICH appears to be particularly strong in children and neonates relative to adults. The existing pediatric data are somewhat limited, however, by reliance on small sample sizes, retrospective studies, non-uniform definitions, and unclear or unspecified follow-up durations.
The present study by Beslow et al describes data obtained prospectively from both neonates (> 37 weeks gestational age and < 28 days old) and children (28 days to 18 years) who presented with ICH from three institutions over a 5-year period. There were 87 eligible subjects, of which 73 were enrolled into the study. Of the 20 neonates, 70% had intraparenchymal hemorrhage (IPH) with extension into the ventricles (IVH), while 15% each had isolated IPH or IVH. Of 53 children, 55% had IPH, 11% IVH, and 34% with both IPH and IVH. The etiology of ICH in neonates was not found in 60% of cases, while 25% had an underlying coagulopathy, 10% had a cavernous malformation, and 5% had an arteriovenous malformation. In contrast, only 17% of children had an unknown etiology for ICH, with 50% of children found to have either an arteriovenous or cavernous malformation, and roughly 10% each diagnosed with an aneurysm, coagulopathy, or were on anticoagulants. There was one child (2%) with moyamoya and one child with a developmental venous anomaly.
The study divided the temporal occurrence of seizures into three categories: seizures at presentation, acute seizures (after presentation but within 7 days of ICH), and remote seizures > 7 days from presentation. The decision to obtain either a routine EEG or continuous EEG monitoring was determined by the treating physician, as was the initiation and choice of any antiepileptic drugs. For analysis, seizures included either clinically evident seizures or electrographic seizures. In the neonatal group, 60% had seizures as at least one of their presenting symptoms, compared with only 36% in children (P = 0.07). Of the neonates presenting with seizures, 83% were defined as being in status epilepticus (seizures lasting > 30 minutes) compared to 26% in children. Neither cortical location of the ICH nor the presence of a vascular malformation predicted risk of seizure at presentation. Seven children (13%) had a seizure in the acute period. None of the neonates had seizures in the first 7 days after presentation.
Of 67 surviving subjects, there was a trend toward children being more likely to have a remote seizure compared to neonates (24% vs 12% with P = 0.05, but P increased to 0.27 after a correction for multiple comparisons). Children also tended to be at increased risk to develop epilepsy (16% vs 6%, P = 0.04, but 0.20 after correction), defined as two or more unprovoked remote symptomatic seizures during follow-up, with the median duration of follow-up approximately 1 year for each group.
Twenty-six of the surviving subjects had elevations in intracranial pressure (ICP) in the acute period that required urgent intervention such as hypertonic solutions, cerebral spinal fluid drainage, or surgical decompression. Elevated ICP requiring intervention was the only statistically significant risk factor, after correction, for the development of remote seizures (P = 0.03) or epilepsy (P = 0.04). None of the following were risk factors for either remote seizures or epilepsy: seizure during the first 7 days, etiology or location of ICH, use of seizure medications, or epileptiform discharges on EEG.
Commentary
This relatively large, prospective study provides additional evidence that children with ICH, and in particular neonates, are more likely to present with seizures in the acute period than adults. The strongest risk factor for predicting epilepsy was elevated ICP requiring intervention. It is unclear whether elevated ICP was merely a proxy for the severity of the bleed, or if perhaps this represented a “second hit” to a brain already at risk for developing seizures.
It is interesting to note that although both infants and children had similar incidence of seizures during the first 7 days after ICH, the non-neonates were 2-3 times more likely to develop remote seizures or epilepsy. The use of antiseizure medication did not seem to prevent remote seizures or epilepsy. However, medication use and choice of drug was not uniform, and subgroup analysis was limited by the relatively small size of the subgroups. How seizures can best be prevented in children with ICH will require randomized controlled studies. But it is clear that the risk of seizure extends beyond the acute period, and further studies will hopefully provide additional data about which children are most at risk.
Children with intracerebral hemorrhage are at increased risk for seizures and epilepsy compared to adults, particularly those who develop elevated intracranial pressures.Subscribe Now for Access
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