Introduction. Early-onset seizures are common in children with arterial ischemic stroke, but the clinical features and effects on the outcome of early-onset seizures have not been studied enough. Material and methods. In our study we included children aged 1 month to 18 years presenting with first-time and image-confirmed arterial ischemic stroke. Results. A total of 78 survivors of arterial ischemic stroke were enrolled. Twenty (25.6%) had early-onset seizures, and 90% were initial presentation. Younger children (mean, 3.4±3.9 versus 9.0±6.2 years; P<0.001) and cortical involvement (5% versus 63.8%; P=0.01) are more likely to have early-onset seizures. Thirteen of 20 survivors with early-onset seizures had late-onset seizures after the acute stage, and 12 of them were diagnosed as poststroke epilepsy. Conclusions. Early-onset seizures occurred in 25.6% of children with arterial ischemic stroke. Younger age and cortical involvement were risk factors for early-onset seizures. Sixty-five percent of children with early-onset seizures had late-onset seizures after the acute stage.
Keywords: children, epilepsy, seizures, stroke.
Arterial ischemic stroke is an acute phenomenon found in the pediatric population, having an incidence of 1,25 out of 100000 children per year. The previous studies [1,2,3] have highlighted a correlation between the early onset of seizures and the arterial ischemic stroke, them being diagnosed in 19% up to 44% post stroke. By comparing the incidence of this phenomenon at adults (from 2,4 % up to 5,4%) we can make the conclusion that symptomatic seizures at the debut of arterial ischemic strokes are more likely to appear in the children population. Also, the adults are not so likely to have seizures in the initial phase of cerebral stroke, in comparison with children [1,3].
THE AIM OF THE STUDY
Determining the incidence of seizures in the initial phase of arterial ischemic strokes and their impact in the child development.
We have included children hospitalised in the department of neurology (early aged children), Hospital of Mother and Child Health Care, being diagnosed with arterial ischemic stroke, confirmed through a CT or cerebral MRI. In the study we have defined the arterial ischemic sroke as an acute, focal neurological syndrome, caused by a cerebral infarction on the trace of an artery. The children not having an imagistic confirmation of arterial ischemic stroke were excluded.
Clinical characteristics of seizures
Eary-onset seizures were defined as seizures that appear up to 7 days after the arterial ischemic stroke. Late- onset seizures appear later than 7 days after the onset of the ischemic stroke, and post arterial ischemic stroke epilepsy can be defined by the presence of more than 2 seizures that emerged after the acute phase of arterial ischemic stroke (longer than 1 month). The types of seizures are defined after the International League Against Epilepsy criteria.
In order to get the most truthful results the t student test was applied for comparing continuous variables and the χ2 test for discrete variables. We have used the Kaplan-Meier estimator for determining the comulative incidence of previously unprovoked seizures. The log-rank test was used in order to compare the risk of appearence of subsequent unprovoked seizures at children with and without early-onset seizures. Values with p<0.05 were considered statistical significant values.
The study lot was composed of 78 children, who corresponded to all the inclusion criteria for this study. Early-onset seizures were present at 20 children out of 78 (25,6 %), the average age of debut being 1,4±1,9 years, the children being younger than the ones who were not diagnosed with this type of seizures, 3,2± 6,2 years, p<0.001. Out of them, for 20 children (90 %), the seizures were the first manifestations of the clinical picture. The repartition of this convulsive acceses after the structure was: focal seizures diagnosed at 15 children (75%), 3 children had generalised seizures (15%) and in 2 cases the debut could not be determined neither as focal nor as generalized (10%). Out of all analyzed cases the frequent (daily) seizures were determined at 12 children (60%). Cases with only one seizure at the debut of the ischemic stroke were noted at 5 children (25%) and 3 children have developed status epilepticus (fig.1, fig. 2).
In the study grup, EEG picture, this modifications were noted: slow diffusion of the route in 8 cases (40%), focal slowing in 7 cases (35%) and epileptiform activity in 5 cases (25%) (fig. 3).
Children who had developed early-onset seizures, in comparison with those who had late-onset seizures have a predisposition to infections as a risk factor for arterial ischemic stroke (30 % vs 8,6 %, p=0.03), more frequent cortical affectations (95 % vs 63,8 %, p=0.01), and knowledge disturbances from the begining (45% vs 15,5%, p=0.01). The neuronal focal shortage was more frequent at children with late-onset seizures (60% vs 93,1%, P=0.001) (fig. 4).
THE STUDY DURATION
The study duration was 53,7±48.8 months. The early-onset seizures did not influence the mortality after the acute phase of arterial ischemic stroke (0 % versus 8,6 %, p=0.32).
During 4,5 years, 13 children (65%) out of the group with early-onset seizures and 5 children (8.6%) out of the ones without early-onset seizures were diagnosed with unprovoked seizures. During all these years, the cumulative incidence of the developement of the repeated seizures in the both groups was 52,5% and 3,5% for 1 year after the onset, 52.5% and 6.2% for 2 years after the debut and 72.3% and 14.4% at 4.5%. The children from the early-onset seizures group have developed a more significant risk of the appearance of repeated seizures during the years after the arterial ischemic stroke, in comparison with those with late-onset seizures (P<0.001). The majority (67%) of the subsequent repeated crises had their onset during the first post-arterial ischemic stroke year vs 27% after 2 years after the evolution (fig. 5).
Early-onset seizures and post arterial ischemic stroke epilepsy
Out of 20 children who were diagnosed with earlyonset seizures, 13 (65%) had seizures that continued after 7 days post arterial ischemic stroke. One child (5%) who suffered from repeated seizures has developed new ischemic injuries, seen on MRI (fig. 6).
Out of 13 children with late-onset seizures, 12 (92%) had more than one episode of subsequent unprovoked seizures, that were defined as post arterial ischemic stroke epilepsy. Four children (20%) were diagnosed with refractory epilepsy to treatment, requiring the association of different antiepileptic means. 17 children (21.8%) have developed post arterial ischemic stroke epilepsy (p<0.001). Post arterial ischemic stroke epilepsies were found at small children (3.6±5.6 versus 8.7±5.9 years; p=0.002). Unfortunately, the prophylaxis with the used antiepileptic drugs did not decrease the recurrence of subsequent seizures (50% versus 37.5%; P=0.67) (table I).
In this study we have concluded that the frequence of children who have presented early-onset seizures after the arterial ischemic stroke is 25.6%, in comparison with other studies that present values starting with 19% till 44% [1,5]. Also in the existing studies it is proved that the incidence of this kind of seizures is higher amongst the children than amongst the adults [3,4]. In our study we have confirmed this through the higher incidence of seizures among the younger children, in comparison with those who are older.
We have determined a connection between early-onset seizures and post arterial ischemic stroke epilepsy. The cumulative incidence of the development of late-onset seizures was of 72,3% for 4.5 years of follow-up. Children with early-onset seizures have developed post arterial ischemic stroke epilepsy in 60% of the cases. In the existent studies it was determined that children with post arterial ischemic stroke seizures were more likely to have epilepsy in the future [6,7,8], a fact confirmed n our study too. In this study we tried to determine the risk factors for the recurrence of the post arterial ischemic stroke debut strokes in the future, but there were not found any statistically significant differences linked with the age or the sex of the children implied in this study or with the usage of the antiepileptic means in a prophylactic purpose. A lot of the existent studies have shown that the antiepileptic drugs used in the initial phases of the arterial ischemic stroke with the purpose of stopping the acute seizures do not reduce the risk of the development of epilepsy. In addition, the previous studies concerning the adult population have proved that the usage of antiepileptic medicines in the initial phases, in order to prevent the recurrence of seizures is not necessary . However, we would like to mention that the therapeutic tactics is different in the adult vs pediatric population and additional studies are required for proving this hypothesis.
Following that study, we have noticed that the majority of children out of those from the earlyonset seizures group have presented recurrent seizures after the acute phase of arterial ischemic stroke. It is necessary to study further the bond between the earlyonset seizures, late-onset seizures and the risk of the development of post arterial ischemic stroke epilepsy, as well as the elaboration of an efficient method of preventing the subsequent recurrent seizures.
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