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Development of epilepsy after neonatal seizures
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 5 ) 1 e2
Official Journal of the European Paediatric Neurology Society
Letter to the Editor
Development of epilepsy after neonatal seizures Dear Sir, We read with great interest the article by Pisani et al. that reviewed the literature regarding the development of epilepsy after neonatal seizures.1 Outcome studies confirmed that neonatal seizures are a major risk for death or subsequent neurological disability and can independently confer an adverse neurodevelopmental outcome in high-risk neonates. Despite advances in perinatal and neonatal care, the development of childhood epilepsy after neonatal seizures still occurs in a substantial proportion of children. There is uncertainty about the true incidence of epilepsy after neonatal seizures due to the lack of population-based studies including newborns with clinical and/or EEG confirmed seizures. Additionally, the incidence of epilepsy reported between 1.8% and 41.3%2,3 is questionable due to inconsistent inclusion criteria and duration of the follow up. There are some surprising findings in Pisani's study, namely that none of the revised studies focused on the presence/ absence of clinical manifestations during electrographic seizures with regard to the incidence of postneonatal epilepsy.1,4 The need for further research in estimating the true incidence and long-term morbidity and mortality therefore cannot be overemphasized. The findings of Pisani's study also provide further evidence that children with epilepsy after neonatal seizures are at a higher risk of motor and cognitive disabilities. In 80.7%, epilepsy was associated with other neurological impairments; 18% of them developed epilepsy and intellectual impairment.1 The question which still needs to be addressed is the presence of less severe forms of disability, such as a minor motor impairment, attention deficit-hyperactivity disorder, perceptual-motor, cognitive and behavioural problems in children after neonatal seizures. Almost all of the reviewed studies in the article by Pisani et al. have been carried out in order to identify the correlation between antenatal/perinatal and neonatal risk factors for the development of epilepsy after neonatal seizures.1 Obviously, risk factors for the development of epilepsy are not significantly prognostic. The strongest predictors of outcome are the underlying cause and background electroencephalographic activity. The prevalence of later epilepsy is high following status epilepticus although the background EEG pattern before the onset of seizures may correlate better with outcome than the duration of seizures.5 The prognostic significance of many
other risk factors is almost equivocal in different studies and may reflect variation in data collection, classification, and analysis. We are aware that the reviewed article included data published up to the end of 2013, but our article, which was published shortly afterwards, also gave a contribution to this issue. The follow up period in our study was from 2 to almost 12 years, which is quite long when compared to other studies; the incidence of epilepsy in our cohort was 18.2% and was the highest in the first 12 months.6 In addition to the other risk factors, we identified that the duration of seizures after the first month was as an independent risk factor for developing epilepsy, so our data support the evidence that recurrent and prolonged neonatal seizures may act on epileptogenic substrate mainly observed in synaptogenesis, causing further damage including synaptic reorganization which is responsible for the subsequent clinical expression of epilepsy. In our study we aimed to design a scoring system for the prediction of epilepsy, but contrary to the three previous studies which were designed to predict overall adverse neurologic outcome we concluded that the construction of a universal scoring system was not possible due to the interaction between duration of seizures after the first month as the best predictor of epilepsy and gestational age.6 The duration of seizures after the neonatal period had a different effect on the development of epilepsy with respect to the gestational age. Although no scoring system will fully capture individual risks of epilepsy, models designed for more uniform populations such as term infants with hypoxia ischaemia may achieve the best prognostic power. Out of all highlighted facts in Pisani's study, we can conclude that in order to achieve the best prognostic information maximum efforts should be made to identify the underlying aetiology. MRI including special neonatal sequences should be considered a standard criterion for determining the prognosis in neonates presenting with seizures. In Weeke's study, MRI was an important tool in the diagnostic process aimed at identifying aetiology of neonatal seizures, since the finding of important imaging abnormalities would have been missed in 11.9% of infants, and MRI added significantly to the information obtained in 39.8% of infants.7 Despite some minor methodological issues concerning the complexity of the problem, the authors have to be complimented for conducting this comprehensive and detailed study, which provides the clinician with invaluable
Please cite this article in press as: Soltirovska Salamon A, et al., Development of epilepsy after neonatal seizures, (2015), http:// dx.doi.org/10.1016/j.ejpn.2015.05.005
2
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 5 ) 1 e2
information to improve individually tailored counselling on long-term outcomes and intervention in newborns with neonatal seizures.
Conflict of interest The authors have no conflicts of interest to disclose.
references
1. Pisani F, Facini C, Pavlidis E, Spagnoli C, Boylan G. Epilepsy after neonatal seizures: literature review. Eur J Paediatr Neurol 2015;19(1):6e14. 2. Connell J, Oozeer R, De Vries L, Dubowitz LM, Dubowitz V. Continuous EEG monitoring of neonatal seizures: diagnostic and prognostic consideration. Arch Dis Child 1989;64:452e8. 3. Khan RL, Nunes ML, Garcias Da Silva LF, Da Costa JC. Predictive value of sequential electroencephalogram in neonates with seizures and it relation to neurological outcome. J Child Neurol 2008;23:144e50. 4. Uria-Avellanal C, Marlow N, Rennie JM. Outcome following neonatal seizures. Semin Fetal Neonatal Med 2013;18(4):224e32. 5. van Rooij LGM, de Vries LS, Handryastuti S, Hawani D, Groenendaal F, van Huffelen AC, Toet MC. Neurodevelopmental outcome in term infants with status epilepticus detected with amplitude-integrated elctroencephalography. Pediatrics 2007;120(2):e354e63.
6. Soltirovska-Salamon A, Neubauer D, Petrovcic A, Paro-Panjan D. Risk factors and scoring system as a prognostic tool for epilepsy after neonatal seizures. Pediatr Neurol 2014;50(1):77e84. 7. Weeke LC, Groenendaal F, Toet MC, Benders MJ, Nievelstein RA, van Rooij LG, de Vries LS. The aetiology of neonatal seizures and the diagnostic contribution of neonatal cerebral magnetic resonance imaging. Dev Med Child Neurol 2015;57(3):248e56.
Aneta Soltirovska Salamon University Medical Centre Ljubljana, Division of Paediatrics, Department of Neonatology, Ljubljana, Slovenia David Neubauer University Medical Centre Ljubljana, Division of Paediatrics, Department of Neurology, Ljubljana, Slovenia Darja Paro-Panjan* University Medical Centre Ljubljana, Division of Paediatrics, Department of Neonatology, Ljubljana, Slovenia *Corresponding author. Department of Neonatology, Division of Paediatrics, University Medical Centre Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia. E-mail address: [email protected] 1090-3798/$ e see front matter © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejpn.2015.05.005
Please cite this article in press as: Soltirovska Salamon A, et al., Development of epilepsy after neonatal seizures, (2015), http:// dx.doi.org/10.1016/j.ejpn.2015.05.005
Official Journal of the European Paediatric Neurology Society
Letter to the Editor
Development of epilepsy after neonatal seizures Dear Sir, We read with great interest the article by Pisani et al. that reviewed the literature regarding the development of epilepsy after neonatal seizures.1 Outcome studies confirmed that neonatal seizures are a major risk for death or subsequent neurological disability and can independently confer an adverse neurodevelopmental outcome in high-risk neonates. Despite advances in perinatal and neonatal care, the development of childhood epilepsy after neonatal seizures still occurs in a substantial proportion of children. There is uncertainty about the true incidence of epilepsy after neonatal seizures due to the lack of population-based studies including newborns with clinical and/or EEG confirmed seizures. Additionally, the incidence of epilepsy reported between 1.8% and 41.3%2,3 is questionable due to inconsistent inclusion criteria and duration of the follow up. There are some surprising findings in Pisani's study, namely that none of the revised studies focused on the presence/ absence of clinical manifestations during electrographic seizures with regard to the incidence of postneonatal epilepsy.1,4 The need for further research in estimating the true incidence and long-term morbidity and mortality therefore cannot be overemphasized. The findings of Pisani's study also provide further evidence that children with epilepsy after neonatal seizures are at a higher risk of motor and cognitive disabilities. In 80.7%, epilepsy was associated with other neurological impairments; 18% of them developed epilepsy and intellectual impairment.1 The question which still needs to be addressed is the presence of less severe forms of disability, such as a minor motor impairment, attention deficit-hyperactivity disorder, perceptual-motor, cognitive and behavioural problems in children after neonatal seizures. Almost all of the reviewed studies in the article by Pisani et al. have been carried out in order to identify the correlation between antenatal/perinatal and neonatal risk factors for the development of epilepsy after neonatal seizures.1 Obviously, risk factors for the development of epilepsy are not significantly prognostic. The strongest predictors of outcome are the underlying cause and background electroencephalographic activity. The prevalence of later epilepsy is high following status epilepticus although the background EEG pattern before the onset of seizures may correlate better with outcome than the duration of seizures.5 The prognostic significance of many
other risk factors is almost equivocal in different studies and may reflect variation in data collection, classification, and analysis. We are aware that the reviewed article included data published up to the end of 2013, but our article, which was published shortly afterwards, also gave a contribution to this issue. The follow up period in our study was from 2 to almost 12 years, which is quite long when compared to other studies; the incidence of epilepsy in our cohort was 18.2% and was the highest in the first 12 months.6 In addition to the other risk factors, we identified that the duration of seizures after the first month was as an independent risk factor for developing epilepsy, so our data support the evidence that recurrent and prolonged neonatal seizures may act on epileptogenic substrate mainly observed in synaptogenesis, causing further damage including synaptic reorganization which is responsible for the subsequent clinical expression of epilepsy. In our study we aimed to design a scoring system for the prediction of epilepsy, but contrary to the three previous studies which were designed to predict overall adverse neurologic outcome we concluded that the construction of a universal scoring system was not possible due to the interaction between duration of seizures after the first month as the best predictor of epilepsy and gestational age.6 The duration of seizures after the neonatal period had a different effect on the development of epilepsy with respect to the gestational age. Although no scoring system will fully capture individual risks of epilepsy, models designed for more uniform populations such as term infants with hypoxia ischaemia may achieve the best prognostic power. Out of all highlighted facts in Pisani's study, we can conclude that in order to achieve the best prognostic information maximum efforts should be made to identify the underlying aetiology. MRI including special neonatal sequences should be considered a standard criterion for determining the prognosis in neonates presenting with seizures. In Weeke's study, MRI was an important tool in the diagnostic process aimed at identifying aetiology of neonatal seizures, since the finding of important imaging abnormalities would have been missed in 11.9% of infants, and MRI added significantly to the information obtained in 39.8% of infants.7 Despite some minor methodological issues concerning the complexity of the problem, the authors have to be complimented for conducting this comprehensive and detailed study, which provides the clinician with invaluable
Please cite this article in press as: Soltirovska Salamon A, et al., Development of epilepsy after neonatal seizures, (2015), http:// dx.doi.org/10.1016/j.ejpn.2015.05.005
2
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 5 ) 1 e2
information to improve individually tailored counselling on long-term outcomes and intervention in newborns with neonatal seizures.
Conflict of interest The authors have no conflicts of interest to disclose.
references
1. Pisani F, Facini C, Pavlidis E, Spagnoli C, Boylan G. Epilepsy after neonatal seizures: literature review. Eur J Paediatr Neurol 2015;19(1):6e14. 2. Connell J, Oozeer R, De Vries L, Dubowitz LM, Dubowitz V. Continuous EEG monitoring of neonatal seizures: diagnostic and prognostic consideration. Arch Dis Child 1989;64:452e8. 3. Khan RL, Nunes ML, Garcias Da Silva LF, Da Costa JC. Predictive value of sequential electroencephalogram in neonates with seizures and it relation to neurological outcome. J Child Neurol 2008;23:144e50. 4. Uria-Avellanal C, Marlow N, Rennie JM. Outcome following neonatal seizures. Semin Fetal Neonatal Med 2013;18(4):224e32. 5. van Rooij LGM, de Vries LS, Handryastuti S, Hawani D, Groenendaal F, van Huffelen AC, Toet MC. Neurodevelopmental outcome in term infants with status epilepticus detected with amplitude-integrated elctroencephalography. Pediatrics 2007;120(2):e354e63.
6. Soltirovska-Salamon A, Neubauer D, Petrovcic A, Paro-Panjan D. Risk factors and scoring system as a prognostic tool for epilepsy after neonatal seizures. Pediatr Neurol 2014;50(1):77e84. 7. Weeke LC, Groenendaal F, Toet MC, Benders MJ, Nievelstein RA, van Rooij LG, de Vries LS. The aetiology of neonatal seizures and the diagnostic contribution of neonatal cerebral magnetic resonance imaging. Dev Med Child Neurol 2015;57(3):248e56.
Aneta Soltirovska Salamon University Medical Centre Ljubljana, Division of Paediatrics, Department of Neonatology, Ljubljana, Slovenia David Neubauer University Medical Centre Ljubljana, Division of Paediatrics, Department of Neurology, Ljubljana, Slovenia Darja Paro-Panjan* University Medical Centre Ljubljana, Division of Paediatrics, Department of Neonatology, Ljubljana, Slovenia *Corresponding author. Department of Neonatology, Division of Paediatrics, University Medical Centre Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia. E-mail address: [email protected] 1090-3798/$ e see front matter © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejpn.2015.05.005
Please cite this article in press as: Soltirovska Salamon A, et al., Development of epilepsy after neonatal seizures, (2015), http:// dx.doi.org/10.1016/j.ejpn.2015.05.005