neonatal seizures: the journey so far

2
Editorial Neonatal seizures: The journey so far Neonatal seizures continue to pose a challenge for clinicians worldwide because they are difcult to diagnose and treat and are associated with poor outcomes.We have been using this state- ment, or something very similar, to introduce the topic of neonatal seizures when we give lectures or write papers for the last fteen years and in that period of time, unfortunately, very little has changed in the management and outcome of neonatal seizures. One of the major stumbling blocks facing clinicians who take care of neonates with seizures is the lack of effective antiepileptic drugs. The most commonly used rst line treatments, phenobarbi- tone and phenytoin are at best effective in about 50% of babies, although when used in neonates receiving therapeutic hypother- mia, phenobarbitone appears to be more effective in reducing seizure burden. 1 The Paediatric Medicines Regulation, 2 which was introduced in Europe in 2006, is certainly helping in the quest for effective antiepileptic drugs for neonates. This regulation aims to facilitate the development and accessibility of medicinal products for use in the paediatric population and to ensure that medicinal products used are based on high-quality ethical research. 3 In response to this regulation, the European Union, set up a new paediatric medicines call under the framework seven programme (FP7) for research consortia who wished to engage in research on paediatric medicines. In 2009 a group of clinicians and scientists, predominantly in Europe, were successful in their application to this FP7 funding call and set out to study seizures in neonates more carefully and in particular to assess the efcacy of antiepileptic drugs (http:// www.nemo-europe.com). The NEMO consortium has evaluated bumetanide as a potential second line treatment for neonatal sei- zures in a multi-centred study across Europe and the results of this study are soon to be published. The consortium now plans to study other antiepileptic drugs for neonates and have worked hard to gain new insights into neonatal seizures. In this edition of SFNM, many in the NEMO consortium have authored reviews on various aspects of neonatal seizures. These re- views generally reect the insights gained from managing many newborns with seizures across Europe. It also reects the results of in depth discussions on this topic, the sharing of ideas and the substantial collaborative efforts of all involved; all with one goal in mind - to improve our understanding of neonatal seizures and improve long term outcomes in this group. In our rst review, Nardou and colleagues provide an update on the differences between the immature and adult brain, with a particular focus on the developmental sequence of GABA. They describe how the neonatal brain is altered by seizures and how this knowledge has led to the identication of potential novel treat- ments for seizures. Chakrapani and Levene then present a review of the epidemiology and etiology of neonatal seizures. It is clear that although there have been shifts in some etiologies over the last few decades, overall little has changed and we will never really be able to comprehend the true incidence of neonatal seizures until EEG monitoring is widespread in neonatal intensive care units. The review by Cross clearly outlines the key clinical features that distinguish epileptic from non-epileptic behaviours, their manage- ment and prognosis. Hallberg and Blennow highlight the importance of searching for the correct cause of seizures in neonates and use a number of case examples to illustrate this. They also emphasise the importance of a multidisciplinary approach to the management of neonatal sei- zures. The differential diagnosis of seizures in the neonatal period is very important in order to optimise management and prognosis. When seizures are suspected, it is important to conrm the diagnosis using EEG monitoring and the review by Boylan and col- leagues outlines the options available for monitoring and updates on recent advances in automated seizure detection for neonates. Therapeutic options for neonatal seizures are a major focus area for the NEMO consortium and the review by Van Rooij and colleagues provides an update on the efcacy of currently available treatments for seizures in both term and preterm infants while emphasizing the lack of evidence from multi-centered trials. Pressler and Mangum provide a comprehensive overview on newly emerging therapies for neonatal seizures and outline the importance of using innovative methods for seizure trials to provide the best possible scientic evi- dence with high ethical standards. The nal review concentrates on the very important area of outcome and Uria-Avellanal and colleagues update on the current outcome statistics for neonatal seizures and emphasises the importance of synthesizing all available evidence before conveying the best estimate of risk to families. The journey for the scientic community continues and there is much work to do in order to improve outcomes for neonates with seizures. Recent outstanding preclinical research on seizures in the immature brain has signicantly advanced our understanding of the mechanisms underlying neonatal seizures. However, little has changed at the cot-side in our neonatal intensive care units. We need to understand more about why neonatal seizures are so very different to seizures in older children and adults. Thus, research must continue - at no time of life is this more important than in the neonatal period. If the vulnerable developing brain is injured, the consequences can include lifelong disability disabil- ities with detrimental effects for the child and their families as well as substantial societal and global healthcare costs. Acknowledgements The editors of this edition of SFNM would like to thank all NEMO partners for their contributions as well as add their specic thanks Contents lists available at SciVerse ScienceDirect Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny Seminars in Fetal & Neonatal Medicine 18 (2013) 173174 1744-165X/$ see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.siny.2013.05.011

Upload: ronit-m

Post on 01-Jan-2017

213 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Neonatal seizures: The journey so far

at SciVerse ScienceDirect

Seminars in Fetal & Neonatal Medicine 18 (2013) 173–174

Contents lists available

Seminars in Fetal & Neonatal Medicine

journal homepage: www.elsevier .com/locate/s iny

Editorial

Neonatal seizures: The journey so far

“Neonatal seizures continue to pose a challenge for cliniciansworldwide because they are difficult to diagnose and treat andare associated with poor outcomes.”We have been using this state-ment, or something very similar, to introduce the topic of neonatalseizures when we give lectures or write papers for the last fifteenyears and in that period of time, unfortunately, very little haschanged in the management and outcome of neonatal seizures.

One of the major stumbling blocks facing clinicians who takecare of neonates with seizures is the lack of effective antiepilepticdrugs. The most commonly used first line treatments, phenobarbi-tone and phenytoin are at best effective in about 50% of babies,although when used in neonates receiving therapeutic hypother-mia, phenobarbitone appears to be more effective in reducingseizure burden.1 The Paediatric Medicines Regulation,2 which wasintroduced in Europe in 2006, is certainly helping in the quest foreffective antiepileptic drugs for neonates. This regulation aims tofacilitate the development and accessibility of medicinal productsfor use in the paediatric population and to ensure that medicinalproducts used are based on high-quality ethical research.3

In response to this regulation, the European Union, set up a newpaediatric medicines call under the framework seven programme(FP7) for research consortia who wished to engage in research onpaediatric medicines.

In 2009 a group of clinicians and scientists, predominantly inEurope, were successful in their application to this FP7 fundingcall and set out to study seizures in neonates more carefully andin particular to assess the efficacy of antiepileptic drugs (http://www.nemo-europe.com). The NEMO consortium has evaluatedbumetanide as a potential second line treatment for neonatal sei-zures in a multi-centred study across Europe and the results ofthis study are soon to be published. The consortium now plans tostudy other antiepileptic drugs for neonates and have workedhard to gain new insights into neonatal seizures.

In this edition of SFNM, many in the NEMO consortium haveauthored reviews on various aspects of neonatal seizures. These re-views generally reflect the insights gained from managing manynewborns with seizures across Europe. It also reflects the resultsof in depth discussions on this topic, the sharing of ideas and thesubstantial collaborative efforts of all involved; all with one goalin mind - to improve our understanding of neonatal seizures andimprove long term outcomes in this group.

In our first review, Nardou and colleagues provide an update onthe differences between the immature and adult brain, with aparticular focus on the developmental sequence of GABA. Theydescribe how the neonatal brain is altered by seizures and howthis knowledge has led to the identification of potential novel treat-ments for seizures. Chakrapani and Levene then present a review ofthe epidemiology and etiology of neonatal seizures. It is clear that

1744-165X/$ – see front matter � 2013 Published by Elsevier Ltd.http://dx.doi.org/10.1016/j.siny.2013.05.011

although there have been shifts in some etiologies over the lastfew decades, overall little has changed and we will never reallybe able to comprehend the true incidence of neonatal seizures untilEEG monitoring is widespread in neonatal intensive care units.

The review by Cross clearly outlines the key clinical features thatdistinguish epileptic from non-epileptic behaviours, their manage-ment and prognosis.

Hallberg and Blennow highlight the importance of searching forthe correct cause of seizures in neonates and use a number of caseexamples to illustrate this. They also emphasise the importance of amultidisciplinary approach to the management of neonatal sei-zures. The differential diagnosis of seizures in the neonatal periodis very important in order to optimise management and prognosis.

When seizures are suspected, it is important to confirm thediagnosis using EEG monitoring and the review by Boylan and col-leagues outlines the options available for monitoring and updateson recent advances in automated seizure detection for neonates.

Therapeutic options for neonatal seizures are a major focus areafor theNEMOconsortiumand the reviewbyVanRooij and colleaguesprovides an update on the efficacy of currently available treatmentsfor seizures in both term and preterm infants while emphasizingthe lack of evidence frommulti-centered trials. Pressler andMangumprovide a comprehensive overview on newly emerging therapies forneonatal seizures and outline the importance of using innovativemethods for seizure trials to provide the best possible scientific evi-dence with high ethical standards. The final review concentrates onthevery importantareaofoutcomeandUria-Avellanal andcolleaguesupdate on the current outcome statistics for neonatal seizures andemphasises the importance of synthesizing all available evidencebefore conveying the best estimate of risk to families.

The journey for the scientific community continues and there ismuch work to do in order to improve outcomes for neonates withseizures. Recent outstanding preclinical research on seizures in theimmature brain has significantly advanced our understanding ofthe mechanisms underlying neonatal seizures. However, little haschanged at the cot-side in our neonatal intensive care units.

We need to understand more about why neonatal seizures areso very different to seizures in older children and adults. Thus,research must continue - at no time of life is this more importantthan in the neonatal period. If the vulnerable developing brain isinjured, the consequences can include lifelong disability – disabil-ities with detrimental effects for the child and their families aswell as substantial societal and global healthcare costs.

Acknowledgements

The editors of this edition of SFNMwould like to thank all NEMOpartners for their contributions as well as add their specific thanks

Page 2: Neonatal seizures: The journey so far

Editorial / Seminars in Fetal & Neonatal Medicine 18 (2013) 173–174174

to Dr Janet Rennie, University College London Hospitals and Profes-sor David Henshall, Royal College of Physicians in Ireland for theirvaluable help during the review process.

References

1. Low E, Boylan GB, Mathieson SR, Murray DM, Korotchikova I, Stevenson NJ,Livingstone V, Rennie JM. Cooling and seizure burden in term neonates:an observational study. Arch Dis Child Fetal Neonatal Ed 2012 Jul;97(4):F267–72.

2. Regulation (EC) no. 1901/2006 of the European Parliament and of the Council of12 December 2006 on medicinal products for paediatric use and amendingRegulation (EEC) no. 1768/92, Directive 2001/20/EC, Directive 2001/83/EC andRegulation (EC) no. 726/2004 (text with EEA relevance). Official Journal of theEuropean Union L 378/1, 27 December 2006.

3. Donnelly F. EU initiatives for research involving children. Eur J Pediatr 2008Jul;167(7):837–8.

Geraldine B. Boylan*

Neonatal Brain Research Group,Department of Paediatrics & Child Health,

University College Cork and Cork University Maternity Hospital,Cork, Ireland

Ronit M. PresslerDepartment of Clinical Neurophysiology, Great Ormond Street

Hospital for Children NHS Trust and Institute of Child Care,London, UK

E-mail address: [email protected]

* Corresponding author.E-mail address: [email protected]