Clinical Management of Seizures in Newborns

Department of Neonatology, KE 04.123.1, Wilhelmina Children's Hospital, University Medical Centre Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands, .
Paediatric Drugs (Impact Factor: 1.98). 01/2013; 15(1). DOI: 10.1007/s40272-012-0005-1
Source: PubMed


Neonatal seizures can be classified as tonic, clonic, myoclonic, and subtle. A clinical diagnosis is not easy as seizures are usually subtle in neonates. In the majority of newborn infants seizures are subclinical. On the other hand, not all abnormal movements identified by clinicians as clinical seizures are accompanied by electroencephalographic seizure discharges in the EEG. Precise incidence is difficult to delineate and depends on study population and criteria used for diagnosis of seizures. Controversy exists as to whether neonatal seizures themselves cause damage to the developing brain, or if the damage is primarily due to the underlying cause of the seizures. As a result of this controversy there is ongoing discussion whether all seizures (both clinical and subclinical) should be treated. In addition, when (sub)clinical seizures are treated, there is no consensus about the most appropriate treatment for neonatal seizures and how to assess the efficacy of treatment.Current therapeutic options to treat neonatal seizures (i.e. primarily first-generation antiepileptic drugs [AEDs]) are relatively ineffective. In practice, phenobarbital still remains the drug of first choice for EEG confirmed or suspected seizures. Benzodiazepines are also used in (phenobarbital) refractory cases. Several (small) studies indicate that lidocaine is an effective drug for refractory seizures as second- or third-line treatment. Although data are scarce, some AEDs with a wide acceptance in adult and pediatric neurology practice are being used to treat neonatal seizures (i.e. second-generation AEDs). These drugs are chemically different from all first-generation AEDs and they have an effect on other pathways so they provide new pharmacological targets for controlling seizures in newborns. Levetiracetam, topiramate, felbamate, bumetanide, lamotrigine and vigabatrin are examples of these second-generation AEDs.There is an urgent need for prospective, randomized, controlled trials to assess the efficacy and safety of these second-generation AEDs in neonates.The aim of this review is to provide an overview of the current knowledge of diagnosis, the effect on brain injury, and the treatment of neonatal seizures.

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    ABSTRACT: The treatment of neonatal seizures has not changed significantly over the last 50 years despite advances in antiepileptic drug (AED) development for older children and adults. Recently new drugs have emerged some of which address age-specific challenges or mechanisms and will be discussed in this review. The loop diuretic bumetanide blocks the neuronal NKCC1 co-transporter and is thought specifically to supress seizures in the immature brain. Levetiracetam has been used in children and infants with good efficacy, an excellent safety profile, and near-ideal pharmacokinetic characteristics. Randomised controlled trials are now underway to test the efficacy of some newer AEDs for neonatal seizures. Topiramate has been shown to have neuroprotective properties in addition to its antiepileptic action and trials in babies with hypoxic-ischaemic encephalopathy are now planned. There is an urgent need to develop age-specific AEDs for preterm and term babies. These drugs must be evaluated with multicentre, collaborative trials using innovative methods and high ethical standards to overcome age-specific challenges with the ultimate aim of improving the outcome for neonates with seizures.
    Full-text · Article · May 2013 · Seminars in Fetal and Neonatal Medicine
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    ABSTRACT: We read with great interest the article by Lundqvist et al (1), that evaluated the efficacy and safety of lidocaine for treating neonatal seizures in infants (gestational age ≥ 37 week, age ≤ 28 days) following benzodiazepines, but not preceding phenobarbital treatment. The authors reported that the treatment stopped seizures in 16 of the 30 infants studied. Suspected adverse effects were only seen in one patient, who developed a transient bradycardia. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2013 · Acta Paediatrica
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    ABSTRACT: In den USA erleiden 1,5–3,0/1000 Neugeborene (NG) einen Anfall in der Neugeborenenperiode; die Rate bei Frühgeborenen (FG) ist deutlich größer. Das Erkennen von Anfällen bei reifen und v. a. bei unreifen NG ist unverändert schwierig. Die Semiologie der Anfälle im NG-Alter unterscheidet sich erheblich von der in späteren Lebensabschnitten. Nicht immer kommen das klinische und das EEG-Anfallsbild zur Deckung. Die Einführung von amplitudenintegrierten EEG als ,,bedside monitoring“ hat sicherlich dazu beigetragen, Anfälle früher zu erkennen und die Therapie besser zu steuern. Die Grunderkrankung bestimmt in erster Linie die Prognose der Kinder. In den letzten Jahren erhobene tierexperimentelle Daten weisen jedoch nach, dass die Anfälle selbst zu morphologischen Veränderungen beitragen können. Diese sind bei Vorschädigungen des Zentralnervensystems (ZNS) stärker ausgeprägt. Die Bedeutung dieser zusätzlichen Schädigung durch Anfälle tritt jedoch hinter die durch die Grunderkrankung deutlich zurück. Für zahlreiche Antiepileptika [u. a. Phenobarbital (PB), Valproat (VPA), Phenytoin (PHT), Carbamazepin (CBZ), Lamotrigin (LTG)], nicht jedoch für Levetiracetam (LEV) und Topiramat (TPM) konnte eine gesteigerte Apoptoserate bei der neonatalen Ratte nachgewiesen werden. Ob diese Daten wirklich vollständig auf den Menschen übertragen werden können, ist noch nicht entschieden. Diese Diskussion hat aber dazu beigetragen, dass LEV, für das in kleinen Fallserien die Wirksamkeit belegt werden konnte und keine gesteigerte Apoptose berichtet wurde, von vielen Kliniken als Alternative bzw. sogar als 1. Medikament bei Anfällen in der NG-Periode eingesetzt wird.
    No preview · Article · Aug 2013 · Zeitschrift für Epileptologie
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