Journal of Pediatric Neurology - Volume 7, issue 1

Authors: Ferriero, Donna M. | Silverstein, Faye S.

Article Type: Research Article

DOI: 10.3233/JPN-2009-0264

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 1-3, 2009

Authors: Jensen, Frances E.

Article Type: Research Article

Abstract: Neonatal seizures are inherently different from seizures in the child and the adult. The phenotype, often exhibiting electroclinical dissociation, is unique: neonatal seizures can be refractory to antiepileptic drugs otherwise effect for older patients. Recent experimental and human-based research reveals that the mechanism of neonatal seizures, as well as their long-term sequelae on later brain development, appears to involve a large number of age-specific factors. These observations help explain the resistance of …neonatal seizures to conventional therapy as well as identify potential areas of risk for later neurocognitive development. Emerging targets from this research may suggest new therapies for this unique population of patients. Show more

Keywords: Epilepsy, hypoxia/ischemia, developing brain, learning disability, development, neurotransmitters

DOI: 10.3233/JPN-2009-0270

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 5-12, 2009

Authors: Glass, Hannah C. | Wu, Yvonne W.

Article Type: Research Article

Abstract: Neonatal seizures are common and frequently indicate significant underlying brain abnormality. The epidemiology of neonatal seizures has been evaluated in several population and hospital-based studies and these investigations have lead to identification of important maternal, intrapartum and infant risk factors. Identifying and avoiding risks factors for neonatal seizures may lead to lower infant neurological morbidity and mortality.

Keywords: Seizure, infant, newborn

DOI: 10.3233/JPN-2009-0265

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 13-17, 2009

Authors: Hellström-Westas, Lena | de Vries, Linda S.

Article Type: Research Article

Abstract: Introducing amplitude integrated electroencephalography in the neonatal intensive care unit has made us aware of the common occurrence of seizures in high risk newborn infants. Using this technique or conventional multi-channel electroencephalography we now know that clinical seizures are often not confirmed as seizure patterns on the amplitude integrated electroencephalography, that subclinical seizures are very common in newborn infants, especially after administration of a first antiepileptic drug, which is called electroclinical dissociation …or decoupling. A status epilepticus is also not uncommon and is also usually entirely subclinical. We are well aware that focal, low amplitude and very brief seizures will not be detected using this technique. The amplitude integrated electroencephalography technology has greatly been improved over the last decade, changing from analogue to digital and from strictly one-channel to now mostly two channel recordings. The major improvement is the simultaneous display of the raw electroencephalography and in some machines even access to a seizure detection algorithm. These developments have made it possible to find the best electrode placements and to study the effects of antiepileptic drugs more effectively. Show more

Keywords: Amplitude integrated EEG, seizure, electroencephalography

DOI: 10.3233/JPN-2009-0268

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 19-23, 2009

Authors: Cilio, Maria Roberta

Article Type: Research Article

Abstract: Despite the evolution of new technologies for assessing neonatal brain function, electroencephalography (EEG) remains a powerful tool for neurological diagnosis and prognosis in neonates. It is considered the gold standard for distinguishing epileptic seizures from non-epileptic paroxysmal events and for detecting subclinical seizure activity in high-risk babies. In those babies severely ill, EEG is even more efficient as predictive test than the neurological examination. The prognostic value of neonatal EEG has been …long recognized in term as well as in preterm infants. Background patterns, more that patterns of ictal discharges, correlate significantly with the long-term outcome. Although most abnormalities on the neonatal EEG are nonspecific, certain patterns can be highly suggestive for diagnosis. Prognostic value can be increased by obtaining early recordings, possibly within the first 48 hr of life, prolonged recordings to include samples of different activity states, and serial EEGs at short intervals to assess rapid changes that are likely to occur in high-risk infants. It is important to distinguish neonatal seizures from neonatal-onset epilepsies and epilepsy syndromes. Both benign and malignant neonatal epilepsy syndromes exist. While benign familial neonatal seizures represents a neonatal syndrome with benign outcome, early myoclonic encephalopathy and Ohtahara syndrome are the earliest form of age-dependent severe epilepsy syndromes. Early myoclonic encephalopathy and Ohtahara syndrome are both characterized by the presence of a burst-suppression EEG pattern. This pattern is usually associated with a poor prognosis and is considered the electroencephalographic correlate of a complete disconnection within the thalamocortical systems. Migrating partial seizures in infancy is a newly recognized epilepsy syndrome whose onset can be in the neonatal period. It is characterized by multifocal intractable seizures associated with psychomotor impairment. No etiology has been found so far. Different drugs currently used in neonatal intensive care unit, especially if in the toxic range, can alter the EEG background. Those effects need to be taken in account in the interpretation of neonatal EEG. Show more

Keywords: EEG, newborn, epilepsy, seizures

DOI: 10.3233/JPN-2009-0272

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 25-43, 2009

Authors: Shah, Divyen K. | Lawrence, Russell | Inder, Terrie E.

Article Type: Research Article

Abstract: Electrographic seizures are an important manifestation of cerebral pathology in the newborn. Over the last few decades, automated seizure detection systems have been devised in order to assist the clinician's review. Basic principles and approaches of systems applied to the newborn, using multiple channels are compared. The application of a system using two channels of electroencephalography with amplitude-integrated electroencephalography monitoring in the newborn is also described. Newer and novel approaches to automated …seizure detection are also discussed. Show more

Keywords: EEG, aEEG, seizures, newborn, algorithms

DOI: 10.3233/JPN-2009-0267

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 45-49, 2009

Authors: Scher, Mark S.

Article Type: Research Article

Abstract: Current advances in clinical and translational research bring into sharper focus the importance of epidemiologic, neurobiologic and pathophysiologic factors that contribute to neonatal seizure occurrence, and potential consequences for subsequent neurologic deficits. Diagnostic and therapeutic algorithms must integrate prenatal, peripartum and postnatal contributions to neonatal seizures with or without the expression of neonatal encephalopathy. Neonatal seizure classifications must consider time-dependent vulnerabilities to injury from different etiologies in specific brain regions …as a function of gestational maturity. The design of therapeutic protocols for neuroprotection must consequently consider both prenatal and postnatal strategies for prevention as well as rescue and repair. Neonatal neurointensive care programs need to integrate these protocols into the care paths of preterm and/or full-term neonates who express neonatal seizures in the context of acute and/or chronic brain disorders. A newborn with seizures represents a complex phenotype of past, present and future risks for brain injury. Show more

Keywords: Seizures, neonate, fetus, placenta, maternal factors, antiepileptic medications, neuroprotection

DOI: 10.3233/JPN-2009-0274

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 51-60, 2009

Authors: Bonifacio, Sonia L. | Miller, Steven P.

Article Type: Research Article

Abstract: Neonatal seizures are a symptom of brain dysfunction and frequently signal the clinician to look further for evidence of a pathologic intracranial or systemic process. Imaging the newborn brain is a critically important part of the evaluation of the newborn with seizures. Determining the underlying diagnosis is critical for appropriate treatment and accurately counseling the caregivers of affected newborns. Brain imaging provides the best aid in identification of causative brain abnormalities, including injury, and …ultimately provides important insight into the prognosis of the newborn with seizures. Recent advances in specialized magnetic resonance techniques provide the opportunity to further study the effects of neonatal seizures in vivo, by measuring regional brain metabolism. As these advanced magnetic resonance imaging modalities can identify newborns at high risk of seizures, as well as those newborns at highest risk of adverse neurodevelopmental outcomes, they will further enable the study of emerging anti-seizure therapies on the newborn brain. Show more

Keywords: Seizures, term newborn, asphyxia, hypoxic-ischemic encephalopathy, neonatal encephalopathy, stroke, MRI, MRS

DOI: 10.3233/JPN-2009-0269

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 61-67, 2009

Authors: Lawrence, Russell | Inder, Terrie E. | Mathur, Amit M.

Article Type: Research Article

Abstract: Seizures, a common clinical manifestation of neurological dysfunction in the neonate, occur in 1–4 per 1000 live births and are associated with very poor outcomes. However, the role of seizures as merely associative or contributory to poor outcomes remains unclear. Clinical and laboratory studies have demonstrated a deleterious effect of seizures on the developing brain. There is a lack of consensus among the neonatal and neurologic community about how to monitor and treat patients at risk …for seizures. Currently used antiepileptic drugs lack efficacy and may potentially cause apoptosis in the developing brain. Continuous conventional electroencephalography with video is the gold standard for detection and monitoring of electrographic seizures but may not be practical in a study design or 24 h widespread clinical use. New drugs such as bumetanide, levetiracetam, and topiramate hold promise as new therapies, but safety, pharmacokinetic, and efficacy data remain limited. In this article, current challenges in designing seizure trials are discussed including potential options to accurately assess the seizure burden, possible antiepileptic drug choices, and potential outcome measures. Ongoing trials in the field of neonatal seizures are also discussed including two separate drug trials and a multicenter trial evaluating the impact of subclinical seizure treatment using limited channel amplitude-integrated electroencephalography. Show more

Keywords: Neonatal seizures, amplitude integrated EEG, hypoxic ischemic injury

DOI: 10.3233/JPN-2009-0273

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 69-77, 2009

Authors: Sharpe, Cynthia | Haas, Richard H.

Article Type: Research Article

Abstract: Levetiracetam has properties which make it a promising candidate for the treatment of neonatal seizures. The mechanism of action and evidence of broad spectrum clinical efficacy in adults and older children is reviewed along with the limited reported experience in neonates. The safety profile, pharmacokinetic properties and evidence of neuroprotective qualities are discussed together with the current status of pharmacokinetic studies in neonates.

Keywords: Levetiracetam, neonatal seizures

DOI: 10.3233/JPN-2009-0275

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 79-83, 2009

Authors: Soul, Janet

Article Type: Research Article

Abstract: Novel medications to treat neonatal seizures have been the subject of numerous recent basic science research and clinical papers describing the potential and need for more effective and safe antiepileptic drugs (AEDs) for this unique population. This interest has been fueled in part by the notion that seizures, particularly when refractory, likely contribute to brain injury, later epilepsy and neurodevelopmental impairments. The population of newborns with seizures presents unique challenges, because of the often significant …differences in the pharmacokinetics, safety and efficacy of medications when compared with older children and adults. Bumetanide and topiramate are two novel AEDs that have mechanisms of action uniquely suited to suppressing seizures in the newborn brain, with promising basic science data supporting their use in human newborns. Furthermore, these novel medications offer the potential of neuroprotective effects when used to treat refractory seizures caused by acute insults to the neonatal brain. The available data regarding the mechanism of action, pharmacokinetics, and safety of these two AEDs will be described, as well as the data needed to bring these two agents into routine use in the human newborn with seizures. Show more

Keywords: Neonatal seizures, bumetanide, topiramate, hypoxic-ischemic encephalopathy, brain injury, pharmacokinetics, safety, neuroprotection, neurologic outcome

DOI: 10.3233/JPN-2009-0271

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 85-93, 2009

Authors: Guillet, Ronnie

Article Type: Research Article

Abstract: The treatment of infants with antiepileptic medications after the resolution of neonatal seizures is highly variable and controversial. Infants are commonly treated with phenobarbital after their seizures have resolved to prevent recurrence. Data to support this practice are lacking but animal models suggest that the neonatal brain is vulnerable to repeated seizures. Yet exposure of the developing brain to phenobarbital for prolonged periods may have deleterious consequences. We discuss current clinical practice and present …information on risks and benefits of continued treatment with phenobarbital after resolution of neonatal seizures. Show more

Keywords: Phenobarbital, neonate, seizures, brain development

DOI: 10.3233/JPN-2009-0266

Citation: Journal of Pediatric Neurology, vol. 7, no. 1, pp. 95-99, 2009