A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic–ischemic encephalopathy

Rao, Lekha M.; Hussain, Shaun A.; Zaki, Timothy A.; Cho, Alexander; Chanlaw, Teresa; Garg, Meena; Sankar, Raman

doi:10.1016/j.yebeh.2018.09.015

Cited by 45 publications

(43 citation statements)

References 37 publications

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“…Levetiracetam has a favourable pharmacokinetic profile with a wide therapeutic range and few adverse events reported in paediatric population (Egunsola et al, 2016). A number of retrospective (for example (Abend et al, 2011;Neininger et al, 2015;Rao et al, 2018) and open perspective studies (for example , Gowda et al, 2019, Ramantani et al, 2011, Sedighi et al, 2016 have indicated that levetiracetam may be as effective or even be superior than phenobarbital for the treatment of seizures in the neonatal period. However, the majority of these studies did not use EEG as an outcome measures, tested a variety of different doses (ranging from 5-80mg/kg for the loading dose and 5-100mg/kg for maintenance) and did not control for polytherapy.…”

Section: Evidence Base Of Current Neonatal Seizure Treatmentmentioning

confidence: 99%

Why we urgently need improved seizure and epilepsy therapies for children and neonates

Pressler

Lagae

2020

Neuropharmacology

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In contrast to epilepsy in adolescents and adults, neonatal seizures and early onset epilepsy poses unique challenges with significant repercussion for treatment choices. Most importantly, high seizure burden and epileptic encephalopathy are associated with developmental, behavioural and cognitive problems. The causes are multifactorial and include etiology, seizure burden, epileptic encephalopathy, but also antiseizure medication. In contrast to adults and older children only very few drugs have been licenced for infants and neonates, and after a long delay. Very recently, extrapolation of adult data has become possible as a path to speed up drug development for younger children but this is not necessarily possible for infants and neonates. With the advances in understanding the molecular basis of many epilepsies, targeted therapies become available, for example for KCNQ2 mutation related epilepsies, Dravet syndrome or tuberous sclerosis complex. Drug trials in neonates are particularly challenging because of their inconspicuous clinical presentation, the need for continuous EEG monitoring, high co-morbidity, and poor response to antiepileptic drugs. There is an urgent need for development of new drugs, evaluation of safety and efficacy of current antiseizure drugs, as well as for national policies and guidelines for the management of seizures and epilepsy in neonates and infants. Highlights  Treatment of early onset seizures and epilepsies pose a clinical challenge to clinicians.  Only very few drugs have been licenced due to lack of randomised controlled trials.  Systematic reviews no good evidence for the choice of treatment.  Precision medicine is so far only available for a small number of syndromes.

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Section: Evidence Base Of Current Neonatal Seizure Treatmentmentioning

confidence: 99%

Why we urgently need improved seizure and epilepsy therapies for children and neonates

Pressler

Lagae

2020

Neuropharmacology

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“…In yet another study by Rao et al (2018), there was again male preponderance among neonates with seizures. In another study conducted in the NICU of a tertiary care hospital in Nasik 156 , out of the 127 neonates studied, 118(92.91%) neonates were full term while 7(5.51%) were preterm.…”

Section: Discussionmentioning

confidence: 88%

Study of Clinical Profile of Neonatal seizures in a NICU of Rural Central India

Varma¹,

Meshram²,

Darvhekar³

et al. 2020

ijrps

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Seizures are common neonatal illness amongst neurological disorders. The study was conducted to determine the clinical profile of neonatal seizures. A hospital based prospective observational study was undertaken in the NICU of a rural set up in central India. A total of 82 neonates admitted with seizures or who developed seizures later during the stay in NICU were subject population of the study. Of 82 neonates with seizures, the overall mean for duration of stay was 14.34 (±10.41) days and the interquartile range was 1-32 days and male predominance. Majority of neonates included were extramural deliveries (62.19%). The distribution of neonates in the study according to their gestational age, birth weight, route of delivery & MSAF was found to be statistically insignificant (p Value >0.05). The vaginal route of delivery was more common than the caesarean section among neonates with seizures in the study. The overall mortality rate was 17.07% (14/82) .In most of the cases, the causes of neonatal seizures were present. Birth asphyxia was the main etiology identified. The antenatal services and intrapartum monitoring is important.

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“…Rao et al retrospectively evaluated the effectiveness of PHB and levetiracetam (LEV) as a first-line AED in a cohort of neonates with HIE and seizures. 35 LEV was noted to be associated with faster seizure freedom, even after adjustment of initial seizure frequency and HIE severity. However, as with previous other studies, the major limitation of this particular study was the retrospective design and nonrandom treatment allocation.…”

Section: First-and Second-line Therapy and Relevant Studiesmentioning

confidence: 91%

Recent Advances in the Diagnosis and Treatment of Neonatal Seizures

Samanta

2020

Neuropediatrics

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Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroencephalogram (EEG) is the gold standard for monitoring neonatal seizures, amplitude-integrated EEGs have gained significant popularity in resource-limited settings. There is tremendous progress in the automated seizure detection algorithm, including the availability of a fully convolutional neural network using artificial machine learning (deep learning). There is a substantial need for ongoing research and clinical trials to understand optimal medication selection (first line, second line, and third line) for neonatal seizures, treatment duration of antiepileptic drugs after cessation of seizures, and strategies to improve neuromorbidities such as cerebral palsy, epilepsy, and developmental impairments. Although in recent times, levetiracetam use has been significantly increased for neonatal seizures, a multicenter, randomized, blinded, controlled phase IIb trial confirmed the superiority of phenobarbital over levetiracetam in the acute suppression of neonatal seizures. While there is no single best choice available for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.

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A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic–ischemic encephalopathy

Cited by 45 publications

References 37 publications

Why we urgently need improved seizure and epilepsy therapies for children and neonates

Why we urgently need improved seizure and epilepsy therapies for children and neonates

Study of Clinical Profile of Neonatal seizures in a NICU of Rural Central India

Recent Advances in the Diagnosis and Treatment of Neonatal Seizures

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