Neonatal seizures in hypoxic–ischaemic encephalopathy – risks and benefits of anticonvulsant therapy

Abstract

The risk of seizures is at its highest during the neonatal period, and the most common cause of neonatal seizures is hypoxic–ischaemic encephalopathy (HIE). This enhanced vulnerability is caused by an imbalance in the expression of receptors for excitatory and inhibitory neurotransmission, which is age dependent. There has been progress in detecting the electrophysiological abnormalities associated with seizures using amplitude‐integrated electroencephalography (aEEG). Data from animal studies indicate a variety of risk factors for seizures, but there are limited clinical data looking at the long‐term neurodevelopmental consequences of seizures alone. Neonatal seizures are also associated with increased risk of further epileptic seizures; however, it is less clear whether or not this results from an underlying pathology, and whether or not seizures confer additional risk. Phenobarbital and phenytoin are still the first‐line antiepileptic drugs (AEDs) used to treat neonatal seizures, although they are effective in only one‐third of affected infants. Furthermore, based on findings from animal studies, there are concerns regarding the risks associated with using these AEDs. Clinicians face a difficult challenge because, although seizures can be easily identified using aEEG, treatment options are limited, and there are uncertainties regarding treatment outcomes. There is a need to obtain long‐term follow‐up data, comparing groups of infants treated with or without current therapies. If these analyses indicate a definite benefit of treating neonatal seizures, then novel therapeutic approaches should be developed.

Time and sex dependent effects of magnesium sulphate on post‐asphyxial seizures in preterm fetal sheep

“…). Whether all seizures increase brain injury, and thus should be treated, remains debated (Shetty, ). However, resolving this issue is difficult because anti‐seizure treatments for neonates are limited in number, potentially injurious themselves, and for many infants simply ineffective or effectiveness is lost over time (Hellstrom‐Westas et al .…”

“…However, resolving this issue is difficult because anti‐seizure treatments for neonates are limited in number, potentially injurious themselves, and for many infants simply ineffective or effectiveness is lost over time (Hellstrom‐Westas et al . ; Shetty, ; Thoresen & Sabir, ). There is a need for more evidence‐based studies to guide neonatal seizure management (Hellstrom‐Westas et al .…”

Models of hypoxia and ischemia-induced seizures

“…Hypoxic and/or ischemic encephalopathy (HIE), a complex condition due to inadequate brain blood flow and oxygen supply, is the most common cause for neonatal seizures, and accounts for more than two-thirds of neonatal seizure cases (Jensen, 2009;Shetty, 2015). The onset of these neonatal seizures with HIE injuries often occur within 1-2 days of birth.…”

Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways

“…Nowadays, no effective therapies are available to prevent or minimize brain damage associated with HIE injury to the perinatal brain. Some therapies have been developed for adults; however, implementation of these therapies on newborns has not been successful because pathologic changes in the brain are age-dependent (Zhu et al, 2005;Shetty, 2015). Therefore, additional treatments that are safe for children and can improve the prognosis of severe neonatal HIE are urgently needed.…”