Keppra Use in Neonatal Seizures

Neonatal seizures are a common problem in the NICU and are associated with severe morbidity and mortality. A seizure is a symptom of a neurological dysfunction and not a disease itself. Seizures result from excessive simultaneous electrical discharge or depolarization of neurons. Most neonatal seizures are sub clinical with no visible signs. Causes include ischemia, hypoxia, hypoglycemia, hypo or hypernatremia, among other metabolic disorders; structural causes from IVH or trauma; intracerebral meningitis; drug withdrawal; and genetics. The main prediction of outcome of seizure is the underlying etiology. Those with hypoxic ischemic encephalopathy (HIE) or major brain malformations do worse than those with transient hypoglycemia or small subarachnoid hemorrhage. There is debate as to whether neonatal seizures are harmful, however, animal studies suggest they are indeed harmful. According to these studies a strong increase in damage to the neonatal (rat) brain associated with seizures was noted when the brain had been exposed to HI, and seizures accelerated anoxia induced death in rat hippocampus. In a human infant study, 68 infants with risk for seizures were monitored. Their baseline etiologies, Apgars, blood gasses, etc., were all similar, but their baseline EEG’s were not. The group that went on to seize had more abnormality of the background EEG. The occurrence of electrographic seizure activity (ESz) was correlated with micronencephaly, severe cerebral palsy and failure to thrive. Also those with the greatest number of ESz were more likely to have these severe outcomes. Data suggests an association between the amount of ESz and subsequent mortality and morbidity in at-risk infants in general and infants with perinatal asphyxia. Therefore, seizure detection is extremely important. But, currently detection rates for clinically apparent seizures are 52% inaccurate. 50 to 90% of all neonatal seizures are sub clinical with absolutely no clinical signs detected by experts.
Treatment: Phenobarbital and phenytoin are still the drugs of choice but are only about 45% effective at eliminating ESz individually and 57% effective when used together.  Side effects include hypotension, apnea, and other common AED side effects.  Recent rat data suggest that Phenobarbital, Phenytoin and benzodiazepines may themselves accelerate apoptotic (cell death) neurodegeneration in the developing brain.  New drug treatments in the pipeline include Topamax, Levetiracetam, Lidocaine, Bumatenide (+Phenobarbital). Of these, a recently released IV formulation of Levetiracetam (Keppra) is a good candidate for treatment of neonatal seizures. It has been determined to be safe, have no drug interactions, is neuroprotective, and does not cause neuronal apoptosis in animals.
 
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