Neonatal seizures
Myron Yaster MD
SPA’s quality and safety committee’s checklist and PediCrisis app committees recently approved a new “seizure” checklist. As many of you may recall from a previous PAAD, I personally didn’t think this was necessary because the most potent anti-convulsants known to man are general anesthetics, so my thinking was (is), if a patient is seizing post operatively, after ruling out causes like hypoxia, hypoglycemia, hyponatremia, and local anesthetic overdoses, all we need to do is simply treat with either an IV or vapor general anesthetic to stop the seizure. Nevertheless, many (most?) of you, and the checklist committee clearly disagreed.
Neonatal seizures, defined as seizures occurring with 4 weeks after birth in full-term infants or within 44 weeks of postmenstrual age in preterm infants, is a unique subset of pediatric seizures. Neonatal age, the age at the onset of seizures, and clinical semiology provide clues to the cause of seizures, which in turn lead to tailored treatments, and current practice stresses the importance of EEG monitoring. In today’s PAAD we’ll review a recently published article on this topic in the New England Journal of Medicine.(1) As anesthesiologists we see some of these patients when they undergo diagnostic imaging, lumbar punctures, central line placement, and occasionally neurosurgical treatment. Myron Yaster MD
Original article
Yozawitz E. Neonatal seizures. N Engl J Med 2023; 388:1692-1700. DOI: 10.1056/NEJMra2300188 PMID: 37133587
“Most neonatal seizures are transient and result from acute metabolic disturbances, infectious processes, or acute focal cerebral lesions. Such seizures are considered to be provoked. In full-term neonates, the most common cause of provoked seizures is hypoxic ischemic encephalopathy, followed in frequency by stroke and infection. In preterm neonates, the most common cause is intraventricular hemorrhage. Identifying the provoking event is essential for determining management”.(1)
Neonatal seizures start focally but can spread to involve the entire body. Seizures that start as generalized seizures are rare. “Several common nonepileptic motor phenomena may be difficult to differentiate from seizures in neonates. Tremor, jitteriness, and some myoclonic movements can be mistaken for seizures. They can occur without obvious cause or as symptoms of drug withdrawal, electrolyte abnormalities, hypoglycemia, or infection”.(1)
A proposed diagnostic workup from the article is shown below.
Treatment: First line therapy is with IV phenobarbital. If the neonate does not have a response to phenobarbital, phenytoin, levetiracetam, midazolam, or lidocaine may be used as second-line intervention. If seizures continue despite the administration of conventional anti-seizure medication, a pyridoxine challenge may be attempted, since the rare condition known as pyridoxine-dependent developmental and epileptic encephalopathy responds to pyridoxine, “Therapeutic hypothermia for 72 hours is now used routinely for term and near-term infants with moderate-to-severe hypoxic ischemic encephalopathy in an effort to ameliorate the brain injury and improve later developmental outcomes”.(1,2)
Finally, “early infantile developmental and epileptic encephalopathy is a newly characterized entity that is manifested as medication-resistant seizures of various types in the first 3 months of life, associated with severe developmental impairment, abnormal findings on neurologic examination, and an EEG background with burst suppression, or multifocal epileptiform discharges with diffuse slowing. Neuroimaging, genetic testing, and metabolic studies show an underlying cause in up to 80% of infants.”.(1,3)
References
1. Yozawitz E. Neonatal Seizures. N Engl J Med 2023;388:1692-700.
2. Montaldo P, Lally PJ, Oliveira V, Swamy R, Mendoza J, Atreja G, Kariholu U, Shivamurthappa V, Liow N, Teiserskas J, Pryce R, Soe A, Shankaran S, Thayyil S. Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study. Archives of Disease in Childhood - Fetal and Neonatal Edition 2019;104:F515-F20.
3. Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022;63:1349-97.