Treating the symptom or treating the disease in neonatal seizures: a systematic review of the literature

Abstract

Aim The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic protocols. We systematically reviewed the available literature examining neonatal seizure treatments to clarify which drugs are the most effective for the treatment of specific neurologic disorders in newborns. Method We reviewed all available, published, literature, identified using PubMed (published between August 1949 and November 2020), that focused on the pharmacological treatment of electroencephalogram (EEG)-confirmed neonatal seizures. Results Our search identified 427 articles, of which 67 were included in this review. Current knowledge allowed us to highlight the good clinical and electrographic responses of genetic early-onset epilepsies to sodium channel blockers and the overall good response to levetiracetam, whose administration has also been demonstrated to be safe in both full-term and preterm newborns. Interpretation Our work contributes by confirming the limited availability of evidence that can be used to guide the use of anticonvulsants to treat newborns in clinical practice and examining the efficacy and potentially harmful side effects of currently available drugs when used to treat the developing newborn brain; therefore, our work might also serve as a clinical reference for future studies.

Polymorphisms of the sodium voltage-gated channel, alpha subunit 1 (SCN1A -A3184G) gene among children with non-lesional epilepsy: a case-control study

“…Several studies were carried out to select the most appropriate AEDs in different types of epilepsy [9,35]. The current study suggested that levetiracetam and carbamazepine were more frequently used in the AG-genotyped responders than those with the AA genotype.…”

“…Carbamazepine, oxcarbazepine, phenytoin, lamotrigine, lacosamide and lidocaine prevent seizure activity through blocking the movement of sodium ions across sodium ion channels during the propagation of action potentials. This group of antiepileptic drugs (AEDs) has an additional advantage through acting on potassium channels, due to structural similarities, thus controlling genetic epilepsies due to mutations of voltage-gated potassium channel genes [9].…”

Medical treatment in infants and young children with epilepsy: Off‐label use of antiseizure medications. Survey Report of ILAE Task Force Medical Therapies in Children

“…More recently, many centers have started to favor levetiracetam as first‐ or second‐line ASM in neonatal seizures due to its favorable pharmacokinetics and excellent tolerability. 17 , 18 , 19 , 20 In addition, preclinical studies have led to concerns about safety of phenobarbital 20 , 21 as well as its efficacy in the neonatal period. 22 , 23 However, a recent RCT comparing phenobarbital vs. levetiracetam has provided first class evidence that phenobarbital is the most effective ASM in this age group: the primary outcome measure (seizure control at 24 hours) was achieved in 24/30 neonates in the phenobarbital group vs. only 15/53 neonates in the levetiracetam group (RR 0.35, CI: 0.22, 0.56).…”

“…More recently, many centers have started to favor levetiracetam as first-or second-line ASM in neonatal seizures due to its favorable pharmacokinetics and excellent tolerability [17][18][19][20] . In addition, preclinical studies have led to concerns about safety of phenobarbital 20,21 as well as its efficacy in the neonatal period 22,23 .…”

New insights in pediatrics in 2021: choices in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine

“…The authors of this systematic review deepen the controversies about therapy of neonatal seizures [ 97 ]. In recent years, advances in the diagnosis [ 98 ] and etiological definition of neonatal seizures have allowed more precise therapeutic approaches [ 99 ].…”