Neonatal Seizures: Diagnosis, Etiologies, and Management

Julie Ziobro, MD, PhD; Renée A. Shellhaas, MD, MS


Semin Neurol. 2020;40(2):246-256. 

In This Article

Diagnosis and Evaluation of Etiology for Neonatal Seizures

Neonates with high-risk scenarios (Table 4) are at an increased risk for seizures, and more than half of these seizures are subclinical.[17,46,47] Neonatal seizures are typically difficult to identify based on clinical observation alone. Focal seizures that provoke sensory or experiential phenomena cannot be recognized clinically in a neonate. Additionally, many neonatal behaviors are predominantly under brainstem control while cortical pathways mature, making clinically observable seizures even more unlikely in this population.[46] Multiple studies have demonstrated that even experienced clinicians often misidentify neonatal seizures and abnormal nonseizure movements, which can lead to delayed treatment of seizures or inappropriate overtreatment of nonseizure paroxysms with potentially harmful drugs.[48,49]

Continuous electroencephalography (cEEG) recording is the gold standard for evaluation of neonatal seizures, and the American Clinical Neurophysiology Society (ACNS) has released guidelines to help physicians determine when cEEG may be appropriate.[50,51] Paroxysmal movements in neonates that may raise concern for seizures include focal clonic or tonic movements, intermittent forced gaze deviation, myoclonus, tonic posturing, brainstem release phenomena (oral-motor stereotypical movements, swimming movements, bicycling movements), and paroxysms with autonomic features.[50] Infants with concerning events should be monitored until multiple typical episodes are captured on EEG. If events are found not to have an electrographic correlate, or if events resolve spontaneously, EEG monitoring can be discontinued. High-risk infants should undergo cEEG screening for a minimum of 24 hours. If seizures are detected and treated, cEEG monitoring should generally be continued until the patient is seizure free for 24 hours,[50] as administration of ASMs often leads to electroclinical dissociation in which clinical symptoms of seizures may no longer be observed during the electrographic (EEG-defined) event.[46,47]

At the same time as EEG is initiated, or even before, all newborns with suspected seizures should undergo a thorough medical evaluation to establish the underlying seizure etiology. Information from family history, antenatal, birth, and postnatal history can help in determining if there were provoking factors or a genetic predisposition. In addition, placental pathology can identify other signs of infection or perinatal insult.

Importantly, it is not uncommon for an individual neonate to have more than one seizure etiology. For example, a fetus with an inborn error of metabolism or neuromuscular disease may decompensate during labor and delivery and sustain acute hypoxic–ischemic brain injury. One study demonstrated that up to one-third of neonates with epilepsy due to structural brain malformations had concurrent illnesses that predisposed to acute seizures.[2] Thus, every neonate with seizures should be evaluated thoroughly to exclude potentially treatable or reversible etiologies.

Initial laboratory investigation for neonatal seizures should include studies to evaluate for hypoglycemia or electrolyte imbalance that may provoke seizures. Laboratory testing to evaluate for acute infection should be considered. Lumbar puncture and head ultrasound should be considered in the appropriate clinical context to assess for evidence of central nervous system infection, structural brain abnormality, or ICH. Brain MRI should be obtained when the patient is clinically stable. Further workup can be tailored to the suspected diagnosis following first-line testing, and may include additional studies to examine metabolic or genetic causes of neonatal seizures.

Therapeutic hypothermia for neuroprotection in HIE has become standard of care. Though hypothermia itself may have an anticonvulsant effect, approximately 50% of neonates have seizures during therapeutic hypothermia.[14,17] As such, current state-of-the-art clinical practice often includes EEG monitoring during hypothermia and often through the rewarming period.