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

Acute Symptomatic Neonatal Seizures

Acute symptomatic seizures occur in response to a brain insult (Table 1). Underlying conditions such as hypoxic–ischemic encephalopathy (HIE), stroke, intracranial hemorrhage (ICH), infection, hypoglycemia, or electrolyte imbalance are the most common provoking factors.[13] HIE is the most prevalent cause of acute symptomatic seizures in neonates, accounting for 40 to 45% of all neonatal seizures. Seizure onset in HIE is typically in the first 12 to 24 hours of life, even in the setting of therapeutic hypothermia.[14] Identification of seizures in HIE is imperative, as they occur in 25 to 50% of neonates with HIE and may exacerbate the underlying brain injury.[15–17] Seizure semiology varies based on the region of brain injury, but there is a high prevalence of subclinical seizures in neonates, which underscores the need for electroencephalography (EEG) recording as discussed later.

Cerebrovascular events are the second most common cause of neonatal seizures. Arterial ischemic perinatal strokes are typically the result of embolism from the placenta or umbilical cord, carotid artery, or heart. Maternal risk factors include oligohydramnios, chorioamnionitis, premature rupture of membranes, preeclampsia, diabetes, and smoking. Neonatal risk factors include congenital cardiac abnormalities, systemic infection, coagulation disorders, placental abnormalities, and male sex. Seizures resulting from focal strokes often present somewhat later than those caused by neonatal HIE, frequently up to 24 to 48 hours after birth or later.[18–20] The seizure semiology among neonates with perinatal arterial ischemic strokes is classically focal clonic seizures due to involvement of the motor cortex in the middle cerebral artery territory.

ICH can cause acute symptomatic seizures, with severity and semiology determined by the size and location of the hemorrhage. Subdural hemorrhage in the anterior and middle cranial fossae may have associated subarachnoid hemorrhage and may result in seizures. Parenchymal hemorrhages frequently cause seizures, and are often caused by underlying vascular malformations. Intraventricular hemorrhages rarely cause seizures in term infants unless the hemorrhage is large and involves parenchymal injury.[19] However, ICH is the second most common etiology of seizures in preterm infants (<32 weeks of gestation).[21]

Transient metabolic disturbances of sodium, calcium, or glucose can lead to neonatal seizures. Reversal of the abnormal electrolyte level results in resolution of the seizures, but identification and treatment of the underlying medical etiology for the metabolic disturbance is important to prevent recurrence. Conventional antiseizure medications (ASMs) are often ineffective and unnecessary in this clinical scenario, unless the metabolic derangement is severe or prolonged. Severe hypoglycemia, for example, can result in bilateral posterior brain injury and resultant neonatal seizures as well as risk for postneonatal epilepsy.[22]

Acute symptomatic seizures can also result from bacterial or viral pathogens infecting the neonatal brain or meninges in the antenatal, perinatal, or postnatal period. Seizures as a symptom of infection are important to recognize and diagnose accurately to minimize central nervous system or systemic injury due to the underlying infection. Infection-related seizures can occur at any time during the neonatal period, as in late group B streptococcal or herpes simplex virus infections.[19] All neonates with suspected infection should undergo a lumbar puncture to aid in accurate diagnosis and treatment; if an infant is too unstable for this procedure then empiric treatment for meningoencephalitis is often warranted. Seizures related to infections often persist longer than those related to ischemic or hemorrhagic injury; extended EEG monitoring may be necessary to ensure adequate ASM treatment.[19]