What is the treatment for neonatal seizures?

Treatment of Neonatal Seizures

Immediate Stabilization and Diagnostic Workup

Begin with immediate airway, breathing, and circulation assessment, continuous monitoring of vital signs, and establish IV/IO access while simultaneously performing point-of-care glucose testing to exclude hypoglycemia. 1, 2, 3

Critical Initial Steps (First 5-10 Minutes)

• Secure airway and ensure adequate ventilation with equipment immediately available for respiratory support 4, 5
• Check point-of-care glucose immediately and correct hypoglycemia with D10%-containing isotonic IV solution at maintenance rate if present 1, 3
• Draw blood for electrolytes (sodium, calcium, magnesium), complete blood count, blood gas, and blood culture 1, 2
• Correct hypocalcemia and hypomagnesemia BEFORE initiating anticonvulsants, as these metabolic derangements must be addressed first 1, 3

Diagnostic Imaging Algorithm

• Use head ultrasound as initial bedside imaging if the infant is unstable or MRI is unavailable, which can identify intraventricular hemorrhage, hydrocephalus, and white matter changes 6, 1, 2
• MRI with diffusion-weighted imaging is the gold standard and should be performed when the infant is stable, as it identifies etiology in 39.8% more cases than ultrasound alone and is most sensitive for hypoxic-ischemic encephalopathy 6, 1, 2
• CT head has limited role but may be useful for detecting hemorrhagic lesions in encephalopathic infants with birth trauma, low hematocrit, or coagulopathy 1

Pharmacologic Treatment Algorithm

First-Line Treatment

Phenobarbital remains the first-line antiseizure medication for neonatal seizures regardless of etiology, unless a channelopathy is suspected based on family history, in which case phenytoin or carbamazepine should be used. 7

• This recommendation is based on the 2023 ILAE Task Force guidelines, which represent the most recent high-quality consensus 7
• Phenobarbital is effective despite being relatively ineffective compared to adult antiepileptic drugs 8

Second-Line Treatment

For seizures not responding to phenobarbital, use phenytoin, levetiracetam, midazolam, or lidocaine as second-line agents. 7

• In neonates with cardiac disorders, levetiracetam is the preferred second-line agent to avoid cardiac effects of other medications 7
• Lidocaine is effective for refractory seizures as second- or third-line treatment, though experience is limited 8
• Lorazepam 0.05 mg/kg IV (up to 4 mg) given slowly at 2 mg/min may be used for acute seizure cessation, though this is primarily studied in older patients 4

Third-Line and Refractory Cases

For seizures unresponsive to second-line agents, consider a trial of pyridoxine if clinical features suggest vitamin B6-dependent epilepsy. 7

• Second-generation antiepileptic drugs (levetiracetam, topiramate, bumetanide) provide alternative pharmacological targets but lack robust neonatal data 8

Etiology-Specific Considerations

Hypoxic-Ischemic Encephalopathy (46-65% of Cases)

Therapeutic hypothermia may reduce seizure burden in neonates with HIE and should be initiated when appropriate. 7

• 90% of HIE-related seizures occur within the first 2 days of life 6, 1, 3
• Absence of major cerebral lesions on MRI is highly predictive of normal neurological outcome 1, 2

Infection-Related Seizures

Treat suspected infection with empirical antibiotics immediately after obtaining blood culture 1, 3

• Perform lumbar puncture if meningism is present, after complex convulsion, or if the infant is unduly drowsy or systemically ill 1
• Do NOT perform lumbar puncture in comatose infants due to herniation risk 1, 3

Drug Withdrawal-Associated Seizures

Pharmacologic therapy is indicated for withdrawal-associated seizures, with oral morphine solution and methadone supported by limited evidence. 6

• Other causes of neonatal seizures must be evaluated even when withdrawal is suspected 6

Treatment Goals and Monitoring

Treat both clinical and electrographic-only seizures to achieve lower seizure burden, as this may be associated with improved outcomes. 7

• Continuous video-EEG monitoring is essential to recognize seizures and assess prognosis, as many neonatal seizures are subclinical 1, 8, 9
• Not all clinical movements have EEG correlates, and not all EEG seizures have clinical manifestations 1, 8

Medication Discontinuation

Following cessation of acute provoked seizures without evidence of neonatal-onset epilepsy, discontinue antiseizure medications before discharge home, regardless of MRI or EEG findings. 7

• This represents a significant practice point: do not continue ASMs indefinitely for acute symptomatic seizures 7

Critical Pitfalls to Avoid

• Never delay metabolic correction (hypoglycemia, hypocalcemia, hypomagnesemia) while waiting for anticonvulsants 1, 3
• Do not assume all abnormal movements are seizures without EEG confirmation, as many movements lack electrical correlates 1, 8
• Avoid lumbar puncture in comatose infants without experienced evaluation due to herniation risk 3
• Do not use prophylactic antiseizure medications in neonates without confirmed seizures 2