Neonatal seizures and encephalopathy — formative SAQs

SAQ 1 — The encephalopathic term infant with seizures (20 marks, ~15 minutes)

A term infant is born after an emergency caesarean for placental abruption. Cord blood pH is 6.85, base deficit 16 mmol/L. Apgar scores are 1, 3, and 5 at 1, 5, and 10 minutes. At 2 hours of age the infant is lethargic with hypotonia and depressed primitive reflexes, and begins having rhythmic focal clonic movements of the left arm. [1]

Questions

1. Define the clinical syndrome and grade the encephalopathy using the Sarnat criteria. (4 marks) [1]
2. Outline the immediate bedside management, naming the first bedside test and the first-line antiseizure medication with its dose and route. (5 marks) [5]
3. Describe the neuroprotective intervention for which this infant is eligible, including the target temperature, duration, and the maximum window for initiation. State the evidence that supports it. (6 marks) [1]
4. Explain the role of continuous EEG and the recommended treatment endpoint. (5 marks) [8]

Model answer (must-hit)

1. The infant has hypoxic-ischaemic encephalopathy (HIE) with neonatal seizures. The Sarnat stage is moderate (stage 2): lethargy, hypotonia, and depressed primitive reflexes, with seizures. Cord blood acidosis (pH under 7.0, base deficit at least 12 mmol/L) and the Apgar history confirm perinatal asphyxia as the cause. [1]
2. Immediate management follows ABC: airway and breathing first, then check the blood glucose (the first bedside test). Give the first-line antiseizure medication — phenobarbital 20 mg/kg intravenously over 10 to 20 minutes. If the glucose is low, give 10% dextrose 2 mL/kg intravenously. Start continuous video-EEG to confirm and guide treatment. [4] [5]
3. The infant is eligible for therapeutic hypothermia: target 33.5 to 34.5 °C for 72 hours, started within 6 hours of life. This is supported by the TOBY trial (Azzopardi 2009), the NICHD whole-body hypothermia trial (Shankaran 2005), and the Jacobs 2013 Cochrane meta-analysis, which collectively showed that cooling reduces death and major disability in term infants with moderate-to-severe HIE. Rewarm slowly at 0.5 °C per hour. [1]
4. Continuous video-EEG is the gold standard because most NICU seizures are subclinical (electrographic-only); clinical observation alone misses them. The ACNS 2011 guideline recommends continuous EEG for any infant with a suspected seizure or at high risk (cooling HIE), continued for at least 24 hours after the last electrographic seizure. The treatment endpoint is electrographic cessation, not clinical cessation. [8]

SAQ 2 — The refractory neonatal seizure (20 marks, ~15 minutes)

A term, well-appearing infant begins having frequent focal seizures on day 2 of life. The seizures persist despite a loading dose of phenobarbital 20 mg/kg and a second-line dose of levetiracetam 50 mg/kg. The blood glucose and electrolytes on the initial screen were normal. The infant is encephalopathic between seizures. [5]

Questions

1. Define refractory neonatal seizures and state the principle that should guide the next diagnostic step. (4 marks) [5]
2. List the additional metabolic and infective investigations that should be performed, and name two treatable causes that must not be missed. (6 marks) [5]
3. Outline the antiseizure-medication escalation options for refractory seizures, naming agents and routes. (5 marks) [5]
4. Discuss the evidence and equipoise around the choice of first-line antiseizure medication, citing the Painter 1999 and Sharpe 2020 trials and the 2023 Cochrane review. (5 marks) [4]

Model answer (must-hit)

1. Refractory neonatal seizures are seizures that persist despite the first-line antiseizure medication and at least one second-line agent. The guiding principle is that a refractory neonatal seizure is often a missed cause, not a drug-ladder failure — so the priority is to re-screen for a treatable provocation (metabolic, structural, infective) rather than escalate drugs blindly. [5]
2. Re-check glucose, ionised calcium, magnesium, sodium, blood gas, and add ammonia, lactate, plasma amino acids, and urine organic acids. Perform a lumbar puncture (cell count, protein, glucose, culture, HSV PCR) and cranial MRI. Two must-not-miss causes are HSV encephalitis (treat empirically with aciclovir 20 mg/kg IV every 8 hours) and a pyridoxine- or pyridoxal-phosphate-dependent seizure (trial of the cofactor). [5]
3. Escalation options include a continuous midazolam infusion, or in some centres a lidocaine infusion, intravenously — while the search for a treatable cause continues and while treating to an EEG endpoint. Avoid polypharmacy pile-up: each escalation should be guided by the continuous EEG and the evolving diagnosis. [5]
4. The Painter 1999 NEJM trial found phenobarbital and phenytoin each achieved complete cessation in only about 45 to 50 percent of infants — a humbling result that underpins the escalating ladder. The Sharpe 2020 randomised trial found levetiracetam non-inferior to phenobarbital as a first-line agent for short-term electrographic seizure reduction, supporting its use as a well-tolerated alternative. The 2023 Abiramalatha Cochrane review found no single agent proven superior, so the 2023 ILAE Task Force recommends phenobarbital as the traditional first choice while acknowledging genuine equipoise. [4] [5] [7]