Neonatal Seizures – Introduction and Etiological Classification
Neonatal seizures are the most frequent neurological emergency in the first 28 days of life, with an
incidence of 1–3.5 per 1,000 live births. These seizures are often the first clinical sign of underlying
cerebral dysfunction and carry significant implications for long-term neurodevelopment. The
neonatal brain has a low seizure threshold due to unique maturational factors such as enhanced
excitatory neurotransmission (via glutamate and immature GABA signaling) and reduced inhibitory
mechanisms, rendering it highly susceptible to seizures. Neonatal seizures are broadly classified
into two categories based on their etiology: 1. Acute symptomatic seizures: Most common;
provoked by acute insults such as hypoxic-ischemic encephalopathy (HIE), stroke, infections,
metabolic derangements, or intracranial hemorrhage. 2. Neonatal-onset epilepsy: Less frequent;
arise due to genetic, metabolic, or structural brain abnormalities and often require long-term
management. Pathophysiology includes reversed GABAergic function due to high NKCC1 and low
KCC2 expression in preterm neonates, leading to depolarization and excitation. Glutamate activity
via NMDA and AMPA receptors is also high. Synaptogenesis and high dendritic spine density
during this stage contribute to excitability. Etiologies: - Acute symptomatic: HIE, stroke, ICH,
infection, metabolic disturbances, inborn errors - Epileptic: Genetic syndromes (KCNQ2, SCN2A),
brain malformations, metabolic epilepsies Accurate classification is critical for appropriate
management and prognosis.
Neonatal Seizures – Types, Diagnosis, and Management
Types: - Based on etiology: Acute symptomatic vs. neonatal-onset epilepsy - Semiology: Clonic,
tonic, myoclonic, subtle, autonomic - Electrographic: Electroclinical, electrographic-only,
clinical-only Diagnosis: - Clinical suspicion: High-risk neonates (HIE, stroke, infection) - EEG: Gold
standard; cEEG recommended for 24+ hours - Investigations: Labs (RBS, Ca, Na), CSF, MRI,
metabolic and genetic workup Management: - First-line ASM: Phenobarbital 20–40 mg/kg -
Second-line: Fosphenytoin, levetiracetam - Refractory: Midazolam, lidocaine (with caution) -
Specific therapies: Pyridoxine, biotin, sodium benzoate for metabolic causes - ASM duration: May
be short (discontinued before discharge) for acute symptomatic seizures; long-term for epilepsy
syndromes - Prognosis: High seizure burden and abnormal EEG/MRI predict poor outcome
NEOLEV2 trial confirms phenobarbital’s superiority to levetiracetam in seizure control.
Difference Between Seizure and Epilepsy
Seizure: A transient, abnormal, excessive neuronal discharge causing a clinical or electrographic
event. Usually provoked by an acute insult. May occur once and not recur. Epilepsy: A condition
with recurrent unprovoked seizures due to a persistent predisposition. Diagnosed with ≥2
unprovoked seizures or one with high recurrence risk. In neonates, most seizures are acute
symptomatic, while about 13% are due to neonatal-onset epilepsy requiring long-term therapy.
Neonatal Epilepsy Syndromes
1. Self-Limited Neonatal Seizures: Day 4–6, clonic, good prognosis, often idiopathic or rare KCNQ2
variant. 2. Self-Limited Familial Neonatal Epilepsy: Day 2–3, focal tonic, autosomal dominant
(KCNQ2/3, SCN2A), responsive to carbamazepine. 3. Early Infantile Epileptic Encephalopathy
(EIEE / Ohtahara): Tonic seizures, burst-suppression EEG, structural/genetic causes (STXBP1,
ARX), poor prognosis. 4. Early Myoclonic Encephalopathy (EME): Multifocal myoclonus, metabolic
causes (nonketotic hyperglycinemia), burst-suppression EEG, poor prognosis. 5. Epilepsy of
Infancy with Migrating Focal Seizures (EIMFS): Focal migrating seizures, KCNT1/SCN2A/others,
refractory, poor prognosis. 6. Metabolic Epileptic Encephalopathies: Pyridoxine-dependent epilepsy
(ALDH7A1), PNPO deficiency, biotinidase deficiency, GLUT1 deficiency, etc. Summary: Neonatal
epilepsies range from self-limited benign syndromes to catastrophic epileptic encephalopathies.
Genetic and metabolic testing are essential. Prognosis varies with etiology.
