What are the possible causes of seizures in an infant and how should the initial evaluation and management be performed?

Causes of Seizures in Infants

Hypoxic-ischemic encephalopathy is the dominant cause of neonatal seizures, accounting for 46-65% of cases, with 90% occurring within the first 2 days of life. 1, 2, 3

Primary Etiologies by Timing

Early Neonatal Period (First 7 Days)

Hypoxic-Ischemic Injury (46-65% of cases)

• Perinatal asphyxia is by far the most common cause in both term and preterm infants 1, 2, 3
• Seizure onset typically occurs within 48 hours after birth in 90% of affected infants 1, 2
• This represents the single most important etiology to identify given its prognostic implications and treatment with therapeutic hypothermia 2

Intracranial Hemorrhage and Perinatal Stroke (10-12% combined)

• Second most common structural cause in neonates 1, 3
• Includes intraventricular hemorrhage, subdural hematomas, and arterial ischemic stroke 1

Metabolic Derangements

• Hypoglycemia requires immediate point-of-care glucose testing and correction with D10%-containing isotonic IV solution 2, 3
• Hypocalcemia and hypomagnesemia must be corrected before initiating anticonvulsants 2, 3
• Hyponatremia can precipitate seizures and requires electrolyte monitoring 3

Late Neonatal Period (Beyond 7 Days)

Infections

• Seizures occurring after the seventh day of life are more likely related to infection 1
• Meningitis and encephalitis require urgent consideration with empirical antibiotics if suspected 2, 3
• Blood culture, urine culture, and lumbar puncture should be performed when infection is suspected, but avoid lumbar puncture in comatose infants due to herniation risk 2, 3

Genetic Disorders and Malformations

• Malformations of cortical development become more prominent causes after the first week 1
• Vitamin B6-dependent epilepsy should be considered in seizures unresponsive to second-line medications 4

Initial Evaluation Algorithm

Immediate Stabilization (First Priority)

• Ensure patent airway, adequate breathing, and circulation with continuous monitoring of heart rate, blood pressure, temperature, and oxygen saturation 2, 3
• Establish IV/IO access immediately 2, 3
• Point-of-care glucose testing is mandatory to exclude hypoglycemia 2, 3

Essential Laboratory Workup

• Electrolytes including sodium, calcium, and magnesium 2, 3
• Blood gas analysis 2
• Complete blood count 2
• Blood culture if infection suspected 2

Critical Metabolic Corrections (Before Anticonvulsants)

• Correct hypoglycemia with D10%-containing isotonic IV solution at maintenance rate 2, 3
• Correct hypocalcemia and hypomagnesemia before initiating anticonvulsants 2, 3
• This sequence is essential as metabolic derangements may be the primary cause 2, 3

Neuroimaging Strategy

Unstable Infants or Limited MRI Access

• Head ultrasound as initial bedside imaging identifies intraventricular hemorrhage, hydrocephalus, white matter changes, and cystic periventricular leukomalacia 1, 2, 3
• Ultrasound alone identifies an etiology in approximately 38% of cases 1
• Major limitation: low sensitivity for hypoxic-ischemic injury and small infarctions 1

Stable Infants

• MRI with diffusion-weighted imaging is the gold standard for identifying etiology 1, 2, 3
• MRI provides additional diagnostic information beyond ultrasound in 39.8% of patients 1
• Diffusion-weighted imaging is most sensitive for hypoxic-ischemic encephalopathy when performed at the appropriate time interval 1
• Absence of major cerebral lesions on MRI is highly predictive of normal neurological outcome 1, 2

Limited Role for CT

• CT has a specific but limited role in detecting hemorrhagic lesions in encephalopathic infants with history of birth trauma, low hematocrit, or coagulopathy 1

Special Considerations

Febrile Seizures (6 Months to 5 Years)

• Simple febrile seizures (generalized, <15 minutes, no recurrence in 24 hours) require no imaging 1
• Complex febrile seizures (>15 minutes, recurrent, or focal) have same imaging recommendations as simple febrile seizures unless meningitis, encephalitis, or trauma are clinically suspected 1

Post-Traumatic Seizures

• Abusive head trauma, subdural hematoma, and young age are independent predictors for post-traumatic seizures 1
• Neuroimaging is essential to detect treatable pathology and identify children at greater risk 1

Critical Pitfalls to Avoid

• Do not delay metabolic correction while waiting for imaging or other workup 2, 3
• Do not perform lumbar puncture in comatose infants without experienced physician evaluation due to herniation risk 3
• Do not start anticonvulsants before correcting hypocalcemia and hypomagnesemia 2, 3
• Recognize that an underlying cause can be identified in approximately 95% of neonatal seizures with systematic evaluation 2
• Many neonatal seizures are subclinical or lack clinical correlation, requiring high clinical suspicion based on history or presence of encephalopathy 5, 6