Etiology of Infantile Spasms in Children
Hypoxic-ischemic injury is the most common cause of infantile spasms, accounting for 46-65% of cases, followed by structural brain abnormalities, genetic conditions (particularly tuberous sclerosis), infections, and metabolic disorders. 1
Primary Etiological Categories
Prenatal Causes (Most Common Category)
- Hypoxic-ischemic encephalopathy (HIE) represents the single most frequent etiology at 10-21% of all cases, occurring in both term and preterm infants 1, 2
- Tuberous sclerosis complex accounts for 7-8% of cases and is strongly associated with infantile spasms 1, 2
- Chromosomal abnormalities are identified in approximately 8% of cases 2
- Malformations of cortical development represent 8% of cases and include various structural brain abnormalities 3, 2
- Congenital infectious diseases (TORCH infections) contribute to the prenatal etiology group 3
- Inborn errors of metabolism are less common but important to identify 3
- Genetic syndromes such as Aicardi syndrome represent rare but specific causes 3
Perinatal Causes
- Intracranial hemorrhage and perinatal ischemic stroke account for 10-12% of cases 1
- Periventricular leukomalacia or hemorrhage represents 5% of cases 2
- Approximately 90% of infants with hypoxic-ischemic encephalopathy experience seizure onset within 2 days after birth 1
Postnatal Causes
- Infections occurring beyond the seventh day of life are more likely to cause infantile spasms 1
- Postnatal acquired brain injuries represent a smaller proportion (approximately 4% in the UKISS study) 2
Timing-Based Diagnostic Considerations
Seizures occurring within the first week of life are most commonly related to hypoxic-ischemic injury or perinatal complications 1
Seizures occurring beyond the seventh day of life are more likely related to infection, genetic disorders, or malformations of cortical development 1
Idiopathic Cases
A small percentage of patients (approximately 33% in contemporary studies) have no identified etiology despite thorough investigation, with normal growth and development prior to the onset of infantile spasms 3, 2
Molecular and Genetic Pathways
Emerging evidence indicates that infantile spasms may result from disturbances in key genetic pathways of brain development, specifically in the gene regulatory network of GABAergic forebrain dorsal-ventral development and abnormalities in molecules expressed at the synapse 4
Critical Diagnostic Pitfall
The most common pitfall is failing to recognize that the timing of seizure onset provides crucial etiological clues: onset within 2 days suggests HIE, while onset after 7 days suggests infection, genetic disorders, or cortical malformations 1. Brain MRI is essential for identifying structural etiologies and should be obtained when there is rapid head growth, changes in neurological examination, or regression of skills 5.