Terminology
The Infantile Spasms Syndrome (ISs) belongs to the group of “early epileptic encephalopathies” (EEE), characterized by severe, drug-resistant epileptic disorders, with onset in early life, associated to persistent EEG abnormalities and cognitive deficits. In several reports West syndrome, infantile spasms, epileptic spasms, and infantile spasms syndrome (WS, IS, ES and ISs) are used interchangeably. Some authors have preferred to use use the term “IS” to indicate the ictal phenomenon and the term “ISs” to describe the (spectrum of) disorder(s) associated with IS (Pavon P et al., 2020).
Etiology
- ISs can result from various etiologies, including:
- Etiologic factors may act as single causal events or in complex associations.
- Structural defects
- Infectious agents
- Metabolic and immunologic defects
- Genetic abnormalities
- Hypoxic-ischemic encephalopathy is a frequent cause of ISs.
- Prenatal cerebral infections and stroke can cause permanent cerebral damage, leading to ISs.
- Many etiologic events share similar pathogenic mechanisms, such as those seen in tuberous sclerosis, complex malformation syndromes, or chromosomal abnormalities.
- Vascular events, infections, and metabolic and immunologic defects often act on a genetic predisposition.
- In approximately 35% of cases, the cause is unknown, often leading to a more favorable outcome.
- Different events may contribute to ISs, making a clear etiologic distinction challenging.
- Yuskaitis et al. [2013]:
- Among 133 infants with ISs of unknown origin:
- 15% had normal development
- 85% had developmental delays
- Among 127 of 207 patients with proven etiological diagnosis:
- 10% had hypoxic-ischemic encephalopathy
- 8% had chromosomal abnormalities, complex malformation syndromes, or perinatal stroke
- 7% had tuberous sclerosis
- 5% had periventricular leukomalacia or hemorrhage
- Among 250 ISs patients, etiologic causes were identified in 161 (64.4%):
- 14.4% had genetic factors
- 10.0% had genetic-structural factors
- 10.8% had structural-congenital factors
- 22.4% had structural-acquired factors
- 4.8% had metabolic factors
- 2% had infectious factors
- Modern genetic technologies (array-CGH, NGS, WES, WGS) have identified more genes and copy number variants (CNVs) involved in ISs.
- Molecular/cellular anomalies can cause ISs:
- Directly by generating the neuronal/brain structural phenotype
- Indirectly by causing complex syndromic phenotypes (e.g., recognizable malformation syndromes, inborn errors of metabolism)
- By predisposing to vascular or infectious events
- Among 133 infants with ISs of unknown origin: