Abstracts

Rationale: The molecular mechanisms which lead to long-term consequences of infantile spasms are poorly understood. Insulin-like growth factor 1 (IGF-1) is crucial for early brain development. The aims of the present study were to study the role of IGF-1 in cognitive decline, and its possible correlation with HPA axis function, cortical damage and early stress factors Methods: We studied cerebrospinal fluid (CSF) IGF-1 concentrations in 7 infants with cryptogenic IS (CIS), 18 children with symptomatic IS (SIS), and in 14 control children. CSF ACTH concentrations were studied in 5 infants with CIS and in 18 children with SIS. Results: Infants with CIS had CSF IGF-1 concentrations similar to those of the control children, but children with SIS had markedly low CSF IGF-1 concentrations. Also CSF ACTH concentrations were significantly lower in the children with SIS than in those with CIS. Normal CSF IGF-1 concentrations were associated with a cryptogenic etiology, absence of early (pre- or perinatal) stress factors, normal brain imaging studies, good response to ACTH therapy, and favourable cognitive outcome. The patients with low CSF IGF-1 had all SIS and a high amount of early stress factors, neuroradiological brain atrophy, poor response to therapy and poor cognitive outcome. These patients had also low CSF ACTH concentrations. Conclusions: Early stress leads to disrupted IGF-1 signalling. Highly damaged brain cannot produce steroids, which stimulate secretion of IGF-1, an essential growth factor for survival of synapses. Low IGF-1 may also play a role in the reduction of certain cognitive functions.