Insulin‐like growth factor‐1 is associated with cognitive outcome in infantile spasms

Abstract

and yHUSLAB, Helsinki, Finland SUMMARY Purpose: The molecular mechanisms that lead to longterm consequences of infantile spasms (IS) are poorly understood. Insulin-like growth factor-1 (IGF-1) is regulated by insults that might be stressful to the brain, and is crucial for early brain development. The aim of the present study was to correlate cerebrospinal fluid (CSF) levels of IGF-1 with antecedent insults and cognitive outcome. Methods: We studied CSF IGF-1 and the adrenocorticotropic hormone (ACTH) concentrations in infants with idiopathic IS (IIS), symptomatic IS (SIS), and controls. Results: Infants with IIS had CSF IGF-1 concentrations similar to those of the control children, but children with SIS had markedly low CSF IGF-1 concentrations. In addition, CSF ACTH concentrations were significantly lower in the children with SIS than in those with IIS. High CSF IGF-1 concentrations were associated with an idiopathic etiology, absence of early (pre-or perinatal) insults or stress, normal brain imaging studies, good response to ACTH therapy, and favorable cognitive outcome. Low CSF IGF-1 concentrations were associated with low CSF ACTH concentrations, a history of early insults or stress, cerebral atrophy, poor response to therapy, and poor cognitive outcome. Discussion: In children with IS, insults or stress in early life may affect the synthesis of IGF-1, which might play a role in the reduction of certain cognitive functions.

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

“…The IGF-1 increase in CSF depicted in Fig. 1 is comparable to the one in positive responders to fluoxetine (34) or adrenocorticotropic hormone (35). The levels of IGFBP3, the main IGF-1-binding protein (10), were unaffected by the increase in IGF-1.…”

The Association between IGF-1 Polymorphisms, IGF-1 Serum Levels, and Cognitive Functions in Healthy Adults: The Amsterdam Growth and Health Longitudinal Study

“…The meta-analysis of Arwert et al [18] and several more recent studies [36–38] report a (overall) positive correlation between IGF-1 levels and cognitive performance in healthy older people. In addition, associations between IGF-1 and cognition also have been found in growth hormone deficient children [39] and adults [15, 19], children with infantile spasms [40], people with Parkinson's disease [41], Alzheimer [42], and delirium [43]. An important difference between these studies and ours is that we investigate the relationship between IGF-1 levels and cognition in healthy adults, whereas all previous studies used elderly or patient groups.…”

Update to guidelines on treatment of infantile spasms

“…Patients who respond poorly to treatment express low levels of insulin like growth factor, a factor that is essential for synaptic development. 7 In addition, vigabatrin therapy itself might have toxic effects on the developing brain. 8 In 2009, the US FDA approved vigaba trin for use in infantile spasms, with a warn ing of potential permanent visual impairment.…”