Cerebrospinal fluid obstruction and malabsorption in human neonatal hydrocephaly

Abstract

The pathophysiology involved in human neonatal high-pressure hydrocephalus (HC) includes both cerebrospinal fluid (CSF) malabsorption and obstruction. The aim was to estimate the relative contribution between CSF malabsorption and obstruction in three different etiological groups of neonatal high-pressure HC by assessment of specific CSF biomarkers indicative of growth factor- and fibrosis-related CSF malabsorption (transforming growth factor beta-1 (TGF beta-1), aminoterminal propeptide of type 1 collagen (PC1NP)]. Patients were subdivided into three groups. Group A: spina bifida HC (n=12); group B: non-haemorrhagic triventricular HC (n=4); and group C: posthaemorrhagic HC (n=6). To exclude for confounding differences in pro-inflammatory state between the three groups, interleukin-6 (IL-6) CSF concentrations were assessed. Consecutively, the CSF concentrations of TGF beta-1 and PC1NP were compared between the different groups. Median CSF concentrations of IL-6 were low and did not differ between groups. Median CSF concentrations of PC1NP were significantly lower in group A (median: 180 ng/ml, range 90-808) than in group C (median: 1,060, range 396-1194; p=0.002). TGF beta-1 concentrations were significantly higher in group C (median 355 pg/ml, range 129-843) than in groups A (median 103, range 78-675 pg/ml) and B (median 120 pg/ml, range 91-188; p=0.01 and 0.03, respectively). In neonatal posthaemorrhagic HC, high concentrations of malabsorption-related biomarkers contrast with lower concentrations in SB and non-haemorrhagic triventricular HC. During the early development of high pressure HC in SB neonates, CSF biomarkers strongly indicate that CSF obstruction contributes more to the development of HC than malabsorption.