Cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid concentrations in pediatric patients with hydrocephalus.

OBJECTIVE

To ascertain if cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid, reflecting potential biomarkers of overall neuronal injury and lipid peroxidation, respectively, are elevated in hydrocephalus patients compared with controls, and if cleaved-tau and 9-hydroxyoctadecadienoic acid levels correlate with each other.

DESIGN

Prospective clinical observational study.

SETTING

Tertiary-care children's hospital.

PATIENTS

Children younger than or equal to 18 yrs who underwent ventriculoperitoneal shunt placement or revision surgery for intrinsic hydrocephalus.

MEASUREMENTS AND MAIN RESULTS

During the study period 12 patients with intrinsic hydrocephalus required ventriculoperitoneal shunt placement or revision. Cerebrospinal fluid cleaved-tau levels were significantly elevated in patients with hydrocephalus (44.7 +/- 9.6 ng/mL, n = 11) compared with control patients (0.0 +/- 0.0 ng/mL, n = 9; p < 0.0001). Cleaved-tau levels correlated with patient age (r = .609, p = 0.047) and duration of symptoms (r = .755, p = 0.007). No significant difference in cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels between patients with hydrocephalus (24.6 +/- 5.7, n = 8) and control patients (24.9 +/- 9.3 ng/mL, n = 7) was detected (p = 0.25). There was also no statistically significant correlation between 9-hydroxyoctadecadienoic acid levels and duration of symptoms (r = .668, p = 0.07), nor was there a significant correlation between 9-hydroxyoctadecadienoic acid levels and patient age (r = -.011, p > 0.10). There was no significant relationship between 9-hydroxyoctadecadienoic acid levels and signs of elevated intracranial pressure, nor was there a correlation between 9-hydroxyoctadecadienoic acid levels and cleaved-tau levels.

CONCLUSION

Children with hydrocephalus who have clinical signs of increased intracranial pressure and require ventriculoperitoneal shunt placement or revision exhibit markedly elevated cerebrospinal fluid cleaved-tau levels, suggesting evidence of axonal damage. However, this axonal injury does not seem to be associated with significant lipid peroxidation, at least as assessed by quantifying cerebrospinal fluid 9-hydroxyoctadecadienoic acid at a single, concurrent time point. The significant relationship between age and cerebrospinal fluid cleaved-tau levels suggest that brain injury associated with hydrocephalus may be more pronounced in older children.