Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is a treatable cause of dementia, gait disturbance, and urinary incontinence in elderly with ventriculomegaly, and its unique morphological feature, called disproportionately enlarged subarachnoid-space hydrocephalus (DESH), is reported to be diagnostic. Lipocalin-type prostaglandin D synthase (L-PGDS) is a major protein in cerebrospinal fluid (CSF), produced mainly by arachnoid cells, and its concentration in CSF was reportedly decreased in iNPH. L-PGDS is a PGD2-producing enzyme, and is a lipophilic ligand carrier acting as a chaperone to prevent aggregation of neurotoxic agents, such as amyloid β (Aβ). The aim of this study was to confirm the L-PGDS decrease in DESH type iNPH and to clarify its relationship with clinico-radiological features. We evaluated 22 patients (Age 75.7±7.8, M 10/F 12) referred for ventriculomegaly without CSF pathway obstruction, and conducted CSF tap test to determine the surgical indication. NPH symptoms were evaluated by idiopathic NPH grading scale, MMSE, FAB and the timed up and go test. The extent of DESH was approximated by callosal angle, and the severity of parenchymal damage was evaluated by age related white matter change (ARWMC) score. L-PGDS levels are significantly decreased in DESH patients compared to non-DESH patients (14.4±1.0 vs. 20.8±2.0μg/ml, p=0.01). Among clinical profiles, FAB negatively correlated with L-PGDS levels in whole patients (Spearman r=−0.59, p=0.005) and DESH patients (Spearman r=−0.68, p=0.02). Moreover, L-PGDS levels positively correlated with callosal angle (Spearman r=0.59) and ARWMC (Spearman r=0.65). Our data not only support the diagnostic value of L-PGDS as a CSF biomarker of iNPH, but also propose the potential role of this protein as a surrogate marker of frontal lobe dysfunction, DESH feature and white matter damage.
