SYDNEY — The cerebrospinal fluid (CSF) protein lipocalin-type prostaglandin D synthase (L-PGDS) has diagnostic potential in cases of idiopathic normal pressure hydrocephalus (iNPH), new research shows.

"Our data not only support the diagnostic value of L-PGDS as a CSF biomarker but also propose the potential role of this protein as a surrogate marker of frontal lobe dysfunction of iNPH," study investigator Hiroki Toda, MD, PhD, Department of Neurosurgery, Tazuke Kofukai Medical Research Institute and Kitano Hospital, Osaka, Japan, told Medscape Medical News.

The study was presented here at the Movement Disorder Society (MDS) 17th International Congress of Parkinson's Disease and Movement Disorders.

NPH is a cause of treatable dementia, gait disturbance, and urinary incontinence in the elderly, yet some of its etiology remains unknown. CSF levels of L-PGDS in patients with NPH may decline, possibly as a consequence of damage to arachnoid cells, the main site of its production.

L-PGDS is a bifunctional protein, they explain, acting not only as a PGD2-producing enzyme but also as a lipophilic ligand carrier and a chaperone preventing amyloid β (Aβ) misfolding aggregation implicated in Alzheimer's disease. Aβ decrease was also reported in iNPH.

Dr. Toda and colleagues investigated the role of L-PGDS in iNPH in 24 elderly patients referred for ventriculomegaly. Twelve of the 24 patients were diagnosed with iNPH on the basis of shunt or CSF tap test response and "typical" magnetic resonance imaging (MRI) findings of disproportionately enlarged subarachnoid space hydrocephalus (DESH), the researchers report.

According to the team, L-PGDS levels were significantly decreased in patients with DESH relative to those without DESH (13.3 vs 20.8 µg/mL, P = .009).

The researchers also analyzed the relationships between CSF L-PGDS concentration and frontal lobe function using the frontal assessment battery (FAB).

They observed a significant correlation between the FAB score and L-PGDS levels in all patients (P = .005) and patients with DESH (P = .02). In addition, L-PGDS levels showed positive correlation with FAB increase after treatment (P = .04), they say.

This study suggests that "a low CSF L-PGDS concentration can be a diagnostic marker of iNPH," said Dr. Toda, adding that "low CSF L-PGDS concentration correlates with high FAB score in the iNPH patients."

"This is the first report documenting that iNPH patients have lower CSF L-PGDS concentration than non-iNPH patients. We are continuing our iNPH-biomarker studies in conjunction with frontal lobe functional analysis," Dr. Toda said.

The study was funded by Grants-in-Aid for Scientific Research. The authors have disclosed no relevant financial relationships.

Movement Disorder Society (MDS) 17th International Congress of Parkinson's Disease and Movement Disorders. Abstract 1014. Presented June 20, 2013.


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