title: Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus.
abstract: OBJECTIVE
  Cerebrospinal fluid (CSF) shunting can improve symptoms of elderly patients' idiopathic normal pressure hydrocephalus (iNPH). However, adjunctive means for confirming the diagnosis remain unavailable. We have previously reported the specific increase of leucine-rich alpha-2-glycoprotein (LRG) in iNPH CSF, and the present study investigates its potential clinical applications.
  
  
  METHODS
  We performed CSF tap test (TT) on 90 patients (mean age 73.4 years) and shunting in 52 patients (mean age 73.5 years), evaluating symptom improvement and higher cerebral functions-mini-mental state examination (MMSE) and Frontal Assessment Battery (FAB) before and 12 months after shunting. LRG and tau protein concentrations in TT CSF were simultaneously measured using enzyme-linked immunosorbent assay. We then compared the predictive value of these concentrations with TT results regarding successful shunting outcomes.
  
  
  RESULTS
  Positive combinations of TT and LRG concentrations of 67 ng/ml or higher, gave 81.6% sensitivity and 78.6% specificity. Therefore we used LRG (67 ng/ml) and tau (200 pg/ml) cut-off values, dividing patients into four groups. In group A (LRG ≥ 67 ng/ml and tau < 200 pg/ml) 31 of 34 patients (91.2%) had a positive TT and all operated 22 patients were shunt responders. Dementia MMSE and FAB scores in them increased from a baseline of 22.05(SE ± 0.96) to 25.65 (±0.85) and 11.38 (±0.68) to 13.08 (±0.57) respectively. In group B, (LRG ≥ 67 ng/ml and tau ≥ 200 pg/ml), the mean MMSE score increased from 17.62 (±2.03) to 21.62 (±1.96), and the FAB decreased slightly from 9.25 (±1.15) to 10.5 (±1.59), without improvement beyond the range of dementia. In group C, (LRG < 67 ng/ml, tau < 200 pg/ml), the mean MMSE score improved from 22.06 (±1.25) to 24.29 (±1.23) and the FAB score improved slightly from 12.0 (±0.72) to 12.87 (±0.72). Finally, in group D, (LRG < 67 ng/ml, tau ≥ 200 pg/ml), there was almost no improvement in MMSE score
  
  
  CONCLUSIONS
  A combination of positive TT and biomarkers quantification such as LRG and tau protein, can reliably predict shunting outcome in iNPH patients.
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan. madoka66@juntendo.ac.jp
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakajima
authors.forename: Masakazu
authors.initials: M
authors.lastname: Miyajima
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogino
authors.forename: Maki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyata
authors.forename: Kostadin L
authors.initials: KL
authors.lastname: Karagiozov
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Segawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000134:cerebrospinal fluid*; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000601:surgery; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D017287:Ventriculoperitoneal Shunt; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D006023:Glycoproteins; C015246:LRG1 protein, human; C054369:MAPT protein, human; D016875:tau Proteins