Use of cerebrospinal fluid amyloid-β and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocephalus

Clinical article

Restricted access

Object

The prognostic value of CSF biomarkers in patients with idiopathic normal pressure hydrocephalus (iNPH) has not been adequately studied to date. The aim of this study was to identify CSF markers of favorable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt.

Methods

Ventricular CSF was collected intraoperatively from 22 patients with iNPH and enzyme-linked immunosorbent assay was used to analyze the levels of amyloid-β 1–42 (Aβ1–42) and total tau protein. The Black grading scale was used to assess outcomes at 6 months. Receiver operating characteristic (ROC) curves were obtained and discriminant function analysis was undertaken to provide sensitivity and specificity figures for each marker as well as their combination.

Results

The mean age of the patients was 71.45 years (± 9.5 years [SD]). Follow-up was achieved in 21 patients. Seventeen patients had a favorable outcome and 4 patients had unfavorable outcome at 6 months. An Aβ1–42 level of 180 pg/ml had a sensitivity of 35% and a specificity of 20% for predicting a favorable outcome at 6 months. A total tau level of 767 pg/ml will have a sensitivity of 17% and a specificity of 20% for predicting a favorable outcome at 6 months. A combination of Aβ1–42 and total tau levels predicted favorable outcomes with a sensitivity of 80% and specificity of 82.4%.

Conclusions

In this pilot study a combination of Aβ1–42 levels and total tau protein levels predicted favorable surgical outcomes at 6 months with adequate accuracy to be of clinical use. Further study in a larger group with longer follow-up is warranted.

Abbreviations used in this paper: Aβ1–42 = amyloid-β 1–42; AD = Alzheimer dementia; ELISA = enzyme-linked immunosorbent assay; iNPH = idiopathic normal pressure hydrocephalus.
Article Information

Contributor Notes

Address correspondence to: Andrew Tarnaris, M.R.C.S., Department of Neurosurgery, National Hospital for Neurology & Neurosurgery, Box 32, Queen Square, London WC1N 3BG. email: andrewtarnaris@gmail.com.Please include this information when citing this paper: published online March 25, 2011; DOI: 10.3171/2011.2.JNS101316.

© AANS, except where prohibited by US copyright law.

Headings
References
  • 1

    Benzel ECPelletier ALLevy PG: Communicating hydrocephalus in adults: prediction of outcome after ventricular shunting procedures. Neurosurgery 26:6556601990

    • Search Google Scholar
    • Export Citation
  • 2

    Black PM: Idiopathic normal-pressure hydrocephalus. Results of shunting in 62 patients. J Neurosurg 52:3713771980

  • 3

    Black PMOjemann RGTzouras A: CSF shunts for dementia, incontinence, and gait disturbance. Clin Neurosurg 32:6326511985

  • 4

    Iseki CKawanami TNagasawa HWada MKoyama SKikuchi K: Asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on MRI (AVIM) in the elderly: a prospective study in a Japanese population. J Neurol Sci 277:54572008

    • Search Google Scholar
    • Export Citation
  • 5

    Jones HCKlinge PM: Hydrocephalus 2008, 17–20th September, Hannover Germany: a conference report. Cerebrospinal Fluid Res 5:192008

  • 6

    Klinge PMarmarou ABergsneider MRelkin NBlack PM: Outcome of shunting in idiopathic normal-pressure hydrocephalus and the value of outcome assessment in shunted patients. Neurosurgery 57:S40522005

    • Search Google Scholar
    • Export Citation
  • 7

    Kondziella DSonnewald UTullberg MWikkelso C: Brain metabolism in adult chronic hydrocephalus. J Neurochem 106:151515242008

  • 8

    Lemcke JMeier UMüller CFritsch MEymann RKiefer M: Is it possible to minimize overdrainage complications with gravitational units in patients with idiopathic normal pressure hydrocephalus? Protocol of the randomized controlled SVASONA Trial (ISRCTN51046698). Acta Neurochir Suppl 106:1131152010

    • Search Google Scholar
    • Export Citation
  • 9

    Marmarou ABergsneider MKlinge PRelkin NBlack PM: The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 57:3 SupplS17282005

    • Search Google Scholar
    • Export Citation
  • 12

    Ross CAPoirier MA: Opinion: what is the role of protein aggregation in neurodegeneration?. Nat Rev Mol Cell Biol 6:8918982005

  • 10

    Raftopoulos CDeleval JChaskis CLeonard ACantraine FDesmyttere F: Cognitive recovery in idiopathic normal pressure hydrocephalus: a prospective study. Neurosurgery 35:3974051994

    • Search Google Scholar
    • Export Citation
  • 11

    Relkin NMarmarou AKlinge PBergsneider MBlack PM: Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 57:3 SupplS4S162005

    • Search Google Scholar
    • Export Citation
  • 13

    Scollato ATerreni ACaldini ASalvadori BGallina PFrancese S: CSF proteomic analysis in patients with normal pressure hydrocephalus selected for the shunt: CSF biomarkers of response to surgical treatment. Neurol Sci 31:2832912010

    • Search Google Scholar
    • Export Citation
  • 14

    Silverberg GD: Normal pressure hydrocephalus (NPH): ischaemia, CSF stagnation or both. Brain 127:9479482004

  • 15

    Silverberg GDMayo MSaul TRubenstein EMcGuire D: Alzheimer's disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis. Lancet Neurol 2:5065112003

    • Search Google Scholar
    • Export Citation
  • 16

    Talab RValis MRehak SKrejsek J: Abnormalities of tauprotein and beta-amyloid in brain ventricle cerebrospinal fluid. Neuro Endocrinol Lett 30:6476512009

    • Search Google Scholar
    • Export Citation
  • 17

    Tamaoka AKondo TOdaka ASahara NSawamura NOzawa K: Biochemical evidence for the long-tail form (A beta 1-42/43) of amyloid beta protein as a seed molecule in cerebral deposits of Alzheimer's disease. Biochem Biophys Res Commun 205:8348421994

    • Search Google Scholar
    • Export Citation
  • 18

    Tarkowski ETullberg MFredman PWikkelsö C: Normal pressure hydrocephalus triggers intrathecal production of TNF-alpha. Neurobiol Aging 24:7077142003

    • Search Google Scholar
    • Export Citation
  • 19

    Tarnaris AToma AKChapman MDPetzold AKitchen NDKeir G: The longitudinal profile of CSF markers during external lumbar drainage. J Neurol Neurosurg Psychiatry 80:113011332009

    • Search Google Scholar
    • Export Citation
  • 20

    Tarnaris AToma AKKitchen NDWatkins LD: Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus. Biomarkers Med 3:7878052009

    • Search Google Scholar
    • Export Citation
  • 21

    Tarnaris AWatkins LDKitchen ND: Biomarkers in chronic adult hydrocephalus. Cerebrospinal Fluid Res 3:112006

  • 22

    Tullberg MBlennow KMånsson JEFredman PTisell MWikkelsö C: Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus. Cerebrospinal Fluid Res 5:92008

    • Search Google Scholar
    • Export Citation
  • 23

    Tullberg MRosengren LBlomsterwall EKarlsson JEWikkelsö C: CSF neurofilament and glial fibrillary acidic protein in normal pressure hydrocephalus. Neurology 50:112211271998

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 122 120 0
Full Text Views 106 67 0
PDF Downloads 126 68 0
EPUB Downloads 0 0 0
PubMed
Google Scholar