Skip to main content Accessibility help
  • Print publication year: 2014
  • Online publication date: February 2014

15 - Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus

from Section 3 - Diagnosis


This chapter provides an overview of incontinence and lower urinary tract symptoms in normal pressure hydrocephalus (NPH), and covers areas including dementia and incontinence, differential diagnosis, physiology and pathophysiology, symptoms, evaluation, and treatment. The relationship between gait disturbances, dementia, and incontinence has profound importance because of the potential heightened risk of falls. In the central nervous system, there are two main areas involved in the motor control and reciprocal coordination of lower urinary tract function. Our understanding of lower urinary tract dysfunction in NPH is limited by a lack of detailed knowledge of the supraspinal pathways involved in the control of micturition. Urodynamic studies may be the most important investigative procedures performed in patients with significant urinary symptoms and idiopathic NPH (iNPH), as the results will help identify etiologies and guide treatments. Patients may be treatment refractory to standard doses or may require higher than recommended doses or combination therapies.

Related content

Powered by UNSILO


1. AtkinsonAJ, ColburnWA, DeGruttolaVG, et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89–95.
2. RadebaughT, KhachaturianZS. Consensus report of the working group on: “Molecular and Biochemical Markers of Alzheimer’s Disease.” Neurobiol Aging 1998;19(2):109–16.
3. SørensenPS, HammerM, VorstrupS, GjerrisF. CSF and plasma vasopressin concentrations in dementia. BMJ 1983;46(10):911–16.
4. SørensenPS, GjerrisF, IbsenS, BockE. Low cerebrospinal fluid concentration of brain-specific protein D2 in patients with normal pressure hydrocephalus. J Neurol Sci 1983;62(1–3):59.
5. AhlbergJ, BlomstrandC, RonquistG, WikkelsøC.Dementia-and adenylate kinase activity in cerebrospinal fluid. Acta Neurol Scand 1985;72(5):525–7.
6. AlbrechtsenM, SørensenPS, GjerrisF, BockE. High cerebrospinal fluid concentration of glial fibrillary acidic protein (GFAP) in patients with normal pressure hydrocephalus. J Neurol Sci 1985;70(3):269–74.
7. KudoT, MimaT, HashimotoR, et al. Tau protein is a potential biological marker for normal pressure hydrocephalus. Psychiatry Clin Neurosci 2000;54(2):199–202.
8. LinsH, WichartI, BancherC, et al. Immunoreactivities of amyloid beta peptide ((1–42)) and total tau protein in lumbar cerebrospinal fluid of patients with normal pressure hydrocephalus. J Neural Transm 2004;111(3):273–80.
9. TarnarisA, WatkinsLD, KitchenND. Biomarkers in chronic adult hydrocephalus. Cerebrospinal Fluid Res 2006;3(1):11.
10. TarnarisA, TomaAK, KitchenND, WatkinsLD. Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus. Biomarkers 2009;3(6):787–805.
11. TisellM, HöglundM, WikkelsøC. National and regional incidence of surgery for adult hydrocephalus in Sweden. Acta Neurol Scand 2005;112(2):72–5.
12. TrenkwalderC, SchwarzJ, GebhardJ, et al. Starnberg trial on epidemiology of Parkinsonism and hypertension in the elderly. Prevalence of Parkinson’s disease and related disorders assessed by a door-to-door survey of inhabitants older than 65 years. Arch Neurol 1995;52(10):1017–22.
13. GellingL, IddonJ, McVicarA, PickardJD. CSF circulation disorders: measuring progress in patients through quality of life and hope. J Clin Nurs 2004;13(5):589–600.
14. PocaMA, SolanaE, Martinez-RicarteFR, et al. Idiopathic normal pressure hydrocephalus: results of a prospective cohort of 236 shunted patients. Acta Neurochir Suppl 2012;114:247–53.
15. RelkinN, MarmarouA, KlingeP, BergsneiderM, BlackPM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S4–16; discussion ii–v.
16. MarmarouA, BergsneiderM, KlingeP, RelkinN, BlackPM. The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S17–28; discussion ii–v.
17. Del BigioMR. Hydrocephalus-induced changes in the composition of cerebrospinal fluid. Neurosurgery 1989;25(3):416–23.
18. LemckeJ, MeierU. Idiopathic normal pressure hydrocephalus (iNPH) and co-morbidity: an outcome analysis of 134 patients. Intracranial Pressure and Brain Monitoring XIV. 255–9.
19. CabralD. Frequency of Alzheimer’s disease pathology at autopsy in patients with clinical normal pressure hydrocephalus. Thesis, The University of Arizona College of Medicine; 2011.
20. SeppäläTT, NergO, KoivistoAM, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology 78(20):1568–75.
21. SilverbergGD, MillerMC, MachanJT, et al. Amyloid and Tau accumulate in the brains of aged hydrocephalic rats. Brain Res 2010;1317:286–96.
22. KapakiEN, ParaskevasGP, TzerakisNG, et al. Cerebrospinal fluid tau, phospho-tau181 and beta-amyloid1–42 in idiopathic normal pressure hydrocephalus: a discrimination from Alzheimer’s disease. Eur J Neurol 2007;14(2):168–73.
23. Agren-WilssonA, LekmanA, SjobergW, et al. CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus. Acta Neurol Scand 2007;116(5):333–9.
24. WikkelsøC, BlomstrandC. Cerebrospinal fluid proteins and cells in normal-pressure hydrocephalus. J Neurol 1982;228(3):171–80.
25. VannesteJA. Three decades of normal pressure hydrocephalus: are we wiser now?BMJ 1994;57(9):1021–5.
26. BlackPM, OjemannRG, TzourasA. CSF shunts for dementia, incontinence, and gait disturbance. Clin Neurosurg 1985;32:632.
27. Grundke-IqbalI, IqbalK, TungYC, et al. Abnormal phosphorylation of the microtubule-associated protein (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986;83(13):4913–17.
28. BraakH, BraakE. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 1991;82(4):239–59.
29. ZemlanFP, RosenbergWS, LuebbePA, et al. Quantification of axonal damage in traumatic brain injury: affinity purification and characterization of cerebrospinal fluid tau proteins. J Neurochem 1999;72(2):741.
30. GloecknerSF, MeyneF, WagnerF, et al. Quantitative analysis of transthyretin, tau and amyloid-β in patients with dementia. J Alzheimer’s Dis 2008; 14(1):17–25.
31. BlennowK, WallinA, AgrenH, et al. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?Mol Chem Neuropathol 1995;26(3):231.
32. MiyajimaM, NakajimaM, OginoI, et al. Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus. Eur J Neurol 2013;20(2):236–42.
33. MazurekMF. CSF vasopressin concentration is reduced in Alzheimer’s disease. Neurology 1986;36(8):1133–7.
34. CacabelosR, BarqueroM, GarciaP, AlvarezXA, Varela de Seijas E. Cerebrospinal fluid interleukin-1 beta (IL-1 beta) in Alzheimer’s disease and neurological disorders. Methods Findings Exp Clin Pharmacol 1991;13(7):455.
35. NooijenPT, SchoonderwaldtHC, WeversRA, HommesOR, LamersKJ. Neuron-specific enolase, S-100 protein, myelin basic protein and lactate in CSF in dementia. Dement Geriatr Cogn Disord 1997;8(3):169–73.
36. MalmJ, KristensenB, EkstedtJ, AdolfssonR, WesterP. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters. J Neurol Neurosurg Psychiatry 1991;54(3):252–9.
37. FutakawaS, NaraK, MiyajimaM, et al. A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH. Neurobiol Aging 2012;33(8):1807–15.
38. TullbergM, ManssonJE, FredmanP, et al. CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy. J Neurol Neurosurg Psychiatry 2000;69(1):74–81.
39. TullbergM, HultinL, EkholmS, et al. White matter changes in normal pressure hydrocephalus and Binswanger disease: specificity, predictive value and correlations to axonal degeneration and demyelination. Acta Neurol Scand 2002;105(6):417–26.
40. WikkelsøC, EkmanR, WestergrenI, JohanssonB. Neuropeptides in cerebrospinal fluid in normal-pressure hydrocephalus and dementia. Eur Neurol 1991;31(2):88–93.
41. DelgadoM, VarelaN, Gonzalez-ReyE.Vasoactive intestinal peptide protects against beta-amyloid-induced neurodegeneration by inhibiting microglia activation at multiple levels. Glia 2008;56(10):1091–103.
42. FerreroP, BennaP, CostaP, et al. Diazepam binding inhibitor-like immunoreactivity (DBI-LI) in human CSF: correlations with neurological disorders. J Neurol Sci 1988;87(2–3):327–49.
43. MaseM, YamadaK, ShimazuN, et al. Lipocalin-type prostaglandin D synthase (beta-trace) in cerebrospinal fluid: a useful marker for the diagnosis of normal pressure hydrocephalus. Neurosci Res 2003;47(4):455–9.
44. EspayAJ, NarayanRK, DukerAP, BarrettET, de Courten-MyersG. Lower-body parkinsonism: reconsidering the threshold for external lumbar drainage. Nat Clin Pract Neurol 2008;4(1):50–5.
45. MandirAS, HilfikerJ, ThomasG, et al. Extrapyramidal signs in normal pressure hydrocephalus: an objective assessment. Cerebrospinal Fluid Res 2007;4(1):7.
46. KraussJK, RegelJP, DrosteDW, et al. Movement disorders in adult hydrocephalus. Mov Disord 1997;12(1):53–60.
47. StolzeH, Kuhtz-BuschbeckJP, DruckeH, et al. Comparative analysis of the gait disorder of normal pressure hydrocephalus and Parkinson’s disease. J Neurol Neurosurg Psychiatry 2001;70(3):289–97.
48. BealMF. CSF somatostatin-like immunoreactivity in dementia. Neurology 1986;36(2):294–7.
49. AraiH, TerajimaM, MiuraM, et al. Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 1995;38(4):649–52.
50. DawsonTM, DawsonVL. Molecular pathways of neurodegeneration in Parkinson’s disease. Am Assoc Adv Sci 2003:819–22.
51. RotaE, BelloneG, RoccaP, et al. Increased intrathecal TGF-α1, but not IL-12, IFN-α and IL-10 levels in Alzheimer’s disease patients. Neurol Sci 2006;27(1):33–9.
52. PatelS, LeeEB, XieSX, et al. Phosphorylated tau/amyloid beta 1–42 ratio in ventricular cerebrospinal fluid reflects outcome in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 2012;9(1):7.
53. LeinonenV, MenonLG, CarrollRS, et al. Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus. Int J Alzheimers Dis 2011; doi:10.4061/2011/312526.
54. TarnarisA, TomaAK, ChapmanMD, et al. Use of cerebrospinal fluid amyloid-β and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocephalus. J Neurosurg 2011;115(1):145–50.
55. ScollatoA, TerreniA, CaldiniA, et al. CSF proteomic analysis in patients with normal pressure hydrocephalus selected for the shunt: CSF biomarkers of response to surgical treatment. Neurol Sci 2010;31(3):283–91.
56. NakajimaM, MiyajimaM, OginoI, et al. Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien) 2011;153(6):1339–46.
57. BlennowK.Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx 2004;1(2):213–25.
58. GolombJ, WisoffJ, MillerDC, et al. Alzheimer’s disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response. J Neurol Neurosurg Psychiatry 2000;68(6):778–81.
59. TeunissenCE, PetzoldA, BennettJL, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 2009;73(22):1914–22.
60. DeisenhammerF, BartosA, EggR, et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 2006;13(9):913–22.
61. MarmarouA, BergsneiderM, RelkinN, KlingeP, BlackPM. Development of guidelines for idiopathic normal-pressure hydrocephalus: introduction. Neurosurgery 2005;57(3 Suppl):S1–3; discussion ii–v.
62. KlingeP, HellströmP, TansJ, WikkelsøC. One-year outcome in the European multicentre study on iNPH. Acta Neurol Scand 2012;126(3):145–53.