Skip to main content Accesibility Help
×
×
Home

Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review

  • Tyler Pfanner (a1), Alexandre Henri-Bhargava (a2) (a3) and Stephanie Borchert (a4)
Abstract

Background: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. Methods: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. Results: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. Conclusions: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-β2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-β1, TBR-II, homocysteine, and interleukins (particularly IL-1β, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aβ42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

Revue systématique du rôle prédicteur de la réponse à une dérivation au moyen de bio-marqueurs du liquide céphalo-rachidien : les cas de patients atteints d’hydrocéphalie à pression normale de type idiopathique. Contexte: Le traitement le plus communément admis pour l’hydrocéphalie à pression normale de type idiopathique (HPNi) est d’utiliser du liquide céphalo-rachidien (LCR) à l’aide de tubes ou de drains de dérivation (shunt), intervention à l’égard de laquelle environ 80 % des patients répondent positivement. L’objectif de cette revue systématique a donc été d’identifier les bio-marqueurs du LCR aptes à prédire une telle réponse et analysés au fil des années et d’évaluer leur validité en fonction des preuves. Méthodes: Pour repérer tous les articles pertinents sur le sujet, nous avons effectué une recherche exhaustive à l’aide des bases de données suivantes : Medline, Embase et PsycINFO. Résultats: Notre recherche documentaire nous a permis d’identifier 344 citations uniques. Au total, 13 études ont satisfait à nos critères d’inclusion et ont été analysées dans le cadre de cette revue systématique. À noter qu’elles ont fait état de 37 bio-marqueurs uniques. Conclusions: Les études disponibles suggèrent que les bio-marqueurs du LCR sont utiles pour prédire la réponse à une dérivation chez des patients HPNi, et ce, bien qu’aucun de ces marqueurs n’a semblé pouvoir prédire une telle réponse de façon très sensible ou spécifique. Pour prédire la réponse à une dérivation, nous avons par ailleurs noté qu’il n’existe aucune preuve qui supporte l’utilisation des bio-marqueurs suivants : Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, le sulfatide, MBP, L-PGDS, la cystatine C, la transthyrétine, TGF-β2 et YKL-40. De plus, il n’existe que de faibles preuves supportant l’utilisation de ces bio-marqueurs : TGF-β1, TBR-II, l’homocystéine et les interleukines (en particulier IL-1β, IL-6 et IL-10). Toutefois, les preuves dont on dispose indiquent qu’il serait justifié de se pencher de façon plus approfondie sur ces bio-marqueurs. Enfin, Aβ42, t-Tau, p-Tau, NFL et LRG sont tous des bio-marqueurs dont la capacité à prédire la réponse de patients HPNi à une dérivation est supportée par de nombreuses preuves. Ainsi, les travaux de recherche à venir sur le sujet devraient être orientés par ces bio-marqueurs sans nécessairement s’y limiter.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review
      Available formats
      ×
Copyright
Corresponding author
Correspondence to: Tyler Pfanner, Faculty of Medicine, University of British Columbia, Box 1702, Chetwynd, British Columbia, Canada, V0C 1J0. Email: tyler_pfanner@alumni.ubc.ca.
References
Hide All
1. Ishikawa, M. Clinical guidelines for idiopathic normal pressure hydrocephalus. Neurol Med Chir (Tokyo). 2004;44(4):222-223.
2. Relkin, N, Marmarou, A, Klinge, P, Bergsneider, M, Black, PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57(3 Suppl):S4-S16; discussion ii–v.
3. Mori, E, Ishikawa, M, Kato, T, et al. Guidelines for management of idiopathic normal pressure hydrocephalus: second edition. Neurol Med Chir (Tokyo). 2012;52(11):775-809.
4. Toma, A, Papadopoulos, M, Stapleton, S, Kitchen, N, Watkins, L. Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus. Acta Neurochir (Wien). 2013;155(10):1977-1980.
5. Halperin, JJ, Halperin, JJ, Kurlan, R, Schwalb, JM, Cusimano, MD, Gronseth, G, Gloss, D. Practice guideline. Idiopathic normal pressure hydrocephalus: response to shunting and predictors of response. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2015;85(23):2063-2071.
6. Virhammar, J, Laurell, K, Cesarini, KG, Larsson, E. Preoperative prognostic value of MRI findings in 108 patients with idiopathic normal pressure hydrocephalus. AJNR Am J Neuroradiol. 2014;35(12):2311-2318.
7. Kojoukhova, M, Koivisto, A, Korhonen, R, et al. Feasibility of radiological markers in idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2015;157(10):1709-1719.
8. Lee, J, Park, D, Back, D, et al. Comparison of cerebrospinal fluid biomarkers between idiopathic normal pressure hydrocephalus and subarachnoid hemorrhage-induced chronic hydrocephalus: a pilot study. Med Sci Monit. 2012;18(12):PR19-PR25.
9. Tullberg, M, Blennow, K, Månsson, J, Fredman, P, Tisell, M, Wikkelsö, C. Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus. Cerebrospinal Fluid Res. 2008;5(1):9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387137/. Accessed August 21, 2017.
10. Pyykkö, OT, Lumela, M, Rummukainen, J, et al. Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus. PLoS One. 2014;9(3):e91974. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956805/. Accessed August 21, 2017.
11. Djukic, M, Spreer, A, Lange, P, Bunkowski, S, Wiltfang, J, Nau, R. Small cisterno-lumbar gradient of phosphorylated tau protein in geriatric patients with suspected normal pressure hydrocephalus. Fluids Barriers CNS. 2016;13(1):15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007695/. Accessed August 21, 2017.
12. American Academy of Neurology. Clinical Practice Guideline Process Manual. St. Paul, MN: The American Academy of Neurology; 2011.
13. Nakajima, M, Miyajima, M, Ogino, I, et al. Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus. J Neurol Sci. 2015;357(1–2):88-95.
14. Li, X, Miyajima, M, Mineki, R, Taka, H, Murayama, K, Arai, H. Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics. Acta Neurochir (Wien). 2006;148(8):859-864.
15. Li, X, Miyajima, M, Jiang, C, Arai, H. Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus. Neurosci Lett. 2007;413(2):141-144.
16. Miyajima, M, Nakajima, M, Ogino, I, Miyata, H, Motoi, Y, Arai, H. 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):236-242.
17. Sosvorová, L, Besták, J, Bicíková, M, et al. Determination of homocysteine in cerebrospinal fluid as an indicator for surgery treatment in patients with hydrocephalus. Physiol Res. 2014;63(4):521-527.
18. Sosvorová, L, Vcelak, J, Mohapl, M, Vitku, J, Bicikova, M, Hampl, R. Selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in normal pressure hydrocephalus. Neuro Endocrinol Lett. 2014;35(7):586-593.
19. Agren-Wilsson, A, Lekman, A, Sjöberg, W, et al. CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus. Acta Neurol Scand. 2007;116(5):333-339.
20. Moriya, M, Miyajima, M, Nakajima, M, Ogino, I, Arai, H. Impact of cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus on the amyloid cascade. PLoS One. 2015;10(3):e0119973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379026/. Accessed August 21, 2017.
21. Laiterä, T, Kurki, MI, Pursiheimo, J, et al. The expression of transthyretin and amyloid-β protein precursor is altered in the brain of idiopathic normal pressure hydrocephalus patients. J Alzheimers Dis. 2015;48(4):959-968.
22. Jeppsson, A, Höltta, M, Zetterberg, H, Blennow, K, Wikkelsø, C, Tullberg, M. Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS. 2016;13(1):13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967298/. Accessed August 21, 2017.
23. Nakajima, M, Miyajima, M, Ogino, I, et al. Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2011;153(6):1339-1346.
24. Luikku, A, Hall, A, Nerg, O, et al. Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2016;158(12):2311-2319.
25. Williams, M, Malm, J. Diagnosis and treatment of idiopathic normal pressure hydrocephalus. Continuum (Minneap Minn). 2016;22(2 Dementia):579-599.
26. Chakraborty, S, Kaushik, DK, Gupta, M, Basu, A. Inflammasome signaling at the heart of central nervous system pathology. J Neurosci Res. 2010;88(8):1615-1631.
27. Tullberg, M, Blennow, K, Månsson, JE, Fredman, P, Tisell, M, Wikkelsö, C. Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus. Eur J Neurol. 2007;14(3):248-254.
28. Fredman, P, Wallin, A, Blennow, K, Davidsson, P, Gottfries, CG, Svennerholm, L. Sulfatide as a biochemical marker in cerebrospinal fluid of patients with vascular dementia. Acta Neurol Scand. 1992;85(2):103-106.
29. Whitaker, JN. Myelin basic protein in cerebrospinal fluid and other body fluids. Mult Scler. 1998;4(1):16-21.
30. Kanekiyo, T, Ban, T, Aritake, K, et al. Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid. Proc Natl Acad Sci U S A. 2007;104(15):6412-6417.
31. Costa, R, Ferreira-da-Silva, R, Saraiva, MJ, Cardoso, I. Transthyretin protects against A-beta peptide toxicity by proteolytic cleavage of the peptide: a mechanism sensitive to the Kunitz protease inhibitor. PLoS One. 2008;3(8):e2899. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483353/. Accessed August 21, 2017.
32. Tizon, B, Ribe, EM, Mi, W, Troy, CM, Levy, E. Cystatin C protects neuronal cells from amyloid-beta-induced toxicity. J Alzheimers Dis. 2010;19(3):885-894.
33. Dobolyi, A, Vincze, C, Pál, G, Lovas, G. The neuroprotective functions of transforming growth factor beta proteins. Int J Mol Sci. 2012;13(7):8219-8258.
34. Ansari, R, Mahta, A, Mallack, E, Luo, JJ. Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol. 2014;10(4):281-288.
35. Rathcke, CN, Vestergaard, H. YKL-40: an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol. 2009;8(1):61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789050/. Accessed August 21, 2017.
36. Olsson, B, Olsson, C, Lautner, R, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673-684.
37. Cabral, D, Beach, TG, Vedders, L, et al. Frequency of Alzheimer’s disease pathology at autopsy in patients with clinical normal pressure hydrocephalus. Alzheimers Dement. 2011;7(5):509-513.
38. Bech-Azeddine, R, Høgh, P, Juhler, M, Gjerris, F, Waldemar, G. Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting. J Neurol Neurosurg Psychiatry. 2007;78(2):157-161.
39. Hamilton, R, Patel, S, Lee, EB, et al. Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology. Ann Neurol. 2010;68(4):535-540.
40. Hiraoka, K, Narita, W, Kikuchi, H, et al. Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus. J Neurol Sci. 2015;356(1–2):124-128.
41. Koga, S. Elucidating the etiology of normal pressure hydrocephalus (NPH) and the spectrum of surgically treatable dementias. Am Assoc Neurol Surg. 2010;113(2):A418.
42. Turner, PR, O’Connor, K, Tate, WP, Abraham, WC. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Progr Neurobiol. 2003;70(1):1-32.
43. Coulson, EJ, Paliga, K, Beyreuther, K, Masters, CL. What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int. 2000;36(3):175-184.
44. Jacobsen, KT, Iverfeldt, K. Amyloid precursor protein and its homologues: a family of proteolysis-dependent receptors. Cell Mol Life Sci. 2009;66(14):2299-2318.
45. Yanagida, K, Okochi, M, Tagami, S, et al. The 28-amino acid form of an APLP1-derived Aβ-like peptide is a surrogate marker for Aβ42 production in the central nervous system. EMBO Mol Med. 2009;1(4):223-235.
46. van Harten, AC, Kester, MI, Visser, P, et al. Tau and p-tau as CSF biomarkers in dementia: a meta-analysis. Clin Chem Lab Med. 2011;49(3):353-366.
47. Rosengren, LE, Karlsson, JE, Karlsson, JO, Persson, LI, Wikkelsø, C. Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem. 1996;67(5):2013-2018.
48. Gisslén, M, Price, RW, Andreasson, U, et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine. 2016;3:135-140.
49. Serada, S, Fujimoto, M, Terabe, F, et al. Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis. Inflamm Bowel Dis. 2012;18(11):2169-2179.
50. Andersen, J, Boylan, K, Jemmerson, R, et al. Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients. J Ovarian Res. 2010; 3(1):21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949730/. Accessed August 21, 2017.
51. Kakisaka, T, Kondo, T, Okano, T, et al. Plasma proteomics of pancreatic cancer patients by multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis (2D-DIGE): up-regulation of leucine-rich alpha-2-glycoprotein in pancreatic cancer. J Chromatogr B Analyt Technol Life Sci. 2007;852(1):257-267.
52. Strieter, R, Kunkel, S, Bone, R. Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med. 1993;21(10 Suppl):S447-S463.
53. Esposito, E, Cuzzocrea, S. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Curr Med Chem. 2009;16(24):3152-3167.
54. Leinonen, V, Menon, LG, Carroll, RS, et al. Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus. Int J Alzheimers Dis. 2011: 1-6.
55. Schulz-Schaeffer, WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta Neuropathol. 2010;120(2):131-143.
56. Malek, N, Swallow, D, Grosset, KA, Anichtchik, O, Spillantini, M, Grosset, DG.. Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson’s disease: a systematic review. Acta Neurol Scand. 2014;130(2):59-72.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Canadian Journal of Neurological Sciences
  • ISSN: 0317-1671
  • EISSN: 2057-0155
  • URL: /core/journals/canadian-journal-of-neurological-sciences
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Type Description Title
WORD
Supplementary materials

Pfanner et al supplementary material 1
Appendix

 Word (13 KB)
13 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed