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Cerebrospinal Fluid Biomarkers of Hydrocephalus

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Cerebrospinal Fluid Disorders

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Abstract

Hydrocephalus is a complex neurological disorder that is characterized by overaccumulation of cerebrospinal fluid (CSF) within the cerebral ventricles, affecting 1 in every 500–1000 individuals worldwide. From an etiological standpoint, there are several forms of hydrocephalus predefined by their respective antecedent neurologic events, including: posthemorrhagic hydrocephalus (PHH), which occurs following severe intraventricular hemorrhage (IVH) in neonates; postinfectious hydrocephalus (PIH), which results from ventriculitis typically in the setting of perinatal sepsis, congenital hydrocephalus (CHC), which is associated with a range of genetic aberrations; spina-bifida-associated hydrocephalus (SB/HC), which typically occurs in patients myelomeningocele; and idiopathic normal pressure hydrocephalus (iNPH), an adult form with unknown etiology.

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References

  1. Tully HM, Dobyns WB. Infantile hydrocephalus: a review of epidemiology, classification and causes. Eur J Med Genet. 2014;57(8):359–68.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rekate HL. A contemporary definition and classification of hydrocephalus. Semin Pediatr Neurol. 2009;16(1):9–15.

    Article  PubMed  Google Scholar 

  3. Volpe JJ. Intraventricular hemorrhage and brain injury in the premature infant. Neuropathology and pathogenesis. Clin Perinatol. 1989;16(2):361–86.

    Article  CAS  PubMed  Google Scholar 

  4. Kahle KT, Kulkarni AV, Limbrick DD Jr, Warf BC. Hydrocephalus in children. Lancet. 2016;387(10020):788–99.

    Article  PubMed  Google Scholar 

  5. Chu SM, Hsu JF, Lee CW, et al. Neurological complications after neonatal bacteremia: the clinical characteristics, risk factors, and outcomes. PLoS One. 2014;9(11):e105294.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Li L, Padhi A, Ranjeva SL, et al. Association of bacteria with hydrocephalus in Ugandan infants. J Neurosurg Pediatr. 2011;7(1):73–87.

    Article  PubMed  Google Scholar 

  7. van der Knaap MS, Valk J. Classification of congenital abnormalities of the CNS. AJNR Am J Neuroradiol. 1988;9(2):315–26.

    PubMed  PubMed Central  Google Scholar 

  8. Muniz-Talavera H, Schmidt JV. The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis. PLoS One. 2017;12(12):e0184957.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Zhang J, Williams MA, Rigamonti D. Genetics of human hydrocephalus. J Neurol. 2006;253(10):1255–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. Symptomatic occult hydrocephalus with “normal” cerebrospinal-fluid pressure.A treatable syndrome. N Engl J Med. 1965;273(3):117–26.

    Article  CAS  PubMed  Google Scholar 

  11. Warf BC, East African Neurosurgical Research Collaboration. Pediatric hydrocephalus in East Africa: prevalence, causes, treatments, and strategies for the future. World Neurosurg. 2010;73(4):296–300.

    Article  PubMed  Google Scholar 

  12. McAllister JP 2nd, Chovan P. Neonatal hydrocephalus. Mechanisms and consequences. Neurosurg Clin N Am. 1998;9(1):73–93.

    Article  PubMed  Google Scholar 

  13. Wellons JC 3rd, Holubkov R, Browd SR, et al. The assessment of bulging fontanel and splitting of sutures in premature infants: an interrater reliability study by the Hydrocephalus Clinical Research Network. J Neurosurg Pediatr. 2013;11(1):12–4.

    Article  PubMed  Google Scholar 

  14. Murphy BP, Inder TE, Rooks V, et al. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed. 2002;87(1):F37–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57(3 Suppl):S4–16; discussion ii–v

    PubMed  Google Scholar 

  16. O’Hayon BB, Drake JM, Ossip MG, Tuli S, Clarke M. Frontal and occipital horn ratio: a linear estimate of ventricular size for multiple imaging modalities in pediatric hydrocephalus. Pediatr Neurosurg. 1998;29(5):245–9.

    Article  PubMed  Google Scholar 

  17. Warf B, Ondoma S, Kulkarni A, et al. Neurocognitive outcome and ventricular volume in children with myelomeningocele treated for hydrocephalus in Uganda. J Neurosurg Pediatr. 2009;4(6):564–70.

    Article  PubMed  Google Scholar 

  18. Tarnaris A, Toma AK, Pullen E, et al. Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus. Alzheimers Dement. 2011;7(5):501–8.

    Article  CAS  PubMed  Google Scholar 

  19. Santangelo R, Cecchetti G, Bernasconi MP, et al. Cerebrospinal fluid amyloid-beta 42, total tau, and phosphorylated tau are low in patients with normal pressure hydrocephalus: analogies and differences with Alzheimer’s disease. J Alzheimers Dis. 2017;60:183–200.

    Article  CAS  PubMed  Google Scholar 

  20. Del Bigio MR. Cellular damage and prevention in childhood hydrocephalus. Brain Pathol. 2004;14(3):317–24.

    Article  PubMed  Google Scholar 

  21. Williams MA, McAllister JP, Walker ML, et al. Priorities for hydrocephalus research: report from a National Institutes of Health-sponsored workshop. J Neurosurg. 2007;107(5 Suppl):345–57.

    PubMed  Google Scholar 

  22. Del Bigio MR, McAllister JP II. Pathophysiology of hydrocephalus. In: Choux M, DiRocco R, Hockley AD, Walker ML, editors. Pediatric neurosurgery, vol. 4. Philadelphia: Churchill Livingstone; 1999. p. 217–36.

    Google Scholar 

  23. Del Bigio MR. Neuropathology and structural changes in hydrocephalus. Dev Disabil Res Rev. 2010;16(1):16–22.

    Article  PubMed  Google Scholar 

  24. McAllister JP 2nd, Williams MA, Walker ML, et al. An update on research priorities in hydrocephalus: overview of the third National Institutes of Health-sponsored symposium “Opportunities for Hydrocephalus Research: Pathways to Better Outcomes”. J Neurosurg. 2015;123(6):1427–38.

    Article  CAS  PubMed  Google Scholar 

  25. Iliff JJ, Chen MJ, Plog BA, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci Off J Soc Neurosci. 2014;34(49):16180–93.

    Article  CAS  Google Scholar 

  26. Petraglia AL, Dashnaw ML, Turner RC, Bailes JE. Models of mild traumatic brain injury: translation of physiological and anatomic injury. Neurosurgery. 2014;75(suppl_4):S34–49.

    Article  PubMed  Google Scholar 

  27. Fagan AM, Csernansky CA, Morris JC, Holtzman DM. The search for antecedent biomarkers of Alzheimer’s disease. J Alzheimers Dis. 2005;8(4):347–58.

    Article  CAS  PubMed  Google Scholar 

  28. Fagan AM, Holtzman DM. Cerebrospinal fluid biomarkers of Alzheimer’s disease. Biomark Med. 2010;4(1):51–63.

    Article  CAS  PubMed  Google Scholar 

  29. Pasinetti GM, Ungar LH, Lange DJ, et al. Identification of potential CSF biomarkers in ALS. Neurology. 2006;66(8):1218–22.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  PubMed  Google Scholar 

  31. Laitera T, Kurki MI, Pursiheimo JP, et al. The expression of transthyretin and amyloid-beta protein precursor is altered in the brain of idiopathic normal pressure hydrocephalus patients. J Alzheimers Dis. 2015;48(4):959–68.

    Article  PubMed  CAS  Google Scholar 

  32. Sutphen CL, Jasielec MS, Shah AR, et al. Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age. JAMA Neurol. 2015;72(9):1029–42.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Tsitsopoulos PP, Marklund N. A delayed spinocutaneous fistula after anterior cervical discectomy and fusion. Spine J. 2015;15(4):783–4.

    Article  PubMed  Google Scholar 

  34. Marklund N, Farrokhnia N, Hanell A, et al. Monitoring of beta-amyloid dynamics after human traumatic brain injury. J Neurotrauma. 2014;31(1):42–55.

    Article  PubMed  Google Scholar 

  35. Steinacker P, Fang L, Kuhle J, et al. Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. PLoS One. 2011;6(8):e23600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sosvorova 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):586–93.

    CAS  PubMed  Google Scholar 

  37. Gutierrez-Murgas YM, Skar G, Ramirez D, Beaver M, Snowden JN. IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection. J Neuroinflammation. 2016;13(1):271.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Waybright T, Avellino AM, Ellenbogen RG, Hollinger BJ, Veenstra TD, Morrison RS. Characterization of the human ventricular cerebrospinal fluid proteome obtained from hydrocephalic patients. J Proteome. 2010;73(6):1156–62.

    Article  CAS  Google Scholar 

  39. Veenstra TD, Conrads TP, Hood BL, Avellino AM, Ellenbogen RG, Morrison RS. Biomarkers: mining the biofluid proteome. Mol Cell Proteomics. 2005;4(4):409–18.

    Article  CAS  PubMed  Google Scholar 

  40. Morales DM, Townsend RR, Malone JP, et al. Alterations in protein regulators of neurodevelopment in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus of prematurity. Mol Cell Proteomics. 2012;11(6):M111.011973.

    Article  PubMed  CAS  Google Scholar 

  41. Limbrick DD Jr, Baksh B, Morgan CD, et al. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus. PLoS One. 2017;12(2):e0172353.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Morales DM, Silver SA, Morgan CD, et al. Lumbar cerebrospinal fluid biomarkers of posthemorrhagic hydrocephalus of prematurity: amyloid precursor protein, soluble amyloid precursor protein alpha, and L1 cell adhesion molecule. Neurosurgery. 2017;80(1):82–90.

    PubMed  Google Scholar 

  43. Morales DM, Holubkov R, Inder TE, et al. Cerebrospinal fluid levels of amyloid precursor protein are associated with ventricular size in post-hemorrhagic hydrocephalus of prematurity. PLoS One. 2015;10(3):e0115045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Guerra MM, Henzi R, Ortloff A, et al. Cell junction pathology of neural stem cells is associated with ventricular zone disruption, hydrocephalus, and abnormal neurogenesis. J Neuropathol Exp Neurol. 2015;74(7):653–71.

    Article  PubMed  Google Scholar 

  45. Jimenez AJ, Dominguez-Pinos MD, Guerra MM, Fernandez-Llebrez P, Perez-Figares JM. Structure and function of the ependymal barrier and diseases associated with ependyma disruption. Tissue Barriers. 2014;2:e28426.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Rodriguez EM, Guerra MM, Vio K, et al. A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus. Biol Res. 2012;45(3):231–42.

    Article  PubMed  CAS  Google Scholar 

  47. Ohata S, Alvarez-Buylla A. Planar organization of multiciliated ependymal (E1) cells in the brain ventricular epithelium. Trends Neurosci. 2016;39:543–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lee L. Riding the wave of ependymal cilia: genetic susceptibility to hydrocephalus in primary ciliary dyskinesia. J Neurosci Res. 2013;91(9):1117–32.

    Article  CAS  PubMed  Google Scholar 

  49. Narita K, Takeda S. Cilia in the choroid plexus: their roles in hydrocephalus and beyond. Front Cell Neurosci. 2015;9:39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ohata S, Nakatani J, Herranz-Perez V, et al. Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus. Neuron. 2014;83(3):558–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Heep A, Stoffel-Wagner B, Bartmann P, et al. Vascular endothelial growth factor and transforming growth factor-beta1 are highly expressed in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus. Pediatr Res. 2004;56(5):768–74.

    Article  CAS  PubMed  Google Scholar 

  52. Heep A, Stoffel-Wagner B, Soditt V, Aring C, Groneck P, Bartmann P. Procollagen I C-propeptide in the cerebrospinal fluid of neonates with posthaemorrhagic hydrocephalus. Arch Dis Child Fetal Neonatal Ed. 2002;87(1):F34–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hochhaus F, Koehne P, Schaper C, et al. Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus. BMC Pediatr. 2001;1:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Beems T, Simons KS, Van Geel WJ, De Reus HP, Vos PE, Verbeek MM. Serum- and CSF-concentrations of brain specific proteins in hydrocephalus. Acta Neurochir. 2003;145(1):37–43.

    Article  CAS  PubMed  Google Scholar 

  55. Koehne P, Hochhaus F, Felderhoff-Mueser U, Ring-Mrozik E, Obladen M, Buhrer C. Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus. Childs Nerv Syst. 2002;18(3–4):137–41.

    Article  PubMed  Google Scholar 

  56. Longatti PL, Canova G, Guida F, Carniato A, Moro M, Carteri A. The CSF myelin basic protein: a reliable marker of actual cerebral damage in hydrocephalus. J Neurosurg Sci. 1993;37(2):87–90.

    CAS  PubMed  Google Scholar 

  57. Naureen I, Waheed KA, Rathore AW, et al. Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss. Fluids Barriers CNS. 2013;10(1):34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Naureen I, Waheed Kh A, Rathore AW, et al. Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: inflammatory cytokines. Childs Nerv Syst. 2014;30(7):1155–64.

    Article  PubMed  Google Scholar 

  59. Krauss JK, Droste DW, Bohus M, et al. The relation of intracranial pressure B-waves to different sleep stages in patients with suspected normal pressure hydrocephalus. Acta Neurochir. 1995;136(3–4):195–203.

    Article  CAS  PubMed  Google Scholar 

  60. Williams MA, Relkin NR. Diagnosis and management of idiopathic normal-pressure hydrocephalus. Neurol Clin Pract. 2013;3(5):375–85.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Chen Z, Liu C, Zhang J, Relkin N, Xing Y, Li Y. Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis. Fluids Barriers CNS. 2017;14:13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. 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. 2006;148(8):859–64; discussion 864

    Article  CAS  PubMed  Google Scholar 

  63. 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):141–4.

    Article  CAS  PubMed  Google Scholar 

  64. Patel S, Lee EB, Xie SX, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Tarnaris A, Toma AK, Kitchen ND, Watkins LD. Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus. Biomark Med. 2009;3(6):787–805.

    Article  CAS  PubMed  Google Scholar 

  66. Tullberg M, Blennow K, Mansson JE, Fredman P, Tisell M, Wikkelso C. Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus. Cerebrospinal Fluid Res. 2008;5:9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2(10):605–13.

    Article  CAS  PubMed  Google Scholar 

  68. Tullberg M, Blennow K, Mansson JE, Fredman P, Tisell M, Wikkelso 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):248–54.

    Article  CAS  PubMed  Google Scholar 

  69. Leinonen V, Menon LG, Carroll RS, et al. Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus. Int J Alzheimers Dis. 2011;2011:312526.

    PubMed  PubMed Central  Google Scholar 

  70. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J. Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci Off J Soc Neurosci. 2006;26(27):7212–21.

    Article  CAS  Google Scholar 

  71. Kamenetz F, Tomita T, Hsieh H, et al. APP processing and synaptic function. Neuron. 2003;37(6):925–37.

    Article  CAS  PubMed  Google Scholar 

  72. Dawkins E, Small DH. Insights into the physiological function of the beta-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem. 2014;129(5):756–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Roberts GW, Gentleman SM, Lynch A, Murray L, Landon M, Graham DI. Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 1994;57(4):419–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW. Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett. 1993;160(2):139–44.

    Article  CAS  PubMed  Google Scholar 

  75. Gorrie C, Oakes S, Duflou J, Blumbergs P, Waite PM. Axonal injury in children after motor vehicle crashes: extent, distribution, and size of axonal swellings using beta-APP immunohistochemistry. J Neurotrauma. 2002;19(10):1171–82.

    Article  PubMed  Google Scholar 

  76. Sherriff FE, Bridges LR, Sivaloganathan S. Early detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein. Acta Neuropathol. 1994;87(1):55–62.

    Article  CAS  PubMed  Google Scholar 

  77. Graham DI, Gentleman SM, Nicoll JA, et al. Altered beta-APP metabolism after head injury and its relationship to the aetiology of Alzheimer’s disease. Acta Neurochir Suppl. 1996;66:96–102.

    CAS  PubMed  Google Scholar 

  78. Rajagopal A, Shimony JS, McKinstry RC, et al. White matter microstructural abnormality in children with hydrocephalus detected by probabilistic diffusion tractography. AJNR Am J Neuroradiol. 2013;34(12):2379–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yuan W, McKinstry RC, Shimony JS, et al. Diffusion tensor imaging properties and neurobehavioral outcomes in children with hydrocephalus. AJNR Am J Neuroradiol. 2013;34(2):439–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lewczuk P, Esselmann H, Bibl M, et al. Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease: original data and review of the literature. J Mol Neurosci. 2004;23(1–2):115–22.

    Article  CAS  PubMed  Google Scholar 

  81. Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–84.

    Article  CAS  PubMed  Google Scholar 

  82. Hladky SB, Barrand MA. Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. Fluids Barriers CNS. 2014;11(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Graff-Radford NR. Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus. Neurology. 2014;83(17):1573–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Jeppsson A, Zetterberg H, Blennow K, Wikkelso C. Idiopathic normal-pressure hydrocephalus: pathophysiology and diagnosis by CSF biomarkers. Neurology. 2013;80(15):1385–92.

    Article  CAS  PubMed  Google Scholar 

  85. Tarnaris A, Toma AK, Chapman MD, et al. Rostrocaudal dynamics of CSF biomarkers. Neurochem Res. 2011;36(3):528–32.

    Article  CAS  PubMed  Google Scholar 

  86. Brandner S, Thaler C, Lelental N, et al. Ventricular and lumbar cerebrospinal fluid concentrations of Alzheimer’s disease biomarkers in patients with normal pressure hydrocephalus and posttraumatic hydrocephalus. J Alzheimers Dis. 2014;41(4):1057–62.

    Article  CAS  PubMed  Google Scholar 

  87. Sanders WS, Wang N, Bridges SM, et al. The proteogenomic mapping tool. BMC Bioinformatics. 2011;12:115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ruggles KV, Krug K, Wang X, et al. Methods, tools and current perspectives in proteogenomics. Mol Cell Proteomics. 2017;16(6):959–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Mashayekhi F, Salehi Z. Expression of nerve growth factor in cerebrospinal fluid of congenital hydrocephalic and normal children. Eur J Neurol. 2005;12(8):632–7.

    Article  CAS  PubMed  Google Scholar 

  90. Erol FS, Yakar H, Artas H, Kaplan M, Kaman D. Investigating a correlation between the results of transcranial Doppler and the level of nerve growth factor in cerebrospinal fluid of hydrocephalic infants: clinical study. Pediatr Neurosurg. 2009;45(3):192–7.

    Article  PubMed  Google Scholar 

  91. Tisell M, Tullberg M, Mansson JE, Fredman P, Blennow K, Wikkelso C. Differences in cerebrospinal fluid dynamics do not affect the levels of biochemical markers in ventricular CSF from patients with aqueductal stenosis and idiopathic normal pressure hydrocephalus. Eur J Neurol. 2004;11(1):17–23.

    Article  CAS  PubMed  Google Scholar 

  92. Perez-Neri I, Castro E, Montes S, et al. Arginine, citrulline and nitrate concentrations in the cerebrospinal fluid from patients with acute hydrocephalus. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;851(1–2):250–6.

    Article  CAS  PubMed  Google Scholar 

  93. Cengiz P, Zemlan F, Ellenbogen R, Hawkins D, Zimmerman JJ. Cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid concentrations in pediatric patients with hydrocephalus. Pediatr Crit Care Med. 2008;9(5):524–9.

    Article  PubMed  Google Scholar 

  94. Sutton LN, Wood JH, Brooks BR, Barrer SJ, Kline M, Cohen SR. Cerebrospinal fluid myelin basic protein in hydrocephalus. J Neurosurg. 1983;59(3):467–70.

    Article  CAS  PubMed  Google Scholar 

  95. Gopal SC, Pandey A, Das I, et al. Comparative evaluation of 5-HIAA (5-hydroxy indoleacetic acid) and HVA (homovanillic acid) in infantile hydrocephalus. Childs Nerv Syst. 2008;24(6):713–6.

    Article  CAS  PubMed  Google Scholar 

  96. Lee JH, Park DH, Back DB, 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):PR19–25.

    PubMed  PubMed Central  Google Scholar 

  97. Yang JT, Chang CN, Hsu YH, Wei KC, Lin TK, Wu JH. Increase in CSF NGF concentration is positively correlated with poor prognosis of postoperative hydrocephalic patients. Clin Biochem. 1999;32(8):673–5.

    Article  CAS  PubMed  Google Scholar 

  98. Felderhoff-Mueser U, Herold R, Hochhaus F, et al. Increased cerebrospinal fluid concentrations of soluble Fas (CD95/Apo-1) in hydrocephalus. Arch Dis Child. 2001;84(4):369–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. de Bont JM, Vanderstichele H, Reddingius RE, Pieters R, van Gool SW. Increased total-Tau levels in cerebrospinal fluid of pediatric hydrocephalus and brain tumor patients. Eur J Paediatr Neurol. 2008;12(4):334–41.

    Article  PubMed  Google Scholar 

  100. Kruse A, Cesarini KG, Bach FW, Persson L. Increases of neuron-specific enolase, S-100 protein, creatine kinase and creatine kinase BB isoenzyme in CSF following intraventricular catheter implantation. Acta Neurochir. 1991;110(3–4):106–9.

    Article  CAS  PubMed  Google Scholar 

  101. Cerda M, Vielma J, Martinez C, Basauri L. Polyacrylamide gel electrophoresis of cerebrospinal fluid proteins in children with nontumoral hydrocephalus. Childs Brain. 1980;6(3):140–9.

    CAS  PubMed  Google Scholar 

  102. Lopponen T, Saukkonen AL, Serlo W, Tapanainen P, Ruokonen A, Knip M. Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus. Arch Dis Child. 1997;77(1):32–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gopal SC, Sharma V, Chansuria JP, Gangopadhyaya AN, Singh TB. Serotonin and 5-hydroxy indole acetic acid in infantile hydrocephalus. Pediatr Surg Int. 2007;23(6):571–4.

    Article  CAS  PubMed  Google Scholar 

  104. Longatti PL, Guida F, Agostini S, Carniato B, Carteri A. The CSF myelin basic protein in pediatric hydrocephalus. Childs Nerv Syst. 1994;10(2):96–8.

    Article  CAS  PubMed  Google Scholar 

  105. Killer M, Arthur A, Al-Schameri AR, et al. Cytokine and growth factor concentration in cerebrospinal fluid from patients with hydrocephalus following endovascular embolization of unruptured aneurysms in comparison with other types of hydrocephalus. Neurochem Res. 2010;35(10):1652–8.

    Article  CAS  PubMed  Google Scholar 

  106. Futakawa S, Nara K, Miyajima M, et al. A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH. Neurobiol Aging. 2012;33(8):1807–15.

    Article  CAS  PubMed  Google Scholar 

  107. Jeppsson A, Holtta M, Zetterberg H, Blennow K, Wikkelso C, Tullberg M. Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS. 2016;13(1):13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Herukka SK, Rummukainen J, Ihalainen J, et al. Amyloid-beta and Tau dynamics in human brain interstitial fluid in patients with suspected normal pressure hydrocephalus. J Alzheimers Dis. 2015;46(1):261–9.

    Article  CAS  PubMed  Google Scholar 

  109. Laske C, Stransky E, Leyhe T, et al. BDNF serum and CSF concentrations in Alzheimer’s disease, normal pressure hydrocephalus and healthy controls. J Psychiatr Res. 2007;41(5):387–94.

    Article  PubMed  Google Scholar 

  110. Ray B, Reyes PF, Lahiri DK. Biochemical studies in Normal Pressure Hydrocephalus (NPH) patients: change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Abeta) peptide and phospho-tau. J Psychiatr Res. 2011;45(4):539–47.

    Article  PubMed  Google Scholar 

  111. Fersten E, Gordon-Krajcer W, Glowacki M, Mroziak B, Jurkiewicz J, Czernicki Z. Cerebrospinal fluid free-radical peroxidation products and cognitive functioning patterns differentiate varieties of normal pressure hydrocephalus. Folia Neuropathol. 2004;42(3):133–40.

    CAS  PubMed  Google Scholar 

  112. Castaneyra-Ruiz L, Gonzalez-Marrero I, Carmona-Calero EM, et al. Cerebrospinal fluid levels of tumor necrosis factor alpha and aquaporin 1 in patients with mild cognitive impairment and idiopathic normal pressure hydrocephalus. Clin Neurol Neurosurg. 2016;146:76–81.

    Article  PubMed  Google Scholar 

  113. Kapaki EN, Paraskevas GP, Tzerakis NG, 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.

    Article  CAS  PubMed  Google Scholar 

  114. Elobeid A, Laurell K, Cesarini KG, Alafuzoff I. Correlations between mini-mental state examination score, cerebrospinal fluid biomarkers, and pathology observed in brain biopsies of patients with normal-pressure hydrocephalus. J Neuropathol Exp Neurol. 2015;74(5):470–9.

    Article  CAS  PubMed  Google Scholar 

  115. Agren-Wilsson A, Lekman A, Sjoberg W, et al. CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus. Acta Neurol Scand. 2007;116(5):333–9.

    Article  CAS  PubMed  Google Scholar 

  116. Tullberg M, Rosengren L, Blomsterwall E, Karlsson JE, Wikkelso C. CSF neurofilament and glial fibrillary acidic protein in normal pressure hydrocephalus. Neurology. 1998;50(4):1122–7.

    Article  CAS  PubMed  Google Scholar 

  117. Scollato A, Terreni A, Caldini A, 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.

    Article  PubMed  Google Scholar 

  118. Tullberg M, Mansson JE, Fredman P, et al. CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy. J Neurol Neurosurg Psychiatry. 2000;69(1):74–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sosvorova L, Bestak J, Bicikova M, et al. Determination of homocysteine in cerebrospinal fluid as an indicator for surgery treatment in patients with hydrocephalus. Physiol Res. 2014;63(4):521–7.

    CAS  PubMed  Google Scholar 

  120. Kondo M, Tokuda T, Itsukage M, et al. Distribution of amyloid burden differs between idiopathic normal pressure hydrocephalus and Alzheimer’s disease. Neuroradiol J. 2013;26(1):41–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lim TS, Choi JY, Park SA, et al. Evaluation of coexistence of Alzheimer’s disease in idiopathic normal pressure hydrocephalus using ELISA analyses for CSF biomarkers. BMC Neurol. 2014;14:66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Albrechtsen M, Sorensen PS, Gjerris F, Bock E. High cerebrospinal fluid concentration of glial fibrillary acidic protein (GFAP) in patients with normal pressure hydrocephalus. J Neurol Sci. 1985;70(3):269–74.

    Article  CAS  PubMed  Google Scholar 

  123. Kalamatianos T, Markianos M, Margetis K, Bourlogiannis F, Stranjalis G. Higher Orexin A levels in lumbar compared to ventricular CSF: a study in idiopathic normal pressure hydrocephalus. Peptides. 2014;51:1–3.

    Article  CAS  PubMed  Google Scholar 

  124. Jingami N, Asada-Utsugi M, Uemura K, et al. Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer’s disease. J Alzheimers Dis. 2015;45(1):109–15.

    Article  CAS  PubMed  Google Scholar 

  125. Kang K, Ko PW, Jin M, Suk K, Lee HW. Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test. J Clin Neurosci. 2014;21(8):1398–403.

    Article  CAS  PubMed  Google Scholar 

  126. Lins H, Wichart I, Bancher C, Wallesch CW, Jellinger KA, Rosler N. Immunoreactivities of amyloid beta peptide((1-42)) and total tau protein in lumbar cerebrospinal fluid of patients with normal pressure hydrocephalus. J Neural Transm (Vienna). 2004;111(3):273–80.

    Article  CAS  Google Scholar 

  127. Nakajima M, Miyajima M, Ogino I, et al. Leucine-rich alpha-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus. Acta Neurochir. 2011;153(6):1339–46; discussion 1346

    Article  PubMed  Google Scholar 

  128. Mase M, Yamada K, Shimazu N, 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.

    Article  CAS  PubMed  Google Scholar 

  129. Huang H, Yang J, Luciano M, Shriver LP. Longitudinal metabolite profiling of cerebrospinal fluid in normal pressure hydrocephalus links brain metabolism with exercise-induced VEGF production and clinical outcome. Neurochem Res. 2016;41(7):1713–22.

    Article  CAS  PubMed  Google Scholar 

  130. Sorensen PS, Gjerris F, Ibsen S, Bock E. Low cerebrospinal fluid concentration of brain-specific protein D2 in patients with normal pressure hydrocephalus. J Neurol Sci. 1983;62(1–3):59–65.

    Article  CAS  PubMed  Google Scholar 

  131. Brettschneider J, Riepe MW, Petereit HF, Ludolph AC, Tumani H. Meningeal derived cerebrospinal fluid proteins in different forms of dementia: is a meningopathy involved in normal pressure hydrocephalus? J Neurol Neurosurg Psychiatry. 2004;75(11):1614–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Luikku AJ, Hall A, Nerg O, et al. Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus. Acta Neurochir. 2016;158(12):2311–9.

    Article  PubMed  Google Scholar 

  133. Tarkowski E, Tullberg M, Fredman P, Wikkelso C. Normal pressure hydrocephalus triggers intrathecal production of TNF-alpha. Neurobiol Aging. 2003;24(5):707–14.

    Article  CAS  PubMed  Google Scholar 

  134. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Miyajima M, Nakajima M, Ogino I, Miyata H, Motoi Y, Arai H. Soluble amyloid precursor protein alpha in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus. Eur J Neurol. 2013;20(2):236–42.

    Article  CAS  PubMed  Google Scholar 

  136. Kudo T, Mima T, Hashimoto R, et al. Tau protein is a potential biological marker for normal pressure hydrocephalus. Psychiatry Clin Neurosci. 2000;54(2):199–202.

    Article  CAS  PubMed  Google Scholar 

  137. Tarnaris A, Toma AK, Chapman MD, et al. The longitudinal profile of CSF markers during external lumbar drainage. J Neurol Neurosurg Psychiatry. 2009;80(10):1130–3.

    Article  CAS  PubMed  Google Scholar 

  138. Tarnaris A, Toma AK, Chapman MD, Keir G, Kitchen ND, Watkins LD. Use of cerebrospinal fluid amyloid-beta and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocephalus. J Neurosurg. 2011;115(1):145–50.

    Article  PubMed  Google Scholar 

  139. Chow LC, Soliman A, Zandian M, Danielpour M, Krueger RC Jr. Accumulation of transforming growth factor-beta2 and nitrated chondroitin sulfate proteoglycans in cerebrospinal fluid correlates with poor neurologic outcome in preterm hydrocephalus. Biol Neonate. 2005;88(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  140. Okamoto T, Takahashi S, Nakamura E, et al. Increased expression of matrix metalloproteinase-9 and hepatocyte growth factor in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus. Early Hum Dev. 2010;86(4):251–4.

    Article  CAS  PubMed  Google Scholar 

  141. Schmitz T, Heep A, Groenendaal F, et al. Interleukin-1beta, interleukin-18, and interferon-gamma expression in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus--markers of white matter damage? Pediatr Res. 2007;61(6):722–6.

    Article  CAS  PubMed  Google Scholar 

  142. Felderhoff-Mueser U, Buhrer C, Groneck P, Obladen M, Bartmann P, Heep A. Soluble Fas (CD95/Apo-1), soluble Fas ligand, and activated caspase 3 in the cerebrospinal fluid of infants with posthemorrhagic and nonhemorrhagic hydrocephalus. Pediatr Res. 2003;54(5):659–64.

    Article  CAS  PubMed  Google Scholar 

  143. Kitazawa K, Tada T. Elevation of transforming growth factor-beta 1 level in cerebrospinal fluid of patients with communicating hydrocephalus after subarachnoid hemorrhage. Stroke. 1994;25(7):1400–4.

    Article  CAS  PubMed  Google Scholar 

  144. Douglas MR, Daniel M, Lagord C, et al. High CSF transforming growth factor beta levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus. J Neurol Neurosurg Psychiatry. 2009;80(5):545–50.

    Article  CAS  PubMed  Google Scholar 

  145. Sokol B, Wozniak A, Jankowski R, et al. HMGB1 level in cerebrospinal fluid as a marker of treatment outcome in patients with acute hydrocephalus following aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2015;24(8):1897–904.

    Article  PubMed  Google Scholar 

  146. Brandner S, Xu Y, Schmidt C, Emtmann I, Buchfelder M, Kleindienst A. Shunt-dependent hydrocephalus following subarachnoid hemorrhage correlates with increased S100B levels in cerebrospinal fluid and serum. Acta Neurochir Suppl. 2012;114:217–20.

    Article  CAS  PubMed  Google Scholar 

  147. Sokol B, Wasik N, Jankowski R, Holysz M, Wieckowska B, Jagodzlnski PP. Soluble toll-like receptors 2 and 4 in cerebrospinal fluid of patients with acute hydrocephalus following aneurysmal subarachnoid haemorrhage. PLoS One. 2016;11(5):e0156171.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Schmitz T, Felderhoff-Mueser U, Sifringer M, Groenendaal F, Kampmann S, Heep A. Expression of soluble Fas in the cerebrospinal fluid of preterm infants with posthemorrhagic hydrocephalus and cystic white matter damage. J Perinat Med. 2011;39(1):83–8.

    Article  PubMed  Google Scholar 

  149. Habiyaremye G, Morales DM, Morgan CD, et al. Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with posthemorrhagic hydrocephalus. Fluids Barriers CNS. 2017;14:35.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, USA

    Albert M. Isaacs

  2. Division of Neurosurgery, Department of Clinical Neuroscience, University of Calgary, Calgary, AB, Canada

    Albert M. Isaacs

  3. Department of Neurological Surgery, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO, USA

    David D. Limbrick Jr.

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Correspondence to Albert M. Isaacs .

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  1. Department of Neurological Surgery, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO, USA

    David D. Limbrick Jr.

  2. Nationwide Children’s Hospital, Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA

    Jeffrey R. Leonard

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Isaacs, A.M., Limbrick, D.D. (2019). Cerebrospinal Fluid Biomarkers of Hydrocephalus. In: Limbrick Jr., D., Leonard, J. (eds) Cerebrospinal Fluid Disorders . Springer, Cham. https://doi.org/10.1007/978-3-319-97928-1_3

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