Child's Nervous System

, Volume 30, Issue 5, pp 825–830 | Cite as

Normal pressure hydrocephalus as a failure of ICP homeostasis mechanism: the hidden role of Monro–Kellie doctrine in the genesis of NPH

  • Asem Salma
Review Paper



The theme of this paper is to outline that the genesis of normal pressure hydrocephalus (NPH) is governed by the intracranial pressure (ICP) homeostatic principle. The development of this new concept is based mainly on rethinking the well-known Monro–Kellie doctrine in the way that ICP homeostasis mechanism is not only a mechanism that works to prevent pathologically high ICP but also a mechanism that aims to protect from pathologically low ICP.


The NPH-related literatures are reviewed and reinterpreted to generate a new paradigm for the cascade of pathophysiological events that leads to the genesis NPH, as well as the mechanism of clinical beneficial effects and complications of the shunting procedure.


According to this new paradigm, the suboptimal cerebral perfusion that is associated with the impairment of the cerebral autoregulation is the initial step in the genesis of NPH. When the overall volume of blood that circulates intracranially is diminished, a chronic low ICP with episodes of pathologically low ICP occurs. Since the cranial vault is not collapsible, those episodes of low ICP are compensated by the accumulation of cerebrospinal fluid (CSF) to keep the ICP in normal ideal range. The impairment of brain toxin-flushing mechanism because of CSF pooling combined with the already-established suboptimal cerebral perfusion leads to functional disinhibition of the cerebral cortex.


Recognizing the importance of ICP homeostatic mechanisms in the genesis of the NPH is a simple yet novel view that could change the way we look at NP and can give a basic and fundamental theoretical frame work to achieve better understanding of NPH.


CSF ICP ICP homeostasis mechanism Normal pressure hydrocephalus Monro–Kellie doctrine 


  1. 1.
    Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH (1965) Symptomatic occult hydrocephalus with "Normal" cerebrospinal-fluid pressure. A treatable syndrome. N Engl J Med 273:117–126PubMedCrossRefGoogle Scholar
  2. 2.
    Bateman GA (2008) The pathophysiology of idiopathic normal pressure hydrocephalus: cerebral ischemia or altered venous hemodynamics? AJNR Am J Neuroradiol 29:198–203PubMedCrossRefGoogle Scholar
  3. 3.
    Bradley WG (2000) Normal pressure hydrocephalus: new concepts on etiology and diagnosis. AJNR Am J Neuroradiol 21:1586–1590PubMedGoogle Scholar
  4. 4.
    Bradley WG Jr (2008) Idiopathic normal pressure hydrocephalus: new findings and thoughts on etiology. AJNR Am J Neuroradiol 29:1–3PubMedCrossRefGoogle Scholar
  5. 5.
    Silverberg GD (2004) Normal pressure hydrocephalus (NPH): ischaemia, CSF stagnation or both. Brain 127:947–948PubMedCrossRefGoogle Scholar
  6. 6.
    Di Rocco C, Di Trapani G, Maira G, Bentivoglio M, Macchi G, Rossi GF (1977) Anatomo-clinical correlations in normotensive hydrocephalus. Reports on three cases. J Neurol Sci 33(3):437–452PubMedCrossRefGoogle Scholar
  7. 7.
    Di Rocco C, Pettorossi VE, Caldarelli M, Mancinelli R, Velardi F (1978) Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pressure: experimental studies. Exp Neurol 59(1):40–52PubMedCrossRefGoogle Scholar
  8. 8.
    Pettorossi VE, Di Rocco C, Mancinelli R, Caldarelli M, Velardi F (1978) Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pulse pressure: rationale and method. Exp Neurol 59(1):30–39Google Scholar
  9. 9.
    Preuss M, Hoffmann KT, Reiss-Zimmermann M, Hirsch W, Merkenschlager A, Meixensberger J, Dengl M (2013) Updated physiology and pathophysiology of CSF circulation—the pulsatile vector theory. Childs Nerv Syst 29:1811–1825PubMedCrossRefGoogle Scholar
  10. 10.
    Toma AK, Stapleton S, Papadopoulos MC, Kitchen ND, Watkins LD (2011) Natural history of idiopathic normal-pressure hydrocephalus. Neurosurg Rev 34(4):433–439PubMedCrossRefGoogle Scholar
  11. 11.
    Hayes J, Roguski M, Riesenburger RI (2012) Rapid resolution of an acute subdural hematoma by increasing the shunt valve pressure in a 63-year-old man with normal-pressure hydrocephalus with a ventriculoperitoneal shunt: a case report and literature review. J Med Case Rep 6:393PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Klinge PM (2012) Idiopathic normal pressure hydrocephalus–neurosurgical management of dementia! Med Health R I 95:86–87PubMedGoogle Scholar
  13. 13.
    Nakamizo A, Inamura T, Inoha S, Kuba H, Amano T, Sasaki M, Fukui M (2002) Occurrence of subdural hematoma and resolution of gait disturbance in a patient treated with shunting for normal pressure hydrocephalus. Clin Neurol Neurosurg 104:315–317PubMedCrossRefGoogle Scholar
  14. 14.
    Kamiryo T, Hamada J, Fuwa I, Ushio Y (2003) Acute subdural hematoma after lumboperitoneal shunt placement in patients with normal pressure hydrocephalus. Neurol Med Chir (Tokyo) 43:197–200CrossRefGoogle Scholar
  15. 15.
    Missori P, Coppola G, Paolini S, Pierelli F, Curra A (2012) Intraparenchymal haemorrhage after a cerebrospinal fluid tap-test for secondary normal pressure hydrocephalus. J Clin Neurosci 19:914–916PubMedCrossRefGoogle Scholar
  16. 16.
    Poca MA, Solana E, Martinez-Ricarte FR, Romero M, Gandara D, Sahuquillo J (2012) Idiopathic normal pressure hydrocephalus: results of a prospective cohort of 236 shunted patients. Acta Neurochir Suppl 114:247–253PubMedCrossRefGoogle Scholar
  17. 17.
    Catananti C, Mastropaolo S, Calabrese C, Silveri MC, Onder G (2010) A case of normal-pressure hydrocephalus associated with rheumatoid arthritis. Aging Clin Exp Res 22:189–191PubMedCrossRefGoogle Scholar
  18. 18.
    de Oliveira FF, Cardoso TA, Sampaio-Barros PD, Damasceno BP (2013) Normal pressure hydrocephalus in the spectrum of neurological complications of systemic lupus erythematosus. Neurol Sci 34:1009–1013PubMedCrossRefGoogle Scholar
  19. 19.
    Filippidis AS, Kalani MY, Nakaji P, Rekate HL (2011) Negative-pressure and low-pressure hydrocephalus: the role of cerebrospinal fluid leaks resulting from surgical approaches to the cranial base. J Neurosurg 115:1031–1037PubMedCrossRefGoogle Scholar
  20. 20.
    Hamilton MG, Price AV (2012) Syndrome of inappropriately low-pressure acute hydrocephalus (SILPAH). Acta Neurochir Suppl 113:155–159PubMedCrossRefGoogle Scholar
  21. 21.
    Kitami K, Suzuki A, Hadeishi H, Nishimura H, Yasui N (1986) Normal pressure hydrocephalus after subarachnoid hemorrhage–with regard to pathogenesis and factors influencing the efficacy of shunt surgery. No To Shinkei 38:781–788PubMedGoogle Scholar
  22. 22.
    Mangat HS (2012) Severe traumatic brain injury. Contin (Minneap Minn) 18:532–546Google Scholar
  23. 23.
    Mokri B (2001) The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology 56:1746–1748PubMedCrossRefGoogle Scholar
  24. 24.
    Chang CC, Kuwana N, Ito S, Ikegami T (2000) Impairment of cerebrovascular reactivity to acetazolamide in patients with normal pressure hydrocephalus. Nucl Med Commun 21:139–141PubMedCrossRefGoogle Scholar
  25. 25.
    Chang CC, Kuwana N, Noji M, Tanabe Y, Koike Y, Ikegami T (1999) Cerebral blood flow in patients with normal pressure hydrocephalus. Nucl Med Commun 20:167–169PubMedCrossRefGoogle Scholar
  26. 26.
    Miyamoto J, Tatsuzawa K, Inoue Y, Imahori Y, Mineura K (2007) Oxygen metabolism changes in patients with idiopathic normal pressure hydrocephalus before and after shunting operation. Acta Neurol Scand 116:137–143PubMedCrossRefGoogle Scholar
  27. 27.
    Momjian S, Owler BK, Czosnyka Z, Czosnyka M, Pena A, Pickard JD (2004) Pattern of white matter regional cerebral blood flow and autoregulation in normal pressure hydrocephalus. Brain 127:965–972PubMedCrossRefGoogle Scholar
  28. 28.
    Mori K, Maeda M, Asegawa S, Iwata J (2002) Quantitative local cerebral blood flow change after cerebrospinal fluid removal in patients with normal pressure hydrocephalus measured by a double injection method with N-isopropyl-p-[(123)I] iodoamphetamine. Acta Neurochir (Wien) 144:255–262, discussion 262–253CrossRefGoogle Scholar
  29. 29.
    Owler BK, Momjian S, Czosnyka Z, Czosnyka M, Pena A, Harris NG, Smielewski P, Fryer T, Donovan T, Coles J, Carpenter A, Pickard JD (2004) Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values. J Cereb Blood Flow Metab 24:17–23PubMedCrossRefGoogle Scholar
  30. 30.
    Takaya M, Kazui H, Tokunaga H, Yoshida T, Kito Y, Wada T, Nomura K, Shimosegawa E, Hatazawa J, Takeda M (2010) Global cerebral hypoperfusion in preclinical stage of idiopathic normal pressure hydrocephalus. J Neurol Sci 298:35–41PubMedCrossRefGoogle Scholar
  31. 31.
    Tanaka A, Kimura M, Nakayama Y, Yoshinaga S, Tomonaga M (1997) Cerebral blood flow and autoregulation in normal pressure hydrocephalus. Neurosurgery 40:1161–1165, discussion 1165–1167PubMedCrossRefGoogle Scholar
  32. 32.
    Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, Benveniste H (2013) Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest 123:1299–1309PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 4:147ra111PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Farag E, Abdou A, Riad I, Borsellino SR, Schubert A (2005) Cerebellar hemorrhage caused by cerebrospinal fluid leak after spine surgery. Anesth Analg 100:545–546PubMedCrossRefGoogle Scholar
  35. 35.
    Hara T, Matsuda M, Watanabe S, Nakai K, Yamamoto T, Matsumura A (2013) Remote cerebellar hemorrhage after removal of a supratentorial glioma without perioperative CSF loss: a case report. Case Rep Surg 2013:305039PubMedCentralPubMedGoogle Scholar
  36. 36.
    Hempelmann RG, Mater E (2012) Remote intracranial parenchymal haematomas as complications of spinal surgery: presentation of three cases with minor or untypical symptoms. Eur Spine J 21(Suppl 4):S564–S568PubMedCrossRefGoogle Scholar
  37. 37.
    Akai K, Uchigasaki S, Tanaka U, Komatsu A (1987) Normal pressure hydrocephalus. Neuropathological study. Acta Pathol Jpn 37(1):97–110PubMedGoogle Scholar
  38. 38.
    Metea MR, Newman EA (2006) Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J Neurosci 26(11):2862–2870PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Neurosurgery, Illinois Neurological InstituteUniversity of Illinois College of Medicine at PeoriaPeoriaUSA

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