Skip to main content

Advertisement

Log in

The pathogenesis of normal pressure hydrocephalus: A theoretical analysis

  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles, usually caused by impaired absorption of the fluid into the bloodstream. Despite obstructed absorption and continued secretion of CSF into the ventricles at a near normal rate, the ventricular CSF pressure (VCSFP) is often normal. We attempt to understand how hydrocephalus can exist with normal VCSFP by exploring the role of the brain parenchyma in absorbing CSF in hydrocephalus. We test three theories: (1) the ventricular wall is impermeable to CSF; (2) ventricular CSF seeps into the parenchyma, from which it is efficiently absorbed; and (3) ventricular CSF seeps into the parenchyma but is absorbed inefficiently.

We model the brain as a thick spherical shell consisting of a porous, elastic, solid matrix, containing interstitial fluid and blood. We modify the equations of poroelasticity, which describe flow of fluid through porous solids, to allow for parenchymal absorption. For each of the three theories we calculate the steady state changes in VCSFP and in parenchymal fluid pressure caused by an incremental defect in CSF absorption. We also calculate the steady state changes in fluid content, tissue volume, tissue displacement, and stresses caused by a small increment of VCSFP. We conclude that only the second theory—seepage of CSF with efficient parenchymal absorption—accounts for the clinical features of normal pressure hydrocephalus. These features include sustained ventricular dilatation despite normal VCSFP, increased periventricular fluid content, and localized periventricular white matter damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Auer, L. M., N. Ishiyama, K. C. Hodde, R. Kleinert and R. Pucher (1987). Effect of intracranial pressure on bridging veins in rats. J. Neurosurg. 67, 263–268.

    Google Scholar 

  • Becker, D. P., J. A. Wilson and G. W. Watson (1972). The spinal cord central canal: response to hydrocephalus and canal occlusion. J. Neurosurg. 36, 416–424.

    Article  Google Scholar 

  • Bering, E. A. and O. Sato (1964). Hydrocephalus: changes in formation and absorption of cerebrospinal fluid within the cerebral ventricles. J. Neurosurg. 20, 1050–1063.

    Google Scholar 

  • Biot, M. A. (1941). General theory of three-dimensional consolidation. J. Appl. Phys. 12, 155–164.

    Article  MATH  Google Scholar 

  • Borgesen, S. E. and F. Gjerris (1982). The predictive value of conductance to outflow of CSF in normal pressure hydrocephalus. Brain 105, 65–86.

    Google Scholar 

  • Brooks, D. J., R. P. Beaney, M. Powell, K. L. Leenders, H. A. Crockard, D. G. T. Thomas, J. Marshall and T. Jones (1986). Studies on cerebral oxygen metabolism, blood flow, and blood volume, in patients with hydrocephalus before and after surgical decompression, using positron emission tomograraphy. Brain 109, 613–628.

    Google Scholar 

  • Chawla, J. C., A. Hulme and R. Cooper (1974). Intracranial pressure in patients with dementia and communicating hydrocephalus. J. Neurosurg. 40, 376–380.

    Google Scholar 

  • Clark, R. G. and T. H. Milhorat (1970). Experimental hydrocephalus, Part 3: light microscopic findings in acute and subacute obstructive hydrocephalus in the monkey. J. Neurosurg. 32, 400–413.

    Google Scholar 

  • Cutler, R. W. P., L. Page, J. Galicich and G. V. Watters (1968). Formation and absorption of cerebrospinal fluid in man. Brain 91, 707–720.

    Google Scholar 

  • Dandy, W. E. and K. D. Blackfan (1914). Internal hydrocephalus: an experimental, clinical and pathological study. Am. J. Dis. Child. 8, 406–482.

    Google Scholar 

  • da Silva, M. C., S. Michowicz, J. M. Drake, P. D. Chumas and U. I. Tuor (1995). Reduced local cerebral blood flow in periventricular white matter in experimental neonatal hydrocephalus—restoration with CSF shunting. J. Cerebral Blood Flow and Metabolism 15, 1057–1065.

    Google Scholar 

  • Davson, H., G. Hollingsworth and M. B. Segal (1970). The mechanism of drainage of the cerebrospinal fluid. Brain 93, 665–678.

    Google Scholar 

  • Del Bigio, M. R. and J. E. Bruni (1988). Changes in periventricular vasculature of rabbit brain following induction of hydrocephalus and shunting. J. Neurosurg. 69, 115–120.

    Google Scholar 

  • Deo-Narine, V., D. G. Gomez, T. Vullo, R. P. Manzo, R. D. Zimmerman, M. D. F. Deck and P. T. Cahill (1994). Direct in vivo observation of transventricular absorption in the hydrocephalic dog using magnetic resonance imaging. Invest. Radiol. 29, 287–293.

    Google Scholar 

  • Detournay, E. and A. H. D. Cheng (1993). Fundamentals of poroelasticity, in Comprehensive Rock Engineering: Principles, Practice, and Projects, C. Fairhurst (Ed.), Elmsford, NY: Pergamon, pp. 113–171.

    Google Scholar 

  • Di Rocco, C., G. Maira, G. F. Rossi and A. Vignati (1976). Cerebrospinal fluid pressure studies in normal pressure hydrocephalus and cerebral atrophy. Eur. Neurol. 14, 119–128.

    Google Scholar 

  • Drake, J. M. O., O. Mostachfi, G. Tenti and S. Sivaloganathan (1996). Realistic simple mathematical model of brain biomechanics for computer simulation of hydrocephalus and other brain abnormalities. Can. J. Neurol. Sci. 23, S5.

    Google Scholar 

  • Eisenberg, H. M., J. E. McLennan and K. M. Welch (1974). Ventricular perfusion in cats with kaolin-induced hydrocephalus. J. Neurosurg. 41, 20–28.

    Google Scholar 

  • Fishman, R. A. and M. Greer (1963). Experimental obstructive hydrocephalus. Arch. Neurol. 8, 156–161.

    Google Scholar 

  • Foltz, E. L. and C. Aine (1981). Diagnosis of hydrocephalus by CSF pulse-wave analysis: a clinical study. Surg. Neurol. 15, 283–293.

    Google Scholar 

  • Galford, J. E. and J. H. McElhaney (1970). A viscoelastic study of scalp, brain, and dura. J. Biomech. 3, 211–221.

    Article  Google Scholar 

  • Glees, P., M. Hasan, D. Voth and M. Schwarz (1989). Fine structural features of the cerebral microvasculture in hydrocephalic human infants: correlated clinical observations. Neurosurg. Rev. 12, 315–321.

    Article  Google Scholar 

  • Greitz, T. V. B. (1969). Effect of brain distension on cerebral circulation. Lancet 1, 863–865.

    Article  Google Scholar 

  • Greitz, T. V. B., A. O. L. Grepe, M. S. F. Kalmer and J. Lopez (1969). Pre-and post-operative evaluation of CBF in low pressure hydrocephalus. J. Neurosurg. 31, 644–651.

    Google Scholar 

  • Grubb, R. L., M. E. Raichle, M. H. Gado, J. O. Eichling and C. P. Hughes (1977). Cerebral blood flow, oxygen utilization, and blood volume in dementia. Neurology 27, 905–910.

    Google Scholar 

  • Hakim, S. (1964). Algunas observaciones sobre la presion del L. C. R. sindrome hidrocefalico en un adulto con ‘presion normal’ del L.C.R. Tesis de grado, Universidad Javeriana, Bogotá, Colombia.

    Google Scholar 

  • Hakim, S. and R. D. Adams (1965). The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. J. Neurol. Sci. 2, 307–327.

    Article  Google Scholar 

  • Hakim, S., J. G. Venegas and J. D. Burton (1976). The physics of the cranial cavity, hydrocephalus, and normal pressure hyrocephalus: mechanical interpretation and mathematical model. Surg. Neurol. 5, 187–210.

    Google Scholar 

  • Hall, P. V., J. E. Kalsbeck, H. N. Wellman, R. L. Campbell and S. Lewis (1976). Radioisotope evaluation of experimental hydrosyringomyelia. J. Neurosurg. 45, 181–187.

    Google Scholar 

  • Hasan, D., J. van Peski, I. Loeve, E. P. Krenning and M. Vermeulen (1991). Single photon emission computed tomography in patients with acute hydrocephalus or with cerebral ischaemia after subarachnoid hemorrhage. J. Neurol. Neurosurg. Psychiatry 54, 490–493.

    Google Scholar 

  • Heisy, S. R., D. Held and J. R. Pappenheimer (1962). Bulk flow and diffusion in the cerebrospinal fluid system of the goat. Am. J. Physiol. 203, 775–781.

    Google Scholar 

  • Hochwald, G. M., W. E. Lux, A. Sahar and J. Ransohoff (1972). Experimental hydrocephalus. Changes in cerebrospinal fluid dynamics as a function of time. Arch. Neurol. 26, 120–129.

    Google Scholar 

  • Hochwald, G. M., S. Nakamura and M. B. Camins (1981). The rat in experimental obstructive hydrocephalus. Zeitschrift für Kinderchirurgie 34, 403–410.

    Google Scholar 

  • Holbourn, A. H. S. (1943). Mechanics of head injuries. Lancet 2, 438–441.

    Article  Google Scholar 

  • Holt, J. P. (1969). Flow through collapsible tubes and through in situ veins. IEEE Trans. Biomed. Eng. BME-16, 274–283.

    Google Scholar 

  • Hopkins, L. N., L. Bakay, W. R. Kinkel and W. Grand (1977). Demonstration of transventricular CSF absorption by computed tomography. Acta Neurochirurgica 39, 151–157.

    Article  Google Scholar 

  • Ingraham, F. D., D. D. Matson and E. Alexander Jr. (1948). Studies in the treatment of experimental hydrocephalus. J. Neuropath. Exp. Neurol. 7, 123–143.

    Google Scholar 

  • James, A. E. Jr., E. P. Strecker, G. Novak and B. Burns (1973). Correlation of serial cisternograms and cerebrospinal fluid pressure measurements in experimental communicating hydrocephalus. Neurology 23, 1226–1232.

    Google Scholar 

  • James, A. E., B. Burns, W. F. Flor, E. P. Strecker, T. Merz, M. Bush and D. M. Price (1975). Pathophysiology of chronic communicating hydrocephalus in dogs (Canis familiaris). Experimental studies. J. Neurol. Sci. 24, 151–178.

    Article  Google Scholar 

  • James, A. E., W. J. Flor, G. R. Novak, E. P. Strecker and B. Burns (1978). Evaluation of the central canal of the spinal cord in experimentally induced hydrocephalus. J. Neurosurg. 48, 970–974.

    Google Scholar 

  • Kaczmarek, M., R. P. Subramaniam and S. R. Neff (1997). The hydromechanics of hydrocephalus: steady state solutions for cylindrical geometry. Bull. Math. Biol. 59, 295–323.

    Article  MATH  Google Scholar 

  • Katz, A. I., Y. Chen and A. H. Moreno (1969). Flow through a collapsible tube: experimental analysis and mathematical model. Biophys. J. 9, 1261–1279.

    Article  Google Scholar 

  • Kosteljanetz, M. (1986). CSF dynamics and pressure—volume relationships in communicating hydrocephalus. J. Neurosurg. 64, 45–52.

    Google Scholar 

  • Kumar, A. J., G. M. Hochwald, I. Kricheff and N. Chase (1976). Positive contrast ventriculography in cats with experimental obstructive hydrocephalus. Invest. Radiol. 11, 605–611.

    Google Scholar 

  • Lamas, E. and R. D. Lobato (1979). Intraventricular pressure and CSF dynamics in chronic adult hydrocephalus. Surg. Neurol. 12, 287–295.

    Google Scholar 

  • Levin, V. A., T. H. Milhorat, J. D. Fenstermacher, M. K. Hammock and D. P. Rall (1971). Physiological studies on the development of obstructive hydrocephalus in the monkey. Neurology 21, 238–246.

    Google Scholar 

  • Levine, D. N. (1997). Pathogenesis of cervical spondylotic myelopathy. J. Neurol. Neurosurg. Psychiatry 62, 334–340.

    Google Scholar 

  • Lux, W. E., G. M. Hochwald, A. Sahar and J. Ransohoff (1970). Periventricular water content. Effect of pressure in experimental chronic hydrocephalus. Arch. Neurol. 23, 475–479.

    Google Scholar 

  • Malm, J., B. Kristensen, T. Karlsson, M. Fagerlund, J. Elfverson and J. Ekstedt (1995). The predictive value of cerebrospinal fluid dynamic tests in patients with the idiopathic hydrocephalus syndrome. Arch. Neurol. 52, 783–789.

    Google Scholar 

  • Mamo, H. L., P. C. Meric, J. C. Ponsin, A. C. Rey, A. G. Luft and J. A. Seylaz (1987). Cerebral blood flow in normal pressure hydrocephalus. Stroke 18, 1074–1080.

    Google Scholar 

  • Marmarou, A., K. Shulman and J. LaMorgese (1975). Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system. J. Neurosurg. 43, 523–534.

    Google Scholar 

  • Mathew, N. T., J. S. Meyer, A. Hartmann and E. O. Ott (1975). Abnormal CSF fluid-blood flow dynamics. Arch. Neurol. 32, 657–664.

    Google Scholar 

  • McLaurin, R. L., O. T. Bailey, P. H. Schurr and F. D. Ingraham (1954). Myelomalacia and multiple cavitations of spinal cord secondary to adhesive arachnoiditis. Arch. Path. 57, 138–146.

    Google Scholar 

  • Metz, H. J., J. McElhaney and A. K. Ommaya (1970). A comparison of the elasticity of live, dead, and fixed brain tissue. J. Biomech. 3, 453–458.

    Article  Google Scholar 

  • Milhorat, T. H., R. G. Clark, M. K. Hammock and P. P. McGrath (1970). Structural, ultrastructural, and permeability changes in the ependyma and surrounding brain favoring equilibration in progressive hydrocephalus. Arch. Neurol. 22, 397–407.

    Google Scholar 

  • Mow, V. C., S. C. Kuei, W. M. Lai and C. G. Armstrong (1980). Biphasic creep and stress relaxation of articular cartilage: theory and experiments. J. Biomech. Eng. 102, 73–84.

    Google Scholar 

  • Mow, V. C., M. K. Kwan, W. M. Lai and M. H. Holmes (1986). A finite deformation theory for nonlinearly permeable soft hydrated biological tissues, in Frontiers in Biomechanics, New York: Springer-Verlag, pp. 153–179.

    Google Scholar 

  • Nagashima, T., B. Horwitz and S. I. Rapoport (1990). A mathematical model for vasogenic brain edema. Adv. Neurol. 52, 317–326.

    Google Scholar 

  • Nagashima, T., N. Tamaki, S. Matsumoto, B. Horwitz and Y. Seguchi (1987). Biomechanics of hydrocephalus: a new theoretical model. Neurosurgery 21, 898–904.

    Google Scholar 

  • Naidich, T. P., F. Epstein, J. P. Lin, I. I. Kricheff and G. M. Hochwald (1976). Evaluation of pediatric hydrocephalus by computed tomography. Radiology 119, 337–345.

    Google Scholar 

  • Nakagawa, Y., M. Tsuru and K. Yada (1974). Site and mechanism for compression of the venous system during experimental intracranial hypertension. J. Neurosurg. 41, 427–434.

    Google Scholar 

  • Pappenheimer, J. R., S. R. Heisey, E. F. Jordan and J de C. Downer (1962). Perfusion of the cerebral ventricular system in unanesthetized goats. Am. J. Physiol. 203, 763–774.

    Google Scholar 

  • Penn, R. D. and J. W. Bacus (1984). The brain as a sponge: a computed tomographic look at Hakim’s hypothesis. Neurosurgery 14, 670–675.

    Google Scholar 

  • Price, D. L., A. E. James Jr., E. Sperber and E. P. Strecker (1976). Communicating hydrocephalus. Cisternographic and neuropathologic studies. Arch. Neurol. 33, 15–20.

    Google Scholar 

  • Reulen, H. J., R. Graham, M. Spatz and I. Klatzo (1977). Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J. Neurosurg. 46, 24–35.

    Article  Google Scholar 

  • Sahar, A., G. M. Hochwald and J. Ransohoff (1969). Alternate pathway for cerebrospinal fluid absorption in animals with experimental obstructive hydrocephalus. Exp. Neurol. 25, 200–206.

    Article  Google Scholar 

  • Salmon, J. H. and A. L. Timperman (1971). Effect of intracranial hypotension on cerebral blood flow. J. Neurol. Neurosurg. Psychiatry 34, 687–692.

    Article  Google Scholar 

  • Sklar, F. H., J. T. Diehl, C. W. Beyer Jr. and W. K. Clark (1980). Brain elasticity changes with ventriculomegaly. J. Neurosurg. 53, 173–179.

    Google Scholar 

  • Strecker, E. P., A. E. James, B. Konigsmark and T. Merz (1974). Autoradiographic observations in experimental communicating hydrocephalus. Neurology 24, 192–197.

    Google Scholar 

  • Strecker, E. P., U. Scheffel, J. E. T. Kelley and A. E. James (1973). Cerebrospinal fluid absorption in communicating hydrocephalus. Evaluation of transfer of radioactive albumin from subarachnoid space to plasma. Neurology 23, 854–864.

    Google Scholar 

  • Symon, L. and N. W. C. Dorsch (1975). Use of long-term intracranial pressure measurement to assess hydrocephalic patients prior to shunt surgery. J. Neurosurg. 42, 258–273.

    Google Scholar 

  • Tans, J. J. and D. C. J. Poortvliet (1989). Relationship between compliance and resistance to outflow of CSF in adult hydrocephalus. J. Neurosurg. 71, 59–62.

    Article  Google Scholar 

  • Weed, L. H. (1914). The pathways of escape from the subarachnoid spaces with particular reference to the arachnoid villi. J. Med. Res. 31, 51–91.

    Google Scholar 

  • Weller, R. O. and H. Wisniewski (1969). Histological and ultrastructural changes with experimental hydrocephalus in adult rabbits. Brain 92, 819–828.

    Google Scholar 

  • Weller, R. O., H. Wisniewski, K. Shulman and R. D. Terry (1971). Experimental hydrocephalus in young dogs: histological and ultrastructural study of the brain tissue damage. J. Neuropath. Exp. Neurol. 30, 613–626.

    Article  Google Scholar 

  • Weller, R. O. and K. Shulman (1972). Infantile hydrocephalus: clinical, histological, and ultrastructural study of brain damage. J. Neurosurg. 36, 255–265.

    Google Scholar 

  • Wislocki, G. B. and T. J. Putnam (1921). Absorption from the ventricles in experimentally produced internal hydrocephalus. Am. J. Anatomy 29, 313–320.

    Article  Google Scholar 

  • Yakovlev, P. I. (1947). Paraplegias of hydrocephalus: clinical note and interpretation. Am. J. Ment. Defic. 51, 561–576.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David N. Levine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Levine, D.N. The pathogenesis of normal pressure hydrocephalus: A theoretical analysis. Bull. Math. Biol. 61, 875–916 (1999). https://doi.org/10.1006/bulm.1999.0116

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1006/bulm.1999.0116

Keywords

Navigation