Hydrocephalus: A Review of Current Knowledge

1. Hydrocephalus: A Review of Current Knowledge 11/21/07 LPPD Lab meeting and Discussion Sukhi Basati Laboratory for Product and Process Design, Department of Bioengineering, University of Illinois, Chicago, IL, 60607, U.S.A. Advisor: Andreas Linninger

2. Overview of Presentation • Motivation (Why do we care?) • What do we know about this disease? How can we contribute to scientific research? • Previous Research findings • Are some hypothesis’ and theories contradictory? Do experimental results coincide with simulation results? • Our Research findings • Have we advanced knowledge on Hydrocephalus? Can we compare our results from other researchers’ results? • Future Directions / Conclusions / Discussion • What can we do to improve understanding of Intracranial dynamics or Hydrocephalus?

3. Motivation • The balance of emission and absorption of CSF is critical for normal health. Circumstances that lead to a disruption of this balance lead to a condition known as hydrocephalus. • Despite the amount of research over the years, much of the disease remains a mystery including [1] : • How is cerebrosinal fluid (CSF) absorbed normally and what are the causes of CSF malabsorption in hydrocephalus? • Why do the ventricles dilate in communicating hydrocephalus? • What is the role of cerebrovenous pressure in hydrocephalus? • What causes normal-pressure hydrocephalus? • What causes low-pressure hydrocephalus? • How is the brain of a child with hydrocephalus different from that of a young or elderly adult?

4. Motivation Continued • From the World Health Organization Statistical Information System, during the year 2004 there were 2991 deaths in 52 countries. • A better understanding of Intracranial dynamics can possibly lead to better treatment options. • The current treatment consists of a shunt, which was designed based on a very primitive understanding of intracranial dynamics. Integra Spetzler shunt for normal pressure communicating hydrocephalus

5. Historical Research Leonardo DaVinci accurately drew the ventricular system in 1510. Prior to that, the disease was already known as hydrocephalus. Key and Retzius used India Ink for anatomy examinations in 1875. [2] Occlusion of the aqueduct via cotton swabs to produce occlusive hydrocephalus by Dandy and Blackfan in 1913. [2] Kellie-Monro Doctrine  1783 Monro proposed that an increase in volume of blood, brain, or CSF will lead to an increase in ICP. Thus if one of these elements increases in volume, the other two must decrease. In 1824 Kellie confirmed this.

6. Previous Research • Simulation • Intracranial dynamics (Mathematical Models) • 6 papers • Experimental • Animal • Clinical • 10 papers • Treatment • Shunts

7. Previous Research continued Experimental Bering 1955  Dog experiments in concluded that Choroid Plexus was central in CSF formation. By removing a choroid plexus from one lateral ventricle and creating communicating hydrocephalus he observed that ventricle dilation occurred only with the intact choroid plexus. Hakim 1976  proposed an important model of the brain as a sponge, postulating that large transmural pressure differences between the SAS and ventricles cause ventricular enlargement by squeezing water out of the brain parenchyma. Naidich 1976  Observed blurring of lateral margins of the frontal horns of lateral ventricles on CT scans during hydrocephalic changes. (aka periventricular lucency) Di Rocco 1978  Injected balloons into brains of lambs to obtain CSF dynamic parameters.

8. Previous Research continued Experimental continued Dandy 1919  Conducted experiments on dogs and verified CSF production sites. Placed occlusion in AS and dilation of third and lateral ventricles ensued. Removed choroid plexus along with occlusion of foramen of monro, no dilation occurs and ventricle collapses. Du Boulay 1966  Observed pulsatile movements using pneuomography. Suggested pulsating thalamic pump that drives CSF flow. DelBigio and Bruni 1988  observed collapse of capillaries following hydrocephalus, and found a decrease in cerebral blood flow following long term hydrocephalus. Enzmann and Pelc 1993  Thetiming of systolic CSF flow in the cervical subarachnoid space (SAS)correlated very closely to the brain arteriovenous blood flow differenceduring the cardiac cycle. This arteriovenous difference was a measure ofbrain expansion. Greitz 1993  The CSF-circulation is propelled by a pulsating flow. The intracranial dynamics may be regarded as the result of an interplay between the demands for space by the four components of the intracranial content, i.e. the arterial blood, brain volume, venous blood and the CSF. The outflow from the cranial cavity to the cervical subarachnoid space (SAS) is dependent in size and timing on the intracranial arterial expansion during systole. The instantaneous increase of flow in the superior sagittal sinus at the beginning of the systole reflects a direct pressure transmission via the SAS from the expanding arteries to the cerebral veins. Pickard, Pena, Czosnyka 2004  quantified decrease in cerebral blood flow via PET scans in patients with communicating hydrocephalus.

9. Previous Research continued Simulations / Modeling Marmarou 1978  Created mathematical model with 4 parameters: IC compliance (k), dural sinus pressure (P), resistance to absorption (R), and CSF formation (f). Nagashima 1987  Reinterpreted Biot’s concepts and outlined four principles of the hydrocephalic biomechanical model system: the law of conservation of mass, the Darcy law, Hooke law, and the Terzaghi effective stress principle. Pena 1999  Refined linear poroelastic FEM, creating a time-dependent demonstration of ventricular expansion. Their model also promoted a greater understanding of the extracellular fluid shifts leading to edema and periventricular lucency. [3] Egnor 2002  created electrical RLC circuit for use as an analogy in communicating hydrocephalus (simple harmonic oscillator – wanted to explain asynchrony between pulses in the cranium in the disease state.)

10. Previous Research continued Simulations / Modeling Zagzoule 1986  Created mathematical model of cerebral circulation (blood flow). It was based on non-linear equations of pulsatile fluid flow in distensible conduits and applied to a network simulating the entire cerebral vasculature. The model was also applied to the study of autoregulation during arterial hypotension Sorek 1988  used one lump structure for mathematical model. The model predicts the intracranial pressure waves in the various compartments of the brain in response to pressure changes in the vascular system. (R = resistance, C=compliance, [ ] pressure (mm Hg), () flow (ml min), < > volume (ml)

11. Previous Research continued Simulations / Modeling Pang 1994  studied low-pressure hydrocephalus. Introduced concept of ventricular hysteresis. Created hypothetical P-V curves. Explained effect of alterations in parenchymal elasticity and necessity of restoring the original elasticity to improve treatment outcome. Tenti and Drake 1998  Reviews model and proposes newer approaches. Smillie 2005  combined elements of poroelasticity and fluid mechanics to model brain and ventricular system. included flow through the aqueduct, by incorporating boundary conditions that accurately represent the anatomy of the brain and by including time dependence in their model. Kaczmarek 1997  Used a two-phase model of fluid-saturated material to simulate the steady state of the hydrocephalic brain. The results reproduce the characteristic steady-state distribution of edema seen in hydrocephalus, and are compared with experiment. Says that large transmantle pressure gradients exist in hydrocephalus.

12. Our findings 1st paper: Pulsatile Cerebrospinal Fluid Dynamics in the Human Brain 2005 We found that large transmantle pressure gradients do not exist in communicating hydrocphalus. Created mathematical model using 1st principle fluid dynamics. Reversal of Flow! 13 = Lee 1989 7 = Naidich 1993 23 = Jacobson 1996 5 = Egnor 2002

13. Our findings continued 2nd paper: Cerebrospinal Fluid Flow in the Normal and Hydrocephalic Human Brain 2007 • Took a step further and incorporated: • Complex geometry through image reconstruction • Modeled parenchyma as a static porous medium. • Modeled fluid mechanics in normal and Hydrocephalic cases by measuring velocities and transmantle pressure gradients (discrete measurements). • Validated by experimental data.

14. Our findings continued 3rd paper: Blood, cerebrospinal fluid and brain dynamics in communicating Hydrocephalus in review We created a holistic compartmental model incorporating blood, csf, and the parenchyma - Kellie-Monro doctrine is applied – conservation of volume in the cranium. Spinal canal. Transition from normal to HC Ratio prepontine to aqueduct Blood dynamics and interaction with CSF Validation with bolus injection experimental data

15. Properties of the Brain CSF

16. Future Directions / Conclusions Tenti 1999  noted 2 major future challenges: 1) A nonlinear constitutive stress strain equation must be found that is relevant for all clinical hydrocephalic conditions. 2) Appropriate boundary conditions must be imposed, including not only the material properties of the organs themselves, but also the initial conditions of fthe system (such as ventricular and intraparenchymal pressure). [3] What is the role of cerebrovenous pressure in hydrocephalus?

17. Thank you

18. References: [1] Bergsneider, M. et al., What we don't (but should) know about hydrocephalus., Journal of Neurosurgery, 2006 Mar;104(3 Suppl):157-9 [2] Aschoff, A. et al., The scientific history of hydrocephalus and its treatment., Neurosurgery Review, 1999, vol. 22, pp 67-93 [3] Clarke, M., et al., The history of mathematical modeling in hydrocephalus, Neurosurgery Focus, 2007, vol. 22, version 4., E3. [4] Stavros, M., et al, Changing Concepts of Cerebrospinal Fluid Hydrodynamics Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease, Neurotherapeutics, 2007, vol. 4, pp 511-522