Effects of buoyancy on the dispersion of drugs released intrathecally in the spinal canal.

This paper investigates the transport of drugs delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. Because of the small drug diffusivity, the dispersion of neutrally buoyant drugs has been shown in previous work to rely mainly on the mean Lagrangian flow associated with the CSF oscillatory motion. Attention is given here to effects of buoyancy, arising when the drug density differs from the CSF density. For the typical density differences found in applications, the associated Richardson number is shown to be of order unity, so that the Lagrangian drift includes a buoyancy-induced component that depends on the spatial distribution of the drug, resulting in a slowly evolving cycle-averaged flow problem that can be analysed with two-time scale methods. The asymptotic analysis leads to a nonlinear integro-differential equation for the spatiotemporal solute evolution that describes accurately drug dispersion at a fraction of the cost involved in direct numerical simulations of the oscillatory flow. The model equation is used to predict drug dispersion of positively and negatively buoyant drugs in an anatomically correct spinal canal, with separate attention given to drug delivery via bolus injection and constant infusion.

An analytic model for the flow induced in syringomyelia cavities.

A simple two-dimensional fluid-structure-interaction problem, involving viscous oscillatory flow in a channel separated by an elastic membrane from a fluid-filled slender cavity, is analyzed to shed light on the flow dynamics pertaining to syringomyelia, a neurological disorder characterized by the appearance of a large tubular cavity (syrinx) within the spinal cord. The focus is on configurations in which the velocity induced in the cavity, representing the syrinx, is comparable to that found in the channel, representing the subarachnoid space surrounding the spinal cord, both flows being coupled through a linear elastic equation describing the membrane deformation. An asymptotic analysis for small stroke lengths leads to closed-form expressions for the leading-order oscillatory flow, and also for the stationary flow associated with the first-order corrections, the latter involving a steady distribution of transmembrane pressure. The magnitude of the induced flow is found to depend strongly on the frequency, with the result that for channel flow rates of non-sinusoidal waveform, as those found in the spinal canal, higher harmonics can dominate the sloshing motion in the cavity, in agreement with previous in vivo observations. Under some conditions, the cycle-averaged transmembrane pressure, also showing a marked dependence on the frequency, changes sign on increasing the cavity transverse dimension (i.e. orthogonal to the cord axis), underscoring the importance of cavity size in connection with the underlying hydrodynamics. The analytic results presented here can be instrumental in guiding future numerical investigations, needed to clarify the pathogenesis of syringomyelia cavities.