Subarachnoid pharmacodialysis for central nervous system disorders.

We postulate that alternating use of microcontroller-regulated delivery and drain pumps connected to one or more sealed subarachnoid fluid exchange ports can maintain localized bi-directional molecular fluxes across pia mater covering multiple diseased areas of the cerebral cortex or spinal cord. This system enables local irrigation with drugs and drainage of endogenous neurotoxic molecules normalizing regional neurochemistry and restoring physiological function. Viewing the pia mater as an endogenous dialysis membrane, testing this hypothesis requires demonstrating: (a) benefits of removing neurotoxic molecules from diseased cerebral cortical or spinal areas via subarachnoid dialysis, (b) neuropharmacological effects of subarachnoid drug delivery and (c) evaluating additive effects of combining the two, as a novel, "pharmacodialysis" procedure. Our supporting experimental data show that this procedure can drain proinflammatory cytokines from the neocortex to the subarachnoid cerebrospinal fluid in rats and can prevent focal seizures in monkeys through subarachnoid delivery of muscimol to their neocortex. Subarachnoid pharmacodialysis allows effective site-specific treatment and microcontroller-regulated timing responsive to the evolving course of a disease and can be performed with bedside systems or fully implanted devices. The procedure provides a two-pronged, combined therapy for traumatic brain and spinal cord injuries, cortically localized epilepsy, stroke and tumors as well as psychiatric disorders such as Alzheimer's disease with pathology of the association cortex. Therapeutic subarachnoid pharmacodialysis drainage of endogenous molecules from the neocortical interstitial space offers unprecedented opportunities to gain new insights into the neurochemistry of the human neocortex in real-life conditions over months or even years.