An Investigation of the Mechanism of Sacral Nerve Stimulation in Restoring Voiding Function

Sacral nerve stimulation, or neuromodulation, has been shown to restore voiding in women with a specific type of urinary retention that is attributed to urethral sphincter overactivity. The therapy has gained popularity in this and other voiding dysfunctions, but its mechanism of action remains unexplained. This thesis explores the effects of neuromodulation on women with urinary retention. It incorporates a urodynamic study of the effect of neuromodulation on bladder and urethral (peripheral) function, a functional brain imaging PET (Positron Emission Tomography) study of cerebral (central) effects, and a review of the long-term efficacy of the technique. The urodynamics (including urethral pressure profilometry, cystometry, and sphincter electromyography) showed evidence of persistent urethral overactivity despite successful restoration of micturition. Together with the cystometric findings, this suggests that neuromodulation may facilitate voiding in this group by increasing detrusor contractility rather than by urethral relaxation. Review of the sacral nerve implants performed at this centre over several years reveals that approximately 75% continue to void at upto 5 years after surgery, while considering reasons for the loss of efficacy in other patients. The cerebral perception of bladder fullness was examined using PET scanning in a group of healthy female controls as well as women with retention treated by neuromodulation. The findings show that the brainstem activity which is present in healthy controls is not seen in retention patients until the neuromodulation is activated. The discussion addresses the respective roles of brainstem and cortical brain regions in the control of voiding function, and whether neuromodulation may ‘normalize’ cerebral activity. In conclusion, this thesis provides evidence, for the first time, of changes in brain activity following sacral neuromodulation in urinary retention, confirming that its effects may well be mediated by afferent innervation. There are more things in heaven and earth, Horatio, than are dreamt o f in your philosophy William Shakespeare, 1601 A man will turn over half a library to make a booh Samuel Johnson, 1775