The Acute and Chronic Effects of Sacral Neuromodulation in Patients with Faecal Incontinence

Sacral Neuromodulation (SNM) is an accepted treatment option for Faecal Incontinence (FI) but the mechanism by which SNM exerts its therapeutic effect remains unexplained. Specifically, it is uncertain if the influences of SNM are central i.e. at the level of the central nervous system, peripheral, i.e. at the level of the peripheral nerves, or at the end organ, i.e. the anorectal unit. Research has overwhelmingly focused on the effects of SNM on anal canal and rectal function. However, the results are conflicting, equivocal and correlate poorly to symptoms. These findings suggest the possibility of an effect of SNM outside of the end organ. This thesis investigates the role of ‘central neuromodulation’ in patients with FI via several experimental strategies, including exploring the acute and chronic effects of SNM on central and peripheral pathways through advanced functional neuroimaging and anorectal physiological techniques. The acute effects of SNM were explored in a novel study employing the use of functional Magnetic Resonance Imaging (fMRI) that identified brain regions activated in response to rectal mechanical stimulation in patients with FI. The patients planned for SNM implantation were enrolled in this study prior to intervention and the same cohort of patients were subsequently re-examined following SNM to evaluate changes in brain activity after SNM. It was shown that SNM results in increased neuronal activity within the left insular cortex, frontal lobes, precuneus and post central cortices, which are areas of the brain responsible for bodily awareness, sensory processing and regulation of visceral sensation. Additionally, the chronic effects of SNM were explored in patients with FI in the setting of a randomised, double-blinded crossover controlled trial. Specifically, patients following chronic SNM were randomised to have their devices turned off or on. The results revealed that symptoms of FI and quality of life were maintained despite interruption of active stimulation. Similarly anorectal physiology was unaffected by withdrawal of SNM. In conclusion, for the first time in patients with FI, the body of work presented in this thesis provides objective evidence that SNM is likely to exert, at least part of its action by central neuromodulation