1. Incontinence in children, a symptom complex Daytime incontinence (OAB), enuresis Dyschezia, incontinence for stools Pain 30-35% of these children with incontinence have pelvic floor dysfunction Pelvic floor dysfunction

2. Bladder augmentation

3. InterStim ® Therapy Indications in Urology Urge urinary incontinence Non-obstructive urinary retention Symptoms of urgency-frequency All 3 can be with or without pelvic - perineal pain or bowel disorders (incontinence, IBS, dyschezia, constipation) and Responders with the above symptoms have pelvic floor dysfunction and 35-40% overlap in symptoms

4. MS Bosch 1994 Hyperreflexia Bosch 1998, Chartier-Kastler 2000, 2001 Hohenfellner 2001, Spinelli 2005 Fowler syndrome De Ridder 1996, Swinn 2002 Brain injury Everaert 2004 InterStim ® Therapy Indications in Urology

5. InterStim ® Therapy and UUI p<0.0001 Schmidt RA et al. J Urol 1999;162:352-57

6. Treatment group 1 year5 yearCorrelation between 1 and 5 year success UUI74.7% (n=79)64.2% (n=64)85.7 UR77.4% (n=31)76.0% (n=30)90.5 UF79.2% (n=24)66.7% (n=16)83.3 Sustained Efficacy at 5 years FU No statistical difference between success rates (p=0.57) *van Voskuilen A et al. J Urol 2004;171(4suppl):328 (abs.1246)

7. 1.Brazzelli, M. et al. Efficacy & Safety of Sacral Nerve Stimulation for the Treatment of Urinary Urge Incontinence: A Systematic Review. Journal of Urology. Vol. 175 835-841, Mar. 2006 Systematic Literature Review: Urge Incontinence % of patients achieving continence or > 50% improvement in their symptoms Randomized Controlled Trials vs. Case Series Reports In an independent investigation of 1,827 implants from 34 clinical trials, InterStim Therapy was shown to be an effective treatment option for the treatment of urinary urge incontinence 1

8. 1.Campbell, U.B alt Associates, Inc., Allergan, Inc. Survey Assessment of Compliance and Satisfaction with Treatment for Urinary Incontinence. Poster Presentation, ICS Conference, 2005 2.Amundsen, C.L. et al. Urology 66: 746-750 2005. Adjusted Odds Ratio of age as a predictor of treatment drug discontinuation 1 InterStim Patients with no daily leakage episodes 2 Patients who are most likely to discontinue drug therapy may have the best chance for remaining completely dry Patient Selection: Who Benefits Most?

9. Predictors of Success Retrospective cohort study electrophysiologic, urodynamic studies, voiding charts, validated patient health questionnaire 62 retentions: – 30 Fowlers, – 32 idiopathics AIM: to evaluate whether Fowler's syndrome and psychologic pre-implant screening could be predictive factors for long-term success of SNS RESULTS: PHQ: Fowler: 27% somatisation vs 43% in idiopathic retention (ns) PHQ: 30% depression vs 19% (ns) no correlation with outcome failures: 9 Fowler, 18 idiopathic (p=0.04) Fowler’s benefited longer (Kaplan Meier, p = 0.005) De Ridder D et al. The Presence of Fowler's Syndrome Predicts Successful Long-Term Outcome of SNS in Women with Urinary Retention. Eur Urol. 2007; 51:229.

10. Interstim Therapy after stress incontinence surgery /procedure Roupret M et al. Sacral neuromodulation for refractory detrusor overactivity in women with an artificial urinary sphincter. J Urol. 2004 Jul;172(1):236-9 Adam RA. Urinary retention following tension-free vaginal tape successfully treated by sacral neuromodulation. Int Urogynecol J Pelvic Floor Dysfunct. 2006 Jan 12;:1-2 Sherman ND et al. Sacral neuromodulation for the treatment of refractory urinary urge incontinence after stress incontinence surgery. Am J Obstet Gynecol. 2005 Dec;193(6):2083-7 Starkman JS et al. Management of refractory urinary urge incontinence following urogynecological surgery with sacral neuromodulation. Neurourol. 2006; 26(1):29-35.

11. Methods: 8 pt’s with Fowler’s syndrome and 8 healthy controls underwent brain imaging with positron emission tomography Purpose: to identify regions of brain activity relating to perception of bladder fullness and their modulation by SNS Women with UR showed no significant brainstem activity but did show enhanced limbic cortical activity when the bladder was full in the absence of neuromodulation Neuromodulation restored a normal pattern of midbrain activity and decreased cortical activity in this group

12. Literature Overview: Mechanism of Action Blok BF et al. Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulation. BJU Int. 2006 Dec;98(6):1238-43. - 12 ptns OAB wet chronically implanted: decreased flow cingulated gyrus, ventromedial orbitofrontal cortex, adjacent midbrain, midline thalamus increased flow dorsolateral prefrontal cortex - 8 ptns OAB wet activated for the first time in the PET-scan, right insular cortex decreased flow medial cerebellum increased flow right postcentral gyrus cortex, ventromedial orbitofrontal cortex - group analysis between acute and chronic stimulated ptns showed signif icant differences in the associative sensory cortex, premotor cortex and cerebellum: ALL 3 INVOLVED IN LEARNING BEHAVIOUR. Acute SNS modulates areas involved in sensorimotor learning.

13. Female Sexual Function Index (FSFI) - at baseline and 6 months FU 11 pt’s had permanent implant, 7 pt’s were sexually active before and after placement 3pt’s (43%) felt that device impacted sexual function in positive way (1) by decreasing urgency and (2) by increasing desire Overall sexual frequency increased significantly after the surgery (p=0.047) There were also significant increases in the FSFI total (p=0.002), and domain scores for –desire (p=0.004) and lubrication (p=0.005), –orgasm (p=0.043) and satisfaction (p=0.007), and –pain (p=0.015) No correlation between urinary symptom improvement and FSFI scores. Conclusion: SNM may improve sexual frequency and sexual function scores in subjects with urgency frequency and urge incontinence Int Urogynecol J Pelvic Floor Dysfunct. 2006 Jul 26;

14. OAB wet Urge incontinence OAB dry Urgency/frequency Initial management: - Behavioural therapy, diarries - Medications - Biofeedback – Electrical stimulation -Interventional treatments (catheterisation) InterStim ® Therapy Failure Specialized management: Bladder augmentation-denervation-diversion Failure Botox ® Therapy Failure Non-obstructive urinary retention