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

Bladder augmentation

InterStim® Therapy Indications in Urology

Urge urinaryincontinence

Non-obstructiveurinary retention

Symptoms ofurgency-frequency

All 3 can be with or without pelvic - perineal painor

bowel disorders (incontinence, IBS, dyschezia, constipation)and

Responders with the above symptoms have pelvic floor dysfunction

and35-40% overlap in symptoms

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

47%

29%

15%9%

0%5%

21%

74%

0%

20%

40%

60%

80%

100%

Dry >=50%reduction <50%reduction No reduction

% o

f p

atie

nts

Stimulation group (n=34) Delay group (n=42)

InterStim® Therapy and UUI

p<0.0001Schmidt RA et al. J Urol 1999;162:352-57

Treatment group

1 year 5 year Correlation between 1 and 5 year success

UUI 74.7% (n=79) 64.2% (n=64) 85.7

UR 77.4% (n=31) 76.0% (n=30) 90.5

UF 79.2% (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)

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

67%

80%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

RandomizedControlled Trials

Case SeriesReports

% 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 incontinence1

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.

0

0,5

1

1,5

2

2,5

3

3,5

18-39 40-49 50-59 60-69 70+

Adjusted Odds Ratio of age as a predictor of treatment drug

discontinuation1

65%

37%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Younger than 55 Older than 55

InterStim Patients with no daily leakage episodes2

Patients who are most likely to discontinue drug therapy may have the best chance for remaining completely dry

Patient Selection: Who Benefits Most?

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.

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.

• 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

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 thalamusincreased flow dorsolateral prefrontal cortex

- 8 ptns OAB wet activated for the first time in the PET-scan, right insular cortexdecreased flow medial cerebellumincreased flow right postcentral gyrus cortex, ventromedial orbitofrontal cortex

- group analysis between acute and chronic stimulated ptns showed signif icantdifferences in the associative sensory cortex, premotor cortex andcerebellum: ALL 3 INVOLVED IN LEARNING BEHAVIOUR.Acute SNS modulates areas involved in sensorimotor learning.

• 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;

OAB wetUrge incontinence

OAB dryUrgency/frequency

Initial management:-Behavioural therapy, diarries-Medications-Biofeedback – Electrical stimulation-Interventional treatments (catheterisation)

InterStim®Therapy

Failure

Specialized management:Bladder augmentation-denervation-diversion

Failure

Botox®TherapyFailure

Non-obstructiveurinary retention