1. Nerve Stimulation Therapies for Bowel and Bladder Continence
R. Keith Huffaker, MD, MBA, FACOG
Quillen/ETSU Center for Pelvic Surgery and Urogynecology

2. Objectives Sacral nerve stimulation (SNS)
InterStim
Diagnoses
Percutaneous tibial nerve stimulation (PTNS)
Urgent PC

3. Where do InterStim and Urgent PC fit?

4. Interstim – Sacral Neuromodulation
Indications
Urinary Frequency
Urinary Urgency
Urge Urinary Incontinence
Urinary Retention / Incomplete Bladder Emptying
Fecal Incontinence
Not for SUI

5. Micturition and Storage Reflexes
Leng & Chancellor UNA 2005

6. It’s simply the muscles or the nerves
Where Medications Work
Efferent messages tell muscles to work.
Medication may help muscle comply better
Where InterStim works
Sensory Messages (Afferent) tell the brain what is happening with the bladder and other voiding components
InterStim modulates incorrect messages.
Also has some effect on muscles/motor
Conscious control occurs in the brain (pontine micturition center).
As bladder stores urine, the detrusor relaxes and the pelvic floor tightens around the urinary sphincter.
When bladder is full, and it is time to release the stored urine, the detrusor contracts and the sphincter/pelvic floor relaxes.
InterStim: consider after two
medications fail. Unlikely third
or fourth will work.

7. InterStim Pre-test Requirements
Patient has had condition for > 1 year
Stress incontinence has been eliminated as major urinary complaint
Patient failed conventional therapy:
Behavior modifications
Two medication failures
Cannot comply with other treatment option (I.e. self-cath)
Can complete urinary diary and use device
Patient has improvement of 50% or > during test

8. Mechanism of Action
Mechanism of action for SNS is not fully understood at this time - many theories exist.
Generally agreed that stimulation of the sacral nerves modulates the neural reflexes that influence the bladder, sphincter and pelvic floor that control/influence voiding. (Afferent pathways)
Basic science research is being conducted to better understand the mechanism of action of sacral nerve modulation.
Reference: Chancellor MB, Chartier-Kastler EJ. Principles of sacral nerve stimulation (SNS) for the treatment of bladder and urethral sphincter dysfunctions. International Neuromodulation Society 2000; 3:

9. But is it really doing anything?
Dasgupta and Fowler. Changes in brain activity following sacral neuromodulation for urinary retention.J Urol Dec;174(6):

10. Therapy consists of 2 steps:
Test stimulation procedure – allows trial of InterStim Therapy
-simple (30-45) minutes
-done in office (PNE) or outpatient room (PNE or Stage I)
--test for a ½ to 1 week
-percutaneous wire
-external pulse generator
-voiding diary
2. Implantation of device
--full implant
--Stage II
--both steps target S3 foramen and nerves
System includes a lead placed near the sacral nerve and programmable implantable neurostimulator – system provides stimulation to the sacral nerve.
Two phases of therapy:
Acute: test stimulation is done as an outpatient procedure usually in a clinic.
Chronic: inpatient procedure where the patient is implanted with the InterStim system.

12. After Test Procedure Voiding diary Second step
50% improvement required for implantation
Implantation is not required if you choose not to do so
Second step
PNE wires removed in office, or
OR for staged approach
Place neurostimulator
Remove lead

13. Implant Procedure
Patients with a successful test stimulation go on to implantation of the internal pulse generator. (50%)
A pocket is typically created for the neurostimulator in the upper buttock.

14. Tined Lead

15. Patient Programmer
Physician Programmer

16. Clinical Study Overview
Multi-center randomized, prospective study*
23 centers: 9 European & 14 North American
581 patients (1993 – 1998)
Measurements:
Urge incontinence
Number of leaking episodes /day
Severity of leaking episodes
Number of pads/diapers replaced/day
Urgency-frequency
Number of voids/day
Volume voided/void
Degree of urgency prior to void
Retention
Volume per catheterization
Success was defined as a minimum of 50% improvement in at least one primary diary variable as compared to baseline. This same definition was used for qualifying after test stimulation but also to define clinical success after randomization.
This 50% improvement has been chosen in other studies as well (behavior/ biofeedback training; NIH studies) and has been accepted by the NIH and AHCPR as a standardized measure. For this reason also in this study a 50% improvement in symptoms was chosen.
Study initiated by Medtronic in December 1993 using the traditional implantation procedure (Staged Implant was not performed during this study; tined lead was not available for this study)
Included voiding dysfunctions of: urge incontinence (184 patients), retention (177 patients), urgency/frequency (220 patients).
Urge incontinence indication approved for market clearance on September 29, 1997 by U.S. Food & Drug Administration.
Urgency/frequency and retention indications approved for market clearance on April 15, 1999 by U.S. Food & Drug Administration.
* Staged Implant was not performed during this study

17. Efficacy: Overactive Bladder

18. Efficacy: Urinary Retention

19. Implantation: Ranking of Adverse Events in First 12 Months Post-implant
Pain at neurostimulator site 15.3%
New pain 9.0%
Suspected lead migration 8.4%
Infection 6.1%
Transient electric shock 5.5%
Pain at lead site 5.4%
Adverse change in bowel function 3.0%
Note: Additional events occurred – each less than 2.0%
Additional adverse events include technical problems (1.7%); suspected device problem (1.6%); change in menstrual cycle (1.0%); Adverse change in voiding function (0.6%); persistent skin irritation (0.5%); suspected nerve injury (0.5%); device rejection (0.5%).
Overall surgical revision rate at 12 months = 29%.
No reports of serious adverse device effects or permanent injury associated with the devices or the use of sacral nerve stimulation.
At database closure, 9% of reported events were unresolved.

20. External anal sphincter defect, n=21
Chan and Tjandra. Sacral Nerve Stimulation for Fecal Incontinence: External Anal Sphincter Defect vs. Intact Anal Sphincter. Diseases of the Colon and Rectum:2008.
Prospective study
External anal sphincter defect, n=21
External anal sphincter intact, n=32
3,6,12mo f/u
Anorectal physiology
Wexner’s score
Bowel diary
QOL Q’s

21. All 53 benefited from SNS
EAS defects: Weekly incont. episodes decreased from 13.8 to 5 at 12 mos.
EAS intact 6.7 to 2
QOL scores improved for both groups
+/- pudendal neuropathy irrelevant
Size of EAS defect did not matter up to 120 degrees

22. Double-blind crossover design
LeRoi, et al. Efficacy of Sacral Nerve Stimulation for Fecal Incontinence Results of a Multicenter Double-Blind Crossover Study. Annals of Surgery:2005.
n=27 (most were women)
SNS implanted
Double-blind crossover design
Randomized to on or off for one month periods
Pt then chose the period of preference not knowing whether was actually on or off
Placed in preferred mode for 3 months

23. Outcome measures FI Fecal urgency Delay in postponing defecation
Manometry
QOL
Etc.

24. Significant improvement in all when on
Clinical benefit not due to placebo

25. IE=incomplete bladder emptying; UUI=urge urinary incontinence;
RKH SNS Results
Diagnosis
Procedure
Success
Implant
Implant success IE
SNS PNE No NA
UUI
Yes
IE and UUI
UUI and FI
IE and MUI
MUI
IE and FI
IE=incomplete bladder emptying; UUI=urge urinary incontinence;
FI=fecal incontinence; MUI=mixed urinary incontinence

26. Interstim Bottom Line Interstim is FDA approved for
refractory urgency and frequency
urge incontinence
incomplete bladder emptying
fecal incontinence
Not for pain (PBS/BPS/IC)
Effective therapy with intermediate long-term follow-up.
Support is critical

27. An Option Between Conservative and Surgical Treatments
Urgent® PC
An Option Between Conservative and Surgical Treatments
Simple, Office-based Neuromodulation with Urgent® PC

28. What is PTNS? Defined in a variety of ways:
Percutaneous Tibial Nerve Stimulation
Posterior Tibial Nerve Stimulation
Posterior Tibial Neurostimulation
Example: New CPT® code “Posterior tibial neurostimulation - percutaneous electrode, single treatment, includes programming”

29. Potential Urgent PC Patients

30. Urgent® PC
Easy to administer in twelve 30 minute sessions with maintenance therapy variable
Effective – Approximately 2/3 of patients report a reduction in their symptoms
May work even if other treatments have failed
Low risk – Most common side-effects include transient mild pain or skin inflammation at or near the stimulation site

31. Treatment with Urgent® PC
Stimulation delivered via a 34 ga. needle electrode
Needle electrode inserted above medial malleolus
The needle electrode is connected to a battery-powered stimulator
Provides Percutaneous Tibial Nerve Stimulation (PTNS)

32. Treatment with Urgent® PC
Impulse travels from the ankle along the tibial nerve to the sacral nerves

33. Urgent® PC Neuromodulation System

34. Office-based Treatment
Patient is clothed and comfortable
May be administered by qualified staff, under physician supervision
Physician and staff can treat multiple patients at once

35. Treatment Frequency 12 weekly Urgent PC treatments
Responders may need maintenance treatments to sustain improvements
Slowly increase time between treatments
If symptoms reappear or increase in severity, return to last frequency to sustain relief
In OrBIT study, treatment interval increased to 24 days between treatments during months 6 – 12

36. Urgent PC Contraindications
Patients who are pregnant or planning to become pregnant while using this product
Patients with pacemakers or implantable defibrillators
Patients prone to excessive bleeding
Patients with nerve damage that could impact either percutaneous tibial nerve or pelvic floor function
Not intended for intra-cardiac or trans-thoracic use
Concurrent use of medical monitoring equipment during stimulation is not recommended
Not suitable for use in the presence of a flammable anesthetic mixture with air or with oxygen or nitrous oxide

37. PTNS Clinical Effectiveness
30+ peer reviewed publications demonstrate safety and efficacy
Reduce urgency, urge incontinence & frequency
Significant objective and subjective improvements
No serious adverse events or
side-effects
Improved quality of life
Objective urodynamic data
2/3 of patients respond well
Change reference to MacDiarmid, Staskin, Current Bladder Dysfunction
C01/10

38. Meta-Analysis of 7 PTNS Studies
Martinson, M. (2008). Meta-Analysis of PTNS for Urinary Disorders. Sponsored by Uroplasty, Inc.

39. 60 – 80% Response
Kari: Use the newest patient response chart from PTNS brochure.
MacDiarmid, S., & Staskin, D. (2009). PTNS: A literature based assessment . Curr Bladder Dys , 4,
C01/10

40. PTNS compared to Drug
Patient perception of cure/improvement: 80% in PTNS group; 55% in tolterodine LA group
Physician perception of cure/improvement: 80% in PTNS group; 61% of tolterodine LA group
Comparable reductions in voiding episodes and urge incontinence
Side-effects: No serious adverse events were associated with either treatment. Constipation and dry mouth reported more often in tolterodine LA group
Peters, K.M., Leong, F.C., Shobeiri, S.A., MacDiarmid, S.A., Rovner, E.S., Wooldridge, L.S., et al. (2008). Randomized multicenter study comparing percutaneous tibial nerve stimulation with pharmaceutical therapy for the treatment of overactive bladder. Abstract, American Urologic Association, Annual Meeting, Orlando, FL.

41. PTNS Long-Term Follow-up
Retrospective analysis of 256 patients (178 were treated for OAB symptoms)
Sixty percent (107/178) of patients with OAB symptoms were responders
Results stable at three-year mean follow-up when initial series was followed by maintenance therapy
Only 10% of patients showed significant reduction of the obtained results
Cappellano F., Finazzi Agro E., Giollo A., Petta F., Catanzaro M., Miano R., Germani S., Catanzaro F. (2006). Percutaneous tibial nerve stimulation (PTNS): results at long term follow-up. Abstract presented at the SIUD Congresso Nationale 2006, September, Rome, Italy.

42. OrBIT – UPC vs. Detrol® LA
Multicenter, RCT
12 week phase
12 month responder follow-up
1:1 randomization (n=100)
Physician and patient GRA
Voiding diaries, QoL measures

43. OrBIT Results at 12 Weeks

44. OrBIT Results at 12 Weeks
*p-value:

45. OrBIT – Side Effects
Constipation reported less often in PTNS arm compared to drug arm (p=0.04)
Dry mouth reported less often in PTNS arm compared to drug arm (p=0.0004)
PTNS group reported pain, discomfort or redness at ankle (assessed for PTNS group only)

46. OrBIT Results – Long-term
Statistically significant improvement sustained from 12 weeks thru 12 months
Frequency -2.8 voids/day (p<0.001)
Nighttime voids -0.8 voids/night (p<0.05)
Urgency -3.7/day (p<0.01)
Voided volume +39 cc (p<0.05)
Incontinence episodes -1.6/day (p<0.001)
QOL measure (p<0.01)
No serious adverse events or device malfunctions

47. OrBIT Results – Long-term
Responders continued treatment
90% for 6 months
73% for 12 months
Sustained improvements at 12 months

48. OrBIT – Treatment Interval

49. Risks of Treatment The risks of Urgent PC are low
Side-effects include:
Transient moderate pain at or near the stimulation site
Transient mild pain or skin inflammation at or near the stimulation site
Transient mild bleeding at needle insertion site

50. RKH PTNS Results n=2; both successful Diagnosis Procedure Success UUI
Yes
n=2; both successful

51. What’s Next for PTNS Shorter therapy protocols
Determination of prolonged treatment protocols
Fecal urgency and incontinence
Constipation
Incomplete bladder emptying
Chronic pelvic pain
Chronic non-bacterial prostatitis pain
Pediatric use for LUTS