Sacral Nerve Stimulation: Sacral Nerve Stimulation: Critical Update and Literature Critical Update and Literature

ReviewReview

Magdy Hassouna MD PhDMagdy Hassouna MD PhD

University of TorontoUniversity of Toronto

ObjectivesObjectives

• Basic concept of Sacral Basic concept of Sacral Neuromodulation (SNM)Neuromodulation (SNM)

• Mechanism of Action of SNMMechanism of Action of SNM

• Clinical Indications of SNMClinical Indications of SNM

• Special Circumstances of SNMSpecial Circumstances of SNM

• Timing to offer SNMTiming to offer SNM

DisclosuresDisclosures

• MedtronicMedtronic

• Johnson and JohnsonJohnson and Johnson

Baptiste, Elkelini et al. 2009

Anatomy and Physiology of the lower urinary tract

Sympathetic and Somatic Sympathetic and Somatic Innervation and ReceptorsInnervation and ReceptorsSympathetic and Somatic Sympathetic and Somatic Innervation and ReceptorsInnervation and Receptors

How does it work?How does it work?

• Inhibits spinal tract neurons in the micturation reflex.Inhibits spinal tract neurons in the micturation reflex.

• Inhibits interneurons involved in spinal segmental Inhibits interneurons involved in spinal segmental reflexes.reflexes.

• Inhibits postganglionic neurons directly.Inhibits postganglionic neurons directly.

• Inhibits primary afferent pathway.Inhibits primary afferent pathway.

• Indirectly suppresses guarding reflexes.Indirectly suppresses guarding reflexes.

IndicationsIndications

• SNM is a treatment modality approved by the FDA for SNM is a treatment modality approved by the FDA for patients with:patients with:

• Urinary urge incontinence (1997)Urinary urge incontinence (1997)• Urgency frequency syndrome (1997)Urgency frequency syndrome (1997)• Non-obstructive urinary retention (1999)Non-obstructive urinary retention (1999)

• Indications of SNM include:Indications of SNM include:• Overactive bladderOveractive bladder• Neurogenic disorders: e.g. MS, SCINeurogenic disorders: e.g. MS, SCI• Interstitial cystitis and pelvic painInterstitial cystitis and pelvic pain• Non-obstructive urinary retentionNon-obstructive urinary retention• Pelvic floor muscle dysfunctionPelvic floor muscle dysfunction• Failed prior conservative therapyFailed prior conservative therapy

ContraindicationsContraindications

• Patients who have anatomic changes (sacral bone Patients who have anatomic changes (sacral bone abnormalities).abnormalities).

• Patients with limited mental capacity.Patients with limited mental capacity.

• Patients who use other stimulation devices Patients who use other stimulation devices ( cardiac pacemaker, DBS).( cardiac pacemaker, DBS).

• Patients for whom future MRI studies will be Patients for whom future MRI studies will be critical.critical.

• Patients who underwent unsuccessful SNS test Patients who underwent unsuccessful SNS test trial. trial.

Which Patients are Appropriate Which Patients are Appropriate Candidates for SNMCandidates for SNM

• In General: Patients who have symptoms In General: Patients who have symptoms of VD, that are not helped by other of VD, that are not helped by other measures.measures.

• Overactive bladder syndrome:Overactive bladder syndrome:– WetWet– DryDry

• Chronic idiopathic non-obstructive urinary Chronic idiopathic non-obstructive urinary retention.retention.

• Pelvic pain.Pelvic pain.• Any combination of the above mentioned. Any combination of the above mentioned.

Standardisation of Standardisation of Terminology of LUT Function: Terminology of LUT Function: ICS 2002ICS 2002• Detrusor function during filling Detrusor function during filling

cystometry:cystometry:

– Detrusor overactivity (patterns):Detrusor overactivity (patterns):•Phasic detrusor overactivity Phasic detrusor overactivity (NEW)(NEW)

•Terminal detrusor overactivity Terminal detrusor overactivity (NEW)(NEW)

•Detrusor overactivity incontinence Detrusor overactivity incontinence (NEW)(NEW)

– Detrusor overactivity (causes):Detrusor overactivity (causes):•Neurogenic detrusor overactivity Neurogenic detrusor overactivity (NEW)(NEW)

•Idiopathic detrusor overactivity Idiopathic detrusor overactivity (NEW)(NEW)

What is SNM Therapy?What is SNM Therapy?

• InterStimInterStim

• Implantable, programmable neuromodulation systemImplantable, programmable neuromodulation system

• Two-stage therapyTwo-stage therapy

– PNE: Test stimulation procedure – 3 to 7 days, temporaryPNE: Test stimulation procedure – 3 to 7 days, temporary

– Staged Lead Implant: Placement of potentially permanent Staged Lead Implant: Placement of potentially permanent

lead for up to 4 weekslead for up to 4 weeks

– Chronic Implant: Implantation of neurostimulator (and lead Chronic Implant: Implantation of neurostimulator (and lead

when not done as a staged procedure)when not done as a staged procedure)

®

• Temporary pacing wire Temporary pacing wire (lead)(lead) substitution. substitution.

• Portable, external Portable, external stimulator stimulator ( screener).( screener).

• Cont. stimulation Cont. stimulation (4-5 (4-5 days).. days).. (Sub-Chronic)(Sub-Chronic)

• Parameters:Parameters: Unipolar,monophasic,square Unipolar,monophasic,square pulsepulse Pulse width = 210 msPulse width = 210 ms Frequency = 10 HzFrequency = 10 Hz Maximum voltage = 10 Maximum voltage = 10

voltsvolts

Percutaneous Nerve Evaluation (PNE)

• Success equals ≥ Success equals ≥

50% improvement50% improvement

• Number of leaks/dayNumber of leaks/day

• Number of voids/dayNumber of voids/day

• Voided volume/voidVoided volume/void

• Degree of urgencyDegree of urgency

Trial PeriodTrial Period

InterStim® System InterStim® System

Neurostimulator in BodyNeurostimulator in Body

InterStim® System with InterStim® System with Patient ProgrammerPatient Programmer

InterStim® SystemInterStim® System

• Physician Programmer

• Patient Programmer

• Implanted Pulse Generator

• Patient activator/deactivator

SNM in Neurogenic SNM in Neurogenic DisordersDisorders• Multiple Sclerosis ??Multiple Sclerosis ??• Spinal Cord Injury ??Spinal Cord Injury ??• SNS # CIC / DiversionSNS # CIC / Diversion• Inappropriate Candidates:Inappropriate Candidates:

– Peripheral NeuropathyPeripheral Neuropathy– Cord lesionCord lesion– ParkinsonismParkinsonism– Myelodysplasia Myelodysplasia – MSMS

SNM and neurogenic SNM and neurogenic disordersdisorders• SCI:SCI:

– In a series of 37 patients with SCI who underwent anterior sacral root In a series of 37 patients with SCI who underwent anterior sacral root stimulation, micturation control was maintained in stimulation, micturation control was maintained in 87%87% after 7 years. after 7 years. ((Vastenholt et al, 2003)

– Everaert et al, 1997 reported favourable urodynamic changes in 27 neuromodulation implanted patients with spastic pelvic floor syndrome, bladder neck dysfunction, sphincter hypertonia, sphincter dysfunction, detrusor overdistenstion and hypercontractile detrusor.

– Another study on incomplete spinal cord injured patients suffering from lower urinary tract symptoms showed that SNM is effective in 56%(Lombardi and Del, 2009).

SNM in Neurogenic bladderSNM in Neurogenic bladder

• MS:MS:– In a small series of 5 patients with MS, there was an overall In a small series of 5 patients with MS, there was an overall 81.4% 81.4%

decrease of urgency and frequency with a significant decrease in the decrease of urgency and frequency with a significant decrease in the number of upper urinary tract infections and fever; there was a slight number of upper urinary tract infections and fever; there was a slight improvement in bowel function; and overall improvement in bowel function; and overall 51.8% 51.8% improvement in the improvement in the Qol. (Minardi D, Muzzonigro G., 2005)Qol. (Minardi D, Muzzonigro G., 2005)

• Guillain-Barre syndrome:– Wosnitzer et al showed the voiding dysfunction caused by GB

syndrome responded to SNM treatment. (Wosnitzer et al, 2009

SNM and PBS (painful SNM and PBS (painful bladder syndrome)bladder syndrome)• Several studies reported improvement in pelvic Several studies reported improvement in pelvic

pain, reduction in narcotic requirements, and pain, reduction in narcotic requirements, and improved QoL. improved QoL. (Lukban et al, 2002) (Everaert et al, 2001) (Siegel et al, 2001) (Comiter, 2003)

• We reported in long term follow-up of 21 female patients with painful bladder syndrome in which 52% showed response to PNE and proceeded for permanent IPG implantation, that an improvement in bladder pain, QoL and voiding parameters was maintained after 5 years. (Ghazwani et al, 2011)

SNM and childrenSNM and children• In one study, SNM was effective in controlling In one study, SNM was effective in controlling

urinary and fecal incontinence in 33 children urinary and fecal incontinence in 33 children with neurogenic voiding dysfunction with neurogenic voiding dysfunction

(Haddad M et al, Journal of (Haddad M et al, Journal of Urology, 2010)Urology, 2010)

• Similar results were shown by Humphreys Similar results were shown by Humphreys MR et al, and they showed that SNM was MR et al, and they showed that SNM was effective in the majority of patients with the effective in the majority of patients with the dysfunctional elimination syndrome. dysfunctional elimination syndrome.

(Humphreys MR et al, Journal of (Humphreys MR et al, Journal of Urology, 2006)Urology, 2006)

SNM in ChildrenSNM in Children

• Another study showed that SNM Another study showed that SNM improved voiding dysfunction after improved voiding dysfunction after 27 months of prospective follow-up27 months of prospective follow-up– Urinary incontinence, Urinary incontinence, 88% 88% (14 of 16), (14 of 16), – urgency and frequency, urgency and frequency, 69% 69% (9 of 13), (9 of 13), – nocturnal enuresis nocturnal enuresis 89% 89% (8 of 9), (8 of 9), – constipation constipation 69% 69% (11 of 16).(11 of 16).

(Roth TJ et al, (Roth TJ et al, Journal of Urology, 2008)Journal of Urology, 2008)

SNS for Bowel DysfunctionSNS for Bowel Dysfunction

• Present indications*Present indications*

– Fecal incontinenceFecal incontinence

– Fecal urgency-frequency (IBS)Fecal urgency-frequency (IBS)

– Idiopathic chronic constipationIdiopathic chronic constipation

• Many patients have both GU/GI symptomsMany patients have both GU/GI symptoms

• Often GI improvements most meaningful to Often GI improvements most meaningful to

patientspatients

*Jarret, Br J Surg. 2004; Matzel, Lancet 2004; Kenefic, Br J Surg. 2002

Newer forms of Newer forms of NeuromodulationNeuromodulation

• Percutaneous tibial nerve stimulationPercutaneous tibial nerve stimulation

• External urinary sphincter stimulationExternal urinary sphincter stimulation

• Dorsal genital nerve stimulationDorsal genital nerve stimulation

• Pudendal nerve stimulationPudendal nerve stimulation

Posterior Posterior TTibial ibial NNerve erve SStimulationtimulation

A thin needle is placed along the medial edge of the tibia 5 cm cephalad to

the medial maleolus, with stimulation given weekly for 10 to 12 weeks.

Posterior Posterior TTibial ibial NNerve erve SStimulationtimulation• Afferent stimulation provides central inhibition of the Afferent stimulation provides central inhibition of the

preganglionic bladder motor neurons through a direct preganglionic bladder motor neurons through a direct route in the sacral cord.route in the sacral cord.

• Another technique that is less invasive is using Another technique that is less invasive is using disposable, self-adhesive contact electrodes.disposable, self-adhesive contact electrodes.

• Chronic therapy: few long-term seriesChronic therapy: few long-term series

• Marketed commercially as Urgent PCMarketed commercially as Urgent PC

– FDA approved for OAB 2005FDA approved for OAB 2005

Pudendal Nerve Pudendal Nerve SStimulationtimulation

• Pudendal nerve stimulation by percutaneously Pudendal nerve stimulation by percutaneously implanting a small pellet close to the pudendal implanting a small pellet close to the pudendal nerve is also currently under investigation. This nerve is also currently under investigation. This procedure activates somatic afferent fibers in 3 procedure activates somatic afferent fibers in 3 of the sacral nerves. In contrast, sacral nerve of the sacral nerves. In contrast, sacral nerve stimulation activates only one sacral nerve, stimulation activates only one sacral nerve, usually S3usually S3..

Pudendal nerve Pudendal nerve stimulationstimulation

Dorsal Genital Nerve Dorsal Genital Nerve StimulationStimulation

• Target DGN, a sensory branch of pudendal N.Target DGN, a sensory branch of pudendal N.

• MOA: sensory afferent modulationMOA: sensory afferent modulation

• Trial: percutaneous lead, office basedTrial: percutaneous lead, office based

• Chronic therapy: no information Chronic therapy: no information

• Not a commercial productNot a commercial product

2929

Transcutaneous electrical stimulation of Transcutaneous electrical stimulation of pudendal nerve afferents pudendal nerve afferents (TENS-P) (TENS-P) via via

N.dorsalis penis / N.clitoridisN.dorsalis penis / N.clitoridis

Advantages• Pure sensory branches of the pudendal nerve• Short distance between electrodes and nerves

External Urinary Sphincter External Urinary Sphincter StimulationStimulation

• Target EUSTarget EUS

• MOA: Activation of efferent fibers cause reflex MOA: Activation of efferent fibers cause reflex

detrusor relaxation (guarding reflex)detrusor relaxation (guarding reflex)

• Trial: percutaneous lead, office basedTrial: percutaneous lead, office based

• Chronic therapy: limited info availableChronic therapy: limited info available

• Not a commercial productNot a commercial product

EUS Lead ImplantEUS Lead Implant

SNM and Female Sexual FunctionSNM and Female Sexual Function

• Literature is scarce.Literature is scarce.

• One recent study showed that SNM improved sexual One recent study showed that SNM improved sexual functions in patients with OAB. (Paul R, et al 2007)functions in patients with OAB. (Paul R, et al 2007)

• Another study showed similar results in patients with Another study showed similar results in patients with neurogenic bladder. (Lombardi G, et al 2008)neurogenic bladder. (Lombardi G, et al 2008)

Effects of sacral neuromodulation on female sexual function

• Prospective study.Prospective study.

• SNM; December 2009 - July 2012.SNM; December 2009 - July 2012.

• Dx: Females with OAB, non-obstructive UR.Dx: Females with OAB, non-obstructive UR.

• Female Sexual Function Index (FSFI): Baseline and Female Sexual Function Index (FSFI): Baseline and Postoperatively at 3 months.Postoperatively at 3 months.

Paul R et al, Int Urogynecol J (2007)

Female Sexual Function Index (FSFI):Female Sexual Function Index (FSFI):

• 19 questions.19 questions.

• Patients must be sexually active for 4 weeks.Patients must be sexually active for 4 weeks.

• Questions are grouped and scored:Questions are grouped and scored:– LibidoLibido– ArousalArousal– LubricationLubrication– OrgasmOrgasm– SatisfactionSatisfaction– PainPain

ResultsResults

• 13 patients enrolled; 7 completed the study.13 patients enrolled; 7 completed the study.

• Age: 50 (range 28-75) years.Age: 50 (range 28-75) years.

• Postoperative survery: 5.7 (range 3-12) months.Postoperative survery: 5.7 (range 3-12) months.

• No significant correlation between urinary symptoms improvement No significant correlation between urinary symptoms improvement and FSFI scoresand FSFI scores

FSFI score:D-Desire,A-arousal,L-lubrication, O-orgasm, S-satisfaction, P-pain, T-total.

MR SystemMR System

• GE Signa CV/I; GE Signa CV/I; General Electric General Electric Medical Systems, Medical Systems, Milwaukee, WIMilwaukee, WI

• 1.5 Tesla1.5 Tesla

• Running 9-x Running 9-x softwaresoftware

Reasons to contraindicate MRI Reasons to contraindicate MRI include:include:

– Motion and/or dislocation of the Motion and/or dislocation of the Neurostimulator.Neurostimulator.

– Changes to the Neurostimulator program.Changes to the Neurostimulator program.– Malfunction and damage of the device.Malfunction and damage of the device.– Pain stimulation due to voltages and Pain stimulation due to voltages and

currents in the Neurostimulator induced currents in the Neurostimulator induced by pulsed radiofrequency (RF) fields.by pulsed radiofrequency (RF) fields.

– Heating of the Neurostimulator leads due Heating of the Neurostimulator leads due to to

– electromagnetic RF fields.electromagnetic RF fields.

MRI safety in patients with MRI safety in patients with SNSSNS• 5 on the Brain, and 3 on the cervical vertebrae.5 on the Brain, and 3 on the cervical vertebrae.

• MRI tests were requested by neurologists for medical reasons.MRI tests were requested by neurologists for medical reasons.

• Patients were counseled regarding Patients were counseled regarding the procedure, complications, current the procedure, complications, current recommendations of safety and the value of MRI examination.recommendations of safety and the value of MRI examination.

• During the test: cDuring the test: continuous monitoring for symptoms of heating and/or ontinuous monitoring for symptoms of heating and/or abnormal sensation at the site of the device was performed through abnormal sensation at the site of the device was performed through verbal contact with the patients.verbal contact with the patients.

• After the test:After the test:– PG site was examined and changes were reported.PG site was examined and changes were reported.– Patients were asked to report any abnormal sensation during the MRI session.Patients were asked to report any abnormal sensation during the MRI session.– IPG were then re-programmed to their previous set-up using a programmer (model IPG were then re-programmed to their previous set-up using a programmer (model

7432 Medtronic MN).7432 Medtronic MN).

MRI safety in patients with MRI safety in patients with SNSSNS• Patient Follow-up:Patient Follow-up:

– Voiding diary for 4 days after MRI examination.Voiding diary for 4 days after MRI examination.– The following parameters are compared:The following parameters are compared:

• voided volume in (ML) voided volume in (ML) • frequency of urination per 24 hours frequency of urination per 24 hours • sense of urgencysense of urgency• episode of urinary incontinence episode of urinary incontinence

– Data were compared with previously recorded ones. Data were compared with previously recorded ones.

• Results:Results:– No patient reported heating or any other sensation during MR testing which would have required stopping No patient reported heating or any other sensation during MR testing which would have required stopping

the examination.the examination.– MR images were not affected by the presence of the IPG.MR images were not affected by the presence of the IPG.– IPG devices showed no evidence of malfunction as evidenced battery index “OK” IPG devices showed no evidence of malfunction as evidenced battery index “OK” – Devices were reprogrammed according to the values used prior to MRI procedures.Devices were reprogrammed according to the values used prior to MRI procedures.– Patients mentioned no change in perception of the stimulation once the IPG was reprogrammed to the Patients mentioned no change in perception of the stimulation once the IPG was reprogrammed to the

same stimulation parameters as before the MR test. same stimulation parameters as before the MR test.

• Data collected from voiding diaries 4 days after procedure did not show any significant change in Data collected from voiding diaries 4 days after procedure did not show any significant change in bladder voiding parameters, when were compared to the ones in the latest voiding diary. bladder voiding parameters, when were compared to the ones in the latest voiding diary.

–

Patients with voiding dysfunction

Voiding Diary

PNE

IPG Implantation

Early Group Late Group

Improvement of > 50% of voiding parameters

< 3 weeks > 6 months

Early versus late treatment of Sacral Nerve StimulationEarly versus late treatment of Sacral Nerve Stimulation

ObjectivesObjectives

• The purpose of this study is to determine whether a delay of SNM The purpose of this study is to determine whether a delay of SNM can affect the long-term outcome of treatment in patients with can affect the long-term outcome of treatment in patients with voiding dysfunction.voiding dysfunction.

Urge Urge frequency frequency

Urinary Urinary Retention Retention

Urge IncontinenceUrge Incontinence

Early Group Early Group 1616 22 22

Late Group Late Group 1212 66 44

ResultsResultsPatientsPatients

• Medication intake and co-morbidity were very Medication intake and co-morbidity were very similar in both study groupssimilar in both study groups

• Late patient group:Late patient group:– Mean age at presentation: 40 ± 4.1 yearsMean age at presentation: 40 ± 4.1 years– Duration of urinary symptoms: 5.8 ± 2.6 yearsDuration of urinary symptoms: 5.8 ± 2.6 years

• Early patients group:Early patients group:– Mean age at presentation: 42 ± 3.3 yearsMean age at presentation: 42 ± 3.3 years– Duration of urinary symptoms: 6.6 ± 1.3 yearsDuration of urinary symptoms: 6.6 ± 1.3 years

ResultsResultsPatientsPatients

• Early group: 16 out of 20 patients (Early group: 16 out of 20 patients (80%80%) showed good ) showed good response in their symptoms and overall satisfaction for a response in their symptoms and overall satisfaction for a follow-up period (mean) 32.5 months.follow-up period (mean) 32.5 months.– 3/20 patients had poor response.3/20 patients had poor response.– One had the neurostimulator removed due to lack of efficacy. One had the neurostimulator removed due to lack of efficacy.

• Late group: 13/22 patients (Late group: 13/22 patients (59%59%) showed good response ) showed good response in their symptoms and the overall satisfaction.in their symptoms and the overall satisfaction.– 7/22 had symptoms less than those in post screening diaries but 7/22 had symptoms less than those in post screening diaries but

still better than the baseline diaries.still better than the baseline diaries.– 2 had the neurostimulator removed due to lack of efficacy.2 had the neurostimulator removed due to lack of efficacy.

ResultsResultsUrge/ Frequency GroupsUrge/ Frequency GroupsVoided Volume/ VoidVoided Volume/ Void

UF Early Patients Group (n=16)

Post-implant Follow-up/ months

Baseline PNE 6 12 18 24 30 36 42

Vo

ide

d V

olu

me

/ V

oid

50

100

150

200

250

300

350

400

Early UF REarly UF NR Suceess rate: 87.5%

UF Late Patient Group (n=12)

Post-implant Follow-up/ months

Baseline PNE 6 12 18 24 30 36V

oid

ed V

olu

me/

Vo

id0

100

200

300

400

500

Late UF RLate UF NR

Success rate: 66.66%

ResultsResultsUrinary Retention GroupUrinary Retention Group

Urinary Retention Group Urine Volume per CatheterEarly vs Late Patient Groups

Post-implant Follow-up/ months

Baseline PNE 6 12 18 24 30

Uri

ne

Vo

lum

e (m

l)

0

100

200

300

400

500

Early Cath Volume Late Cath Volume

Asterisk indicates statistical significance.

*

*

* *

ConclusionConclusion

• Patients who received SNS implanted Patients who received SNS implanted shortly after PNE had shown a better shortly after PNE had shown a better outcome compared to patients who had to outcome compared to patients who had to wait for 6 months or longer.wait for 6 months or longer.

• This study suggests that SNS prevents the This study suggests that SNS prevents the progression of the pathophysiologic progression of the pathophysiologic mechanisms (??) involved in voiding mechanisms (??) involved in voiding dysfunction. dysfunction.

ConclusionConclusion

• Newer modalities of SNM are Newer modalities of SNM are promisingpromising

• MRI in patients with SNM is feasibleMRI in patients with SNM is feasible

• Newer Indications of SNM are Newer Indications of SNM are emergingemerging

Thank YouThank You