Percutaneous tibial nerve stimulation - IUGA...

Percutaneous tibial nerve stimulation

Prof. Jan-Paul Roovers, uro-gynaecologist, Head dpt of gynaecology, AMC Amsterdam

Medical director Pelvic floor center “Bergman clinics”

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OAB – Urgency - The Driver for Multiple Symptoms

Urgency

Increased

Frequency

and Reduced

Intervoid

Interval

Nocturia Incontinence

Quality of

Life

Perception

of Bladder

Condition

“Bother”

Reduced Volume

Voided per Micturition

Modified from Chapple CR , Artibani W, Cardozo LD, Castr-Diaz D, Craggs M, Haab F et al. BJU Int. 2005; 95: 335–40

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Bladder Filling Sensations

Different for Detrusor Overactivity and Urodynamic

Stress Incontinence

Urodynamic

diagnosis

Abdominal

sensation

Perineal

sensation

Abdominal &

Perineal

sensation

Total

Detrusor

overactivity 3 13 1 17

Urodynamic

stress

incontinence

12 2 4 18

Mixed

urodynamic

diagnosis

1 6 3 10

Normal

urodynamics 4 7 0 11

Reduced bladder

sensation 1 1 0 2

Basra R et al. Int Urogynecol J 2006; 17(suppl 2): S134 Abst 130 Slide Provided by Mr V Khullar

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Innervation of the Human Bladder

Cortex: permission & attention

Midbrain: safety

Brainstem: relay center „on /off‟

Th10-L2: sympathetic nerve: storage

S2-3: parasympathetic system: voiding

S2-3: pudendal nerve: control

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Innervation of the Bladder

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The Emerging Picture is Complex

Pain Pain C fibres

Gillespie JI, van Koeveringe GA, de Wachter SG, de Vente J. BJU Int. 2009; 103: 1324-1333

Static - mechanical

Chemical

Mechanical

Motor/sensory

medulla

cord

CNS

HT fibres LT fibres

Silent fibres

Stretch receptors Aδ/C Stretch receptors

Urothelial modulation

Myofibroblasts

Motor/sensory

Detrusor contraction

M 3

cortex

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Working mechanism of PTNS

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OAB symptoms are the result of disbalance between

inhibitory and excitatory control systems

1.Sensory input through pudendal nerve inhibits detrusor

activity and enhances external sphincter tone. This facilitates

storage of urine.

2.Bladder normally responds to neural stimulation with rapid

contraction and slow, longer lasting relaxation. With recurrent

repetitive stimuli, the bladder response is down regulated.

Hypothesis working mechanism PTNS

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Finazzi-Agrò, E., et al. (2009). Percutaneous tibial nerve stimulation produces effects on brain activity: study on the modifications of the

long latency somatosensory evoked potentials. Neurourol Urodyn, 28(4):320-24.

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1.

2.

3. Stimulation of afferent sacral nerves in lower extremities

increases the inhibitory stimuli to the efferent pelvic nerve

and reduces detrusor contractility.

4. Affects the neuro-axis and restores balance between

inhibitory and excitatory regulation at various locations.

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Hypothesis working mechanism PTNS

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• It is feasible to effectively influence behaviour of the lower

urinary tract via the Posterior Tibial Nerve

• Discontinuous stimulation can work for some time after the

stimulation has stopped

Concept of PTNS

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Sites of Neuromodulation for LUTS

Mixed

pudendal

nerves

•Anal/Vaginal [Fall et al 1978]

•Dorsal Clitoral/Penile Nerve [Nakamura & Sakurai 1984,

Fjorback et al 2007]

Pudendal

Afferent

nerves

sacral

nerves

•Sacral Nerve Implants

[Schmidt 1988]

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• 1983 – McGuire - treated urge, frequency, and

incontinence with tibial nerve electrical stimulation

• 1999 – Stoller – modified technique using near nerve

needle stimulation

• Tibial nerve stimulation is more acceptable than

genital/anal stimulation

Why the Tibial Nerve?

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Tibial Nerve Pathway

• Innervates muscles

including big toe flexor

• A toe extension may not

be present in all cases

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Tibial Nerve Pathway • Mixed peripheral nerve

• Sensory and motor fibers

• Spinal segments from

L4 to S3

• Contains sensory fibers –

cutaneous afferents

innervating the sole and heel

• Contains motor fibers – flex

& fan toes

• Accessible at ankle &

superficial enough to reach

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Urgent® PC Neuromodulation System

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PTNS: Procedure

• “frog” position (optional)

• puncture 5 cm upwards of the medial malleolus

• attach reference electrode

• connect to stimulator

• adjust stimulator current

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• Sensory response

• radiating sensation in

the sole of the foot

• Motor response

• toe flexion and/or

fanning

PTNS: Procedure

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PTNS: Protocol

• 12 (bi)weekly sessions of 30 min.

• Adjust stimulation intensity during session

• Out-patient setting

• Performed by doctor or nurse practitioner

• Success expected after 6-8 sessions

• Successful cases: continue as the patient requires (tapering protocol) once every 2 - 4 weeks

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Indications

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• OAB syndrome (OAB wet and OAB dry)

• Pelvic Pain

• Voiding Dysfunction

• Fecal incontinence

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• 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

Urgent PC Contraindications

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Clinical data on PTNS

• Meta-Analyses

• OrBIT - RCT compared to drug

• SUmiT - RCT compared to placebo

• Long-Term Data

• OrBIT 12 month – Results sustained for 12 months

• STEP – up to 3 years

• “Real Life” Clinical Studies

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• Reduce leak episodes by > 50%

• Reduce frequency to < 8 voids/24 hr (normal)

• Patient requests continuation of therapy

Clinical Success Measurements

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60 – 80% Response

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• Multicenter, RCT

• 12 week phase

• 12 month responder follow-up

• 1:1 randomization (n=100)

• Physician and patient impression of improvement

• Voiding diaries, QoL measures

OrBIT – PTNS versus tolterodine

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Peters, K., MacDiarmid, S., Wooldridge, L., Leong, F., Shobeiri, S., Rovner, E., Siegel, S., Tate, S., Jarnagin, B., Rosenblatt, P., & Feagins, B.

(2009). Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the

Overactive Bladder Innovative Therapy Trial. J Urol, 182, 1055-61.

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OrBIT Results at 12 Weeks

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OrBIT Results at 12 Weeks

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*p-value: 0.053




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• 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 < 0.001)

• PTNS group reported pain, discomfort or redness

at ankle (assessed for PTNS group only)

OrBIT – Adverse events

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OrBIT 12 Week Conclusion

Urgent® PC and slow release tolterodine provide

similar (significant) objective and subjective

improvement.

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• Double blind, RCT, placebo-controlled

• 220 patients, 23 sites

• Validated, previously published sham

• Patients were not on OAB drugs during the study

• Voiding diaries and QoL measures

• Intent-to-treat analysis

SUmiT Trial – UPC vs. Sham

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Peters, K.M., Carrico, D.J., Perez-Marrero, R.A., Khan, A.U., Wooldridge, L.S., Davis, G.L., & and MacDiarmid, S.A. (2010). Randomized trial of

percutaneous tibial nerve stimulation versus sham efficacy in the treatment of overactive bladder syndrome: results from the

SUmiT Trial. J Urol, 183, 1438–1443.

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SUmit Results

• Statistically significantly better outcome

compared to sham for:

• Urinary urgency (p=0.003)

• Urinary frequency (p<0.001)

• Urinary urge incontinence (p=0.02)

• No serious adverse events or device

malfunctions

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SUmiT Trial conclusion

• Urgent PC is superior to sham,

• Effect is not due to placebo effect

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STEP Study: 36 Months follow-up

• Sustained Therapeutic Effect of Percutaneous Tibial

Nerve Stimulation

• Subjects were participants in the SUmiT trial

• Multi-center, randomized, double-blind

• 29 subjects through 36 months

• Voiding Diary and OAB-q questionnaires

• Evaluation of long-term therapy efficacy

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Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment

of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.

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STEP Study - Results

• 29 subjects completed tapering protocol and followed

up through 36 months

• Subjects received 1 PTNS treatments per month

• Sustained significant efficacy and safety of PTNS for

OAB demonstrated

• No treatment related adverse events

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STEP Study – 36 Months

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Mean number of treatments per month



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OAB-q HRQoL and Symptom Severity Scores by Follow-up Visit ITT-

LVCF n=50 (p<0.0001)



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• Retrospective, single-site

• 141 female refractory OAB patients

When do patients respond?

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Symptom

Weeks to

improvement

(median)

Weeks to

improvement

(range)

Percent

patients w/ late

response

(> 8 txs)

Nighttime Voiding 5 2-12 9.9%

Frequency 7 2-12 8.1%

Urgency 6 2-12 18%

Urge

Incontinence

6 2-12 18.6%

Leong, F.C., et al. (2011). Posterior tibial nerve stimulation in patients who have failed anticholinergic therapy: Efficacy and time to response.

Female Pelvic Med Reconstr Surg, 17(2), 74-5.

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• Comparison of cost-effectiveness between PTNS and

sacral nerve stimulation during 2 years

• The costs were $4,867 and $24,342 for PTNS and SNS,

with 71% and 90% subjective cure rates

• An incremental cost-effectiveness ratio of $99,872 when

staying on therapy was assessed.

• “PTNS and SNS are both safe, effective neuromodulation

therapies for OAB. In this economic model PTNS had

substantially lower cost.”

Cost-effectiveness: PTNS versus SNS

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Martinson, M., MacDiarmid, S. & Black, E. (2013). Cost of Neuromodulation Therapies for Overactive Bladder: Percutaneous tibial nerve stimulation Versus

Sacral Nerve Stimulation. J Urol, 189(6), 210-216.

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AMC data

Phase 1

• Drug therapy combined with behavioral therapy

• Drug therapy

Phase 2

• PTNS

• Botox

Phase 3

• Botox

Phase 4

• Bladder augmentation

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Patient characteristics

• 2012 – 2013

• N = 85 in 2 locations (Amsterdam and Utrecht)

• Previous use of antimuscarinics: 80%

• Previous pelvic physiotherapy: 50%

• Concomitant stress incontinence: 40%

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Outcome of PTNS

Number of treatments:

Response after first 12 weeks:

• No response = 15/80 = 19%

• Positive response: 39/80 = 49%

• Complete response: 26/80 = 33%

Response at end of therapy:

• No response = 25/80 = 31%

• Positive response: 16/80 = 20%

• Complete response: 39/80 = 49%

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• Includes 16 studies, 940 total patients

• Subjective success rate of 61.4% (95% CI 53-72%)

• Objective success rate of 60.6% (95% CI 84-75%)

• Statistically superior to Sham [RR 7.02 CI 1.69 – 29.17]

• No significant differences in the change in bladder diary

parameters compared to antimuscarinics; PTNS

associated with a better side-effect profile

Meta-Analysis – Burton

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Burton, C., Saija, A., Latthe, P.M. (2012). Effectiveness of percutaneous posterior tibial nerve stimulation for overactive bladder:

A systematic review and meta-analysis. Neurourol Urodyn, 31, 1206-16.

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Includes 7 studies, 244 patients

71% of patients improved

Meta-Analysis - MacDiarmid

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Criteria Mean

Improvement

Patients Studie

s

p-value

Daytime Voids 23% 244 7 P<0.001

Nighttime Voids 41% 151 5 P<0.002

Voiding Volume 43% 182 5 P<0.001

Incontinence

Episodes

45% 167 4 p=0.023

I-QoL 17% 122 3 P=0.033

MacDiarmid, S.A., & Staskin, D.R. (2009). Percutaneous tibial nerve stimulation (PTNS): A literature-based assessment.

Curr Bld Dysf Rept, 4, 29-33.

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Take home message

•PTNS based on sound principle

•Approach of the posterior tibial nerve feasible for clinical application

•Outpatient procedure easy to do

•Level 1A proven efficacy in OAB !

Date post:	16-Apr-2018
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Percutaneous tibial nerve stimulation - IUGA...

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