E. Finazzi Agrò

1. Neuromodulazione tibiale:
indicazioni, risultati e limiti
Prof. Enrico Finazzi Agrò
Dept. of Urology, “Tor Vergata” University
Tor Vergata Hospital and IRCCS S. Lucia
Rome, ITALY

2. Agenda
Percutaneous Tibial Nerve Stimulation
 Definition
 History
 Mechanisms of action
 Rationale
 Methods
 Indications
 Results
 Placebo effect?
 Predictive factors of success
 What happens after 10-12 sessions

3. PTNS
Definition

4. Neuromodulation
“Neuromodulation is considered a normal property of
the nervous system that regulates or modifies
electrical impulses flowing through neural tissues…
Interventional neuromodulation is considered
nondestructive and reversible therapy and includes
the use of implanted or nonimplanted electrical
stimulation systems, electrically stimulating
peripheral nerves, dorsal root ganglia, the spinal
cord, or the brain, and chemical neuromodulation,
the infusion of chemical agents directly to the central
nervous system.”
David Abejón MD, Enrique Reig MD, PhD (2003) Neuromodulation 6 (1), 1–3.

6. SISTEMA InterStim®

7.  Neuromodulation
technique of the lower
urinary tract obtained
with electrical
stimulation of the
posterior tibial nerve
Percutaneous Tibial Nerve Stimulation
PTNS

8. PTNS
History

9. PTNS : background
 Punto noto
all’agopuntura
tradizionale (Sp-6)
– Vescica

10. PTNS : background
 E’ difficile urinare
mentre si cammina!

11. PTNS : background
 Inibizione detrusoriale
secondaria a
stimolazione delle
afferenze mieliniche
dall’arto posteriore nel
gatto
Lindstrom, Neurourol Urodyn, 1989

12. PTNS : background
 TENS del n. tibiale in
soggetti con iperattività
detrusoriale
neurogena
McGuire EJ, J Urol 1983

13. percSANS (Urosurge)
(Eur. Urol., 1999)
Urgent PC (CystoMedix)
Stoller Afferent Nerve Stimulation
Marshall Stoller, MD
Bart BLH Bemelmans, MD PhD
Perc. Tibial Nerve Stimulation
Urgent PC (Uroplasty)

14. PTNS
Mechanisms of action

15. Mechanisms of action
 Neuromodulation is supposed to restore the
control at the spinal segmental gate as well as at
supraspinal sites such as the brainstem and limbic
system nuclei
 Neuromodulation is suggested to treat overactive
bladder by restoring the balance between
inhibitory and excitatory control systems,
peripherally and centrally
Schmidt R. Neurosurgery 1986; 19: 1041-1044

16. PTNS : mechanisms of action
 PTNS lowers the mast
cells count in the
bladder wall of the rat
Danisman A et al: Tibial nerve stimulation
diminishes mast cell in the bladder wall
induced by interstitial cystitis urine.Scand
J Urol Nephrol. 2007;41(2):98-102.

17. PTNS : mechanisms of action
 Electro-acupuncture of
the hind leg significantly
reduces c-fos
expression
 Conclusion: electro-
acupuncture reduces
spinal neuronal cell
activity
Chang, Stoller, Lue et al, J. Urol. 1998

18. Suprapontine effects???

19. Suprapontine effects of S3
neuromodulation
PET
 Decrease of activity in areas important for bladder
filling sensation and the onset of micturition
(middle frontal gyrus, left temporal lobe, the right
insula)
Blok B: Neurourol Urodyn 2002
 Increase of activity of primary motor cortical areas
associated with abdominal and pelvic floor
musculature
Blok B: Neurourol Urodyn 2003

20. Suprapontine effects of S3
neuromodulation
LL-SSEPs
In responders pts.:
reproducible LL-SSEPs
have been demonstrated
(in particular on
somatosensory cortex).
Braun PM. Eur Urol. 2002.

21.  Significativo incremento dell’ampiezza delle
prime due componenti dei LL-SEP (P80,
P100)
 Non significativo incremento della terza
componente (P200)
Finazzi-Agrò E et al: Neurourol Urodyn. 2009;28(4):320-4.

23. Conclusioni
 Modificazione a lungo termine nei
meccanismi di elaborazione dello stimolo
sensitivo che si verificano dopo l’arrivo
dell’afferenza somatosensoriale in corteccia
 Prima dimostrazione di un effetto sovra-
pontino della PTNS
 Risultato “long lasting” (almeno 24h)

24. PTNS
Rationale

25. PTNS : razionale
 Elettrostimolazione n.
tibiale posteriore
– Area non genitale
– Stimolazione
ambulatoriale
– Stimolazione
retrograda (afferente)
dei metameri sacrali
sino a S3

26. PTNS: razionale
 N. tibiale posteriore
 Fibre S3
– flessione plantare
alluce (S3)

27. PTNS
Methods

28. PTNS: procedura
 Puntura di Sp-6
– Ago 34 G
 Connessione dell’ago
allo stimolatore
 Parametri di
stimolazione elettrica
fissi eccetto
– ampiezza
 sino a ottenere una risposta
motoria/sensitiva

29. PTNS: procedura
 Trattamento
ambulatoriale
 Una seduta di
stimolazione a
settimana
 30 minuti
 Periodo di valutazione:
12 settimane

30. Stimolazione 3/w
 26 pazienti
 % successo simile a quella della
stimolazione 1/w
 Risultati dopo 6-8 sedute (dopo 2-3
settimane anziché dopo 6-8)
Finazzi Agrò, Minerva Urologica 2003

31. PTNS
Indications

32. PTNS
 Indicazioni:
 Sindrome della vescica iperattiva
 Ritenzione urinaria non ostruttiva
 Dolore pelvico cronico – Cistite interstiziale
 Vescica neurologica
 Indicazioni pediatriche
 Incontinenza fecale

33. PTNS
Results in OAB

34. Literature
Meta-analysis of PTNS for urinary disorders
7/17 papers considered•
 Number of daily voids
244 patients improved an average of 23% (7 papers, p<0.001)
 Nighttime voiding
151 patients improved 41% (5 papers, p=0.002)
 Voiding volume
182 patients improved 43% (5 papers, p<0.001)
 Incontinence episodes
167 patients improved 45% (4 papers, p=.023)
 Incontinence QoL
122 patients improved 17% (3 papers, p=0.033)
 Percent of patients improved
174 of 244 (71%) patients improved (7 papers, p<0.001)
Produced for Uroplasty, Inc. by:
Melissa Martinson, MS PhD
Technomics Research, LL
Minneapolis, MN

36. Placebo controlled study
 Responders
– 12/17 patients (71%) in PTNS group
– 0/15 in placebo group
(p<0.001)
 Statistically significant improvement in
number of incontinence episodes, number of
voids, voided volume and I-QoL score were
found in PTNS group but not in placebo
group

37. PTNS
Predictive factors of success

38. PTNS in OAB (overactive bladder)
 Bad mental health (as measured with SF-36
Mental Component Summary) is a negative
predictive factor for PTNS success.
Van Balken MR: Eur Urol 2006
 Better results in patients without involuntary
detrusor contractions or with involuntary detrusor
contractions at higher volumes
Vandoninck V, Finazzi Agrò E et al: Neurourol Urodyn 2003
 Responders rate is higher in female than in male
patients (66 and 45% respectively)
Finazzi Agrò E et al: Eur Urol Suppl 2007

39. PTNS
What happens
after the first 10-12 sessions?

40. PTNS
Follow-up
PTNS
 11 pts with OAB responders to PTNS
 6-week pause
 Reassessment
– 7/11 pts (64%) showed a significant worsening
of symptoms
 Need of a “chronic” stimulation.
Van der Pal F. et al: BJU int 2006

41. PTNS
Follow-up

42. PTNS
Follow-up
 Assessments at 6 and 12 months from
baseline in PTNS responders
 33 pts
– 32 and 25 subjects completing 6 and 12 months
of therapy, respectively.
– Subjects received a mean of 12.1 treatments
during an average of 263 days, with a mean of
21 days (median 17) between treatments

43. PTNS
Follow-up
 94% and 96% of responders at 6 and 12
months, respectively
 At 12 months mean improvements from
baseline included a frequency of 2.8 voids
daily (p <0.001),urge incontinence of 1.6
episodes daily (p <0.001), nocturia with 0.8
voids (p<0.05) and a voided volume of 39 cc
(p <0.05).

44. Chronic tibial TENS?
 14/16 pts underwent a protocol of tibial TENS
 Mean follow-up 19,7 (6-30) months
 All patients subjective responders
 13/14 objective responders
 Mean number of stimulations/week: 1, 6
Finazzi Agrò et al, Neurourol Urodyn suppl 2011

45. 7 years
 7 year follow up in 8 OAB pts and in 7
NOUR pts
 Most of them satisfied even without further
PTNS sessions in the last years…
Finazzi Agrò et al, unpublished data

46. PTNS
Conclusions

47. PTNS
 PTNS is efficacious in…
–71% of OAB pats
 Similar to Tolterodine ER
 3 papers level 1 evidence

48. Offer, if available, PTNS as an option for
improvement of urgency urinary incontinence in
women, but not men, who have not benefited
from antimuscarinic medication.

49. Neuromodulazione