Device Profile
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CONTENTS
Percutaneous tibial
nerve stimulation
Mechanism of action
Indications
Urodynamic changes
Prognostics
Maintenance therapy
Alternative devices
Expert commentary
Five-year view
Financial disclosure
Key issues
References
Affiliation
Rijnstate Hospital, Department of
Urology, PO Box 9555,
NL-6800 TA, Arnhem,
The Netherlands
Tel.: +31 263 786 082
Fax: +31 263 787 221
mvanbalken@alysis.nl
KEYWORDS:
chronic pelvic pain, incontinence,
lower urinary tract disorders,
neuromodulation, overactive
bladder, percutaneous tibial nerve
modulation, urinary retention
www.future-drugs.com
Percutaneous tibial nerve
stimulation: the Urgent PC® device
Michael R van Balken
Lower urinary tract disorders, with its main representative the overactive bladder, are an
increasing problem that impact patients’ quality of life tremendously. Neuromodulative
treatment may fill the gap between conservative measures and invasive surgery.
Percutaneous tibial nerve stimulation (Urgent PC®) is a neuromodulation technique that is
minimally invasive and easy to perform. Stimulation is carried out in 12 weekly sessions of
30 min each, through a percutaneously placed needle cephalad to the medial malleolus.
Success can be obtained in approximately two-thirds of patients, but the therapy has the
disadvantage of the necessity of maintenance therapy. The development of a small
implantable device may be the future next step in the evolution of the technique.
Expert Rev. Med. Devices 4(5), 693–698 (2007)
Non-neurogenic lower urinary tract dysfunc- overactive bladder [3]. The same goes for neuro-
tion is a common urological problem that modulation, especially for its most successful
strongly affects quality of life. Patients can representative so far: continuous sacral root
complain of urgency and frequency, urge stimulation (Medtronic, Inc., MN, USA) [4–6].
incontinence, chronic pelvic pain or present Although highly effective in selected patients,
with urinary retention. In most patients the eti- this technique is expensive and requires specific
ology of these complaints remains unclear [1]. surgical skills. Not surprisingly, the quest for
Conservative treatment options for overactive better alternatives is ongoing.
bladder, that is, the urgency and frequency
syndrome and/or urge incontinence, consist of Percutaneous tibial nerve stimulation
behavioral techniques with or without biofeed- Inspired by previous work on transcutaneous
back, bladder re-education, pelvic muscle tibial nerve stimulation by McGuire et al. [7],
exercises or pharmacotherapy involving anti- Marshall Stoller began research on percutane-
cholinergics, antispasmodics and tricyclic anti- ous tibial nerve stimulation (PTNS) as neuro-
depressants. Patients with urinary retention modulative treatment in lower urinary tract
can perform clean intermittent or permanent dysfunction. As the tibial nerve has projections
catheterization. For refractory cases of over- to the S3 sacral segment, as is in part the origin
active bladder more aggressive surgical pro- of the sacral nervous plexus that innervates the
cedures, including bladder distension, ileo- bladder, a feedback loop might be anticipated.
cystoplasty or urinary diversion, have been After initial testing in pig-tailed monkeys [8],
advocated. However, high recurrence or com- PTNS was later investigated in humans with
plication rates limit the widespread application promising results [9].
of these treatments. PTNS is performed in patients placed in a
Therefore, other treatment modalities, that comfortable position, supine or sitting, for
are able to fill the gap between conservative easy access to the insertion site; for example,
measures and surgical procedures, are urgently the patient may sit with the soles of the feet
needed. One example may be intravesical together and knees abducted and flexed (‘frog
botulinum toxin injection therapy, first used in position’). A 34-gauge stainless steel needle is
neurological patients only [2], but now also inserted approximately 3–4 cm, approximately
applied to non-neurological patients with three fingerbreadths cephalad to the medial
10.1586/17434440.4.5.693 © 2007 Future Drugs Ltd ISSN 1743-4440 693
van Balken
malleolus, between the posterior margin of the tibia and soleus
muscle. A stick-on grounding pad is placed on the same leg near
the arch of the foot. The needle and electrode are connected to a
low voltage (9-V battery) stimulator (Urgent PC®, Uroplasty
Inc., MN, USA) with an adjustable pulse intensity of 0–9 mA, a
fixed pulse width of 200 µs and a frequency of 20 Hz. The
amplitude is slowly increased until the large toe starts to curl or
toes start to fan. If the large toe does not curl or pain occurs near
the insertion site, the stimulation device is switched off and the
needle is reinserted. If the large toe curls or toes start to fan
stimulation is reduced to an intensity well tolerated by the
patient. If necessary the amplitude can be increased during the
session. In general, patients undergo 12 weekly outpatient treat-
ment sessions, each lasting 30 min. If a good response occurs the
patient is offered chronic treatment [10].
Mechanism of action
Most of what is known regarding the mechanisms of action of
neuromodulation to treat bladder dysfunction was found
studying sacral nerve stimulation (SNS). In chronic pelvic pain
mechanism the mechanism of action is believed to be a gate-
control mechanism [11]. 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. The same goes for the overactive bladder, where a gate-
control mechanism may also play a part. Neuromodulation is
suggested to treat overactive bladder by restoring the balance
between inhibitory and excitatory control systems, peripherally
and centrally [12]. For example, neuromodulation at the sacral
level is believed to inhibit spinal tract neurons, to inhibit
neurons involved in spinal segmental reflexes, as well as
postganglionic and primary afferent pathways [13].
In the case of voiding disorders, theories such as direct affer-
ent pudendal nerve stimulation resulting in a direct change of
pelvic floor behavior [14], a rebound phenomenon [15], suppres-
sion of the guarding reflexes [16] and retuning of the pontine
continence and micturition centers – or ‘on–off ’ switch
mechanism in the brainstem [17] – have been suggested.
The fact that the maximum effect of neuromodulation is not
immediately reached is an indication that neuromodulation
induces learning changes (i.e., neural plasticity). The carry-over
effect may be caused by negative modulation of excitatory
synapses in the central micturition reflex pathway [18].
Mechanisms of action of PTNS are theorized to be similar to
SNS, but studies regarding this subject are yet to be performed.
Indications
Since the introduction of PTNS in 1999 [9], several studies
have been performed evaluating its effectiveness, especially in
patients with overactive bladder, that is the urgency/fre-
quency syndrome and/or urge urinary incontinence, and
nonobstructive urinary retention.
With regard to chronic nonobstructive urinary retention,
studies have shown subjective success in 58–59% of patients,
with success defined as patients request for continuation of
694
treatment to maintain the obtained results [19,20]. More objec-
tive outcome measures improved by over 50% in 41% of
patients. Although in those patients residuals decreased to less
than 100 cc, or even 0 cc, none of them dared to stop catheter-
izations entirely. Besides, in micturition/catheterization para-
meters, significant improvements were also seen in general and
disease-specific quality-of-life measures [20].
Almost all studies on overactive bladder used micturition
diaries and general and/or disease-specific quality-of-life ques-
tionnaires to measure the effects of PTNS [10,19,21–23]. Subjec-
tive success was found in 59–64% of patients [19,21]. Depending
on the definition used, objective success, that is, most of the
time an over 50% decrease in incontinence episodes and/or
micturition frequency, was found in 47–56% of patients [21,22],
a percentage that may increase to approximately 70% if only
25% improvement was aimed for [10,21].
In one study, PTNS for the treatment of refractory chronic
pelvic pain as the main complaint was studied showing only
very modest results: subjective response was seen in 42% of all
patients, objective response (mean Visual Analog Scale for pain
decreased >50%) in only 21% of cases [24]. These results in
chronic pelvic pain, however, are in concordance with the
results of other neuromodulation techniques.
Urodynamic changes
Although one can obtain rather objective parameters from
(micturition) diaries in particular, urodynamic studies may
provide more robust data on the effectiveness of PTNS.
When acute PTNS is performed as soon as detrusor instabili-
ties (DIs) occur on filling cystometry at least in a study in eight
multiple sclerosis patients, no acute effects are demonstrated [25].
This is different for a series of PTNS sessions. In a study on
patients with symptoms related to overactive bladder syndrome
treated with PTNS for 12 weeks, a reduction in the number of
urinary leakage episodes on micturition diaries of 50% or more
per 24 h, could be obtained in 56% [26]. Frequency/volume
chart data and quality-of-life scores improved significantly. Of
the participants with pre- and post-treatment urodynamic data,
only a few showed complete abolishment of DI. Nevertheless,
increments in cystometric bladder capacity and in volume at
DI were significant. Subjects without DI at baseline appeared
1.7-times more prone to respond to PTNS. The more detrusor
overactivity was pronounced, the less these patients were found
to respond to PTNS (area under the ROC curve 0.64).
In a study of patients with chronic voiding dysfunction
enrolled in a comparable prospective trial, objective success was
obtained in 41% of patients [27]. Detrusor pressure at maximal
flow, cystometric residuals and various bladder indices (bladder
contractility index and bladder voiding efficiency) improved
significantly for all patients. Patients with minor voiding
dysfunction were more prone to notice success (odds ratio
[OR]: 0.7).
It can be concluded that PTNS in some of the treated patients
not only results in clinical, but also in more objective uro-
dynamic changes over time. In overactive bladder patients
Expert Rev. Med. Devices 4(5), (2007)

PTNS increases cystometric capacity and delays the onset of,
but not abolishes DI. In patients with voiding disorders PTNS
improves parameters regarding more effective bladder emptying.
Prognostics
In SNS, the result of percutaneous nerve evaluation (PNE) prior
to definitive implantation is the most important prognostic fac-
tor for success. Efforts to establish other predictive (clinical)
parameters proved not to be very successful. For example, age,
duration of complaints, number and kind of former treatments,
indication for neuromodulation therapy and different neuros-
timulation parameters were not proven to be predictive for treat-
ment outcome [28–30]. Although some studies suggest the oppo-
site [28,31], overall, neither gender appears to influence treatment
outcome [29,30]. The only factor rather consistently reported to
predict poor treatment outcome is the history or presence of
psychological disorders or poor mental health [30,32,33]. There-
fore, for optimizing SNS outcome prediction, at present, most is
expected from refining the PNE technique.
For PTNS little data on prognostics are available. Studies on
urodynamic changes by PTNS suggest that if voiding dysfunc-
tion is not too severe or, in case of overactive bladder, DIs are
absent, patients are more prone to a successful treatment out-
come [26,27]. All of the previously mentioned clinical parameters
for predicting SNS outcome were also tested in 132 patients
treated with PTNS, but proved of no significance [34]. Even a
history of sexual and/or physical abuse did not alter PTNS
treatment outcome. However, a low total score at baseline in
the SF-36 general quality-of-life questionnaire proved to be
predictive for not obtaining objective nor subjective success.
Especially patients with a low SF-36 Mental Component Sum-
mary were prone to fail neuromodulation therapy. These
patients also scored worse on disease-specific quality-of-life
questionnaires, although they had no different disease severity
compared with patients with good mental health.
Maintenance therapy
Apart from evaluating which patients may be best suited to
start therapy, it is also important to evaluate how, if possible,
positive results can be sustained. Although Klingler [22] seemed
to suggest otherwise, it is now well known that once a positive
treatment outcome has been obtained, a maintenance program
is needed to avoid recurrence of complaints. In a recent study
the necessity of maintenance therapy was evaluated by means of
a 6-week pause of therapy in successfully treated PTNS
patients, leading to over 50% worsening of main symptoms in
almost all patients. Restarting PTNS afterwards improved
complaints to the level present before the pause [35].
These results have implications beyond the basic idea that
maintenance therapy is indispensable to keep up positive clini-
cal results. Obviously, such maintenance programs put great
strains on caregivers and hospital facilities. Each patient that is
put on a maintenance schedule will visit the outpatients depart-
ment at least 20–30 times per annum. This problem was the
basis for the development of a prototype of an implantable
www.future-drugs.com
Urgent PC®
device that allows a patient to stimulate himself at home as
frequently as the individual situation requires [36]. In prospect,
this implantable device should lessen the burden on medical
professionals and institutions.
Alternative devices
Although many forms of neuromodulative therapies exist [16],
apart from PTNS, only the influence of lower urinary tract
functioning at the level of the sacral roots (SNS, InterStim®
device) seems to stand the test of time. It has the advantage of
preimplant testing possibilities to improve patient selection and
thereby treatment outcome, but it has the drawback of
invasiveness. Furthermore, there is a limited lifespan of the
implant battery and the procedure of SNS is very costly [13].
Compared with the US$20,000 initial cost of the implantable
SNS (InterStim), PTNS’ first year cost is only US$5000–6000.
Even without factoring in the costs incurred as a result of the
high rate of complications associated with SNS, PTNS is the
more cost-effective treatment both initially and over a 10-year
period (assumptions: 30 PTNS sessions the first year, 18 ses-
sions/year thereafter; one generator and lead for SNS
implanted, generator replacement required at year 5 and 10 due
to battery life depletion) [101].
A future alternative might be pudendal nerve stimulation, for
example by means of the Bion® implant, a small size, radio-
frequency-controlled, injectable microstimulator. However, data
up until now are too scarce to draw firm conclusions [37,38].
Expert commentary
PTNS is a minimally invasive, easily accessible neuromodula-
tion technique and has proven its benefit in overactive blad-
der and nonobstructive urinary retention. Regretfully, in
chronic pelvic pain its benefits appear only modest. Although
a placebo-controlled study has yet to be performed, there is
now quite some ‘circumstantial’ evidence for PTNS-related
changes, including animal studies [39,40] and studies with uro-
dynamic data [26,27]. In the case of PTNS becoming an estab-
lished treatment modality, no doubt further indications will
be explored. However, the future role of PTNS, at least in my
view, depends among others on the following two factors.
First, a proper solution for the necessary maintenance ther-
apy has to be sought. If maintenance therapy is continued
percutaneously and often in an outpatient setting as it is now,
in the long run PTNS will lose its popularity. One way to
solve this problem might be the further development of a
small implantable device. However, as PTNS is reimbursed
in the USA, financial stimuli to develop a readily available
implantable device to overcome these drawbacks are, regret-
fully, almost completely absent. Furthermore, the preclinical,
clinical and regulatory pathways for an implantable PTNS
device are not only difficult to navigate, but costly, lengthy in
duration and have unknown outcomes. Second, new promis-
ing treatment options for, in particular, overactive bladder
arise. Botulinum toxin specifically proves increasingly helpful
in patients with DIs and patients that appear less suitable for
695
van Balken
successful PTNS. Therefore, PTNS should make sure to
optimize its attractiveness to patients regarding efficacy, costs
and user-friendliness, as well as to reinforce its scientific
background, in order not to become overpowered by the
previously mentioned emerging therapies.
Five-year view
So far, studies on PTNS are only few; many questions remain
unanswered. The near future of PTNS is therefore most proba-
bly dedicated to further research, which will not only clarify the
many dark areas left behind, but may also shine a light on
ongoing mysteries in other neuromodulation techniques. What
are the main issues in PTNS that have to be resolved?
Does PTNS work?
PTNS therapy results in changes in symptoms, quality-of-life
items, urodynamic features and lower urinary tract disease
accompanying sexual functioning. Furthermore, there are also
CNS changes that areall very indicative for PTNS as an active
treatment modality. Despite that, a placebo effect cannot be
completely ruled out, thus, a placebo-controlled trial still needs
to be performed. However, because of the very specific features
of the PTNS technique, a blinded (let alone a double-blinded)
randomized controlled trial is almost impossible to conduct. In
addition, it should be noted that almost none of the even most
established neuromodulation techniques have been properly
run against placebo. This issue is one of the most challenging
for the near future.
In whom should PTNS be performed?
As PTNS with its 10–12 half-an-hour sessions before results are
obtained is elaborative, predictive factors for successful out-
come are urgently needed. Some studies in sacral as well as
tibial nerve stimulation have now been performed, resulting in
the best candidates being psychologically sound patients with
not too severe overactive bladder or nonobstructive urinary
retention. More research should be performed to tighten these
criteria for neuromodulation therapy increasing positive results.
As soon as a subcutaneous implant for chronic tibial nerve
stimulation is readily available, by analogy with sacral neuro-
modulation, additional efforts should be undertaken to refine
the preimplant testing phase in order to decrease the amount of
unnecessarily treated patients.
By contrast, optimizing the success of PTNS treatment will
without a doubt lead to the exploration of its value in other
indication groups, something that can already be seen in sacral
neuromodulation. Most likely to be subject of further investi-
gation seem to be children, neurologic patients and patients
with fecal incontinence.
Until now, almost all stimulation and neuromodulation
techniques were tested in adults only, with the exception of
intravesical electrostimulation and sacral neuromodulation
[41] in children with neurogenic voiding disorders and trans-
cutaneous electrical nerve stimulation in non-neurogenic
incontinence. The majority of neuromodulation techniques
696
namely seem less suitable to children due to their invasive
nature and the necessity to apply current in the anal and/or
genital area. Although PTNS is not ‘noninvasive’, its focus on
the ankle might be less threatening to children, offering a pos-
sibility for PTNS use in this young age group. Promising
results reported from the first two studies in 31 and
23 children, respectively [42,43], warrant further evaluation.
The second challenging patient group consists of neurologi-
cal patients. In most neuromodulative therapies this group is
not included. However, it can be argued that neuromodulation
treatment in selected cases, especially in multiple sclerosis, may
be of benefit as well. Up to now, experience in this field is very
limited and contradictive [44–46], but results are encouraging
enough to justify more research.
Finally, an area generally spoken beyond the interest of most
urologists but in many ways comparable to lower urinary tract
dysfunction, is that of fecal incontinence. As for urinary leak-
age, fecal incontinence has a high impact on patients’ quality
of life, but seems even more difficult to discuss for both
patients and caregivers. As the first steps are taken in exploring
the value of sacral neuromodulation in this field [47], it can be
anticipated that research on PTNS for this indication will also
be performed [48].
What is the best way to perform PTNS?
Almost all research carried out on PTNS used the same stimu-
lation protocol: PTNS was performed in 10–12 weekly
sessions, each lasting for 30 min. Stimulation parameters were
preset and rather fixed and every time only one needle was
inserted. It may be well anticipated that changes in treatment
scheme and/or stimulation parameters could lead to a different,
possibly even better outcome. The same goes for bilateral
instead of unilateral therapy.
Compared with the once-weekly protocol, an accelerated
scheme of three- to four-times weekly, for example, seems not
to significantly influence treatment outcome, although there
are some conflicting reports on its effect on the necessity of
maintenance therapy afterwards [22,35]. On the other hand, it is
evident that an accelerated scheme has the advantage of
achieving clinical results faster [49].
Regarding stimulation parameters, it is rather widely agreed
that pulse intensity in neuromodulation should be set at a well
tolerable level. Frequency, however, for PTNS set at 20 Hz, has
been varied in the different neuromodulation techniques from
5 to 20 Hz, but even frequencies up to 150 Hz are reported. As
it is suggested that frequency is optimal at more unpleasantly
low levels (5–6 Hz) [50], studies on PTNS with pulse frequen-
cies below 20 Hz may produce interesting results. The same
goes for changes in pulse duration, in PTNS set at 0.2 ms, but
in other techniques also up to 0.5 or even over 1 ms.
Besides research on stimulation scheme and parameters it
may also be interesting to evaluate the possible beneficial effect
of stimulating both legs at the same time. At least in sacral
neuromodulation there is some evidence that bilateral stimula-
tion may improve results not so much in relieving symptoms
Expert Rev. Med. Devices 4(5), (2007)
 Urgent PC®

better than unilateral stimulation once successful, as well in

improving the chance that patients react at all [51–53]. Of course Key issues
a positive outcome of bilateral stimulation in PTNS would
create some new problems with regards to a possible implanta- • Minimally invasive neuromodulation therapy.
ble device. This will eventually be the way it should be heading: • Main indications: overactive bladder and nonobstructive
a readily available subcutaneous implantable device, easily urinary retention.
controllable by patients themselves in flexible, individualized
• Filling the gap between more conservative treatments and
treatment schemes. It is unnecessary to state that there is still a
major surgery.
long way to go.
• Mentally sound patients with not too severe symptoms most
Financial disclosure prone to success.
The author has no relevant financial interests related to this • Maintenance therapy necessary.
manuscript, including employment, consultancies, honoraria,
• Future groups to be explored: fecal problems, neurological
stock ownership or options, expert testimony, grants or patents
patients, children.
received or pending, or royalties.

References
Papers of special note have been highlighted as:
• of interest
•• of considerable interest
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• One of the few animal experiment papers
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Website
101 PTNS clinical evidence overview.
Uroplasty Reimbursement Group
www.uroplasty.com/pdf/PTNSclinical_
0520037a.pdf
Affiliation
• Michael R van Balken
Rijnstate Hospital, Department of Urology,
PO Box 9555, NL-6800 TA, Arnhem,
The Netherlands
Tel.: +31 263 786 082
Fax: +31 263 787 221
mvanbalken@alysis.nl
Expert Rev. Med. Devices 4(5), (2007)