Extracorporeal magnetic innervation therapy: Assessment of clinical efficacy in relation to urodynamic parameters

Article (PDF Available)inScandinavian Journal of Urology and Nephrology 42(5):433-6 · May 2008with59 Reads
DOI: 10.1080/00365590802022177 · Source: PubMed
Abstract
Clinical efficacy and urodynamic changes in women treated by extracorporeal magnetic innervation therapy (ExMI) were studied. Women, presenting with urge, stress and mixed urinary incontinence, were included in a prospective study. ExMI was applied by an electromagnetic chair. To document clinical efficacy, a voiding diary and visual analogue scale were completed before and after treatment, together with a pad test. Detrusor overactivity (DO) and urethral instability (URI) were urodynamically documented. Clinical success was defined as more than 50% improvement in symptoms. Sixteen patients were included. At baseline, DO was observed in 10 patients, and URI in 12 patients. DO did disappear at follow-up in 60%, and a decrease in URI was seen in 66%. No significant clinical improvement was seen at follow-up. Although significant changes in urodynamic variables were observed, no significant improvement in clinical efficacy was seen after ExMI.
Neuromodulation and Urodynamics in
Lower Urinary Tract Symptoms
Pieter M. Groenendijk
Cover photo by Marco Ferrageau de Saint Amand
Naval Air Station Patuxent River, Maryland, USA, May 18 2006
Back cover photo by Pieter M. Groenendijk
Over the Chesepeake Bay, joining up with ‘Tester 11’, Maryland,
USA, October 28 2007
ISBN ...
Printed by Quantes BV, Rijswijk, The Netherlands
Layout by Charissa Boek
Copyright © P.M. Groenendijk, Rijswijk, The Netherlands, 2008
Neuromodulation and Urodynamics in
Lower Urinary Tract Symptoms
Proefschrift
ter verkrijging van de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus prof. mr. P.F. van der Heijden,
volgens besluit van het College voor Promoties
te verdedigen op dinsdag 9 december 2008
klokke 11.15 uur
door
Pieter Marinus Groenendijk
geboren te Nootdorp in 1965
Promotiecommissie
Promotor Prof. Dr. A.A.B. Lycklama à Nijeholt
Co-promotor Dr. J.P.F.A. Heesakkers (UMC Radboud, Nijmegen)
Referent Prof. Dr. B.L.H. Bemelmans (VUMC, Amsterdam)
Overige leden Prof. Dr. Ph.E.V.A. van Kerrebroeck (AZ Maastricht)
Dr. R.C.M. Pelger
Prof. J. Zwartendijk
The publication of this thesis was generously supported by: Medtronic
International Trading Sarl, Medtronic Trading Netherlands BV and Raad van
Bestuur Reinier de Graaf Groep Delft/Voorburg,
Additional support was granted by Abbott BV, Astellas Pharma BV, Astra Tech BV,
AstraZeneca BV, Bayer BV, GlaxoSmithKline, Ipsen Pharmaceutica BV, Lamepro BV, MMS
International, Novartis Pharma BV, Olympus Nederland BV, Pfizer BV, G. Pohl
Boskamp Gmbh&Co. Sanofi Aventis, SCA Health Care and Uroplasty BV
Neuromodulation and urodynamics in lower urinary tract symptoms. Thesis University Leiden,
Leiden, the Netherlands, including a Dutch summary.
© 2008 All rights reserved, including the right of reproduction in whole or in part in any form.
”Let’s go balistic”
Voor mijn ouders
Contents
Introduction Aim of the thesis 10
Neuromodulation treatment modalities 11
Bladder and urethral anatomy 22
Chapter 1 Urethral instability: current pathophysiological concept
(in press for publication in Urologia Internationalis) 32
Chapter 2 Five-year follow-up after sacral neuromodulation (SNM):
single center experience (Neuromodulation, 2007) 46
Chapter 3 Urodynamic evaluation of sacral neuromodulation for urge
urinary incontinence (BJU Int, 2008) 60
Chapter 4 Clinical and urodynamic assessments of the mode of action
of sacral nerve stimulation (in New perspectives in sacral nerve
stimulation, 2002) 72
Chapter 5 Urethral instability and sacral nerve stimulation: a better
parameter to predict the efficacy? (J Urol, 2007) 86
Chapter 6 Functional extracorporeal magnetic stimulation as a treatment
for female urinary incontinence: ‘the chair’ (BJU Int, 2004) 98
Chapter 7 Extracorporeal Magnetic Innervation therapy: assessment
of clinical efficacy in relation to urodynamic parameters
(Scand J Urol Nephrol, 2008) 108
Summary 120
Samenvatting 123
List of publications 126
Nawoord 129
Curriculum vitae 130
Aim of this Thesis
The number of patients with Lower Urinary Tract Symptoms (LUTS) will continue to rise. Most
important cause for this is the increasing average life span of the population of most developed
countries. Furthermore, an increasing knowledge of the general public on this subject, generated
by the media, will cause an increase in demand for health care interventions. This implies that
workload for clinicians involved with treatment of LUTS will rise. Unfortunately, national health
care budgets will not rise in parallel. Therefore, for justification of use of new treatment options,
we must not only prove these new, sophisticated treatments to be more effective but also to be
more cost-effective compared to existing treatments.
LUTS do highly affect patient’s quality of life. Patients with non-neurogenic lower urinary tract
dysfunction may present with different complains: besides obstructive complaints in men, urge
urinary incontinence, urgency and/or frequency, chronic pelvic pain or non-obstructive urinary
retention. Treatments of choice options are firstly conservative and include pharmacotherapy
(anticholinergic) and behavioural techniques (pelvic floor muscle exercises, bladder re-education).
Unfortunately, only a limited number of patients do respond successful to these conservative opti-
ons, leaving a group of patients with refractory complaints. In the past, irreversible and aggressive
surgical procedures, including urinary diversion and bladder augmentation were performed on
these patients.
Monitoring the efficacy of treatment modalities is often disappointing, especially the use of tra-
ditional parameters, like urodynamic proven detrusor overactitivity, does not lead to a better un-
derstanding and patient selection so far. In literature, the value of urethral pressure recording on
traditional filling cystometry in relation to clinical treatment outcome is not clear. This is also true
for the finding of urethral pressure changes (i.e. urethral instability) during filling cystometry.
With an increasing interest in the “pelvic floor” and multi-disciplinary approach to treat patients,
there is a need to look for (urodynamic) parameters, which are valuable for both patient selec-
tion and measurement of treatment modalities. Since the 90’s, selected patients do respond with
good result to new neuromodulation techniques like Sacral Neuromodulation. However, the exact
mode of action is still not known as well as the value of urodynamic evaluation in the process of
patients’ selection and assessment of clinical success. A better understanding of the mechanism of
action is definitely needed for good selection of patients with refractory lower urinary tract dys-
functions, favourable for neuromodulation. Furthermore, increasing knowledge on urodynamic
parameters and their role in patients selection as well as in evaluating treatment, will led to better
clinical results. This thesis gives an outline of different neuromodulation techniques together with
urodynamic changes evoked by neuromodulation. Also the predictive value of some urodynamic
parameters, especially in relation to urethral pressure variations will be assessed. The role of the
urethra and its function seems to be underestimated so far.
10
Introduction
11
Neuromodulation: treatment modalities, indications,
clinical efficacy, and mode of action
Neuromodulation, in all its forms, offers a treatment option for patients with refractory lower
urinary tract symptoms. Complaints in these patients may vary from voiding disorders, impaired
micturition or chronic non-obstructive urinary retention to storing disorders, including complaints
of an overactive bladder to chronic pelvic pain. Cause of the lower urinary tract dysfunction in
patients without an objective neurogenic laesion is mostly unknown.
Neuromodulation is often used in patients with voiding symptoms who do not respond to conser-
vative therapy. Conservative therapies include physiotherapy, pharmacotherapy and behavioural
techniques. In patients with chronic non-obstructive retention, clean intermittent catherization
maybe the treatment of choice. From a patient’s point of view, this however is a burden with tedi-
ous side effects like urinary tract infections. Invasive extensive surgery is irreversible, and in many
patients, does not lower the impact of their illness. Therefore, neuromodulation, especially the
minor invasive techniques, maybe treatment option of choice for patients with refractory voiding
symptoms, who failed all conservative therapeutic options.
Neuromodulation is defined as the physiological process in which the influence of the activity in
one neural pathway modulates the pre-existing activity in another through synaptic interaction
[1]. Different kind of therapies has been developed for different indications with variable clinical
success, illustrating the difficulty to treat lower urinary tract dysfunction [2]. More recent, the
use of Sacral Neuromodulation (SNM) and Percutaneous Tibial Nerve Stimulation (PTNS) has
been emphasized [3,4]. Both treatment modalities have acceptable clinical success rates although
patient selection still is a point of discussion and remains empiric [5]. Further investigation on
patient selection is therefore strongly needed. Other ‘new’ neuromodulation treatment options
included Transcutaneous Electrical Nerve Stimulation (TENS) and modulation of the pelvic floor
by magnetic stimulation (‘magnetic chair’). Unfortunately, clinical success rates of both methods
are limited [6].
The use of neuromodulation treatment in daily practice is relatively new. Most research in this
field is published during the last three decades. With increasing knowledge concerning neurophy-
siology, investigators were looking for therapeutic use of stimulation and modulation of the nerve
system, both peripheral and central. Most of the work was empiric, but with time, clinical suc-
cess was fortunately increasing. Better knowledge of involved neurological connections between
central and peripheral nerve systems and bladder however did not led to a straightforward expla-
nation of the mode of action and even nowadays there is debate on the working mechanisms of
neuromodulation in the treatment of lower urinary tract dysfunction [7]. In recent years, more
applications of various types have been developed. This review presents an overview of neuro-
modulation therapies together with different theories on the mode of action.
Sacral Neuromodulation (SNM)
In SNM therapy, also known as Sacral Nerve Stimulation. the third sacral nerve (S3) is stimulated
by a permanent neurostimulator (InterStim®, Medtronic Inc., Minneapolis, Minnesota, USA).
An electrode is placed in foramen S3 (sometimes S4)of the sacral bone by a dorsal approach and
connected to the stimulator. Stimulation of the nerve occurs with a frequency of 10-20 pulses
per second, a pulse width of 210 μsec, and variable amplitude. The procedure is considered as
minimally invasive. Unfortunately, reported complication rate in the past was relative high and
up to 30% of patients required a new operation. The improved temporary lead design makes the
Peripheral Nerve Evaluation more reliable while new techniques, like the tined lead, make the
procedure easier. This will hopefully lead to a decrease in re-operations and adverse events ratio
over time.
Several groups have studied the efficacy of SNM with the InterStim implantable neurostimulator
intensively. Tanagho and Schmidt first reported on this treatment in 1982 after conducting ani-
mal studies [3]. In 1988, the three stages of electrode placement were discussed by Schmidt [8].
Reported results vary between 41% and 100%, depending on patient’s selection and treatment
indication [9]. However, one should kept in mind that the reported success rates are obtained
after patient selection based on a positive Percutaneous Nerve Evaluation (PNE) test. Patients are
mostly considered for permanent implant after an improvement of more than 50% in their main
voiding symptoms, as described by Schmidt, Senn and Tanagho [10]. Approximately 40% of
selected candidates do not pass the PNE. Therefore, reported cure rates must be evaluated with
some precaution. A prolonged testing with tined lead seems to be more reliable for accurate pa-
tient selection with implantation rate increased to 80%. At median follow-up of 22 months 88%
of the implanted patients remain successful. No infection was reported during prolonged test
period [11]. This new approach for patient selection will lead to more patients positively selected
for permanent implant.
Indications for SNM
In 1997, SNM therapy was approved by the FDA for refractory urge urinary incontinence, fol-
lowed by urgency and frequency symptoms and chronic non-obstructive urinary retention in
1999. Nowadays, patients with complaints of an ‘overactive bladder’ are considered candidates
for SNM when their symptoms are persistent, do affect their quality of life significantly and do not
respond to conservative treatment modalities. Contraindications are few. Patients with anatomic
variations, like bone abnormalities of the sacrum cannot be treated by SNM due to difficulty to
access the sacral foramen. Patients, in which future MRI studies are critical, must also be conside-
red as poor candidates. Furthermore, patients must be able to operate the device and report on
comfort of stimulation. This is essential for optimal clinical result. Of course, patients who have
failed the PNE test are inappropriate for permanent implant.
12
Introduction
SNM success rates for different indications
SNM for urge urinary incontinence (UI) and urgency/frequency (UF)
Reports on SNM outcome on symptoms of an overactive bladder (OAB), i.e. urgency and/or fre-
quency are mostly presented together with patients implanted with a permanent neurostimulator
because of refractory UI.
The efficacy of SNM for symptomatic treatment of refractory UI has been published extensively.
Hassouna et al reported in 2000 on efficacy and safety for patients treated with sacral neuro-
modulation. Sacral neuromodulation is safe and shows significant clinical benefit in treated ur-
gency and frequency patients [12]. Long-term effectiveness, with an average follow-up of 30.8
months, showed sustained benefit for urge urinary incontinence patients [13]. In 2006, Latini et
al. reported an improvement in symptoms of 50% in 90% of patients with refractory UI, after
one-staged or two-staged InterStim implant [14]. Number of urge incontinence episodes reduced
by 74% and number of pads used per day by 83% compared to baseline. Statistically significant
improvement in number of UI episodes and quality of life in both younger and older patients
is seen [15]. The cure rates in patients with UI are associated with age, with individuals youn-
ger than 55 years having a statistically significant better cure rate. Long-term follow-up shows
sustained benefit in over 2/3 of patients with refractory complaints of an OAB, implanted with a
permanent neurostimulator [16]. Our 5-years follow-up results show a comprehensive outcome
with a significant decrease in symptoms in 10 out of 15 UI patients [17]. In an independent inves-
tigation of 1827 implants from 34 clinical trials, InterStim therapy was shown to be an effective
treatment option for the treatment of UI. In randomized controlled trials 80% of the patients
achieved continence or more than 50% improvement in their symptoms, for case series reports
this was 67% [18]. SNM may improve sexual frequency and sexual function scores in female
patients with UF and UI. Device implant impacted sexual function in a positive way by decreasing
urgency and by increasing desire [19]. Recently, the long-term results of 152 patients, enrolled
in the worldwide MDT-103 study, were published. At 5-year follow-up, sacral neuromodulation
was successful in 68% of patients with urge urinary incontinence, 56% with urgency/frequency
and 71% with urinary retention [20].
SNM for chronic non-obstructive urinary retention
Jonas et al reported effectiveness in 83% of patients with urinary retention, 18 months after im-
plantation [21]. Efficacy rates up to 77%, with spontaneous voiding, have been reported on the
long term in women with Fowler’s syndrome, treated by SNM. Mean post-void residual volume
was 75 ml, which is acceptable [22]. Similar good results, defined as complete and lasting disap-
pearance of symptoms or satisfactory symptoms for the patients, were found by van Voskuilen et
al. [16]. The presence of Fowler’s syndrome, with specific electromyography abnormalities of the
external sphincter, is a positive predictive factor for SNM in female urinary retention. Idiopathic
urinary retention patients do benefit as well, but the success rate might be less predictable [23].
13
SNM for constipation and faecal incontinence
Following the use of SNM in patients with voiding disorders, beneficial effects for patients with
concomitant bowel dysfunction was seen. SNM in faecal incontinence is not effective for all
patients eligible for the procedure. A PNE test period of 2-3 weeks allows selection of those
patients who are likely to respond with good result to a permanent implant [24]. Aetiology of
faecal incontinence is various and idiopathic, obstetric, surgical and spinal cord pathology causes
are mentioned. Complete faecal continence after SNM was reported in 41% to 75% of patients
whereas an improvement of more than 50% in number of incontinence episodes was seen in
96% of patients after permanent implant [25,26]. Similar results have been noted in patients with
idiopathic constipation [27].
A total of 30000 patients are treated worldwide with InterStim therapy so far. With changing
techniques, the procedure can now be performed under local anaesthesia and therefore be con-
sidered as minimally invasive.
SNM mode of action
Recently, van der Pal et al. published on the mode of action of all neuromodulation techniques [7].
Once again, it is evident that a straightforward explanation on the mode of action is hard to give.
Several hypothesis have been reported in the past. Generally, and adapted by most investigators,
it is believed that SNM works via stimulation of afferent rather than efferent nerves [28]. Others
however stated that direct stimulation of the nervus pudendus does explain working mechanism
of SNM [29]. It is clear that further investigation is needed before this debate will be ended.
By novel neuroimaging techniques (Positron Emission Tomography, PET scan), the existence of
abnormal interaction between brainstem and cortical centres in women with urinary retention
was seen. The therapeutic effect of SNM is achieved through restoration of activity associated
with brainstem auto regulation and attenuation of cingulate activity [30]. Blok et al. performed
a PET-scan study on UI patients, previously implanted with a neurostimulator and UI patients,
stimulated for the first time in the PET-scan. Group analysis between acute and chronic stimulated
patients showed significant differences in the associative sensory cortex, premotor cortex and
cerebellum, all three involved in learning behaviour. They concluded that acute SNM modulates
brain areas involved in sensorimotor learning. Furthermore, chronic SNM influences, presumably
via the spinal cord, brain areas previously involved in detrusor hyperactivy, awareness of bladder
filling, the urge to void and timing of micturition. Also SNM affects areas involved in alertness
and awareness [31].
Expanding indications for SNM
New frontiers for SNM therapy are patients with interstitial cystitis (IC), chronic pelvic pain syn-
dromes, neurogenic bladder dysfunctions (MS) and erectile dysfunction.
IC symptoms include pelvic pain, dyspareunia, small voided volumes, frequency, nocturia, and
urgency. Pharmacological therapy is varied and efficacy is often poor, indicating the difficulty to
treat IC. A sustained clinical improvement in symptoms is reported by Comiter in a prospective
study, evaluating SNM for refractory IC [32]. A decrease in narcotic requirement for refractory IC
patients implanted by a permanent neurostimulator is noted. Patients were overwhelmingly satis-
14
Introduction
fied with SNM compared with prior therapies [33]. SNM elevates urinary levels of antiproliferative
factor and epidermal growth factors in IC patients. This may explain restoration of normal voiding
[34]. SNM improves quality of life and decreases severity and duration of patients with chronic
genitourinary pain [35]. Cavernous nerve stimulation achieved full erections in a serie of 15 men
with erectile dysfunction [36]. This therapy however is anecdotal at the moment.
Percutaneous Tibial Nerve Stimulation (PTNS)
In PTNS, formerly called Stoller Afferent Nerve Stimulation (SANS), a needle electrode is placed
near the tibial nerve, a few centimetres above the ankle. This spot is known by acupuncturists
and considered of significance in treatment of urological symptoms [37]. The needle electrode is
connected to an external neurostimulator generating 1-10 mA. Working mechanism is unknown.
Patients are mostly treated weekly during a 9-week period. After this period, clinical benefit is
evaluated and the treatment may be continued with an increasing time interval between tre-
atments. If treatment is terminated this usually results in return of patient’s symptoms. PTNS is
indicated for refractory symptoms of an OAB, including UF and UI. Treatment is conducted in an
outpatient setting and normally, the tibial nerve is stimulated for 30 minutes at an amplitude just
below pain threshold. The tibial nerve is sometimes mentioned as posterior tibial nerve, indicating
the existence of an anterior tibial nerve. Review of anatomy however shows there is no such
nerve. Therefore, it is better to speak of tibial nerve in literature. The tibial nerve originates from
spinal roots L4 through S3 and is a mixed sensory-motor nerve. A neuro feedback mechanism
via the plexus pelvicus may reduce bladder activity, resulting in a decreased symptom awareness.
Modulation of the somatic and autonomic nerve system may influence urinary sphincter and
bladder behaviour.
Approximately 50% of all patients do respond positively on PTNS. Treatment however is relative-
ly time consuming and it remains unclear how and/or when treatment can be stopped. Increasing
amount of patients may frustrate other activities at the outpatient department. For this reason,
some urologists do perform PTNS in day care treatment. Fortunately, only minor side effects,
mostly pain at the puncture site, have been reported.
PTNS efficacy is studied by several groups. In 1998, Payne published on a statistically significant
improvement in 98 patients with frequency, incontinence and pelvic pain [38]. Van Balken et al.
reported a success rate of 60% for urge urinary incontinence, defined as the wish of the patient
to continue treatment after an initial 12-week treatment period. A decrease in leaking episodes of
63% was observed, compared to 24% for those patients who did not respond successful. Seven
out of 12 patients with non-obstructive retention were considered successful while no significant
urodynamic changes could be observed for this group [39].
15
Transcutaneous Electrical Nerve Stimulation (TENS)
In TENS, carbon-rubber electrodes are placed on the skin and an external stimulator is connec-
ted. Intensity, pulse rate and pulse frequency of the stimulation vary in literature. Generally, two
methods of TENS are used and published in literature, one providing direct S2 or S3 dermatome
stimulation, the other placed suprapubically. First publication on this neuromodulation technique
was by Fall et al. in 1980. In this study, suprapubical transcutaneous electrical nerve stimulation
was used in interstitial cystitis patients with OAB symptoms and pain. Especially, this method was
shown to be effective in relieving pain and decreasing frequency [40]. More recent studies on
suprapubical TENS reported an improvement in voiding pattern of 26 to 73% in patients with
non-neurogenic voiding dysfunctions [41,42]. By placement of the electrodes over S2 and S3
dermatomes, a better clinical outcome was expected. Reported efficacy however was low and not
favourable over anticholinergic drug therapy [43]. Promising results with sacral dermatomes TENS
were noted by Walsh et al. Urgency improved in 60% while daytime voiding frequency even
improved by 76% [44]. Unfortunately, if stimulation is stopped, symptoms return almost im-
mediately. Although stimulation is given at maximum tolerable intensity, the threshold for proper
electrical stimulation of the nerves involved might not be reached by TENS. Unfortunately, this
promising non-invasive technique did not show enough clinical outcome for a wide spread use in
patients with non-neurogenic voiding dysfunctions. Side events seen in 1/3 of treated patients,
are mainly local skin irritation at the site of the carbon-rubber electrodes.
Functional Electro Stimulation (FES)
Different minimally invasive techniques for neuromodulation have been tested, including various
direct and indirect percutaneous, vaginal and anal modalities.
Transvaginal stimulation is not well accepted by most patients. Disadvantages include the long
period of treatment time and stimulation at high intensity, not easily tolerated by women with
normal sensation in the pelvic region. Cure rates vary between 22 and 49% while an improve-
ment in outcome of 81% is reported [45,46].
The use of anal electrical stimulation did not find broad acceptance. Main reason for this is the
physical and psychological discomfort, experienced by the patients. With newer more comfor-
table stimulation techniques, publications on this topic are rare nowadays. Studies published in
the 70’s and 80’s often use both vaginal and anal stimulation. Improvement rates up to 100%
are mentioned [47], but the average outcome is an improvement in symptoms of approximately
50% [48].
16
Introduction
Functional Magnetic Stimulation (FMS) or Extracorporeal Magnetic Innervation
therapy (ExMI)
Announced as a promising non-invasive technique some years ago, the ‘magnetic chair’ is not
widely used in urologic daily practice nowadays. Main reason for this is the poor reported success
ratio and relatively high costs of this new technique. Magnetic induction means that a current will
flow in response to a changing magnetic field. FMS induces a controlled depolarization of adja-
cent nerves and subsequent muscle contraction Hypothesis for its mode of action may be ‘pelvic
floor re-education’ by stimulation of the pelvis. By creating a strong magnetic field, nerves and
muscles are stimulated, leading to contractions of all pelvic muscles.
Several studies show different clinical outcome. It has to be stated that a wide variety of patients,
with various refractory micturition disorders, are treated with this technique. In 74 patients with
complaints of urge urinary incontinence, urgency/frequency, stress incontinence, mixed inconti-
nence and defecation problems, no change in pelvic floor function was seen [6]. According to
Chandi et al. FMS for the treatment of urinary incontinence in women is a safe, non-invasive and
painless treatment, and effective and easy to administer in an outpatient setting. In 58% of the
patients an objective (>50%) improvement of incontinence was observed, 71% of the treated
patients noticed a subjective improvement. Filling cystometry parameters post treatment did not
show statistically significant changes compared to the data recorded prior to treatment [49]. A
significant increase in urodynamic parameters maximum intraurethral pressure and maximum
urethral closure pressure is seen during and after FMS [50]. A significant reduction in urinary in-
continence, measured by median number of pads, detrusor overactivity on cystometry and num-
ber of leakages, is reported by Galloway et al. [51]. Groenendijk et al. demonstrated significant
urodynamic changes after ExMI; this however could not be correlated with clinical efficacy [52].
17
Conclusions
Most of these neurostimulating or neuromodulating treatment modalities are tested and evalua-
ted in patients with different lower urinary tract symptoms like urge urinary incontinence, stress
incontinence, combined urge- and stress urinary incontinence, symptoms of urgency or frequency
and voiding difficulty. However, reported results are mostly not based on single blinded, placebo
controlled studies. Therefore, it should be kept in mind that the reported results may be flawed
due to patients selection, patients expectations and so on.
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Introduction
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constipation. Br J Surg 2002; 89: 882-888
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outcome of sacral neuromodulation. J Urol 2003: 170: 2323-2326
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504-507
30. Dasgurpta R, Critchley HD, Fowler CJ. Changes in brain activity following sacral neuromodulation for urinary
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643-646
35. Siegel S, Paskiewicz E, Kirkpatrick C et al. Sacral nerve stimulation in patients with chronic intractable pelvic pain. J Urol
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and oxybutynin in patients with detrusor overactivity. J Urol 2001; 166: 146-149
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Scand J Urol Nephrol 2008 Apr 2: 1-4
20
Introduction
21
22
Bladder and urethra anatomy
Improved knowledge of the female lower urinary tract is essential for a better understanding of
pathophysiology of this tract. However, several problems still remain. Correlations between uro-
dynamic recordings and clinical observations remain insolvent, as we do not always know how to
interpret the recorded findings. Therefore, anatomical understanding is of importance.
Bladder
The bladder consists of an outer adventitial layer of connective tissue, a smooth muscle layer and
an inner layer of mucous membrane. A large complex meshwork of bundles of smooth muscle
cells forms the muscular coat of the bladder; this structure is mostly known as the detrusor mus-
cle. Longitudinally orientated muscle bundles tend to predominate on the inner and outer aspects
of the detrusor muscle coat [1]. Orientation of the smooth muscle detrusor bundles in a random
fashion and at all depths of the bladder wall without an arrangement as discrete layers is reported
by Elbadawi. Furthermore, there is no evidence for gross anatomic differences in males and fema-
les [2]. From a functional point of view, the detrusor comprises a single unit of interlaying smooth
muscle fibres. On contraction, this will cause a reduction in all dimensions of the bladder lumen.
The smooth muscle of the trigone consists of two distinct layers, often called deep and superficial
trigonal muscles. The deep layer merges into the posteroinferior portion of the detrusor muscle.
The superficial trigonal muscle is composed of relatively small diameter muscle bundles that are
morphologically distinct from the detrusor muscle. Proximally, this layer is continuous with the
urethral wall and distally with the smooth muscle of the proximal urethra [3].
Urethra
The mature female urethra has a length of 3 to 4 centimetre. The female urethra consists of an
inner mucosal lining, continuous with the urothelium of the urinary bladder. Two layers of muscle
bundles can be identified in the female urethra; an inner layer of smooth muscle fibres, and an
outer layer of circularly arranged straited muscle fibres, the rhabdosphincter [3]. A thick inner
sheet of longitudinal oriented fibres and a thin outer layer of circular fibres can be distinguished
in the urethral smooth muscle layer. A spiral orientation of the inner circular smooth muscle layer
was noticed by von Hayek [4]. Proximally, the urethral smooth muscles are continuous with the
muscle bundles of the bladder neck. Distally, urethral smooth muscle fibres terminate in the sub-
cutaneous tissue surrounding the external urethral meatus.
Anatomical studies have shown that the female urethra is a much more sophisticated system than
was previously thought. In 1979, Huisman published his study on morfology of the female ure-
thra [5]. This study suggests that the longitudinal muscular layer of the detrusor muscle does not
extend into the dorsal wall of the urethra. Other studies however concluded that the longitudinal
muscular layer of the urethra is formed by extension of the inner detrusor muscle and that the
semi-circular musculature of the urethra is an extension of the outer detrusor muscle layer [6,7].
This hypothesis is supported by others on basis of embryological studies [8].
The rhabdosphincter is circularly oriented with its thickest part in the middle third section of the
Introduction
23
urethra. It is composed of both fast- and slow-twitch myofibers, with the slow-switch fibres
dominating [9]. According to Gosling however, all myofibers of the rhabdosphincter are of the
slow-twitch variety [10]. Rhabdosphincter fibres are therefore able to exert tone upon the ure-
thral lumen over a prolonged period. The urethral sphincter fibres (rhabdosphincter) are anato-
mically separate from the adjacent periurethral straited muscle of the anterior pelvic floor. In the
third middle section, the straited muscle fibres do completely surround the urethra [1]. Cranially,
rhabdosphincter fibres extend to the level of the bladder neck while caudally; the rhabdosphincter
is attached to the lateral vaginal wall [11].
Innervation of urethra and bladder
After years of extensive anatomical studies, even nowadays there is still debate on the innervation
of the human pelvic floor. Only few anatomical studies were performed. Even a straightforward
approach to determine the origin of a peripheral nerve, leads to a variety of conclusions. Especi-
ally, this is true for the pudendal nerve, the pelvic plexus and for the innervation of the external
urethral sphincter [12]. All these structures are of major importance for pelvic floor function and
control. For optimal control on pelvic floor function and micturition several organs and systems,
from ‘top’ (brain) to ‘bottom’ (bladder and urethra), have to cooperate in a strict and decent way
to ensure normal function of the lower urinary tract, including the autonomic nervous system
(sympatic and parasympatic nerves) and somatic nervous system. Striated musculature of the
pelvic floor, including the urethra, is innervated by the somatic pudendal nerve.
Brain
Cerebellum, basal ganglia, limbic system, thalamus and hypothalamus are all involved in the
control of micturition. The brain stem controls external urethral sphincter and detrusor tone [13].
Stimulation of the M-region in the dorsolateral pons, also called pontine micturition center or
Barrington’s nucleus [14] produce detrusor contraction while bilateral destruction leads to chronic
urinary retention [15]. Located more laterally in the dorsolateral pontine tegmentum is an area
called the L-region. This area sends fibres to the nucleus of Onuf in the sacral cord, and is involved
in motor innervation of the pelvic floor, including anal and external urethral sphincters. Electrical
stimulation of the L-region leads to contraction of pelvic floor and urethral sphincter [14], bilateral
lesions produce ‘urge’ urinary incontinence [15]. The M-region can be considered as micturition
control center while the L-region is in control of storage of urine. Afferents in the pelvic nerves
send sensory information with regard to bladder filling to sensory neurons in caudal lumbar and
sacral spinal cord. This information enters the Peri Aqueductal Gray (PAG) that stimulates the M-
region. Micturition starts by inhibition of the urethral sphincter tone and activation of the detrusor
muscle by sacral parasympatic neurons [16].
Spinal Center
The spinal center is the connexion between afferent and efferent pathways. In Onuf’s nucleus in
the anterior horn of S2-S4, somatic efferents are located [17]. Th11-L2 in the spinal cord is the
location of the sympatic neurons, parasympatic neurons are located in S2-S4 [18].
24
Innervation of bladder and urethra
Parasympatic and sympatic afferent nerves of stimuli from the bladder wall proceed towards
the spinal cord by the pelvic nerve, consisting of small myelinated A-δ and unmyelinated C-
fibres [19]. A-δ fibres detect bladder distension, C-fibres transfer bladder sensations like pain and
temperature to the myelum. A-α fibres can be activated by sacral nerve stimulation while the
threshold of A-δ and C-fibres is too high to achieve proper stimulating effects. The role of sym-
patic nerve afferents is still under investigation but they probably pass nociceptive information to
the spinal cord.
Sacral nerves mainly consist of neurons originating from the sacral anterior horn. Fine radiculi of
myelinated and unmyelinated axons leave the spinal cord both dorsal and ventral to constitute
radiculi. The ventral radiculi fuse to form the radi and after passing the sacral foramen S1-S4, the
rami enter the pelvic floor. Sympatic branches and efferent parasympatic neurons join these rami.
Sacral nerves also contain afferent neurons, connected to the spinal cord by dorsal rami. Informa-
tion from the pelvic floor, and the bladder including for instance bladder filling, is transferred to
the spinal cord by these afferent neurons. Sacral nerves form the sacral plexus, with both afferent
and efferent nerve fibres [12]. The inner smooth muscle layer, orientated along the length of the
urethra, is parasympatic innervated by the pelvic nerve while the mainly circulary orientated outer
smooth muscle layer is innervated by the sympatic hypogastric nerve. The striated muscle layer
receives its nerve fibres from the somatic branches of S2 and S3.
Both the autonomic nervous system (parasympatic and sympatic nerves), and the somatic ner-
vous system are involved in controlling the lower urinary tract. Knowledge on these pathways is
mainly based on animal studies and so far, consensus has not been established. Innervation and
longitudinal orientation of the majority of the muscle fibres suggest that urethral smooth muscle
in the female may be active during micturition, serving to shorten and widen the urethral lumen
[1].
The external intrinsic urethral sphincter (the straited rhabdosphincter around the membranous
urethra) and external extrinsic urethral sphincter, formed by the musculi levator ani and trans-
versus perinei muscles (pelvic floor), receive their innervation through somatic nerve components
that emanate from S2 and primarily S3 [20].
Function of the lower urinary tract
Both bladder and urethra form a functional unit. The bladder functions as a reservoir while the
urethra is the outlet. There has to be a close relation in working mechanism for proper voiding
behaviour. The outmost layer of the urethra, formed by the straited circular muscle is also known
as straited sphincter or rhabdosphincter. Most important function of this straited muscle is to
achieve increase of urethral pressure during physical stress, thus leading to continence. Almost
70% of the external urethral sphincter pressure derives from neural impulses from the S3 ventral
root (m. levator ani en rhabdosphincter), the other 30% is contributed by S2 (pudendal nerve)
[20]. Pelvic floor muscles are involved in the closing mechanisme of the female urethra. Training
of pelvic floor muscles does diminish genuine stress incontinence.
Introduction
25
From a functional point of view, it is necessary for the pressure in the urinary bladder to exceed
the closing pressure within the urethral lumen during voiding. Normally, a fall in urethral pres-
sure precedes a rise in pressure in the bladder lumen by active contraction of the smooth muscle
detrusor. In case of unvoluntary contraction of the detrusor muscle, the pressure in the lumen of
the urinary bladder may exceed that in the lumen of the urethra, thus resulting in undemand loss
of urine. This complaint of involuntary leakage may be accompanied by or preceded by urgency
and is now defined as urge urinary incontinence [21].
During bladder filling, somatic and sympatic arc reflexes are activated to promote continence
[22]. Tension receptors in the bladder wall transport information concerning bladder filling by the
afferent sympatic pelvic nerve. The efferent limb of the sympatic reflex travels within the nervus
hypogastricus. This results in an increase in urethral smooth muscle tone and relaxation of the
bladder wall [23]. The somatic reflex is conveyed in the pudendal nerve and leads to contraction
of the external striated muscle urethral sphincter. If there is only small filling of the bladder, one
is unconscious of this guarding reflex. If bladder filling increases, the spinal guarding pathway is
transferred to a supraspinal mechanism, the pontine micturition centre, leading to a desire to void.
If this reflex pathway is blocked, i.e. in patients with a complete spinal cord injury, this may lead
to detrusor-sphincter dyssynergie [24]. Activation of this guarding reflexes may well be achieved
by sacral neuromodulation, leading to a larger bladder capacity and increased First Sensation of
Filling, seen in patients who respond well on the therapy [25]. This mechanism may also influence
urethral pressure variations and diminished urethral instability [26].
‘Detrusor overactivity’
Well accepted nowadays is the urodynamic observation of unstable detrusor contractions during
filling cystometry. According to the International Continence Society committee on standardisa-
tion of terminology in 1988, the “unstable detrusor” is “one that is shown objectively to contract,
spontaneously or on provocation, during the filling phase while the patient is attempting to inhibit
micturition” [27]. In 2002, the ICS changed the definitions of detrusor function during filling
cystometry. “Detrusor overactivity” (DO) is now defined as an urodynamic observation charac-
terised by involuntary detrusor contractions during the filling phase that may be spontaneous
or provoked. Idiopathic DO replaces “detrusor instability” when there is no defined cause [21].
The urodynamic finding of DO is recorded on filling cystometry. Filling velocity is mostly 50 ml/
minute, although several groups prefer 25 ml/minute for a more physiologic recording. Diuresis
cystometry is advocated by van Venrooij and may increase the observation of DO [28]. However,
cystometric results should be read with caution since involuntary detrusor contractions can be
missed or provoked. About 30% of anamnestic urge cannot be confirmed on traditional cysto-
metry [29]. Therefore, some investigators advice natural filling of the bladder during an ambulant
urodynamic registration [30]. Although far from standard, ambulant cystometric recordings can
help to explain lower urinary tract symptoms in patients where conventional cystometry did not
show abnormalities [31]. The diagnosis DO may be twice as high compared to traditional cys-
tometry [32]. However, ambulatory urodynamics has some important drawbacks and recordings
should be read with precaution.
26
The importance of urodynamically observed idiopathic DO is still debated. Most important reason
for this is lack of correlation between clinical success of a treatment modality and urodynamic
recordings. Furthermore, DO is found in males and females without any micturition complaints.
Also, in patients with severe lower urinary tract symptoms, often DO cannot be found on cysto-
metry. A rise in detrusor pressure of 15 cm water is mostly considered as sign of an involuntary
detrusor contraction. Other thresholds have been used as well. Several studies tried to correlate
urodynamically observed bladder function with lower urinary tract symptoms [33,34]. No evident
correlations were found in voiding symptoms of several groups of patients compared to their
cystometric recordings. Therefore, the diagnosis of idiopathic DO cannot be made clinically but
is a strictly urodynamic one.
An attempt to define urethral instability based on our experiences
At the urology department of the Leiden University Medical Center, Leiden, The Netherlands, fil-
ling cytometry in females is performed with the MMS UD-2000 (Medical Measurement Systems,
Enschede, the Netherlands) and a Gaeltec CTU/2E/L-4 12F (Gaeltec Ltd, Dunvegan, Isle of Skye,
Scotland) catheter with 3 urethral sensors and 1 bladder sensor. Space between each urethral sen-
sor is 7 mm; distance between bladder pressure sensor and mid urethral pressure sensor is 50 mm.
The mid urethral pressure sensor is positioned at the maximum urethral pressure. Urethral and
detrusor function are monitored, both during filling and voiding. Three urethral sensors are neces-
sary to rule out artefacts due to movements of the catheter in the urethra during filling. Pressure
changes caused by movement of the catheter will give a shift in recorded pressures. Only pressure
changes that occur on all 3 urethral sensors are considered relevant, because these are caused by
pressure changes in the major part of the urethra itself. We define URI when urethral pressure
variations of more than 15 cm water are observed in all three urethral recordings. We have the
impression that classification into ‘minor’ urethral pressure changes (16-30 cm water) and ‘major’
(>31 cm water) may be important for clinical practice. Slow periodical urethral pressure variations
with durations of more than 10 seconds and with low amplitude, are considered as normal. The
impact of presence or absence of DO for defining URI remains controversial in literature. We do
not consider the presence or absence of DO of importance to define URI. Review of the literature
did not reveal clear understanding whether sphincter EMG recording is necessary for diagnosing
URI. Therefore, we do not take EMG recordings into consideration for the diagnosis of URI. Most
studies on urethral pressure variations during filling cystometry use only one urethral sensor. We
measure urethral pressure variations with 3 urethral pressure sensors to rule out artefacts. The use
of only one urethral pressure sensor may give incorrect recordings and result in a false prevalence
for the presence of ‘truly’ URI. In order to achieve optimal localisation of the pressure sensors in
the urethra, at least one sensor has to be positioned at the site of the maximum urethral pres-
sure. In the minority of cases it is impossible, as a result of urethral anatomy, to obtain urethral
registration with all 3 sensors.
Introduction
27
Figure 1 shows the urodynamic recording of both urethral and detrusor behaviour during filling
cystometry. Urethral pressure variations are clearly visible on all three urethral pressure recordings.
Concomitant DO is not present in this female patient with symptoms of an OAB.
Figure 1: Urethral pressure changes are present in all three urethral pressure measurements. The
finding is defined as major URI, exceding an amplitude of more than 30 cm water.
28
Only when urethral pressure variations are seen on all three urethral pressure recordings, we
define the observation as URI. In this patient therefore, with urethral pressure changes only in
the proximal and mid urethral sensor, the observation is not defined as URI. If only one urethral
pressure sensor would have been used in the same patient, the observation might well be named
URI (figure 2).
A clear drop in urethral pressure together with a non-physiological early FSF at 60 ml is demon-
strated seen in figure 3. With continuing filling, following FSF (a sensory parameter indicated
by the patient), more pronounced URI is observed. In this patient, DO is also present. Figure 3
illustrates clearly that drops in urethral pressure are synchronic with rises in detrusor pressure. In
figure 4, the FSF and a drop in urethral pressure is observed, together with an involuntary rise in
detrusor pressure, indicating DO. During the filling phase further on, urethral pressure variations
are seen without concomitant DO.
Introduction
Figure 2: Urethral pressure variations are only seen in 2 urethral recordings. This observation is
not defined as URI.
29
Figure 3: A pathological low First Sensation of Filling is seen at the start of major urethral pressure
changes. In this patient detrusor overactivity is also present throughout the filling phase.
Figure 4: In figure 4, the First Sensation of Filling and a drop in urethral pressure is observed at
15 ml of bladderfilling, together with an involuntary rise in detrusor pressure, indicating detrusor
overactivity. During the filling phase urethral pressure changes are seen without concomitant
detrusor overactivity.
30
Introduction
References
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22. de Groat WC, Steers WD. Autonomic regulations of the urinary bladder and sexual organs. In: Loewy AD, Spyer KM,
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25. Latini JM, Alipour M, Kreder Jr KJ. Efficacy of sacral neuromodulation for symptomatic treatment of refractory urinary
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31
26. Groenendijk PM, Heesakkers JPFA, Lycklama à Nijeholt AAB. Urethral instability and Sacral Nerve Stimulation: a better
parameter to predict the efficacy? J Urol 2007; 178: 568-572
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Scan J Urol Nephrol 1988; Suppl 114: 5-19
28. van Venrooij GE, Boon TA. Extensive urodynamic investigation: interaction among diuresis, detrusor instability, urethral
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Chapter 1
1
1
Urethral Instability: current
pathophysiological concept
P.M. Groenendijk, J.P.F.A. Heesakkers, T.J. Ouwerkerk
and A.A.B. Lycklama à Nijeholt
Accepted for publication in Urologia Internationalis
Summary
The role of urethral pressure variations during filling cystometry is seldom assessed as a poten-
tial cause of voiding dysfunction and/or storage disorders. In this atricle, we review on current
research in the field of urethral pressure variations and discuss the way of determining urethral
pressure variations, the value for clinical practice and hypothesize the origin of urethral pressure
variations. The observation and recognition of urethral pressure variations (urethral instability)
could be valuable in the diagnosis and evaluation of therapy in functional lower urinary tract
disorders.
1 Urethral Instability: current pathophysiological concept
34
35
Introduction
The role of urodynamics in diagnosis as well as evaluation of treatment for storage disorders is
scrutinized by many involved in this area. Correlations between traditional urodynamic outcome
parameters and outcome of different treatment modalities remain poor. This is even true for the
well-accepted and defined observation of rise in detrusor pressure during filling cystometry (i.e.
detrusor overactivity). Filling cystometry is performed to register the impact of natural bladder
filling on behaviour of the lower urinary tract. In this process both bladder and urethral behaviour
are involved. So far only bladder behaviour during filling cystometry has been studied extensi-
vely. However, urethral function may be even more important in influencing bladder function
than vice versa, if one takes the concept of the guarding reflex into account. The urethral external
sphincter appears to serve as the ‘on-off’ switch for voiding, relaxation of the external urethral sp-
hincter (releaving the guarding reflex) initiates micturition, whereas contraction suppresses blad-
der contractility [1]. Consequently it makes sense to measure and register detrusor and urethral
function during filling and voiding, in an as much as possible physiological setting. It is known and
accepted that for optimal bladder function as a storage organ a stable, non-fluctuating detrusor
pressure is of eminent importance. Logically, this should also hold true for the urethra. In this
respect, urethral instability (URI) remains a controversial item and the debate on the importance
and clinical relevance of observed urethral pressure variations during filling cystometry is still on.
These urethral pressure variations are considered as physiological or artificial, or even irrelevant
and therefore ignored by most authors [2]. The definition and the term detrusor overactivity (DO)
have been changed several times over the past years by the sub-committee on terminology of the
International Continence Society (ICS). However, despite an increased interest in the relevance of
urethral pressure for urgency [3], till now, the ICS has not succeeded in defining the term “ure-
thral instability” although it has attempted in the past [4]. Urethral pressure measurement is still
first and foremost a research tool [5].
We herewith review the literature on the observation of URI, terminology for urethral pressure
changes, association with clinical symptoms, relevance in daily practice, and hypothesize its origin.
Survey on terminology and observations of urethral
pressure fluctuations
‘The unstable urethra’
Although urethral pressure variations during filling cystometry are not frequently routinely dealt
with in clinical practice, the observation of urethral pressure variations during filling cystometry is
studied intensively by several authors. In 1981, the ICS committee on standardisation of termi-
nology defined URI as a condition in which there is an involuntary fall in urethral pressure during
filling, resulting in urinary leakage, in the absence of detrusor activity [6]. In 1988 however, the
ICS did not to redefine URI and stated that further investigations would be necessary to formulate
a proper definition [7]. In 2002, a revision on terminology of lower urinary tract function was
published by the standardisation sub-committee of the ICS [4]. Again, the sub-committee did
not define the term “unstable urethra” by arguing that the clinical significance of decreases in
urethral pressure during filling cystometry is unclear and does not correlate with symptoms. Ac-
cording to the ICS, it is better to give a full description if symptoms are seen in association with a
decrease in urethral pressure during cystometry.
Most of the literature dealing with the phenomenon of URI was published decades ago. Study of
the literature makes it evident that different definitions for the entity of URI are used by various
authors. Furthermore, the clinical implication of urethral pressure variations during filling cysto-
metry for explaining lower urinary tract symptoms is not consistent.
Clinical implications of the ‘Unstable urethra’
Various descriptions are used for urethral pressure variations during filling cystometry. In order to
correlate urodynamic findings with clinical significant findings, McGuire reported on 11 patients
with incontinence and large post void residual volumes [8]. Complete urethral relaxation, associa-
ted with perineal floor electrical silence and an observed decrease in urethral closing pressure was
found in this group of patients. McGuire suggested that in this group of patients, urethral behavi-
our is compatible with that seen in reflex micturition, in spite of the lack of bladder contraction.
Turner Warwick did notice voiding without any detectable detrusor pressure rise in a few females,
apparently by reflex relaxation of their urethral sphincter mechanisms. Conceptually, disturbance
of this reflex may result in inappropriate relaxation and “urethral instability” may be an occasional
cause of incontinence in females [9].
Pressure based definitions of URI.
Most authors consider momentary urethral pressure variations, exceeding an amplitude of 15 cm
water, as an abnormal finding [10-17]. Others defined an unstable urethra as an urethral pres-
sure decrease of at least 20 cm water unrelated to a detrusor contraction, an increase of intra-
abdominal pressure, or pulsations of the vascular bed [18,19]. Plevnic and Janez used a lower
cut-off value and defined pressure variations of > 10 cm water as URI [20]. Wise et al. advocated
the definition of URI as a spontaneous fall in maximum urethral pressure of one-third or more, in
the absence of detrusor activity, over a 2-minute period [21].
1 Urethral Instability: current pathophysiological concept
36
Pathological urethral pressure variations should be distinguished from physiological urethral pres-
sure variations according to Vereecken. One should focus on the following criteria: amplitude,
duration, sphincteric EMG, repetition throughout the filling phase and loss of urine. A pronounced
amplitude of at least one-third of the maximum urethral closure pressure (usually >25 cm water),
a short duration (1-5 sec), a simultaneous inhibition of EMG activity in urethral and/or anal sp-
hincter, and the occurrence of the phenomena starting at the beginning of bladder filling indicates
pathological urethral pressure variations. [22].
McLennan et al. defined URI by recording resting urethral pressure for 2-minutes after 50 ml
bladder filling and, later on, during filling cystometry. Urethral pressure variations were calculated
as the ratio of ΔMUP (difference between highest and lowest maximal urethral pressure), divided
by the highest MUP. URI was defined if a ratio >33% was documented during the 2-minute res-
ting period. Using this definition, URI occurred in 12.6% whereas if in the same group the defini-
tion of pressure changes of > 15cm water was used, the prevalence increased to 31% [23]. Four
patterns of urethral pressure variations during a 2-minute resting cystometry (with 50 ml bladder
filling) as well as during filling cystometry were observed by McLennan et al. They observed; a)
resting pressure variations without detrusor activity; b) resting URI as well as DO during filling;
c) no resting URI but detrusor contraction preceded by a fall in urethral pressure (so called type II
DO); d) resting URI and type II DO. Because it is well-known than with the exception of patients
with detrusor-sphincter dyssynergia, the urethra always relaxes prior to a detrusor contraction,
urethral abnormality (eg URI) may be the primary disorder in patients with complaints of OAB. It
was stated that differentiation between subtypes of URI may be important for directing therapy.
Clinical significance of urethral pressure variations
The observation of urethral pressure changes during filling cystometry may indicate functional or
morphological changes in or around the urethra. Vereecken and Das showed URI in 14.4% of
173 patients with a history of incontinence [13]. In 52% of these patients, no concomitant DO
was present. Urethral pressure variations over 35 cm water provoked urgency. Weil et al. found
URI associated with DO in 27% of 427 patients [14]. Most investigators suggest a link between
URI and DO. A close association between URI and DO was also reported by Clarke. In patients
with URI, DO was present in 64%. In 608 patients, a prevalence of URI of 6.4% was found.
URI appeared to cause urgency/frequency and seemed to be a negative prognostic factor that
increased the risk of urinary incontinence [16]. In contrast to the believed association of URI
and pathology, Kulseng-Hansen found urethral pressure variations of more than 20 cm water in
more than 50% of normal females [19]. Hence, other than in previous definitions, he considered
urethral pressure variations of more than 10, 15 or 20 cm water not as pathologic anymore. The
urethral pressure variation (MUP) was calculated as the difference between the highest (MUPH)
and the lowest (MUPL) maximum urethral pressure observed during one minute of urodynamic
recording. In his study however, the maximum urethral pressure in patients during filling cysto-
metry was significantly lower than in the control group of normal females [19]. This suggests
differences in studied groups. Venema and Kramer studied 71 female patients with complaints of
urge, stress or mixed incontinence. URI was seen in 66%. DO was reported to occur in 24% of
all patients [10].
37
1 Urethral Instability: current pathophysiological concept
38
Symptoms related to urethral instability
The ICS does not define urethral pressure changes during filling cystometry since the significance
of the fluctuations and the term ‘unstable urethra’ lack clearity. It is difficult to fully interpret the
variations in urethral pressure during filling cystometry, but they should not be ignored. Although
studies are few, often there is a focus on the role of urethral pressure variations or URI in sensory
storage symptoms [24]. It is getting more and more clear that sensations, e.g. urgency, noticed
by the patient during filling cystometry, without changes in the traditional urodynamic parame-
ters, are important in understanding symptoms. URI might explain symptoms related to sensory
symptoms. URI, defined as pressure changes >15 cm water and occurring in the absence of any
bladder event, was reported to be a common condition in enuretic male and female patients.
Combined URI and DO was seen in 35%, isolated URI in 45%, and isolated DO in 10% of these
patients [12]. URI is a common condition in enuretic patients. In this respect, URI might play a
causal role in enuresis, as isolated DO is present in only the minority of these patients. Further-
more, a significant drop in urethral pressure can trigger detrusor contraction [12]. In 427 female
patients with lower urinary tract symptoms, urethral pressure variations of >15 cm water that
were not related to an increase in intra-abdominal pressure or to vascular pulsations, were found
in 16.4%. URI was related to frequency, nocturia, urgency, and a history of urethral syndrome
(2 or more symptoms like dysuria, frequency or urgency). However, DO was stronger associated
with urge urinary incontinence, nocturia and urgency than URI [14]. According to Vereecken
pressure variations, exceeding 35 cm water may provoke urgency [13]. On the contrary, Wise et
al. reported no difference between patients with or without URI in terms of prevalence or severity
of urgency/frequency, nocturia or urge incontinence. Combined URI and DO was significantly
more common in women presenting with stress incontinence [21]. Venema and Kramer already
stated that URI is an expression of sensory urge [10]. URI may also be an important element in
dysfunctional voiding. URI may cause the urge sensation during filling and the staccato voiding
phase in patients with dysfunctional voiding [25].
39
Discussion
Filling cystometry is most often used as a representative of natural bladder filling. Data recorded
by filling cystometry give an impression of the storage phase of the micturion cycle. Throughout
the day, the bladder is filled with urine and emptied during voiding. Unfortunately, the co-opera-
tion between bladder and urethra may be affected and lead to storage disorders. For this reason,
both bladder and urethral pressure recording should be done during filling cystometry when
evaluating storage disorders.
Various descriptions have been used in the past to define the entity of urethral pressure changes
during filling cystometry. There is still debate on whether certain urethral pressure variations
should be regarded as physiological or pathophysiological (i.e. URI). The prevalence of URI in
literature varies, due to the use of different definitions, together with inappropriate urethral pres-
sure recordings. To rule out artefacts, like movement or incorrect position of the urethral pressure
sensor, the use of more than one urethral pressure sensor is advocated. Only in this way, correct
urethral pressure recordings are achieved and results can be compared.
Urethral pressure is defined as the fluid pressure needed to just open a closed (collapsed) urethra
[26]. Due to lack of general agreement on the relevance of urethral pressure measurements,
the use of urethral pressure measurement in routinely performed filling cystometry is limited
[5]. The significance for clinical practice of urethral pressure variations, often defined as URI, is
still not fully understood and thus often neglected. Moreover urethral pressure variations du-
ring filling cystometry are considered as an artefact and therefore of no relevance for explaining
patients symptoms by some investigators [2]. Slow wave, rhythmic urethral pressure variations
have been shown in healthy volunteers and may be an aspect of normal urethral physiology that
could contribute to continence and urinary tract infection prevention, and need to be considered
as pathophysiological [27]. McLennan et al. published on the significance of urethral pressure
measurements during filling cystometry. When accepting certain urethral pressure variations as
pathological (URI), differentiation in URI subtypes might be important for directing therapy. It has
to be stated that in this study, as well as in many other studies, only 1 urethral pressure sensor
was used together with one sensor measuring detrusor pressure [23]. To rule out artefacts, like
movement of the pressure sensor during urodynamic testing, the use of more than one urethral
sensor is to be preferred. Only in this way, more accurate recordings are achieved.
The prevalence of urethral pressure variations and the clinical significance is matter of discus-
sion. Review from the literature shows different prevalence’s in different studies with different
definitions for ‘urethral instability’. One might wonder if all authors are discussing the same topic.
Furthermore, what is the explanation for the reported urethral pressure variations and how should
these pressure variations be interpreted?
Schaefer et al. noticed urethral pressure changes to be important for the sensation of urgency.
The sensation of urgency was better synchronized with decline in urethral pressure than with
subsequent detrusor activity. Current concepts of OAB, DO and urge urinary incontinence, ori-
ginate from traditional cystometry, without measuring urethral pressure variations, and need to
be reconsidered [3].
It is postulated that urethral pressure variations can be found in females with and without lower
urinary tract complaints. A prevalence of 7-14% is found in females without voiding complaints
[24]. The prevalence of URI in patients with lower urinary tract symptoms is considerably higher
(up to 84%) and depends on patient selection, the technique used to measure urethral pres-
sure changes, and interpretation of these pressure variations. URI is demonstrated significantly
more often in patients compared to healthy volunteers and therefore is an important topic in
describing storage symptoms. Urethral pressure variations are seen in patients with urge urinary
incontinence (both with and without DO) more often than in patients with complaints of stress
incontinence. URI is more related to symptoms of an OAB and is relevant to understand bladder
storage dysfunction.
Morphological changes in the urethra are considered to be related to the occurrence of urethral
pressure variations during filling cystometry. In fact, a significant shorter functional urethral length
was present in women with unstable urethra behaviour [23]. Chaliha et al. demonstrated a sig-
nificant decrease in functional urethral length in women with DO. It was suggested that urethral
function was affected by the presence of DO. She suggested that for a correct assessment of
urethral function, DO has to be treated first [28]. Earlier reports also found morphological chan-
ges of the urethra in patients with DO compared to those with normal urodynamic testings. A
smaller total urethral diameter and circumference as a result of loss of smooth muscle thickness
was found. This could result in a decrease in urethral resistance, enabling urine to enter the blad-
der neck, initiating detrusor contraction. It however remains unclear whether urethral function
differences are the result of DO rather than its cause [29]. By observing both bladder and urethral
pressure we often observe that the changes in urethral pressure are (just) prior to the changes
in bladder pressure: the concept that urethral function is more leading bladder function than the
other way around, is supported by the concept of the guarding reflex [1].
In therapy evaluation like in SNM, it was evident that the delay in FSF was correlated with the
success of the treatment [30]. In our data on SNM therapy, abolishment of URI was noticed in
successful patients after SNM [31]. URI is most likely a better parameter to predict the outcome
of SNM than DO. In this study, URI was defined when pressure changes of more than 15 cm
water in all 3 urethral pressure sensors were observed with the mid urethral sensor positioned at
the maximum urethral pressure. Furthermore, in patients successfully treated with SNM because
of refractory complaints of an OAB, we demonstrated an instant recurrence of both DO and
URI after a bilateral pudendal blockage with lignocaine whereas these observations were absent
before the pudendal blockage [32]. This observation draws attention on the importance of the
pudendal nerve in understanding the origin of both URI and DO. In our opinion, FSF is often de-
rived from observed urethral pressure changes. In accordance with the criteria of Vereecken [22]
we find a pathological early FSF in the majority of patients with URI. A drop in urethral pressure is
often present at the FSF. Therefore, we believe that the importance of URI as a cause of sensory
urgency and therefore as a ‘sensory’ marker is underestimated in literature.
The origin of URI is still not fully understood. Kenton et al. observed no increase in urethral pres-
1 Urethral Instability: current pathophysiological concept
40
sure during filling cystometry and suggested that urethral pressure changes do not reflect the
integrity of the striated urethral sphincter. Urethral pressure measurements, performed intralumi-
nally, reflect to all anatomical components surrounding the lumen of the urethra. It is possible that
these measurements are not sensitive enough to detect changes in the striated rhabdosphincter
[33]. In contrast, others observed that urethral pressure changes were found to be caused by
activity of the urethral sphincter or pelvic floor muscles. Urethral muscle contractions are of the
fast type whereas pelvic floor activity can be either slow or fast, resulting in slow or fast urethral
pressure fluctuations [34].
The neurophysiologic explanation of URI is unclear. URI may be caused by diminished sympatic
influence or by increased parasympatic activity. More in general, urethral pressure variations are
considered as a pudendal nerve reflex mechanism, and as an expression of abnormal reflex acti-
vity in sympatical and/or parasympatical nerves.
We experienced that SNM therapy is capable in abolishing URI [31]. By stimulation of sacral ner-
ves at the level of the sacral foramen, both afferents and efferents are activated. Only A-α fibers
are stimulated, the threshold for stimulation of C-fibers and A-δ fibers is too high. It is generally
accepted that the modulating effect of SNM is generated by stimulation of the afferent nerves.
Somatic and sensory fibers from the pudendal nerve and tibial nerve converge at S3. Stimulation
of the afferent pudendal nerve branches of the dorsal penile and clitoral nerve leads to inhibition
of detrusor activity. This is also seen by stimulation of the afferent pelvic nerve fibers from bladder,
urethra and anorectal region [35]. These afferent pudendal and pelvic fibers enter the spinal cord
via the dorsal rami. It seems that these nerves are responsible for the afferent signal transmission
of SNM. A hypothesis for the inhibition of detrusor activity generated by stimulation of the af-
ferent sacral nerves is a diminished parasympatic motoric response.
If URI is due to increased parasympatic activity and SNM results in decreased parasympatic activi-
ty, then this does explain our observations of decreased URI in successful treated SNM patients.
41
Conclusions
The presence of urethral pressure variations during filling cystometry is well documented by vari-
ous investigators. Unfortunately, this did not lead to a better understanding of the phenomenon
so far. Different definitions for different types of pressure variations patterns have been reported.
For a good and reliable recording of urethral pressure changes, the use of more than one urethral
pressure sensor is advocated.
Urethral pressure variations particularly cause sensory urge complaints. Reflexes like the guarding
reflex illustrate the “leading” role of urethral function. Morpholgical changes within the urethra
together with sympatic activity might expain urethral pressure fluctuations.
Too often, investigations failed to illustrate treatment results (e.g. medical treatment) by only
observing bladder function and/or DO. Given the growing acceptance of the relevance of sen-
sory parameters, the often disappointing outcomes of bladder-function-only related studies, we
recommend recording of urethral pressure variations, with more than one pressure sensor, in the
diagnosis and evaluation of treatment modalities in patients with complaints of an OAB. In the
future, urethal pressure variations should be recorded with a reliable and standarized method.
1 Urethral Instability: current pathophysiological concept
42
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19. Kulseng-Hansen S. Prevalence and pattern of unstable urethral pressure in one hundred seventy-four gynecologic
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20. Plevnik S, Janez J. Urethral pressure variations. Urology 1983; 21: 207-209
21. Wise BG, Cardozo LD, Cutner A, Benness CJ and Burton G. Prevalence and significance of urethral instability in women
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23. McLennan MT, Melick C, Bent AE. Urethral instability: clinical and urodynamic characteristics. Neurourol Urodyn 2001;
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Phys Med Biol 1985; 30: 951-963
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1 Urethral Instability: current pathophysiological concept
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45
Chapter 2
2
2
Five-year follow-up after
Sacral Neuromodulation
(SNM): single center
experience
P.M. Groenendijk, A.A.B. Lycklama à Nijeholt, T.J. Ouwerkerk and U. van den Hombergh
Neuromodulation 2007; 10(4): 293-298
Abstract
Objective: We studied long term clinical efficacy of sacral neuromodulation (SNM) therapy in
patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty
(VD), together with urodynamic data at baseline and six months post implant.
Materials and Methods: Twenty-two patients were implanted with a neurostimulator after a
positive response to a Percutaneous Nerve Evaluation test defined as a greater than 50% impro-
vement in symptoms.
Results: At five-year follow-up, for 10 out of 15 UI patients the number of incontinent episodes
and pad usage per day decreased significantly. Two of five UF patients were successfully treated
with SNM with the number of daily voids for all UF patients decreasing from 25 to 19 and aver-
age voided volume increased from 98 to 212 ml. One of the two VD patients was able to void
to completion. Mean first sensation of filling (FSF) at the six months urodynamic investigation
for the UI and UF patients increased from 78 to 241 ml and 141 to 232 ml respectively, and the
maximum bladder capacity increased from 292 to 352 ml and 223 to 318 ml respectively. Five of
22 patients underwent device explant and one patient still has an inactive stimulator implanted.
Conclusion: SNM is an effective treatment modality that offers sustained clinical benefit in the
majority of patients with refractory urgency incontinence, urgency/frequency and voiding dif-
ficulty that do not respond to other, more conservative therapies.
2 Five-year follow-up after Sacral Neuromodulation (SNM)
48
49
Introduction
For voiding disorders characterized by symptoms of urgency incontinence, urgency/frequency
and voiding difficulty, a wide variety of initial treatment modalities are available including beha-
voural techniques such as pelvic floor muscle exercises and biofeedback, pharmacotherapeutic
options that include anticholinergic and antispasmodic agents, and for complete and incomplete
retention, clean intermittent (self) catheterization. However, many of these disorders cannot be
treated successfully with these conservative treatment modalities [1,2] leaving various types of
invasive surgeries as “last resort” options. For patients with refractory voiding complaints who
do not respond favorably to conservative therapies, sacral neuromodulation therapies may be a
valuable option before more invasive and irreversible surgical approaches are applied.
Sacral Neuromodulation (SNM) is widely accepted as a novel treatment modality for a variety
of different voiding disorders. In 1988 Tanagho and Schmidt first reported on this therapy [3].
Since then, more than 30.000 patients worldwide have received permanent neurostimulators.
Cure rates from 60 to 100% have been reported in the literature for patients with refractory voi-
ding dysfunctions that include urgency incontinence (UI), urgency/frequency (UF) and voiding
difficulty (VD) due to chronic non-obstructive retention [4-7]. Although the exact mechanism/
mechanisms of action for SNM is still not fully understood, two hypotheses have been reported.
Neuromodulation may enhance urethral and pelvic floor tone, inhibiting detrusor overactivity
thus restoring normal bladder function [8-11], or it may affect bladder function via afferent nerve
fibers [12].
At the Leiden University Medical Center, Leiden, The Netherlands, patients with symptoms
of urgency incontinence, urgency/frequency and voiding difficulty (incomplete and complete
retention) were enrolled in a prospective randomized study evaluating the clinical efficacy and
safety of SNM. Urodynamic evaluation was a secondary study end point that was performed
at baseline and six-months post implant and not used to define success but to monitor possible
changes in bladder and urethral behaviour during stimulation. This present study was part of a
large multicenter trial (Medtronic MDT-103) and we now report on the long-term efficacy and
safety results of patients included in our hospital together with the urodynamic changes at six
months post implant.
Materials and Methods
Patients with voiding dysfunction symptoms refractory to standard physical and medical the-
rapy were included in a large multicenter trial (Medtronic MDT-103). Baseline screening included
physical examination, detailed medical history, completion of a voiding diary, urodynamic testing
and quality of life questionnaires (SF-36 and BDI). A Percutaneous Nerve Evaluation (PNE) test
with a temporary lead (model 041830 Medtronic Inc., Minneapolis, USA) was performed after
obtaining written informed consent. A permanent neurostimulator model 3023 (Medtronic Inc.,
Minneapolis, USA) was implanted in patients responding with an improvement of more than
50% in their main symptoms during the PNE test. The technique used in all patients was an open
transforaminal surgical technique with non-tined leads, Medtronic #3080 (Medtronic Inc, Min-
neapolis, Minnesota, USA) with a fixed anchor, anchored to the periosteum. The 3080 lead has 4
equal length electrodes, equally spaced. All implants were performed unilaterally after completion
of a positive PNE (i.e., no staged approach). Unipolar stimulation was used where the implanted
neuropulse generator was positive and one of the four electrodes was negative. Parameters were
evaluated every six months during regular follow-up and were changed only in case of lack of
efficacy or adverse events.
Urodynamic evaluation was performed at baseline and at six months after implant and included
simple uroflowmetry with residual determination and filling cystometry with a detrusor pres-
sure/flow study. Patients completed a voiding diary at baseline, during and after the PNE test, at
one, three, and six months follow-up and thereafter at every other half-year follow-up visit after
implantation to document voiding habits and symptoms. In addition, patients rated the severity
of their leaking episodes on a scale of 0 to 3 (0=dry, 1=mild, 2= moderate and 3=heavy). In
our hospital, filling cystometry was performed with the MMS UD 2000 (Medical Measurement
Systems, Enschede, the Netherlands) and a Gaeltec CTU/2E/L-4 12F (Gaeltec Ltd, Dunvegan, Isle
of Skye, Scotland) microtip catheter.
Statistics
Comparison of test results was completed using a two-sample Student’s t-test. Results in the
figures are presented as mean ± standard deviation. Statistical results were adjusted according to
the equality of variances and for multiple comparisons of the data.
Results
Twenty-two patients, 21 females and 1 male, were implanted with a permanent neurostimulator
after responding successfully (>50% improvement in main symptoms) to the PNE. Seventeen
patients (77%) succeeded on the first PNE, three patients underwent two test evaluations, while
the remaining two underwent three test evaluations before becoming a candidate for perma-
nent implantation. Reason for this was test lead displacement or some but unsatisfactory results.
Fifteen patients suffered from refractory urgency incontinence (UI), five from urgency/frequency
2 Five-year follow-up after Sacral Neuromodulation (SNM)
50
(UF) and two from voiding difficulty (VD) due to chronic, non-obstructive urinary retention requiring
intermittent self-catheterization. Mean age at study enrolment was 45.7 years (range 31-58) and
mean duration of symptoms was 8.5 years. No significant changes were seen in quality of life in all
patients post implant.
Urgency incontinence (UI)
Twelve out of 15 patients implanted for UI reached their five-year follow-up, one patient was
considered a late failure and two were explanted after 17 and 20 months. One of these explanted
patients died nine months after the explantation due to a non-treatment related cause. One out
of three failure patients with UI had progressive fecal incontinence due to an unknown neurolo-
gical cause and another had a severe progressive psychiatric disorder. These three failure patients
were included in the analysis. Based on voiding diary data, UI patients showed statistically signi-
ficant improvement in their symptom reduction. At five-year follow-up, the number of inconti-
nence episodes per 24 hours decreased from 11.6 to 3.7 (p=0.002) and the number of pads used
per day from 6.9 to 2.5 (p=0.004). The severity of leaking episodes decreased from an average of
2.2 at baseline to 1.9. At five-year follow-up, 10 out of 12 patients (83%) had more than 50%
improvement in symptoms, including two patients who were completely dry.
Urodynamic data, available for 11 UI patients at six months post implant, showed an increase of
mean first sensation of filling from 78 to 241 ml (p=0.0008) corresponding with 30% and 72%
of bladder capacity respectively (Table 1). No significant changes were observed in simple uro-
flowmetry data (Table 2).
51
*Statistical Comparison: paired t-test
Table 1. Water Cystometry: Baseline through 6 months, all implanted Urgency Incontinence patients
Avg. at
Baseline
Avg. at six
months
p-value*
First Sensation of Fullness (FSF)
Bladder Volume (ml)
Maximum Bladder Volume
prior to void (ml)
Detrusor pressure prior to void
(cm H
2
O)
Bladder Volume at FSF
(% of bladder capacity)
78.0 ± 77.4
292.4 ± 105.8
30.0 ± 15.1
240.6 ± 162.9
352.8 ± 180.5
21.5 ± 12.1
0.0008
0.13
0.18
Urodynamic Test Variable
n
11
11
11
30.0 ± 30.2 71.8 ± 29.0 0.0017
11
Urgency/frequency
Three out of 5 patients with UF attended a five-year follow-up visit and two were explanted (one
male patient and one patient with a positive response but postoperative complaints of “swol-
len abdomen”). The treatment was unsuccessful in one patient (who also had progressive fecal
incontinence of unknown etiology, which resulted in urinary and fecal diversion). SNM was suc-
cessful in two patients (67%) at five-year follow-up as measured by average voided volume per
void. According to the voiding diary data, the average voided volume per void increased from 98
ml to 212 ml and the number of voids per 24 hours decreased from 24 to 11.
In all five patients, at the six months urodynamic evaluation, the mean first sensation of filling in-
creased from 141 ml to 232 ml (p=0.18) and maximum bladder capacity increased from 223 ml to
318 ml (Table 3). Simple uroflowmetry did not show significant changes at six months follow-up
(Table 2). Due to the small sample size the results of SNM treatment were not statistically signifi-
cant, even though clear clinical benefit could be demonstrated in two out of the five patients.
2 Five-year follow-up after Sacral Neuromodulation (SNM)
52
Table 2. Simple Uroflowmetry: Baseline versus 6 months for 7 patients with Urgency Incontinence and 2 with
Urgency/Frequency symptoms
Avg. at
Baseline
Avg. at six
months
Peak flow rate (ml/sec)
Mean flow rate (ml/sec)
Total voided volume (ml)
Flow time (sec)
n
7
7
7
7
Urgency Incontinence Urgency/Frequency
16.93 ± 6.34
7.20 ± 4.44
211.43 ± 89.79
6.57 ± 6.53
16.16 ± 9.78
5.74 ± 2.52
192.57 ± 106.54
8.57 ± 4.76
n
2
2
2
2
17.50 ± 7.78
7.50 ± 4.95
133.00 ± 18.38
6.00 ± 1.41
15.00 ± 2.83
5.50 ± 0.71
276.00 ± 90.51
8.00 ± 2.83
Avg. at six
months
Avg. at
Baseline
Voiding difficulty
Five-year follow-up was available for the two voiding difficulty patients. One patient was able to
void to completion without catheterization, while the other had less than 50% improvement in
reduction of the residual volume.
Adverse events/Failures
Since study enrolment, five out of 22 implanted patients (two UI, two UF and one VD) underwent
device explantation. The mean time to device explant was 20 months (range 15-26). Reasons
for device explant were lack of efficacy in two patients and pain at the neuropulse generator site
in two patients. The fifth patient who complained of a “swollen abdomen” during stimulation
which failed to respond to conservative therapies was advised to undergo explantation of the
device despite a good response to SNM treatment. One patient, considered a treatment failure,
still has the inactive neurostimulator in place. Data from all of these patients was included in the
analysis of efficacy. All failure patients (except for the patient with the complaint of “swollen ab-
domen”) underwent revision operations that consisted mainly of repositioning of the electrode.
Dislodgement of the electrode array, rendering it refractory to reprogramming, was found in one
case of lack of efficacy. Electrode repositioning/replacement was required to regain clinical benefit
once again. During the five-year follow-up, five of the 13 successfully treated patients underwent
electrode repositioning because of diminishing results.
53
*Statistical Comparison: paired t-test
Table 3. Water Cystometry: Baseline through 6 months, all implanted Urgency Incontinence patients
Avg. at
Baseline
Avg. at six
months
p-value*
First Sensation of Fullness (FSF)
Bladder Volume (ml)
Maximum Bladder Volume
prior to void (ml)
Detrusor pressure prior to void
(cm H
2
O)
Bladder Volume at FSF
(% of bladder capacity)
142.2 ± 40.8
223.0 ± 64.5
15.2 ± 8.9
231.8 ± 148.0
318.2 ± 121.0
13.2 ± 8.64
0.18
0.11
0.70
Urodynamic Test Variable
n
5
5
5
66.3 ± 20.9 68.3 ± 37.6 0.87
5
Discussion
The present study expands the already available evidence on the long-term efficacy and safety of
SNM for the treatment of refractory UI, urgency/frequency syndromes and non-obstructive urinary
retention [12,13]. Clinical efficacy has been reported to be as high as 100% in different studies,
depending on patient selection, symptom severity and the reported follow-up time. As previously
reported by other investigators, the success rate (more than 50% improvement) in our series de-
creased to approximately 60% at the long-term follow-up of five years. The reason for this is not
fully understood by us since these patients were selected for implantation based on their positive
response to SNM during PNE testing. However, all patients implanted were severely affected by
their urological disorder, which lasted for more than 8.5 years, on average, and for which they had
undergone more than 36 surgical procedures without success. If this therapy had not been offe-
red to this group of patients, many of them would have been considered candidates for bladder
augmentation or urinary diversion, irreversible surgical procedures. In fact, three out of five SNM
treatment failures from this study have already undergone urinary diversion surgery.
It is recognized that one of the challanges of SNM therapy is patient selection. Not all patients with
a successful PNE test that uses temporary electrode, show benefit on implantation of a permanent
neurostimulator. However, the new technique that requires immediate implant of a permanent
tined lead aims to avoid lead migration and allows prolonged patient testing/screening [14]. This
testing is much more reliable and ensures a better positive response rate and less re-operations.
The percentage of patients proceeding to permanent implantation of the INS is almost doubled
when using the tined lead as compared to the temporary PNE test approach [15]. Much research
is being done to find more objective parameters that could predict and improve patient outcomes
[16]. Considering urodynamic changes clinical results are often better than expected. This may
indicate that the urodynamic parameters that we are focused on are not the true parameters to
monitor efficacy or the mode of action of SNM.
In our study, when we excluded the two explanted and the one true-failure patient, four UI pa-
tients (33%) were completely dry and an additional six (50%) had more than 50% improvement
at three year follow-up, when compared to baseline. At five-year follow-up, two (17%) patients
remained dry while another eight (67%) had more than 50% improvement, resulting in a total
success rate of 83%. When we include all failures, the total success rate (>50% improvement), at
five-year follow-up, was 67% (10 out of 15 patients).
The majority of published data on the subject of SNM for urinary disorder reflects only short
term results, while only a limited literature on the long term results demonstrates similar success
rates as we present here from our institution. Shaker and Hassouna cured 44% of refractory UI
patients with SNM; an additional 22% had an average of one leakage episode or less per day.
All 18 patients were treated successfully in this study with an average follow-up of 18.8 months
[17]. Successful treatment was reported in 68% of 44 patients with refractory UI, three-years
post implant by Weil et al. [18]. Bosch and Groen reported a cure rate, defined as more than 90%
2 Five-year follow-up after Sacral Neuromodulation (SNM)
54
improvement in incontinence episodes, in 18 out of 45 patients (40%) with refractory UI with
detrusor overactivity and an additional partial success, defined as 50% to 90% improvement in
pad use and/or incontinence episodes, in 9 (20%), at an average follow-up of 47.1 months [19].
A greater than 50% improvement in presenting symptoms and quality of life for refractory uri-
nary UI is reported by Latini et al. [20]. A significant decrease in pad use and number of leaking
episodes after one-staged or two-staged InterStim Model 3023 (Medtronic Inc., Minneapolis,
USA) implants was seen in 90% of patients. The follow-up for this study was relatively short,
however.
Treatment was successful in two out of five of our UF patients. For these patients, the voiding frequen-
cy had decreased significantly, at five-year follow-up. When we disregard the two explanted failures,
dramatic clinical benefit in the other patients was demonstrated (number of voids decreased from
24 to 11), which is congruent with the data previously reported in the literature [5]. A similar clinical
outcome was noted by van Voskuilen et al. [21]. In their group of 107 patients treated with SNM for
urgency, 63.6% showed a good result. Mean time for follow-up for these patients was 69.8 months.
Our study included only two retention patients of whom one was able to void without clean,
intermittent, self-catherization at five-year post implant. SNM treatment in idiopathic non-ob-
structive chronic urinary retention was reported as successful in all 20 patients studied by Shaker
and Hassouna. Post-void residual urine decreased from 78 to 10% of total urinary output at 15
months follow-up [22]. Another study, performed by Vapnek and Schmidt showed clinical success
in five of seven patients (71%) with non-obstructive urinary retention [23]. Van Voskuilen found
good results in 76.2% of 42 patients treated with implant of a neurostimulator because of non-
obstructive urinary retention [21].
Subjective and/or objective clinical benefit of various treatment modalities for voiding dysfunc-
tions are often not supported by significant urodynamic changes [19,24,25]. To better select
patients who will benefit from SNM we need to understand its mode/modes of action and know
which urodynamic studies correlate with improvement in clinical outcomes. In our study, FSF (first
sensation of filling) appeared to be the most subtle parameter to monitor SNM therapy. Predictors
of success for SNM therapy have been studied intensively. Recently, Cohen et al. reported on
predictors of success for first stage neuromodulation. They concluded that motor response may
be a better indicator than sensory response in predicting a positive outcome during intraoperative
lead placement of a neurostimulator [26]. Groen et al. published on the urodynamic changes
seen after SNM therapy. Using volume independent parameters in women with idiopathic detru-
sor overactivity, no effects on urethral resistance and bladder contraction strength during voiding
were found [27]. For our study in UI patients, we did not discriminate between those with or
without detrusor overactivity. However, it is our impression that SNM is more successful in UI
patients who do not show detrusor overactivity compared to those with detrusor overactivity
(unpublished data).
55
Conclusions
In recent years, new indications for neuromodulation are being investigated and results look
promising [28-34]. To date, SNM is an effective treatment modality that offers sustained clinical
benefit in the long term in the majority of selected patients with refractory UI, UF and VD who
have failed prior treatments [35,36]. Although the numbers are small, the data presented in this
study show that patients with UI seem to benefit the most, when compared to patients with UF
and idiopathic VD. Due to very small sample size, no conclusions can be made concerning our
VD patients data. Patients were selected for permanent implant when an improvement of > 50%
was observed in their main symptoms during PNE test. However, it should be stated that a few
patients, even though successfully trialed with PNE, will have long-term failures.
2 Five-year follow-up after Sacral Neuromodulation (SNM)
56
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13. Janknegt RA, Hassouna MM, Siegel SW et al. Long-Term Effectiveness of Sacral Nerve Stimulation for Refractory Urge
Incontinence. Eur Urol 2001; 39: 101-106
14. Kessler TM, Buchser E, Meyer S, Engeler DS, Al-Khodairy AW, Bersch U et al. Sacral neuromodulation for refractory
lower urinary tract dysfunction: results of a nationwide registry in Switzerland. Eur Urol 2007; 51 :1357-1363
15. Peters KM, Carey JM, Konstandt DB. Sacral neuromodulation for the treatment of refractory interstitial cystitis:
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16. Benson JT. Sacral nerve stimulation results may be improved by electrodiagnostic techniques. Int. Urogynecol J. Pelvic
Floor Dysfunct 2000; 11: 352-357
17. Shaker HS and Hassouna MM. Sacral nerve root neuromodulation: an effective treatment for refractory urge
incontinence. J Urol 1998; 159: 1516-1519
18. Weil EHJ, Ruiz-Cerda JL, Eerdmans PHA, Janknegt RA, Bemelmans BLH and van Kerrebroeck PhEV. Sacral root
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19. Bosch JHLR and Groen J. Sacral nerve neuromodulation in the treatment of patients with refractory motor urge
incontinence: long-term results of a prospective longitudinal study. J Urol 2000; 163: 1219-1222
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20. Latini JM, Alipour M and Kreder Jr KJ. Efficacy of sacral neuromodulation for symptomatic treatment of refractory
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21. van Voskuilen AC, Oerlemans DJ, Weil EH, de Bie RA and van Kerrebroeck PE. Long term results of neuromodulation
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23. Vapnek J and Schmidt RA. Restoration of voiding in chronic urinary retention using the neuroprothesis. World J Urol
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24. Tapp A, Fall M, Norgaard J et al. Tolterodine: a dose titrated, multicenter study of the treatment of the of idiopathic
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25. Zeegers AGM, Kieswetter H, Kramer AEJL et al. Conservative therapy of frequency, urgency, and urge incontinence:
a double blind clinical trial of flavoxate hydrochloride, oxybutinine chloride, emepronium bromide and placebo. World
J Urol 1987; 5: 57
26. Cohen BL, Tunuguntla HSGR and Gousse A. Predictors of success for first stage neuromodulation: motor versus
sensory response. J Urol 2006; 175: 2178-2181
27. Groen J, Bosch JLHR and van Mastrigt R. Sacral neuromodulation in women with idiopathic detrusor overactivity
incontinence: decreased overactivity but unchanged bladder contraction strength and urethral resistance during
voiding. J Urol 2006; 175: 1005-1009
28. Bosch JLHR, Groen J. Treatment of refractory urinary urge incontinence with sacral spinal nerve stimulation in
multiple sclerosis patients. Lancet 1996; 398: 717-719
29 Chai TC, Zhang C, Warren JW, Keay S. Percutaneous sacral third nerve root neurostimulation improves symptoms and
normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Urology 2000; 55(5):
643-646
30. Chartier-Kastler EJ, Bosch JLHR, Perrigot M, Chancellor MB, Richard F, Denys P. Long-term results of sacral nerve
stimulation (s3) for the treatment of neurogenic refractory urge incontinence related to detrusor hyperreflexia. J Urol
2000; 164: 1476-1480
31. Matzel KE, Stadelmaier U, Hohenfellner M, Hohenberger W. Chronic sacral spinal nerve for fecal incontinence:
long-term results with foramen and cuff electrodes. Dis Colon Rectum 2001; 44: 59-66
32. Feler CA, Whitworth LA, Fernandez J. Sacral neuromodulation for chronic pain conditions. Aesthesiol Clin North
America 2003; 21(4): 785-795
33. Whitmore KE, Payne CK, Diokno AC, Lukban JC. Sacral neuromodulation in patients with interstitial cystitis: a
multicenter clinical trial. Int Urogynecol J Pelvic Floor Dysfunction 2003; 14(5): 305-308
34. Comiter CV. Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective
study. J Urol 2003; 169(4): 1369-1373
35. Abrams P, Blaivas JG, Fowler CJ, Fourcroy JL, Macdiarmid SA, Siegel SW, van Kerrebroeck P. The role of
neuromodulation in the management of urinary urge incontinence. BJU Int 2003; 91(4): 355-359
36. Aboseif S, Tamaddon K, Chalfin S, Freedman S, Mourad MS, Chang JH, Kaptein JS. Sacral neuromodulation in
functional urinary retention: an effective way to restore voiding. BJU Int 2002; 90(7): 662-665
2 Five-year follow-up after Sacral Neuromodulation (SNM)
58
59
Chapter 3
3
3
Urodynamic evaluation of
sacral neuromodulation for
urge urinary incontinence
P.M. Groenendijk, A.A.B. Lycklama à Nyeholt, J.P.F.A. Heesakkers, P.E.V. van
Kerrebroeck, R.A. Schmidt, M.M. Hassouna, J.B. Gajewski, F. Cappellano, S.W.
Siegel, M. Fall, H.E. Dijkema, U. Jonas and U. van den Hombergh
BJU International 2008; 101 (3): 325-329
Abstract
Objective: To evaluate the urodynamic data before and 6 months after implantation of sacral
neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory
urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and
clinical efficacy in patients with UI.
Patients and methods: In all, 111 patients with a > 50% reduction in UI symptoms during a per-
cutaneous nerve evaluation test qualified for surgical implantation of SNM. Patients were catego-
rized in two subgroups, i.e. those with UI with or without confirmed detrusor overactivity (DO) at
baseline. At the 6-month follow-up all patients had a second urodynamic investigation, with the
stimulator switched on.
Results: At baseline, there was urodynamically confirmed DO in 67 patients, while 44 showed
no DO. A review of filling cystometry variables showed a statistically significant improvement in
bladder volumes at first sensation of filling (FSF) and at maximum fill volume (MFV) before voi-
ding for both UI subgroups, compared with baseline. In 51% of the patients with UI and DO at
baseline, the DO resolved during the follow-up. However, those patients were no more clinically
successful than those who still had DO (P = 0.73). At the 6-month follow-up, 55 of 84 implanted
patients showed clinical benefit, having a 50% improvement in primary voiding diary variables.
Patients with UI but no DO had a higher rate of clinical success (73%) than patients with UI and
DO (61%), but the difference was not statistically significant.
Conclusion: These urodynamic results show a statistically significant improvement in FSF and MFV
in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical
improvement in both groups, patients with UI but no DO are at least as successful as patients with
UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for
using SNM.
3 Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
62
Introduction
Urge urinary incontinence (UI) is defined as the complaint of involuntary leakage (of urine) ac-
companied by or preceded by urgency [1]. It is thought that UI can be caused by overactivity of
the detrusor muscle [2], but sensory urgency, urethral instability and psychosomatic factors might
also be related [3]. Detrusor overactivity (DO) incontinence is diagnosed during filling cystometry
when DO is accompanied by involuntary urine loss [1]. However, conventional filling cystometry
is not able to register DO consistently. The reported sensitivity is 77.9% and the specificity 38.7%
[3]. UI with no detectable DO is mostly categorized as sensory UI. Currently, the term ‘overac-
tive bladder’ (OAB) is used when defining the symptom complex, disregarding the urodynamic
features.
Standard treatments for UI include behavioural modification (pelvic floor muscle exercises), phar-
macological therapy (anticholinergics), interventions (biofeedback, external stimulation) and sur-
gery (denervation, bladder dilatation, botulinum toxin injections, urinary diversion, augmentation
cystoplasty). The introduction of sacral neuromodulation (SNM) for treating UI has provided
physicians with an effective and reversible means to address refractory chronic voiding dysfunc-
tion [4–8]. However, the debate about urodynamic changes after SNM therapy and the role
of urodynamic investigations in identifying patients for SNM therapy is still ongoing. Recently,
Groen et al. [9] reported the urodynamic changes after SNM in women with incontinence due
to idiopathic DO. We therefore re-analysed our data in women with UI treated with SNM. The
purpose of the present study was to characterize the urodynamic outcome of SNM therapy af-
ter 6 months of treatment for patients with UI. The prospective, randomized multicentre study
(MDT-103) that evaluated clinical efficacy and safety of SNM therapy in the population with
UI was published by Schmidt et al. [10]. This report describes the urodynamic findings from the
MDT-103 study and their correlation with the efficacy of therapy for UI patients with and without
urodynamically confirmed DO.
Patients and methods
In the prospective randomized multicentre study MDT-103, patients from 16 centres worldwide,
with UI as a primary complaint, and refractory to conservative treatment, were evaluated for
SNM therapy [10]. Only non-neurogenic patients were included in the study. All study candida-
tes had baseline screening, including a detailed medical history, urodynamic testing and quality-
of-life questionnaires. Urodynamic investigations included uroflowmetry, filling cystometry, and
detrusor pressure (Pdet)/flow studies. The primary goal of the urodynamic investigation was to
exclude underlying treatable diseases like bladder outlet obstruction (BOO), and to categorize
patients into those presenting with or without DO.
After written informed consent was obtained, all patients had a trial period of temporary lead
stimulation to quantify the effects of stimulation on UI. This percutaneous nerve evaluation test
(PNE) was described previously [11]. Patients who had a > 50% reduction in UI symptoms,
as shown in voiding diaries, qualified for surgical implantation of the neuromodulation system
63
(InterStim, Medtronic Inc., Minneapolis, USA). Patients had urodynamic investigations at base-
line and 6 months after the implant. The postvoid residual urine volume (PVR) was measured by
catheterization or by ultrasonography.
Baseline urodynamics distinguished patients with UI and DO from those with no DO. The compara-
bility of results within patients at each site was assured by using the same calibrated equipment.
Implanted patients were asked to undergo urodynamic testing, with the neurostimulator activated,
at the 6-month follow-up. At that time, the potential effects of SNM on detrusor function were
evaluated, with the clinical efficacy of the treatment. Clinical success was defined as a > 50% impro-
vement in the reduction of incontinence episodes per day and/or number of pads used.
The test results between the groups were compared using a two-sample Student’s t-test, with
values presented as the mean (SD); the statistical results were adjusted according to the equality
of variances and for multiple comparisons of the data.
Results
Fifty-four patients were assessed by uroflowmetry both at baseline and 6 months after the im-
plant. The PVR was > 50 mL in eight patients at baseline, vs six at the follow-up. There was a sig-
nificant increase only in peak urinary flow rate after SNM (P = 0.049), the other variables (mean
flow time, total voided volume and flow time) showing no significant changes.
As determined from the baseline filling cystometry results, the group of 111 randomized patients
with UI were divided into two subgroups, those with UI and DO (67, 59 women and eight men),
and those with UI and no DO (44). The urodynamic test results are presented for the two groups
separately. Six patients of each group left the study before the follow-up assessment and in some
the data were missing.
At 6 months, the bladder volume at the first sensation of filling (FSF) and maximum bladder capacity,
defined as maximum fill volume (MFV) before the void, indicated larger volumes than at baseline,
and were statistically significantly different (Table 1). The mean bladder volume at first involuntary
detrusor contraction was larger than at baseline, but not statistically significantly (P = 0.30).
The remaining filling cystometry variables for the patients with UI and DO show favourable 6-
month results, as measured by a significantly lower Pdet before voiding and a lower peak Pdet
during involuntary detrusor contraction than at baseline (Table 1). Furthermore, there were no
negative trends in voiding function in patients with UI and DO at 6 months in the filling cysto-
metry data. Urodynamic detrusor behaviour data at the follow-up was available for 51 (76%) of the
67 patients with DO at baseline. Table 2 summarizes the detrusor behaviour before and after SNM, with
3 Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
64
65
Table 1 Water cystometry results at baseline and after 6 months of SNM in patients with UI and DO
Mean (SD)
Urodynamic
variable (n) at baseline at 6 months P*
Bladder volume, mL
At FSF (41) 82.8 (64.7) 167.4 (109.3) < 0.001
% bladder capacity (41) 40.6 (33.3) 54.5 (27.2) 0.03
Pdet, cmH
2
O (39) 14.2 ± 18.9 11.2 ± 13.9 0.36
Bladder volume, mL
at 1st unstable contraction (22) 104.7 (111.0) 133.7 (125.9) 0.30
% of bladder capacity (21) 54.2 (36.3) 49.7 (34.6) 0.63
Pdet, cmH
2
O (21) 38.8 (23.7) 28.6 (23.3) 0.06
Bladder volume, mL
at MFV or just before void (45) 254 (138) 328 (148) 0.001
Pdet, cmH
2
O (43) 27.7 (21.6) 17.7 (16.5) < 0.001
Peak Pdet during cystometry (43) 53.8 (36.4) 33.6 (25.1) < 0.001
Volume at peak Pdet, mL (35) 230 (148) 261 (160) 0.24
*Paired t-test.
the clinical outcome of SNM therapy. Thirty-four patients (51%) with DO at baseline had no DO at the
6-month follow-up, but reported no additional clinical benefit over those who still had DO (P = 0.73).
Based on clinical data, 33 of 54 (61%) patients with UI and DO still present after 6 months showed an
improvement of > 50% in the reduction of incontinence episodes at the 6-month follow-up with the sti-
mulation on.There was no DO at baseline in 40 women and four men; Table 3 summarizes the 6-month
filling cystometry results for these patients, for those who completed both urodynamic investigations.
Comparable with the previous group, there was a statistically significant difference in bladder volume at
FSF and at MFV. Of the patients with UI and stable detrusor function at baseline, three of 32 (9%) had
DO at 6 months; 22 of 30 (73%) patients with UI but no DO (with available clinical data) had clinical
success. Patients with no DO both at baseline and during the follow-up had the best clinical outcome.
Patients with UI and no DO at the follow-up (73%) had a higher rate of clinical success than patients
with UI and DO (61%) at the follow-up, but the difference was not statistically significant (P = 0.26).
Paired results for the Pdet/flow study are shown for 66 of the 102 implanted patients followed
up to 6 months (Table 4). Baseline or 6-month results were not available in the remaining patients
as they were unable to void during the test with the catheter in place. There were significant dif-
ferences in peak flow rate, mean flow rate, total voided volume and Pdet at the start of flow.
Of the urodynamic variables that changed within the study group before and after implantation,
and that correlated highly with clinical success, three were identified in a univariate analysis, i.e.
Pdet at MFV, peak Pdet during filling cystometry, and Pdet at the start of flow (Table 5). Urody-
namic variables that predicted clinical success, defined as a > 50% improvement, were also analy-
sed; the baseline urodynamic variables that were prognostic for a successful clinical outcome were
volume at peak Pdet, Pdet at the start of flow, the bladder volume at first detrusor contraction,
and the bladder volume at MFV (Table 5).
3 Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
66
Table 2:
Detrusor behaviour before and after implant in relation to clinical success
Urodynamics, n (%)
at baseline at 6 months Clinical result
DO present, 67 (60) DO +, 25 (49) success, 19 (40); failure, 3 (6)
DO –, 26 (51) success, 20 (42); failure, 6 (12)
DO absent, 44 (40) DO +, 3 (9) success, 2 (7); failure, 1 (4)
DO –, 29 (91) success, 23 (82); failure, 2 (7)
Table 3: Water cystometry at baseline and 6 months of SNM in patients with UI and no DO at baseline
Mean (SD)
Urodynamic
variable (n) at baseline at 6 months P*
Bladder volume, mL
At FSF (30) 122.2 (78.8) 192.4 (118.4) 0.001
% bladder capacity (30) 42.0 (25.5) 51.1 (25.9) 0.13
Pdet, cmH
2
O (30) 4.3 (5.8) 4.2 (6.3) 0.91
Bladder volume, mL
at MFV or just before void (32) 313 (117) 365 (115) 0.02
Pdet, cmH
2
O (32) 7.4 (6.4) 12.1 (15.4) 0.11
Peak Pdet during cystometry (31) 13.7 (14.1) 15.9 (15.6) 0.50
Volume at peak Pdet, mL (30) 266 (138) 339 (135) 0.02
*Paired t-test
67
Table 4: Detrusor pressure/flow results at baseline and 6 months in 102 patients with UI
Mean (SD)
Variable (n) at baseline at 6 months P*
Peak flow rate, mL/s (65) 14.7 (10.0) 17.9 (8.6) 0.02
Mean flow rate, mL/s (64) 6.3 (3.8) 8.3 (5.4) 0.006
Total voided volume, mL (66) 251 (141) 324 (155) < 0.001
Flow time, s (64) 46.0 (28.4) 54.4 (59.3) 0.29
Time to peak flow, s (63) 25.4 (33.5) 27.0 (54.2) 0.84
Pdet at start of flow, cmH
2
O (54) 27.7 (25.3) 20.6 (15.8) 0.03
Pdet at maximum flow, cmH
2
O (55) 43.0 (30.6) 41.4 (22.7) 0.69
*Paired t-test.
Table 5: Urodynamic variables correlating with clinical success, and the prognostic urodynamic variables best
predicting the clinical outcome
Variable N Pearson correlation P
Pdet at MFV 72 – 0.31 0.007
Peak Pdet during cystometry 73 – 0.25 0.032
Pdet at start of flow 62 – 0.24 0.065*
Best predictors
Volume at peak Pdet 76 – 0.25 0.030
Pdet at start of flow 56 – 0.37 0.004
Bladder volume:
at first detrusor contraction 52 – 0.38 0.005
at MFV 81 – 0.19 0.089*
*Marginally significant.
Discussion
The demand for incontinence treatment will continue to increase as the population age. A better un-
derstanding of the pathophysiology, and mode of action of therapeutic options, is needed. SNM has
been shown to be effective in restoring normal voiding behaviour in various bladder disorders, like UI.
In principle, the mode of action of SNM is by reinforcing detrusor inhibiting mechanisms, although
further exploration is needed to understand in more detail how the micturition reflex is modulated.
Likewise, the role of urodynamics in patient selection for SNM treatment remains to be defined.
The present patients comprised those with refractory UI and implanted with a permanent neuro-
stimulator after completing a successful (> 50% clinical improvement) PNE test. At 6 months of
follow-up SNM was clinically effective for patients presenting with and with no baseline DO. There
was no statistically significant correlation between the likelihood of success and the presence of DO
at baseline, although the group with no DO at baseline tended to have a better clinical outcome.
Simple uroflowmetry is not typically used to diagnose or monitor changes in UI over time. Com-
pared to the uroflowmetry test before implantation, the 6-month data only showed a significant
increase in peak flow rate. There was no increase in total voided volume, although SNM therapy
is known to increase bladder volume during urodynamic investigations after implantation. There-
fore, uroflowmetry seems to have no role in assessing the results of SNM.
Most studies reporting on the mode of action of SNM and urodynamic changes report the chan-
ges during filling cystometry. It is evident that SNM therapy positively influences bladder capacity
and sensory variables like the FSF. A clinical improvement is associated with an improvement in
urodynamic data; voided volumes almost doubled compared to baseline, and the FSF increased
by half [6]. Scheepens et al. [12] reported a correlation between the subjective improvement in
patients with OAB and the use of SNM. During SNM therapy, DO reduced on ambulant cysto-
metry, that reportedly has a higher specificity and sensitivity than classic filling cystometry. The
role of DO detected before SNM is unclear. Recently, Groen et al. [9] reported on the effect of
SNM on voiding in women with idiopathic DO with incontinence. In the present study there were
fewer patients with DO, but bladder contraction strength, urethral resistance during voiding, and
volume-independent urodynamic variables did not change significantly. When focusing on ure-
thral behaviour, urethral pressure variations during filling cystometry appeared to be a valuable
factor to predict the outcome of SNM therapy. Urethral instability (urethral pressure variations
of > 15 cmH2O) disappeared in seven of 13 patients successfully treated with SNM; DO disap-
peared in only one of nine patients who had DO before SNM [13].
Bosch et al. [4] found no correlation between symptomatic improvement and urodynamic fin-
dings in 18 patients with UI. Shaker and Hassouna [5] questioned the clinical relevance of a diag-
nosis of DO during filling cystometry used in patient selection. This discrepancy between clinical
results and urodynamic findings is also reported in drug studies for OAB [14]. Elkelini et al. [6]
reported on SNM treatment in 18 patients with UI; a clinical improvement was associated with
an improvement in urodynamic data, but in only one of four patients with DO before the implant
did the DO resolve. The bladder volume at FSF increased by half while the cystometric bladder
capacity increased by 15% [6]. In the present study DO disappeared in 51% of patients with DO
3 Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
68
69
at the baseline urodynamic evaluation. In agreement with the findings of Elkelini et al., the blad-
der volume at FSF and MFV improved significantly in the present study, in patients with and with
no DO. Our data show that patients with UI were able to sense bladder filling at a higher, more
appropriate bladder volume at the 6-month follow-up, when SNM was applied.
Clinically, 55 of 84 (65%) patients showed a > 50% improvement in their primary voiding complaint,
expressed in the voiding diary as the number of leakage episodes, the number of pads per day or the
severity of leakage episodes. Patients with UI but no DO had a higher rate of clinical success than
patients with UI and DO. However, of the 23 (49%) patients who still had DO at the follow-up, eight
were completely dry, seven had a > 50% improvement and six had < 50% improvement; the 6-
month results were not available for the two remaining patients. This clearly indicates that DO before
SNM, and whether or not DO is still present at 6 months after the implant, is not a useful factor for
either patient selection or assessing the clinical outcome of SNM. Recently, South et al. [15] reached
a similar conclusion about the ability of DO to predict the outcome of PNE testing; there was no cor-
relation between the presence or absence of DO and the likelihood of response to test stimulation.
Perhaps the regaining of control of the pelvic floor and the external sphincter mechanism is the key to
success. This would also explain the association of success and regaining of urethral stability.
While each of the urological tests at baseline provide valuable data for some types of patients pre-
senting with voiding dysfunction, they are not regarded as useful in diagnosing UI [16–19]. In the
present study, both patients with and with no DO could be selected for implantation. Therefore,
in this study, cystometric data were collected to ensure that bladder function was not negatively
affected by SNM therapy. However, there was DO in three of 32 patients (9%) that could not be
detected at baseline. It is known that DO is not consistently registered by filling cystometry, and
therefore can be missed on urodynamic investigation at baseline. In routine urodynamics, DO is
an ‘on-the-spot’ finding affected by several factors. It is not consistently registered, as it might be
influenced by the patient’s mental state, as well as laboratory techniques, and therefore can be
missed on urodynamic investigation at baseline [3].
An increased bladder capacity might lead to a decrease in voiding frequency, as noted from voiding
diary data. This benefit of SNM therapy was also apparent in the present study. There was a signi-
ficant clinical improvement (defined as > 50% improvement) in patients with and with no DO over
baseline for SNM therapy. Patients with no DO seemed to have an additional benefit over patients
with DO, although the difference was not statistically significant. Recently, the clinical benefit of
SNM therapy in the treatment of refractory UI was re-confirmed [7,8]. The present data show a sta-
tistically significant improvement in the urodynamic bladder volume, while the Pdet did not change
significantly between baseline and the 6-month follow-up. In patients with baseline DO there was a
decrease in Pdet, possibly the result of an enhanced control of pelvic floor muscles and the bladder.
However, in patients with no baseline DO there was no decrease in Pdet during voiding. Therefore,
the observed changes in Pdet during voiding are of minor importance in evaluating SNM therapy.
To date, a test stimulation still has the highest predictive value for identifying and selecting pa-
tients for SNM therapy. When seeking urodynamic variables that most accurately predicted the
outcome of SNM in the present study (Table 5), there were significant changes in bladder volume
variables. Combined with the finding that Pdet variables correlated best with clinical success (Ta-
ble 5), this might indicate that patients with a low bladder capacity at baseline might benefit most
from SNM, and this could be confirmed by improved Pdet variables. Urodynamic investigations before
and 6 months after implantation show that urodynamic volume-dependent variables improve during
SNM therapy. Bladder volume and FSF improved significantly, while Pdet during voiding did not change
significantly. This results in improved bladder compliance and improved voiding efficiency.
For patients presenting with baseline DO, SNM eliminated DO in 51% of the patients after 6
months. However, the absence of DO did not necessarily accompany the resolution of UI com-
plaints. Thus urodynamic investigations only focusing on the presence of DO did not appear to
be an accurate tool to measure the efficacy of SNM therapy.
Although there was a urodynamic and clinical improvement in both groups, patients with UI and
no baseline DO seem to have an additional benefit over patients with baseline DO. Therefore in
patients with UI, urodynamically detected DO should not be a prerequisite in the selection criteria
for SNM therapy. The value of classic urodynamics in selecting patients for SNM therapy seems to
be limited, at least in selecting them for the operation and to monitor clinical efficacy, but might
be valuable for scientific purposes when further exploring the mechanism of action of SNM.
3 Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
70
71
References
1. Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the
standardisation sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21: 167–78
2. Swami SK, Abrams P. Urge incontinence. Urol Clin North Am 1996; 23: 417–25
3. Sand PK, Hill RC, Ostergard DR. Incontinence history as a predictor of detrusor instability. Obstet Gynaecol 1988; 71:
257–60
4. Bosch JL, Groen J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence in patients with
detrusor instability. Results of chronic electrical stimulation using an implantable neural prosthesis. J Urol 1995; 154:
504–7
5. Shaker HS, Hassouna M. Sacral nerve root neuromodulator: an effective treatment for refractory urge incontinence. J
Urol 1998; 159: 1516–9
6. Elkelini M, Hassouna MM. Canadian experience in sacral neuromodulation. Urol Clin North Am 2005; 32: 41–9
7. Latini JM, Alipour M, Kreder KJ Jr Efficacy of sacral neuromodulation for Symptomatic treatment of refractory urinary
urge incontinence. Urology 2006; 67: 550–4
8. Van Voskuilen AC, Oerlemans DJ, Weil EH, de Bie RA, van Kerrebroeck PE. Long term results of neuromodulation
by sacral nerve stimulation for lower urinary tract symptoms: a retrospective single center study. Eur Urol 2006; 49:
366–72
9. Groen J, Bosch JLHR, van Mastrigt R. Sacral neuromodulation in women with idiopathic detrusor overactivity
incontinence. decreased overactivity but unchanged bladder contraction strength and urethral resistance during
voiding. J Urol 2006; 175: 1005–9
10. Schmidt RA, Jonas U, Oleson KA et al. Sacral Nerve Stimulation for the treatment of refractory urinary urge
incontinence. J Urol 1999; 162: 352–7
11. Schmidt RA, Senn E, Tanagho EA. Functional evaluation of sacral nerve root integrity, report of a technique. Urology
1990; 35: 388–92
12. Scheepens WA, van Koeveringe GA, de Bie RA, Weil EHJ, van Kerrebroeck PE. Urodynamic results of sacral
neuromodulation correlate with subjective improvement in patients with an overactive bladder. Eur Urol 2003; 43:
282–7
13. Groenendijk PM, Heesakkers JPFA, Lycklama a Nijeholt AAB. Urethral instability and sacral nerve stimulation: a better
parameter to predict the efficacy? J Urol 2007; 178: 568-72
14. Tapp A, Fall M, Norgaard J et al. Terodiline. a dose titrated, multicenter study of the treatment of idiopathic detrusor
instability in women. J Urol 1989; 142: 1027–31
15. South MMT, Romero AA, Jamison MG, Webster GD, Amundsen CL. Detrusor overactivity does not predict outcome
of sacral neuromodulation test stimulation. Inter Urogynecol J Pelvic Floor Dysfunct 2007 Epub ahead of print
16. Blaivas JG. Neurourology and Urodynamics: Principles and Practice. New York: Macmillan Publishing Co., 1988:
155–98
17. Tapp AJ, Cardozo LD, Versi E, Cooper D. The treatment of detrusor instability in postmenopausal women with
oxybutynin chloride: a double-blind placebo controlled study. Br J Obstet Gynecol 1990; 97: 521–6
18. Elia G, Bergman A. Pelvic muscle exercises. When do they work? Obstet Gyn 1993; 81: 283–6
19. Nygaard IE, Kreder KJ, Lepic MM, Fountain KA, Rhomberg AT. Efficacy of pelvic floor muscle exercise in women with
stress, urge, and mixed urinary incontinence. Am J Obstet Gynecol 1996; 174: 120–5
acral neuromodulation for
urge urinary incontinence
Chapter 4
4
4
Clinical and urodynamic
assessments of the mode
of action of sacral nerve
stimulation
A.A.B. Lycklama à Nijeholt, P.M. Groenendijk and J. den Boon
In: New Perspectives in Sacral Nerve Stimulation for control of lower urinary tract dysfunction. Edi-
ted by U. Jonas and V. Grunewald. London: ISIS Medical Cooperation, Chapter 5, pp. 43-54, 2002
Introduction
Sacral nerve stimulation (SNS) can be very effective in the treatment of refractory urge inconti-
nence, urgency/frequency and voiding difficulty. The clinical results of this treatment, published
in recent years, are promising: the reported cure rates varies from 41 to 100%, with an average
of 70% [1].
Explanations for the neurophysiological mode of action of this treatment are based on human
electrophysiological studies and on animal experiments. In SNS treatment, both afferent and ef-
ferent sacral nerve fibers (constituting the pelvic plexus) and pudendal nerve fibers (innervating
the external sphincter and pelvic floor) are stimulated. The thicker myelinated somatic fibers are
affected more than the thinner parasympathic fibers, resulting in a primary effect on urethral ac-
tivity and the pelvic floor; because the threshold for a motor effect on bladder activity is higher, a
direct simultaneous motor effect on the bladder is avoided. According to some investigators [2-5],
the modulating effect of the enhanced urethral sphincter and pelvic floor tone inhibits detrusor
instability. If this is true, the effect of neuromodulation on voiding difficulty can also be explained:
neuromodulation reduces the spastic behaviour of the pelvic floor, which is permanently inhibi-
ting bladder activity. By reducing this inhibitory effect, neuromodulation restores normal bladder
contractility. However, according to another concept [6], neuromodulation primary affects the
bladder via the afferent sacral nerve fibers.
In this chapter we present both clinical and urodynamic data which underline the effect of SNS
treatment on urethral and pelvic floor function.
Patients and methods
Three clinical and urodynamical observations are presented here.
First, the clinical and urodynamic results of 22 patients, undergoing surgery in Leiden during the
international multicenter SNS study (MDT-103), were analysed.
As part of this study, 6 months postoperatively, a urodynamic investigation was performed, du-
ring which the Itrel stimulator was switched off and on. The efficacy of SNS treatment and the ef-
fect of switching the stimulator on and off on both urethral and bladder instability were studied.
Five female patients, in whom bladder stability was achieved by neuromodulation, were selected
for a pudendal block with lignocaine (lidocaine). For the pudendal block we used a trumpet-
needle, isolated by a glove, except for the tip, which was connected to a neurostimulator. On va-
ginal examination the ischial spine was palpated and the pudendal nerve was located by applying
electrical stimulation via the tip on the trumpet-needle. After this nerve has been identified, 15 ml
0.5% lignocaine was injected through the sacrospinous ligament. A bilateral block was applied.
Some 20 minutes after injection, the effect of the pudendal block was assessed by testing the
bulbocavernous reflex and by testing the vulvar and perineal sensibility with a needle and clamp.
A urodynamic study was performed before injection and repeated during the pudendal block.
The final clinical and urodynamic observation was in a female patient with recurrent urge incon-
tinence after a bladder substitution operation. This patient (JV, born in 1963), had presented ori-
4 Clinical and urodynamic assessments of the mode of action of sacral nerve stimulation
74
ginally with severe refractory urgency/frequency (diurnal frequency, 25; nocturnal frequency, 3)
and severe urge incontinence. At that time urodynamic investigation had revealed severe bladder
and urethral instability. Interstitial cystitis was excluded by bladder biopsies. Because the bladder
had a functional capacity of 150 ml, a supra-trigonal cystectomy was performed, in combination
with a bladder substitution according to the Mainz technique. Three years later, this patient pre-
sented again with recurrent, severe urge incontinence. Urodynamic investigation showed urge
incontinence was due to severe urethral instability and minor ‘bladder’ instability. The functional
‘bladder’ capacity was 600 ml. An peripheral nerve evaluation (PNE) test was performed on S3,
on the left side. Both the clinical and urodynamic effects of the subchronic PNE test, which was
carried out over a period of 2 weeks, were documented.
75
Results
At our institution, 22 patients underwent surgery in the course of the multicentre SNS study. The-
se patients were selected as candidates for implantation because of symptomatic improvement of
at least 50% during the subchronic PNE test. Of these patients, 15 were in the urge incontinence
group, 5 patients were in the urgency/frequency group (including one male patient) and 2 under-
went surgery because of chronic voiding dysfunction. In the majority of these patients, especially
in the incontinence group, urethral and bladder instability was noted. In a considerable number of
patients, SNS treatment resulted in marked improvement in both urethral and bladder instability.
Figure 1 refers to patient JB, born in 1952, who had suffered from severe, refractory urge incontinence
and urgency/frequency (diurnal frequency, 30; nocturnal frequency, 4) for 7 years. Urodynamic stu-
dies demonstrated urethral and bladder instability with concomitant incontinence. She was selected
for a PNE test and, because of an impressive improvement, for a SNS implant. At interim analysis at 6
months postoperatively (S3 left), urodynamic investigation (figure 2) showed, in accordance with an
excellent clinical response, stable bladder and urethral function. During this urodynamic study the Itrel
stimulator was switched off (figure 3): this brought about an instant recurrence of urethral and bladder
4 Clinical and urodynamic assessments of the mode of action of sacral nerve stimulation
76
Figure 1. Patient JB, with severe refractory urge incontinence and urgency/frequency: urodynamics before
neuromodulation operation; urethral and bladder instability with concomitant incontinence.
Qura urinary flow (ml/s); scale 0-50 ml/s
Pmed urethral pressure (cm H
2
O; scale 0-100 cm H
2
O)
Pdet detrusor pressure (cm H
2
O; scale 0-100 cm H
2
O)
Pabd abdominal pressure (cm H
2
O; scale 0-100 cm H
2
O)
Pves vesical pressure (cm H
2
O; scale 0-100 cm H
2
O)
77
Figure 2. Patient JB during SNS: interim analysis 6 months postoperatively (S3 left). In accordance with an excel-
lent clinical response there is stable bladder and urethral function during filling, followed by normal voiding.
Figure 3. Patient JB interim analysis 6 months postoperatively; when the Itrel stimulator is switched off there is an
instant recurrence of urethral and bladder instability with concomitant incontinence. According to the timescale,
in the second half of the filling phase the decrease in urethral pressure precedes a rise in bladder pressure.
instability, with concomitant incontinence. According to the timescale, in the second half of the filling
phase the decrease in urethral pressure precedes a rise in bladder pressure.
Five patients, in whom neuromodulation had brought about stability, were selected for a bilateral
pudendal block with lignocaine. The efficacy of the pudendal block was assessed by disappearance
of the bulbocavernous reflex and absence (or marked decrease) of perineal and vulvar sensibility.
In two patients, these clinical parameters indicated a satisfactory pudendal nerve block; however,
in three patients the block was inadequate. The application of the pudendal block, performed by
an experienced gynaecologist, appeared to be rather uncomfortable for the patient and iden-
tification of the pudendal nerve appeared to be more difficult than in patients in labour, which
explains the failure of the pudendal nerve block in three patients. In two patients, the successful
pudendal block was followed by a urodynamic investigation. Figure 4 again refers to patient JB,
after pudendal block: the bulbocavernous reflex was absent; perineal and vulvar sensibility was
absent on the left and markedly decreased on the right. Urodynamic studies showed recurrent
severe bladder and urethral instability with severe incontinence during filling cystometry. This in
sharp contrast to the urodynamic investigation performed before the pudendal nerve block. The
results of this investigation were simulator those depicted in figure 2 in that they showed a stabi-
lity of bladder and urethral function as a result to SNS treatment.
4 Clinical and urodynamic assessments of the mode of action of sacral nerve stimulation
78
Figure 4. Patient JB during SNS after bilateral pudendal block with lignocaine. Recurrence of severe
bladder and urethral instability due to the pudendal block, with severe incontinence during filling. This in
sharp contrast to figure 2.
In patient JV who underwent a bladder substitution operation, it was possible to compare pre-
operative clinical and urodynamic data with such data 3 years later, when she complained of
recurrent urinary incontinence, and with data during the subsequent chronic PNE test. Before
the bladder-substitution operation, JV complained of severe urgency/frequency and severe urge
incontinence. At that time, a urodynamic investigation revealed severe bladder and urethral insta-
bility (figure 5). This investigation illustrates very clearly the initial decrease in urethral pressure,
followed by the rise in bladder pressure. The clinical result of the bladder-substitution operation
was initially satisfactory - a normal functional ‘bladder’ capacity, spontaneous voiding and con-
tinence. However, 3 years later, JV presented again with severe urge incontinence. Urodynamic
studies of the neobladder showed urge incontinence due to severe urethral instability and minor
‘bladder’ instability (figure 6). The pattern of urethral instability, characterised by major fluctu-
ations in urethral pressure, was the same as before: the most significant decreases in urethral
pressure resulted, in combination with minor increases in ‘bladder’ pressure (perhaps as a result
of contractions of the original trigone), in incontinence. Because of the marked urethral insta-
bility, a PNE test was discussed and performed. During the subchronic PNE phase, which lasted
for 2 weeks, JV had no complaints at all of urge incontinence. This was documented in a voiding
diary. A urodynamic investigation (figure 7), performed halfway through this subchronic PNE
test, showed disappearance of the severe urethral and minor ‘bladder’ instability. According to
the patient’s diaries, the average bladder capacity increased from 286 ml to 348 ml. After remo-
val of the temporary wire electrode, the urge incontinence recurred: the patient was selected for
permanent SNS implantation.
79
Figure 5. Patient JV with severe, refractory urgency/frequency and urge incontinence. Urodynamic investigation
before bladder substitution operation; severe bladder and urethral instability with concomitant incontinence. This
investigation illustrates clearly the initial decrease in urethral pressure, followed by the rise in bladder pressure.
4 Clinical and urodynamic assessments of the mode of action of sacral nerve stimulation
80
Figure 6. Patient JV 3 years after bladder substitution. After a good clinical result initially, there is a recurrence
of severe urge incontinence. Urodynamic study of the neobladder with urge incontinence due to severe urethral
and minor ‘bladder’ instability. The pattern of the urethral instability, characterised by major urethral pressure
fluctuations, is as before. The most significant falls in urethral pressure result (in combination with concomitant
minor increases in ‘bladder’ pressure- perhaps as result of contractions of the original trigone) in incontinence.
Figure 7. Patient JV during subchronic PNE. Urodynamic studies, performed halfway through the subchronic
PNE test (which lasted for 2 weeks), showing complete disappearance of the previous severe urethral and minor
‘bladder’ instability. As documented by a diary, the patient was continent during the subchronic PNE test.
Discussion
SNS has proved to be effective for symptoms such as urinary urgency, frequency, incontinence,
pelvic pain and voiding difficulty refractory to conservative treatment. The technique was first
introduced in 1981 by Schmidt and Tanagho after animal studies and an extensive laboratory
programme. The mode of action is discussed in several publications [4,7].
Anatomically, the nerve fibers originating from S2 to S4 are autonomic nerve fibers (comprising
the pelvic plexus which innervates the bladder and the smooth muscle wall of the urethra), and
somatic nerve fibres (forming the pudendal nerve). The pudendal nerve devides into the dorsal
nerve of the penis or clitoris, the rectal branches, the tranversus perinei branch and scrotal or
labial branches; it consists of both motor and sensory fibres [8].
According to Hohenfellner et al. [4] neuromodulation primarily affects the somatic A-α and A-γ
fibres of the pudendal nerve. Depolarisation of these thicker myelinated A-α and A-γ somatomo-
toric pudendal nerve fibres affects the external sphincter and pelvic floor and may inhibit detrusor
activity. This stimulation does not result in depolarisation of the thin, unmyelinated B and C pa-
rasympathetic bladder fibres because of their higher threshold. This is probably due to a greater
membrane capacitance of these small, unmyelinated fibres in comparison with the thicker and
myelinated A-α fibres and skeletal muscle fibres [9]. According to Hohenfellner, the stimulator
has to be switched off to initiate micturition: this is not, however, consistent with currently daily
practice in SNS, were usually a full 24 hours’ stimulation is applied [4].
Thon et al. [3] discussed the concept of neural modulation by stimulation of A-δ myelinated
fibres, typically sacral roots S3 and S4, resulting in a decreased spasticity of the pelvic floor and
enhanced urethral sphincter tone. In the opinion of these authors, voiding dysfunction is often
initiated by unstable urethral activity, which activates voiding reflexes, leading to detrusor in-
stability and associated symptoms. They conclude that detrusor instability is suppressed by the
inhibitory effect of the enhanced urethral sphincter tone, stabilising detrusor activity.
Elabbady et al. [5] state that the most important benefit of neural modulation is rediscovery by
the patient of pelvic floor muscles, because failure to feel the pelvic floor prevents the initiation of
voiding. Neuromodulation suppresses spastic neuronal activity and modulates behaviour of the
pelvic muscles; this must result in recovery of voluntary control of pelvic floor muscles and, sub-
sequently, in better control on voiding. In our opinion, however, this hypothesis cannot explain
the fairly abrupt effect of SNS on urethral and bladder instability that we often see in urodynamic
investigations in operated patients when the stimulator is switched off and on. More recently,
Shaker et al. [10] have concluded that sacral root stimulation exerts its effect by inhibiting the
activity of the reflex arc conveyed by the C-afferent fibres. This finding suggests that blockade of
C-fibre activity is one of the mechanisms of action of sacral root neuromodulation.
According to Thon, Hohenfellner, and Elabbady [3-5], the primary or most relevant effect of
neuromodulation is motor, on urethral and pelvic floor function. According to Bosch and Groen
[6,11], however, the clinical effect of neuromodulation is not related to an effect on urethral and
pelvic floor function but, rather, to a stimulating effect on afferent anorectal branches of the pel-
vic nerve, to afferent sensory fibres in the pudendal nerve and to muscle afferents from the limbs,
81
resulting in an inhibitory effect on detrusor contractility via the spinal inhibitory system. According
to those authors, this concept is supported by the observation that urethral pressure profile pa-
rameters such as Maximum Urethral Closure Pressure (MUCP) and Functional Urethral Length
(FUL) did not show a significant increase with stimulation switched on [9]. In general, the impor-
tance of a centrally regulated effect is supported by a recent study by Fowler et al. [12] indicating
that the motor pelvic floor contraction, observed during PNE is mediated by afferent input and
is not the result of direct efferent stimulation. This centrally-mediated effect is supported by the
clinical observation that pelvic floor contraction in SNS is bilateral, with unilateral stimulation.
If it is true that the primary mode of action of SNS is through afferents, it is still a matter of debate
whether the resulting efferent effect is focussed mainly on bladder activity or on urethral and
pelvic floor activity. We believe that the impact of urethral/pelvic floor function is important, as
we discuss further in this chapter.
The main indications for SNS treatment are urge incontinence and urgency/frequency, which
occur during the filling phase of the bladder. In these conditions, bladder instability can often be
assessed during urodynamic studies. However, urethral function can be assessed urodynamically
only when, during filling, urethral pressure is measured throughout the study. In most published
SNS studies this has not been the case. Only those investigators who have included integral
urethral pressure measurement in the urodynamic set-up, can study the distinct relation between
(unstable) urethral and bladder contractions [13], as well as the distinct effect of neuromodulation
treatment on both forms of instability. We have studied extensively the importance of urethral
instability and its susceptibility to SNS; our results will be published separately (PM Groenendijk,
AAB Lycklama à Nijeholt). By taking the timescale during urodynamic studies into account, it can
be recorded that both during normal voiding and in the presence of concomitant urethral and
bladder instability, the fall in urethral pressure frequently precedes bladder contraction. This fall in
urethral pressure can be experienced by the patient as an ‘urge to void’. When this pressure drop
is followed by a bladder contraction, as is often the case, voiding starts or an unstable bladder
contraction is noted.
In urodynamic literature, it is often argued that urethral instability is a problem in that it cannot
easily be expressed in hard numbers in relation to fluctuations in urethral pressure. However,
this should not deter us from referring to urethral instability when a distinct pattern of urethral
pressure fluctuations can be seen during the filling phase. The relationship with some clinical con-
ditions underlines the relevance of the phenomenon of urethral instability: for instance, we note
quite often that, at filling, urethral instability starts at the first sensation of filling. Frequently we
note urethral instability in a patient with sensory urge, in the absence of bladder instability.
Figures 1,2 and 3 illustrate the effect of SNS not only on bladder instability, but also on urethral
instability. As illustrated in figure 4, a bilateral pudendal nerve block with lignocaine instantly
undermines the stabilising effect of neuromodulation: both urethral and bladder instability recur,
resulting in urge incontinence. Whether this effect is due to blockage of the motor pudendal ef-
fect on urethral and pelvic floor function or is due to blockage of the pudendal afferents towards
the sacral nerves, is unclear. The observation, however, underlines the importance of the puden-
dal nerve in SNS treatment.
4 Clinical and urodynamic assessments of the mode of action of sacral nerve stimulation
82
The urodynamic investigation performed in patient JV clearly illustrates the presence of concomi-
tant urethral and bladder instability in combination with urge incontinence (figure 5). In this pa-
tient, because of recurrent urge incontinence after performing the bladder substitution operation,
the urodynamic investigation also illustrates the distinct fluctuations in urethral pressure and the
concomitant minor unstable ‘bladder’ contractions following a significant drop in urethral pres-
sure (figure 6). The most obvious event during the urodynamic investigation, performed in the
subchronic PNE phase (figure 7), is the complete disappearance of urethral instability. This, and
the stabilised ‘bladder’ function, results clinically in abolition of urge incontinence. With only the
trigone left in this patient, this emphasises the role of this small portion of the bladder and the role
of urethral/pelvic floor function in (in)continence and its susceptibility to SNS.
The above foregoing clinical and urodynamical data stress the importance of urethral and pelvic
floor function in bladder function. They support the hypothesis regarding the impact of SNS via
depolarisation of myelinated somatic (pudendal) nerve fibres resulting in stabilised urethral func-
tion and, subsequently, in stabilisation of bladder function.
The data presented are not in accordance with the hypothesis published by Bosch and Groen [6].
The urodynamic investigations that they performed in patients with SNS lack of permanent ure-
thral pressure measurement in the filling phase. Instead of taking a stabilising effect of neuromo-
dulation treatment into account, they anticipate enhanced urethral pressure if neuromodulation
acts directly on urethral/pelvic floor function. In their opinion, the finding of only an insignificant
increase in urethral pressure profile parameters (MUCP and FUL) indicates the absence of a bene-
ficial effect of neuromodulation on pelvic floor muscles. Instead, the finding of a greater bladder
contractility 6 months postoperatively supports (in their opinion) the hypothesis that the mode of
action of neuromodulation is via stimulation of afferent nerve fibers, resulting in a direct inhibitory
effect on detrusor contractility via a spinal inhibitory system. They consider that animal experi-
ments support this hypothesis because (at least in the cat) afferents from the pelvic floor muscles
have no inhibitory effect on the bladder.
The relationship between the clinical outcome of SNS and the initial presence of bladder instability
is unclear. A poor correlation between clinical improvement and disappearance of the uninhibited
bladder contractions has been reported [6]. This unsatisfactory correlation upholds the idea that
other factors, such as urethral relaxation, play a part in the occurrence of urge incontinence [14].
It is becoming increasingly clear that neuromodulation, for the most successfully treated con-
ditions - such as urge incontinence and urinary retention - probably relies on a combination of
mechanisms that effect function at many levels in the neuroaxis [1].
83
Conclusions
An increasing body of clinical data support the importance of SNS in refractory urge incontinence,
urgency/frequency complaints, and chronic voiding difficulties. In the main, in a number of pu-
blications, two concepts have been put forward to explain the physiological mode of action of
SNS: a primary motor effect on urethral activity and pelvic floor muscles with a secondary effect
on bladder function is postulated, as well as a primary motor effect, via the afferent sacral nerve
fibres, on the bladder itself. In this respect, taking those urodynamic data that includes permanent
urethral pressure measurements into account in several clinical conditions, an important (or even
primary) effect of neuromodulation on urethral and pelvic floor function is endorsed.
The mode of action of SNS, based on our clinical and urodynamic observations, appears to be a
primary afferent effect via pelvic and pudendal nerve fibres, resulting in a motor effect through
the spinal system, mainly on urethral and pelvic floor function and perhaps (to a lesser degree) on
bladder function. The main effect on urethral and pelvic floor function may subsequently, because
of an inhibitory effect, affect bladder function.
In the near future, more studies on the (now well-illustrated) interaction between urethral
and bladder instability and its susceptibility to SNS, may further enrich our knowledge regarding
treatment by sacral neuromodulation.
4 Clinical and urodynamic assessments of the mode of action of sacral nerve stimulation
84
References
1. Bemelmans BLH, Mundy AR and Craggs MD. Neuromodulation by implant for treating lower urinary tract symptoms
and dysfunction, Eur Urol 1999; 36: 81-91
2. Schmidt RA. Advances in genitourinary neurostimulation, Neurosurgery 1986; 19: 1041-1044
3. Thon WF, Baskin LS, Jonas U et al. Neuromodulation of voiding dysfunction and pelvic pain, World J Urol 1991; 9:
138-141
4. Hohenfellner M, Thüroff JW, Schultz-Lampel D et al. Sakrale Neuromodulation zur therapie von Miktionsstörungen,
Aktuel Urol 1992; 23: I-X
5. Elabbady AA, Hassouna MM and Elhilali MM. Neural stimulation for chronic voiding dysfunctions, J Urol 1994; 152:
2076-2080
6. Bosch JHLR, Groen J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence in patients with
detrusor instability: results of chronic electrical stimulation using an implantable neural prothesis, J Urol 1995; 154:
504-507
7. Tanagho EA, Schmidt RA. Electrical stimulation in the clinical management of the neurogenic bladder, J Urol 1988;
140: 1331-1339
8. McFarlane JP, Foley SJ, de Winter P et al. Acute suppression of idiopathic detrusor instability with magnetic stimulation
of the sacral nerve roots, Br J Urol 1997; 80: 734-741
9. Bosch JLHR, Groen J. Effects of sacral nerve stimulation on urethral resistance and bladder contractility: how does
neuromodulation work in urge incontinence patients? [abstract 62], Neurourol Urodyn 1995; 14: 502-504
10. Shaker HS, Wang Y, Loung D et al. Role of C-afferent fibres in the mechanism of action of sacral nerve root
neuromodulation in chronic spinal cord injury, Br J Urol 2000; 85: 905-910
11. Bosch JLHR. Sacral neuromodulation in the treatment of the unstable bladder, Curr Opin Urol 1998; 8: 287-291
12. Fowler CJ, Swinn MJ , Goodwin RJ et al. Studies of the latency of the pelvic floor contraction during peripheral nerve
evaluation show that the muscle response is reflexly mediated, J Urol 2000; 163: 881-883
13. Park JM, Bloom DA, McGuire EJ. The guarding reflex revisited, Br J Urol 1997; 80: 940-945
14. Shaker SS, Hassouna MM. Sacral nerve root neuromodulation: an effective treatment for refractory urge incontinence,
J Urol 1998; 159: 1516-1519
85
Chapter 5
Urethral Instability and
Sacral Nerve Stimulation
(SNS): a better parameter
to predict the efficacy?
P.M. Groenendijk, J.P.F.A Heesakkers and A.A.B. Lycklama à Nijeholt
J Urol 2007; 178: 568-572
Abstract
Purpose: Urodynamic parameters that predict the outcome of sacral nerve stimulation (SNS) are
difficult to define. We studied the predictive value of urethral instability (URI) and other urody-
namic parameters on the efficacy of SNS.
Materials and Methods: Patients with refractory voiding disorders were implanted with
a neurostimulator after responding with an improvement of more than 50% in their main
symptoms after percutaneous nerve evaluation (PNE). Filling cystometry was performed with 3
urethral sensors and 1 bladder sensor, at baseline and at 6 months post implant. Urethral pressure
variations > 15 cm H
2
O were considered as pathological and defined as urethral instability. Clini-
cal efficacy was evaluated by voiding diary data and defined as successful when an improvement
of > 50% was observed.
Results: Nineteen female patients enrolled the study. At baseline, detrusor overactivity (DO) was
observed in 9 of the patients. Eighteen patients showed URI. SNS therapy was successful in 13
patients (68%). The number of pads used per day and the severity of leakages decreased signi-
ficantly. Twelve of the 13 successfully treated patients showed URI at baseline. DO was present
in 4 of the successful treated patients. URI disappeared in 7 of the 13 successful treated patients;
DO disappeared in only 1 of these patients.
Conclusion: In this study URI appeared to be a valuable urodynamic parameter for predicting the
outcome of SNS.
5 Urethral Instability and Sacral Nerve Stimulation (SNS)
88
Introduction
Urethral instability (URI), an expression of fluctuation in the urethral pressure during filling, is still
regarded as a controversial topic in urodynamics. Even today, the ICS has difficulty in defining
this entity. A decrease in urethral pressure, often seen as an initial marker of consecutive urethral
instability, is often associated with the first sensation of filling (FSF). This implies a link between
sensory factors such as FSF and motor expressions, namely fluctuations in urethral pressure du-
ring filling cystometry. Investigators acknowledge more and more the impact of sensory factors
on voiding and various publications have discussed URI and the presence of voiding dysfuncti-
ons. More recently, McLennan et al., found a close correlation between URI and type II bladder
instability, indicating a detrusor contraction preceded by a drop in urethral pressure [1]. They
concluded that further studies are needed for patients with lower urinary tract storage symptoms
and/or urge incontinence to differentiate between detrusor overactivity and URI for treatment
purposes.
Various definitions for URI are used in literature. In 1981 the ICS defined the unstable urethra
when there is an involuntary fall in urethral pressure, resulting in urinary leakage, in the absence
of detrusor activity [2]. In 1988, however, the ICS was unable to define URI [3]. The standar-
disation committee of the ICS in 2002 did not mention the term URI, thus demonstrating the
complexity and difficulty of this urodynamic feature [4]. According to the standardisation sub-
committee of the ICS, the significance of urethral pressure fluctuations lack clarity and therefore,
the term “unstable urethra” is not recommended. Instead, if symptoms are seen in association
with a decrease in urethral pressure, a full description is recommended.
Over the years, terminology describing an involuntary rise in detrusor pressure during filling cys-
tometry has been changed. It can well be understood that the term ‘detrusor instability’ was
abandoned and changed in ‘detrusor overactivity’ (DO). ‘Overactivity’ describes an involuntary
increase in detrusor pressure better than ‘instability’. For urethral pressure variations during filling
cystometry the discussion is different. Only few investigator groups measure integral urethral
pressure during filling cystometry. Reports published by these groups describe the topic as ‘ure-
thral instability’. The term ‘instability’ is selected because both increase and decrease of urethral
pressure is observed.
Most studies define URI as urethral pressure variations of at least 15 cm H
2
O occurring apart from
arterial pulsations and clearly visible during bladder filling [5-8]. Others defined URI as a drop in
urethral pressure of at least 20 cm H
2
O unrelated to a detrusor contraction, an increase of intra-
abdominal pressure, or pulsations of the vascular bed [9]. Wise et al., advocated the definition
of URI as a spontaneous fall in maximum urethral pressure of one-third or more, in the absence
of detrusor activity, over a 2-minute period [10]. The clinical implications of URI are not always
clear and therefore a good treatment strategy remains obscure. However, it is generally accepted
that URI is somehow linked to overactive bladder complaints.
Refractory urge incontinence, urgency/frequency and voiding difficulty can be treated effective
by sacral nerve stimulation (SNS). Reported cure rates vary between 41 and 100%, with an aver-
age of approximately 70% [11]. There is still debate as to its mode of action. Some investigators
believe the modulating effect of SNS is related to an enhanced urethral sphincter and pelvic floor
89
tone, resulting in inhibition of DO [12]. Others, however, believe SNS affects primary the blad-
der via afferent pudendal and sacral nerve fibres [13]. Clinical studies so far failed to explain
the clinical efficacy of SNS by its impact on DO. In our opinion, the significance of the urethral
function is underscored in these investigations. We discuss the significance of sensory factors in
SNS treatment [14] and perform urodynamics including integral urethral pressure measurement in
the filling phase. We analyse the occurrence of urethral pressure variations and the effect of SNS
on both clinical and urodynamic data which underscore the effect of SNS treatment on urethral
and pelvic floor function.
Materials and Methods
Patients with micturition symptoms refractory to physical and medical therapy were implanted
with a neurostimulator (Medtronic Inc., Minneapolis, USA) after responding with an improve-
ment of more than 50% in their main symptoms to PNE. Filling cystometry was performed at
baseline and 6 months post-implant. A micturition diary was filled out at baseline and 6 months
post implant to document voiding dysfunction and its changes after implant. Cystometry was
performed with the MMS UD 2000 and a Gaeltec CTU/2E/L-4 12F catheter, with 3 urethral
sensors and 1 bladder sensor. Urodynamic data of patients with urge incontinence and urgency/
frequency were evaluated. The following items were scored: URI, DO, first sensation of filling
(FSF), relation between URI and both DO and FSF as well as maximum and minimum urethral
pressure during filling cystometry. Two investigators assessed the presence of urethral pressure
variations. Urethral pressure variations of more than 15 cm H
2
O seen on all 3 urethral pressure
recordings during filling cystometry were considered pathological. Pressure variations of 16-30
cm H
2
O were classified as minor, and those exceeding 31 cm H
2
O were considered as major. Pres-
sure variations related to artefacts (mechanical factors, movement of the patient or the catheter,
vascular pulsations) were disregarded. Urethral pressure variations were studied separately from
possible concurrent bladder pressure fluctuations. All other definitions were according to the
guidelines of the ICS [4].
Comparisons between the two groups were done with a two-sample Student’s t-test. Results in the
figures are presented as mean ± standard deviation. Statistical results were adjusted according to
the equality of variances and for multiple comparisons of the data.
5 Urethral Instability and Sacral Nerve Stimulation (SNS)
90
Results
The urodynamic and voiding diary data of 19 female patients who underwent a SNS operation due
to refractory overactive bladder complaints were analysed. Fifteen patients suffered from refractory
urge incontinence (UI), and 4 from urgency/frequency (U/F). Mean age at study enrolment was 45.6
years (range 31-58, SD 7.7) and mean duration of symptoms was 8.1 years (range 1-36, SD 9.4).
Clinical results
At 6 months post implant, SNS therapy was successful in 13 patients (68%), 4 patients showed an im-
provement of less than 50% on primary voiding diary parameters. In 2 patients the neurostimulator was
removed prior to the 6 months follow-up. The data of all these patients were included in the data ana-
lysis. The number of pads used per day, average severity of leakages and number of leaks per day all de-
creased significantly after implant of the neurostimulator at follow-up (table 1). Six out of the 15 patients
with UI were completely dry and 5 demonstrated a more than 50% decrease in leakage episodes.
*Statistical Comparison: paired t-test
Table 1. Clinical parameters: Baseline through 6 months (n=19)
Mean at
baseline
Mean
6 months
post implant
p-value*
Number of leaks/24 h
Average severity of leakages
Number of pads/24 h
13 ± 10
2.2 ± 0.68
8.4 ± 7.0
6 ± 8
1.5 ± 0.45
4.0 ± 6.2
0.001
0.019
0.002
91
Urodynamic characteristics
Baseline cystometry
Filling cystometry at baseline showed DO in 9 patients (47%). The prevalence of URI was high
(95%, table 2). In the 4 patients with urgency/frequency, their complaint was clearly more rela-
ted to the presence of URI (prevalence 100%) than of DO (prevalence 25%). These correlations
were less pronounced in patients with urge incontinence (93% respectively 53%). Furthermore,
in all patients with URI, a drop in urethral pressure was noticed at FSF. All 9 patients with DO
showed urethral pressure variations exceeding 31 cm H
2
O.
URI=Urethral instability; DO=Detrusor overactivity.
Table 2. Urethral and detrusor behaviour for all patients at baseline and 6 months post implant
Baseline 6 months
post
implant,
stimulator
on
6 months
post
implant,
stimulator
switched off
Clinical
success
URI and DO
present
URI present, DO
absent
URI absent, DO
present
URI and DO
absent
N=19 N=17 N=17 N=13
9
9
0
1
4
5
1
7
8
7
0
2
4 (27%)
8 (62%)
0 (0%)
1 (8%)
Cystometric data at 6 months follow up
Urodynamic data were available for 17 patients. Table 2 shows detrusor and urethral behaviour
6 months post implant, with the stimulator on and off.
A disappearance of URI was seen in 7 out of 13 (54%) successfully treated patients. This effect
was seen in 9 (53%) of the 17 urodynamical evaluable patients, In 3 out of 9 (33%) patients with
DO at baseline, no DO was observed at 6 months follow-up. Prior to treatment, 16 out of 19
patients had urethral pressure variations of more than 31 cm H
2
O (84%). However, at 6 months
this phenomenon was present in only 5 out 17 patients (29%). When the stimulator is switched
off, more pronounced urethral pressure changes (> 31 cm H
2
O) reappeared instantly in 6 patients
and DO reappeared in 1 patient.
The dramatic effect of SNS therapy on urethral pressure variations and DO is illustrated in figures
1 and 2. Figure 1 shows the urodynamic recordings in a patient, suffering from UI, 6 months after
successful SNS therapy. In figure 2 the reappearance of both URI and DO in the same patient can
be clearly seen when stimulation is switched off.
5 Urethral Instability and Sacral Nerve Stimulation (SNS)
92
Figure 1: Urethral pressure variations and detrusor overactivity in a patient implanted with a permanent neu-
rostimulator, stimulation switched on showing normalisation of urethral and detrusor behaviour.
Figure 2: Urethral pressure variations and detrusor overactivity in a patient implanted with a permanent neu-
rostimulator, stimulation switched off
93
Table 3 represents 8 urodynamic test values prior to implant and at 6 months follow-up. A sig-
nificant increase in FSF was seen as well as a clinical relevant increase in bladder volume prior
to void. When the resulting changes in urethral pressure are merely expressed as “peak urethral
pressure” or “lowest urethral pressure” instead of the variation in pressure, the changes are not
significant.
* Statistical Comparison: paired t-test
Table 3. Water Cystometry: Baseline through 6 months
Urodynamic Test Variable
Avg. at
Baseline
Avg. at six
months
p-value*
First Sensation of Filling (FSF)
Bladder Volume (ml)
Bladder Volume prior to void (ml)
Peak detrusor pressure (cm H
2
O)
Detrusor pressure at FSF (cm)
Detrusor pressure at maximum fill
or prior to void (cm H
2
O)
Volume at peak bladder pressure (ml)
Peak urethral pressure during cysto-
metry (cm H
2
O)
Lowest urethral pressure during
cystometry (cm H
2
O)
98 ± 88
284 ± 108
10 ± 10
24 ± 14
235 ± 159
346 ± 166
7 ± 7.6
19 ± 12
0.002
0.061
0.14
0.26
42 ± 33 25 ± 14 0.028
239 ±140 317 ± 153 0.041
121 ± 42 113 ± 42 0.15
69 ± 32 86 ± 44 0.86
5 Urethral Instability and Sacral Nerve Stimulation (SNS)
94
Discussion
The consistency and reproducibility of URI and its clinical relevance is still a matter of debate. Our
study, however, shows the relationship of this urodynamic finding to clinical outcome in patients
treated with SNS.
By some investigators, urethral pressure variations during filling cystometry are considered an
artefact and therefore of no relevance to explaining patients symptoms [15]. Most studies discus-
sing urethral pressure variations were published decades ago and used only one urethral pressure
sensor together with one bladder sensor. The prevalence of urethral pressure variations and their
clinical significance is not clear. A URI prevalence of 12% was found in 397 patients with lower
urinary tract complains by McLennan [1]. In relation to the clinical significance of URI, Penders
et al., reported pure URI in 14 out of 31 (45%) patients with complains of refractory nocturnal
enuresis. A prevalence rate of 35% of mixed URI and DO was seen while isolated DO occur-
red in 3 of the 31 patients. When performing traditional cystometry, 17 of their patients would
be considered as ‘normal’. By performing simultaneous urethrocystometry in the same group
of patients, only 3 showed no abnormality. Therefore, URI is shown to be a common condition
in enuretic patients [6]. In a population of 427 gynaecologic patients with lower urinary tract
symptoms, isolated URI was found in 16.4% by Weil et al. [7]. In 27% of all 427 patients, URI
was found associated with DO. In their study, DO was more associated with nycturia, urgency,
and urge incontinence than URI. In 1985 Vereecken and Das published their data on URI in the
Journal of Urology. In 173 patients with a history of incontinence, they showed URI in 25 (14.4%)
[8]. Of these 25 patients, 12 also showed DO. They concluded that URI is associated more often
with DO and furthermore, only urethral pressure variations of more than 35 cm H
2
O provoked
overactive bladder complaints. This is in line with our observations: in patients with urethral pres-
sure variations of more than 31 cm H
2
O, DO was always present. URI appears to be close related
to urgency/frequency and seems to be a bad prognostic marker that increases the risk of urinary
incontinence. In contrast, Wise et al., reported no difference between patients with or without
URI in terms of prevalence or severity of urgency/frequency, nycturia or urge incontinence [10].
Both URI and DO was significantly more common in women presenting with stress incontinence.
Venema and Kramer already regarded URI as an expression of sensory urge that can give rise to
an insufficient sphincter mechanism and may explain incontinence treatment failure [5]. In their
study of 71 incontinent female patients with complains of urge, stress or mixed incontinence, URI
was seen in 66%. DO occur in 24% of these patients.
In the literature, several definitions of the term URI and associated symptoms are used. To rule
out (vascular) artefacts, we perform urethral pressure measurements with 3 urethral sensors. The
mid-urethral sensor is placed at the maximum urethral pressure (MUP) and we diagnose URI
when pressure variations in all 3 measurements are recorded.
When searching for a correlation between clinical improvement due to SNS treatment and change
in urodynamic parameters, the most significant change was seen in FSF. FSF increased from a
mean of 98 ml to 235 ml (p=0.002). With regard to DO and URI, disappearance of URI was seen
in 7 out of 13 (54%) successfully treated patients, whilst DO disappeared in 1 of the 4 patients
95
who responded with good result to the treatment. In the total group, URI disappeared at 6
months in 9 out of 17 patients (53%); in contrast, DO disappeared in 3 out of 9 patients (33%).
Analyses of merely peak or lowest value of the continuous urethral pressure measurements did
not show significant changes after SNS therapy (table 3). We therefore believe that instead of
searching for changes in peak values, the pattern of urethral pressure variations illustrating the
differences between peak and lowest value, indicating URI, is of much more importance for
evaluation of urodynamic data. An increase in FSF after SNS is reported by Elkelini [16]. Bladder
volume at FSF increased by 50% in 18 patients treated with a sacral root implant for urge incon-
tinence. As in our observations, only in one out of four patients who showed DO preoperatively,
this urodynamic finding disappeared after implant.
When including urethral measurement during filling in urodynamic evaluation, we often observed
that FSF is related to the phenomenon of URI: during filling, more pronounced fluctuations in
urethral pressure, indicating URI, often start at FSF. Also, it is often observed that URI is present in
patients with sensory urgency, illustrating the sensory impact of URI. Branches of the rami S2, S3
and S4 give rise to the parasympatic, autonomic plexus pelvicus and somatic pudendal nerve. The
pudendal nerve innervates among others the urethral sphincter. During neurostimulation, the so-
matic A-alpha and A-gamma myelinated pudendal nerve fibres are activated at a lower threshold
compared to the B and C parasympatic fibres [12]. This will result in an efferent effect of enhan-
ced urethral sphincter tone and increase of activity of the pelvic floor. Via afferent fibres this will
also result in inhibition of the detrusor muscle. If this hypothesis on the working mechanism of
neuromodulation were true, one would expect an urodynamic change in urethral function after
SNS. This may well explain diminished urethral pressure fluctuations as observed in this study.
SNS therapy affects detrusor behaviour via the afferent fibr