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Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injury.

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ORIGINAL ARTICLE
Early Sacral Neuromodulation
Prevents Urinary Incontinence After
Complete Spinal Cord Injury
Karl-Dietrich Sievert, MD,1 Bastian Amend, MD,1 G. Gakis, MD,1
P. Toomey,1 A. Badke, MD,2 H.P. Kaps, MD,2 and Arnulf Stenzl, MD1
Background: The study aim was to investigate potential influences on human nerves and pelvic organs through
early implantation of bilateral sacral nerve modulators (SNMs) in complete spinal cord injury (SCI) patients during
the acute bladder-areflexia phase.
Methods: Ten patients with neurologically-confirmed complete spinal cord lesions (SCLs) were provided with
bilateral SNMs during the phase of atonic-detrusor muscle. Modulation was achieved by two electrodes implanted
into each S3-foramen. Six patients declined and served as controls. The mean follow-up was 26.2 months.
Results: Videourodynamics (VU) confirmed detrusor acontractility, resulting in urinary continence as well as significant reductions in urinary tract infections (UTIs). Bowel movements did not require oral laxatives; additional
preprogrammed parameters achieved erections for intercourse.
Interpretation: Early SNM implantation in SCI patients may revolutionize neurogenic lower urinary tract (LUT)
dysfunction management; it prevented detrusor overactivity and urinary incontinence, ensured normal bladder
capacity, reduced UTI rates, and improved bowel and erectile functionality without nerve damage.
Conclusion: Future SCI investigations will be conducted to evaluate the potential benefits of even earlier SNM
placement to progressively enhance pelvic organ functionality. This new approach may provide important clues
required for assessing whether neuronal information is passed through the sympathetic trunk ganglion to the brain
after complete SCI. Further investigations are needed to determine if functional magnetic resonance imaging
(fMRI) might be helpful for analyzing changes in brain function in patients with SNMs and those taking antimuscarinics.
ANN NEUROL 2010;67:74 – 84
I
n animals and humans with para- and tetraplegia, the
initial period of detrusor acontractility is followed by
the emergence of a spinal-reflex-pathway that mediates
autonomic micturition as a result of detrusor overactivity.
Simultaneous contraction of the detrusor and sphincter
overactivity, a condition referred to as detrusor-sphincterdyssynergia (DSD) causes high bladder pressure, which is
the primary risk factor for reflux, resulting in renal deterioration and ultimately failure.1–3 The SCL patient’s
uncontrollable, reflex voiding is often insufficient, with
incomplete bladder emptying.4 Direct urological complications that can occur include vesicoureteral reflux, urinary tract infections (UTIs) or even septic shock, hydronephrosis, and kidney function loss. Possible indirect side
effects include increased blood pressure and intracranial
bleeding. Although SCI mortality due to urinary tract
complications has decreased, UTIs continue to be perceived as a significant danger.5
Decreased pressure of the lower urinary tract (LUT)
may be achieved through detrusor relaxation with oral antimuscarinics combined with intermittent catheterization.
However, relaxation of neurogenic detrusor overactivity
(NDO) using antimuscarinics cannot always be achieved
or tolerated.6,7 Botulinum toxin type A treatments have
been used despite their lack of U.S. Food and Drug Administration (FDA) approval.8,9 Future therapies, such as
stem cell therapy or growth factor use to restore function
after neuronal injury, are currently being investigated.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ana.21814
Received Nov 27, 2008, and in revised form Jul 6, 2009. Accepted for publication Jul 28, 2009.
Address correspondence to Prof Dr Karl-Dietrich Sievert, Department for Urology, University of Tübingen, Germany, Hoppe-Seyler-Str. 3, D-72076
Tübingen, Germany. E-mail: Karl.Sievert@med.uni-tuebingen.de
From the 1Department of Urology, University of Tuebingen, Tuebingen, Germany; and 2Spinal Cord Unit, University of Tuebingen,
BG Trauma Centre, Tuebingen, Germany.
74
© 2010 American Neurological Association
Sievert et al: SNMs in SCI LUT Dysfunction Management
Sacral nerve stimulation has been successful for select cases in both animal models and in humans. Recent
feline SNM studies have further investigated the chronic
spinal cord lesion (SCL).10,11 In contrast, in 1998, Elhilali and colleagues investigated sacral neuromodulation
(SNM) in the dog model during the acute SCI phase12
and later after long-term, chronic application.13 In this
early SNM animal investigation, the acontractile detrusor
resulted in an overactive bladder; with modified stimulation parameters, the researchers subsequently treated the
detrusor overactivity and initiated micturition.13 While a
measure of success has been achieved, no published animal models have been successfully translated to a human
clinical trial.
The current neurostimulation treatment method
employed for human bladder dysfunction after an SCL
has also either achieved limited success14 or required
highly-invasive spinal surgery to implant leads on spinal
roots with additional deafferentiation.15 It is currently believed that high stimulation voltages are required for successful neurostimulation, but the disadvantages can be severe: intact autonomic influences are lost forever, resulting
in a negative effect on organs, including even the heart.
Published urological SNM case reports have been attempted without success in complete chronic SCI human
patients,16 –19 and no published SCI clinical studies initiating treatments to avoid bladder or LUT malfunction
before irreversible effects occur (and can then ultimately
be treated only at the muscle level).
Perhaps even more importantly, no studies have yet
investigated the plasticity of the remaining intact sympathetic ganglion trunk extending to the brain (bypassing
the SCL); the existence of such plasticity could significantly change how and when SCI patients are treated. In
addition, there may be other possible influences of the
direct inhibitory effect of sacral afferents on the parasympathetic efferents at the level of the sacral cord.20 If we
bear in mind that the mechanism of action continues to
be unknown for an intact SCI patient, it is entirely understandable that this mechanism in SCI patients might
elicit even further uncertainties. In the complete SCI patient, we can hypothesize that this information may be
transmitted only through hypogastric-sympathetic nerves
to the brain; this hypothesis might explain the phenomenon of increasing blood pressure correlated with bladder
fillings.21 The external sphincter is innervated by the motor neurons in the Onuf’s nucleus of the sacral cord and
the detrusor muscle is innervated by preganglionic parasympathetic motor neurons in the sacral intermediolateral
cell column (IML).22,23 The SNM might be inhibited in
the complete SCI patient and the activation of pregangliJanuary, 2010
onic parasympathetic motor neurons may avoid detrusor
overactivity. As a putative mechanism of action, it can be
reasoned that hypogastric sympathetic nerves may have an
inhibitory effect on parasympathetic fibers at the pelvic
ganglia.24 –26 If the remaining nerves below the injury
have a degree of plasticity that can be influenced by SNM
and the hypogastric sympathetic nerves can be stimulated,
the combined result might be detrusor overactivity avoidance. The study aim was to demonstrate the potential influence of early bilateral SNM implantation on human
nerves and their pelvic organs in complete SCI patients
during the acute bladder-areflexia phase.
Materials and Methods
Study Approach
This study was approved by the clinic ethics committee. Beginning in December 2005, 16 SCI patients with neurologically
confirmed, trauma-related complete SCLs (above Th12, American Spinal Injury Association [ASIA] Impairment Scale ⫽ A)
were asked to participate in the early SNM study. Bladder functional status was evaluated using videourodynamics (VU) in accordance with International Continence Society (ICS) guidelines27 and a electromyography (EMG) was performed to
confirm pelvic hyperactivity. When bladder acontractility was
verified, the patients were offered bilateral SNM treatment. Six
patients who declined served as controls.
At enrollment, the participants were provided with: (1)
catheterization protocols; (2) bladder, bowel, and erectile function diaries to annotate the catheterization time and amount and
time of fluid intake, incontinence events, bowel movements, and
currently used drugs; and (3) a specific SCI questionnaire. As
patients were enrolled and consent was obtained, relevant examination data were maintained in an Excel (Microsoft威, Redmond, WA) spreadsheet. Participants who aspired erectile functionality were evaluated with Erectile Hardness Score (EHS
Grade 1– 4) criteria.
Subsequent VU and EMG examinations were performed
at 3 and 6 months, as well as every 6 months thereafter. Preceding each periodic examination, the participants were asked to
prepare a special 3-day diary. All VU studies were performed
using a filling speed of 20ml/minute up to involuntary urine
leakage or a capacity of approximately 500ml. An AquariusTT
(Laborie Medical Technology, Ontario, Canada) with a double
micotip catheter UROBAR威 (Raumedic AG, Helmrechts, Germany) was used and the recorded data were analyzed with regard to maximal bladder capacity, bladder reflex volume, maximum detrusor pressure and detrusor compliance. In adherence
with the study’s protocol, the control group was followed using
an identical process, but were prescribed oral antimuscarinics
and, upon request, urinary condoms.
Surgical Approach
Under local anesthesia, the participants were implanted with one
tined lead electrode in each S3-foramen after verification of an
75
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FIGURE 1: Initial VU acontractile detrusor. Bladder pressure does not increase over 20cmH2O and EMG activity is not
present. SCI patient’s coughing does not cause expected autonomic detrusor contraction.
optimal motor response of the intact lower motor neuron (anal
sphincter contraction). The implants were placed 2.9 (range,
0.8 – 4.5) months after the initial trauma. Each lead was connected to an Interstim威 or newly enhanced Interstim-II威.28,29
Compared to the common testing period in non-SCI patients
with LUT or bowel dysfunction,30 no testing phase was utilized;
this decision is in line with the theory that DSD would occur at
a future unspecified time and that its effects would not be reversible, as previously demonstrated by others investigating
SNM in SCI patients.17,18
On the implantation day, all implants were identically
programmed using a specifically selected algorithm; the amplitude parameters were precisely coded so that the electrical field
would not costimulate other nerve roots, cause further involuntary stimulation, or result in lower extremity muscle contraction.
If an implant participant reported involuntary urine loss,
the potential likelihoods of urine infection, electrode dislocation,
and stimulator malfunction were immediately determined using
a 24-hour center. Infections were treated with antibiotics; in the
case of lead dislocation, treatment included repositioning using
the original parameters and programming.
Results
All 16 participants were males (age: mean 31; range,
19 – 47 years) who experienced trauma-related complete
76
SCI at level Th2/3–11. Detrusor acontractility of the implant participants was verified by VU (Fig 1). The mean
follow-up period was 26.2 (range, 5.4 –38.9) months.
Surgical Results
The initial four implant participants received Interstim威
bilateral implants subcutaneously in the lower abdominal
wall. Lead malfunctions or dislocations (Fig 2A, B) occurred and Interstim威 modulators were replaced (3/4)
with new Interstim-II威 in the buttock (Fig 3) using the
initial parameters.29,31 Subsequent participants received
the new Interstim-II威, which is 50% smaller and provides
more programming options (Fig 3).31 Lead repositioning
was mandatory because the leads had moved from their
initial to deeper positions (n⫽6). In three Interstim威 participants, the leads dislocated from their original positions
due to lower extremity spasticity and resulted in NDO
(Fig 2A, B). The dislocations were noted when the implant participant reported involuntary urine loss. After exclusion of urine infection, X-ray, urodynamics, and EMG
studies were performed to ascertain whether an electrode
dislocation or stimulator malfunction had occurred (Fig
4). All participants who were reimplanted achieved contiVolume 67, No. 1
Sievert et al: SNMs in SCI LUT Dysfunction Management
1,000ml without involuntary urine loss. The participants
did not report involuntary urine leakage while the electrodes were in place, nor they did not receive an antimuscarinic or botulinum toxin A prior to their last evaluation,
except the two patients who rejected further study participation(see “Late Dropouts”). With additional InterstimII威 programming, two patients experienced improved
erectile function that permitted satisfying sexual intercourse. The 10 participants had a mean of 0.5 (range,
0 –1) UTIs per year that were treated with oral antibiotics
without hospitalization. Participants reported sufficient
SNM colon movement without oral laxatives. Six of the
participants used Lecicarbon威 suppositories (natrii hy-
FIGURE 2: X-rays of Interstim姞 implanted in the lower abdomen in first four participants. (A) Ruptured lead malfunction. (B) Dislocated dual leads.
nence and demonstrated reestablished detrusor acontractility, as verified by VU, within 1 week (Fig 5). No intraor postoperative complications were reported for the implant participants.
Study Results
The VU follow-up confirmed low bladder pressure
(ⱕ30cmH2O) upon filling (volume mean, 399ml; range,
357–508ml) (Table) without inducing autonomic detrusor contractions. The compliance registered ⬁cmH2O/ml
throughout the filling phase. EMGs did not register pelvic
hyperactivity. The analyzed diaries revealed mean catheterized volumes of 582ml (range, 480 – 650ml). Some
participants occasionally reported bladder volumes up to
January, 2010
FIGURE 3: X-rays of Interstim-II姞 implanted in the buttock.
(A) Abdominal view. (B) Lateral view
77
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FIGURE 4: VU preoperative dual-lead malfunction and typical DSD symptoms. Increased bladder pressure caused urine
leakage and increased EMG activity. Note: Results appear similar to an untreated DSD patient in Fig 6. Implant participants
become “controls of themselves.”
drogenocarbonas [ie, sodium hydrogen carbonate,
NaHCO3] 500mg, and natrii dihydrogenophosphas anhydricus [ie, sodium dihydrogen phosphate dihydrate,
NaH2PO4 2H2O] 680mg) to induce rectum emptying.
Based on the questionnaire, comments, and verbal
conversations with implant participants, all implant patients reported a significantly better quality of life (QoL)
than the controls. The participants commented that they
would suggest a similar treatment to other SCI patients.
“Late Dropouts”
In the last 2 months, patient RD underwent an examination revealing overactivity with recurring involuntary
urine loss. The patient (Table) declined further diagnostic
or surgical intervention, although acontractility was
achieved within 1 week after each revision (four previous
electrode revisions were performed due to electrode malfunction). The patient’s Interstim therapy was supplemented with an antimuscarinic drug. Another patient
(RS) declined the X-ray control examination and potential resultant surgery; Interstim therapy was combined
78
with an oral antimuscarinic to ensure continence and detrusor pressure.
Control Group
Despite taking antimuscarinics, the control patients frequently experienced common SCL symptoms: lower bladder capacities (mean 208ml; range, 57–314ml) and bladder pressure of ⌬pd ⬎ 30cmH2O (Table; Fig 6). They
reported mean catheterized volumes of 294ml (range,
105–390ml) in their diaries. The control group performed more frequent self-catheterizations and used urinary condoms because of involuntary urine loss caused by
low bladder capacity and higher intravesical pressure. To
date, the controls have not received or requested botulinum toxin A as a treatment option. Control group patients experienced a mean of 3.8 (range, 1–7) UTIs. One
patient required a suprapubic catheter and continuous antibiotic drug because of constant UTIs; two patients required hospitalization due to septic situations. All control
patients required oral suppositories; four of six regularly
used oral laxatives and digitally emptied their rectum.
Volume 67, No. 1
Sievert et al: SNMs in SCI LUT Dysfunction Management
FIGURE 5: VU postoperative dual-lead repositioning. Figure 4 leads repositioned to original optimal locations, again demonstrating a strikingly normal VU.
Those who desired intercourse required PDE-5 inhibitors
or vacuum devices.
to prevent LUT malfunctions in SCI patients before irreversible effects occur.
Discussion
Study Approach Rationale
In previous publications, selective nerve blocking using
electrostimulation seemed to offer a promising approach
to induce coordinated, low-pressure voiding. While the
SCI patient-approved Brindley implant requires necessary
bilateral deafferentation of S2– 4, we investigated, using
minimally-invasive, S3-bilateral SNM supply without nerve
interaction. Whereas others reported only selected success,16,35–37 one group has previously reported success
while applying sacral-root-stimulation at the point of injury.12 In a subsequent DSD and detrusor overactivity study,
the storage and micturition functions were influenced by
parameter revisions.13 This is the first successful study to
use SNM with a unique early approach and identical preprogrammed implant parameters in all devices.
Background
DSD development after SCL represents a challenge for all
specialists, but especially for urologists seeking to prevent
possible life-threatening effects like kidney failure. For the
SCI patient, significant QoL issues (eg, involuntary urine
loss, UTIs, frequent catheterization, constipation requiring digital stool removal,9,32,33 and a lack of sexual function) impact the ability to be healthy, function autonomously, and interact socially.
In recent decades, antimuscarinics became the standard oral drug used to treat detrusor overactivity. Inefficient dosages and side effects cause some patients to reduce or discontinue medication. Botulinum toxin A,
although still not approved by the FDA, has been utilized
to treat bladder overactivity more effectively than antimuscarinics.34 However, it can only be used when there is
an individual agreement between the physician and patient. To our knowledge, this is the first human clinical
study utilizing an effective, minimally-invasive approach
January, 2010
Initial Theory
In all cases after upper neuron injury, detrusor overactivity
and DSD will eventually occur if not effectively treated.3 It
is imperative to underscore that DSD and detrusor overac79
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of Neurology
TABLE: Patients’ Characteristics, Urodynamics and Clinical Follow-up Data
Patient Initials, Age (years) at
the Time of Accident
Participants with Interstim威 and
Interstim II implants
1. AB, 23
2. AE, 19
3. MT,b 38
4. RD, 35
5.
6.
7.
8.
KD, 32
JW, 24
RH,b 37
RS, 36
9. BB, 34
10. XF, 27
Controls
1. BA, 47
2. GJ, 38
3. RJ, 37
4. WM, 38
5. SM, 32
6. TD, 27
Injury Lesion
Level
Time (months) to
Implant
Antimuscarinic
2.9b
3.5
2.2
3.2
N
N
N
26.1 oralc
Th 3/4
Th 9/10
Th 5/6
1.9
3.2
4.5
N
N
N
Th 4/5
3.9
14.3 orald
Th 5/6
Th 7/8
3.8
0.8
N
N
Th
Th
Th
Th
—
—
—
—
4.5
5.7
6.4
3.9
—
—
4.3 oral
4.9 oral
Th
Th
Th
Th
2/3
4
4/5
5/6
11
4
10
10
Th 5
Th 5
oral
oral
intravesical
oral
Follow-up
[months (electrode
revisions)]
38.9 (0)
34.5 (1)
30.4 (2)
29.5
26.7
22.7
19.3
(4)
(1)
(1)
(0)
19.2 (0)
19.0 (0)
5.4 (0)
37.6
32.9
26.5
29.1
22.0
25.4
⌬pd ⱕ 30cmH2O is the detrusor pressure. bParticipant used additional Interstim programming to induce an erection for
intercourse. cParticipant required four electrode revisions due to electrode malfunction; declined further participation/surgery in
the last month. A combined therapy was administered. dParticipant declined X-ray control and potential resultant surgery in the
last month to assess possible electrode movement. A combined therapy was administered. e“N, but if urine infection Y” means
that if the patient does not have a urine infection he is continent, but if a urine infection occurs the patient becomes urine
incontinent. N ⫽ No; Y ⫽ Yes; Th ⫽ Thoracic.
a
tivity development are not yet fully understood, particularly
since certain changes transpire before they are reported and
examined in the clinic. It was our intention in this study to
prove that neurostimulation could be even more successful
by providing patients with a minimally-invasive treatment
option before seemingly irreversible pathology occurs and
until the mechanism can be better understood. This study
was intended to provide an initial step in facilitating early
treatment to avoid detrusor overactivity in SCI patients
while further investigating this SCI timeline.
to maintain bladder pressure and prevent DSD. Currently, this low-pressure system has been maintained for
up to 38.9 months without further treatment when the
electrode(s) remained in their optimal positions. In recent
evaluations (⬍2 months), one patient declined further revisions (Table), even though urodynamics demonstrated
normalized detrusor pressure after each revision. Reestablishment of detrusor pressure validated the hypothesis that
the malfunction of the end organ (bladder) can be
avoided by SNM within a specific time-frame.
Clinical Results
In early SNM implantation, detrusor status did not
change from acontractility to overactivity. In addition to
amplitude, preset parameters were specially programmed
Participants vs. Control Group
The implant avoided involuntary urine loss and UTIs (by
maintaining lower bladder pressure with a higher bladder
volume) and improved bowel movement control. Two
80
Volume 67, No. 1
Sievert et al: SNMs in SCI LUT Dysfunction Management
TABLE: Continued
3-Day Diary Outcome
Last Urodynamic Bowel Laxatives
Capacity (ml)
Suppository Oral Laxative ⴙ
with ⌬pd <
Digital Emptying
a
30cmH2O
Average
Results for the Last 12 Months
Bladder
Infections/Treatment
Capacity (ml) Incontinence
550
480
650
350
560
480
500
N
N
N
N
N
N
N
0
1/antibiotic
0
1/antibiotic
0
1/antibiotic
0
500
350
508
320
478
357
500
N
Y
N
Y
Y
N
Y
N
N
N
Y
N
N
N
320
550
570
N
N
N
0
288
1/antibiotic ⫹ cranberry 502
1/antibiotic ⫹ cranberry 506
Y
N
Y
N
N
N
105
260
360
370
Y, suprapubic catheter
Y, urinary condom
Y, urinary condom
N, but if urine
infection Ye
Continuous/ antibiotics
2
6
57
187
314
Y
Y
Y
Y
N
Y
3/cranberry
254
Y
Y
280
390
Y, urinary condom
N, but if urine
infection Ye
7/cranberry ⫹ antibiotics 175
1
337
Y
Y
Y
N
patients requested advanced Interstim-II威 programming
to support erectile function allowing sexual intercourse, a
function that has been previously reported only for the
Brindley model.15 The participants with SNMs reported
more independence and “normal” social participation;
they noted that their QoL was much higher than that of
the control group. Additionally five of the 10 enrolled
participants “became controls of themselves” due to lead
dislocation or rupture that led to detrusor overactivity and
involuntary urine loss (Figs 1–5). During this time period
they experienced similar decreased symptoms as those
who served as “controls.”
Underlying Neurourological Theories
One theory postulates that low amplitudes might be effective; when lead dislocation occurs, however, bladder
January, 2010
malfunction is not sufficiently treated due to the superadditive effect of stimulation.38 A more favorable theory
suggests that SCI influences the end organs detrusor and
urethral sphincter via dominating pathological changes.
This success substantiates for the first time the effectiveness of early SNM implantation in SCI patients.
The study’s achievements may be attributed to a
previously reported, subsensorial threshold proven to be
effective in non-SCI patients who required no amplitude
increase for effective treatment.31 Additionally, early
SNM might imitate central nerve system effects that
would have been lost after complete SCL. Furthermore,
the presented data might help to explain the next steps in
understanding the inhibitory effect of the sympathetic hypogastric nerves or other effects. While electrodes are
81
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of Neurology
FIGURE 6: VU control group DSD development. Bladder pressure rises over 100cmH2O upon 175ml fill, causing involuntary
urine loss. EMG pelvic floor and external urethral sphincter activity reached 1,000␮V prior to increased detrusor pressure.
placed bilaterally into the S3-foramen, the sacral roots
bridge to one another39 and permit a neuronal connection
with the hypogastric nerves. After SCI, this nerve trunk is
typically intact. Because of this quality, SNM seems to inhibit the detrusor and most likely causes the effect observed
in this study, while the two separate pathways controlling
micturition and continence22 are damaged. In contrast,
SNM might become the “pacemaker” in this early SCI
stage, thus imitating the continence pathway.
This minimally-invasive SNM approach for complete SCI patients resolves two primary urological concerns: urine continence and constipation. Early bilateral
SNM implantation prevented neurogenically-induced
high-storage pressure, maintained sufficient bladder capacity, avoided incontinence, and extended selfcatheterization time intervals, and thus most likely reduced UTIs.
Putative Mechanism of Action
Although the mechanism of action for SNM is not well
understood and requires further investigation, it appears
to be afferently mediated. Acute SCI initially leads to detrusor acontractility and complete urinary retention,
82
which is followed by slow overactivity development and
urinary incontinence caused by C-fiber-mediated spinal
reflex pathways,40 probably related to the interrupted regulatory mechanism between the end organ (bladder and
urethral sphincter and midbrain for the two separated
pathways of micturition and continence).22 Early SNM
bilateral implantation during the bladder-areflexia phase
might preserve nerve plasticity, such that C-fibers remain
silent, detrusor overactivity is avoided, and sympathetic
preganglionic neuron activation in the thoracolumbar
cord is suppressed. These changes reduce transmission in
the spinal viscerosympathetic reflex pathway.41– 43
Whether SNM suppressed bladder contractions via the
sympathetic hypogastric nerves or instead blocked the
overactivation of the parasympathetic pelvic excitatory
neurons resulting from SCI currently remains unclear and
requires further investigation.20,44 Currently, SNM seems
to be capable of inhibiting the micturition reflex, resulting
in increased urinary bladder storage function. The pathways demonstrated by Blok and Holstege,22 which influence micturition and storage (continence), underline the
need for bilateral stimulation.
Volume 67, No. 1
Sievert et al: SNMs in SCI LUT Dysfunction Management
Study Limitations and Future Improvements
The initial study aims were to influence the detrusor and
ensure acceptable bladder volumes to prevent involuntary
urine loss and potential antimuscarinic side effects; these
aims were achieved in participants as long as electrodes
maintained their optimal positions. A current study limitation was that participants were not able to micturate. In
the next steps, we will (1) enhance and optimize the programming parameters; (2) examine the implantation timeline to better determine if the window, which influences
external urethral sphincter overactivity, must be initiated
even earlier (patient 10); and (3) examine and correct the
causes of dislocation. Further patient improvement may
occur with even earlier implantation, if we are able to
determine the optimal time of acute intervention to prevent subsequent neuronal changes. Finally, different and
more progressive approaches will be initiated to prevent
further foramen penetration.
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Conclusion
Early SNM implantation in SCI patients may revolutionize neurogenic LUT dysfunction management, as it prevents detrusor overactivity and urinary incontinence, provides normal bladder capacity, and reduces UTI rates.
Bowel and erectile function were additionally improved.
Future investigations will be conducted to evaluate
the potential benefits of earlier SNM implantation to rehabilitate the functional outcome of those organs of the pelvis
and enhance SCI patient QoL. This new approach may
also provide important clues required for assessing whether
certain neuronal information is passed through the sympathetic ganglion trunk to the brain after complete SCI. Further investigations (eg, functional magnetic resonance imaging [fMRI]) might be helpful to analyze altered brain
activation or deactivation states between patients using
SNM and those taking an antimuscarinic agent.
Medtronic, Inc. (Minneapolis, MN) supported this unrestricted study with hardware (neuromodulators and electrodes) to K.D.S.
The authors wish to thank U. Van den Hombergh
(Medtronics, Inc., Europe) for supporting the study concept and finalizing the unrestricted grant, C. Baron (BG
Trauma Center) for candidate preselection and D.
Guertler for VU examinations. Further, the author wishes
to express appreciation to C. Fowler (National Hospital
for Neurology and Neurosurgery, London, UK) and E.A.
Tanagho (University of California–San Francisco, SF,
CA, USA) for their mentoring and support which fostered
the concept of this clinical trial.
January, 2010
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84
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