Repetition of conditional
stimulations as treatment for detrusor hyperreflexia may potentiate the effect
1Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark
2Center for Sensory Motor Interaction, Aalborg University, Denmark
3Department of Urology, Aarhus University Hospital, Denmark
4Department of Urology, Aalborg County Hospital, Denmark
Abstract
Introduction Conditional short duration electrical
stimulation can inhibit hyperreflexic detrusor contractions and increase
cystometric capacity in spinal cord injured patients significantly. Material and Methods Six patients had a
standard cystometry performed as a control. To optimize stimulation parameters
conditional electrical stimulation using 8, 15 and 30 pulses per second (pps)
in randomized order was performed during three subsequent cystometries. The
stimulation was performed on the penile/clitoral nerve in response to one or
more hyperreflexic detrusor contractions during the three cystometries. Results Mean cystometric capacity
increase compared to control: 1st cystometry 48%, 2nd
59%, 3rd 63%. The most effective pulse-frequency was 8 pps. Increase
compared to control: 8 pps 70%, 15 pps 43% 30 pps 57%. Conclusion Our findings suggest that repetition of conditional
stimulation may lead to potentiation rather than habituation. A stimulation
frequency of 8 pps seems to be more effective than 15 pps and 30 pps.
Spinal cord injured patients with a lesion above the
sacral micturition center suffer from detrusor sphincter dyssynergia and
detrusor hyperreflexia. The injury impairs or eliminates the regulatory input
from the higher centres, leading to lower urinary tract dysfunction. Detrusor
hyperreflexia disturbs the storage function and it may cause incontinence and
reflux. The pharmacological treatments are in many cases insufficient to
prevent incontinence episodes and high bladder pressures. More efficient
treatments for detrusor hyperreflexia involve surgery, either in bladder
augmentation procedures or in dorsal rhizotomy. Bladder augmentation procedures
carries side-effects related to the mucosal surface of the neo-bladder, whereas
rhizotomy involves irreversible division of nerves and leads to loss of reflex
erection1,2.
Activity in the dorsal penile/clitoral nerve, which is
an exclusively afferent branch of the pudendal nerve, is inhibitory to the
micturition reflex3-5. Our group performed a study in 10 spinal
cord injured patients using conditional short duration stimulation of the
dorsal penile/clitoral nerve (2-25 s). The parameters were: 20 pulses per
second (pps), pulsewidth 200 s, amplitude 2 times threshold for eliciting the
bulbocavernosus reflex. Hyperreflexic contraction could be inhibited repeatedly
and cystometric capacity was increased by 72%5,6.
In order to optimize the stimulation parameters the
present study was initiated. By performing conditional stimulation using
different pulse-frequencies during 3 consecutive standard cystometries, the
effect of repeated treatments and of different pulse-frequencies can be
investigated. The study is ongoing.
The local ethical committee approved of the study, and
informed consent was obtained from the 6 patients enrolled.
Inclusion criteria were: detrusor hyperreflexia
demonstrated at less than 500 ml infused during a standard cystometry on the
day of the experiment, complete or incomplete suprasacral spinal cord injury
irrespective of pathophysiological origin, age over 18 years and 6 months or
more post injury. Exclusion criteria were: damage to peripheral nerves involved
in the reflex-loops investigated, other serious disease or pregnancy. Medical
treatment for detrusor hyperreflexia or other diseases was not discontinued
prior to the experiment
Cystometries were performed according to
ICS-definitions transurethrally, as one continuous infusion of body-warmth
saline with an infusion-rate of 60 ml/min via a Ch-8 catheter while
intra-vesical pressure was measured through another Ch-8 catheter, using a
Dantec Menuet, Dantec Duet or an MMS Urodynamic Computer. Cystometric
capacity was established as leakage volume, the volume at which hyperreflexic
phase started defined as the part of the cystometry where repeated contractions
merged and led to a prolonged phase of oscillatory high pressures, or the
maximal infused volume of 600 ml. The cystometry performed as part of the
inclusion criteria served as the patients control-cystometry. Electrical
stimulation was performed using a bipolar electrode (HUSH-bar electrode,
Dantec-Medtronic), which was held by the investigator on the skin over the
dorsal penile/clitoral nerve. Switching stimulation-trains on/off was performed
manually, the "stimulation on"-trigger signal being a increase in Pdet
of 5 cmH2O, the "stimulation off"-trigger signal being a
decrease in Pdet. Both trigger-signals were obtained by visual
inspection of the monitor of of the Urodynamic Computer. Pulse-frequencies of
8, 15 and 30 pps were tested in randomised order (Table 1). Repeated
stimulation-sequences were performed in response to repeated bladder
contractions during one cystometry. Control cystometric capacity was compared
to the 3 treatment cystometry capacities.
|
|
No stimulation
|
Conditional stimulation
|
|
|
Control cystometry
|
1st cystometry:
pulses/s
|
2nd cystometry
pulses/s
|
3rd cystometry
pulses/s
|
|
1, Female
|
|
8
|
15
|
30
|
|
2, Male
|
|
30
|
8
|
15
|
|
3, Male
|
|
15
|
8
|
30
|
|
4, Female
|
|
15
|
30
|
8
|
|
5, Male
|
|
8
|
30
|
15
|
|
6, Male
|
|
30
|
15
|
8
|
Table 1.
The 6 possible
combinations of the three different simulation-frequences were randomised
before examinations.
Fig 1.
The cystometric
capacity of the control cystometry and the three consecutive cystometries.
Fig 2.
The cystometric capacity of the control
cystometry and the treatment cystomtries ranked by stimulation frequency.
Results
A typical control cystometry consisted of a normal
compliant storage phase followed by a rapid change into the hyperreflexic
phase.
During the treatment cystometries, inhibition
stimulation was considered effective if a pressure reduction elicited was
markedly lower than observed during the natural pressure oscillations of the
hyperreflexic phase found during the control cystometry. According to this
criterium inhibition was effective in 4 of the 6 patients (Fig 1 and 2). Of the
patients where inhibtion was ineffective, one (# 4) was in treatment for
urinary tract infection and the other patient (#5) was stimulated with
relatively low amplitude (18 mA) due to partially preserved sensation. One
patient (#3) reported some bladder sensation and the occasional use of penis
squeezing to postone voidings.
The mean capacity increased with repetition of the
cystometries (Increase compared to control: 1st cystometry 48%, 2nd
59%, 3rd 63%). Marked difference between the control and the first
stimulated cystometry was noted , whereas the increaments between the three
stimulated cystometries were smaller. The most effective pulse-frequency was 8
pps (Increase compared to control: 8 pps 70%, 15 pps 43% 30 pps 57%).
These preliminary data supports the conclusion of the
previous study performed by this group: conditional stimulation of the dorsal
penile nerve inhibits hyperreflexic detrusor contractions and leads to
increases in cystometric capacity. The fact that one patient uses squeezing of
the penis to postpone voidings, which is equivalent to our experimental
treatment, underlines the potency of the reflex arc exploited. The capacity and
pressure properties of the bladder have been shown to be less adaptive to
repeated bladder fillings than case is with detrusor hyperreflexia in
non-spinalised patients 6-8. Accordingly changes between control and
treatment cystometries seen in the present study can be ascribed to the
stimulation performed. Conditional stimulation increases capacity by 50-60%,
the increase gets slightly larger as treatment cystometries are repeated. Thus,
our findings suggest that repetition of the conditional stimulation may lead to
potentiation rather than habituation. A stimulation frequency of 8 pps seems to
be more effective than 15 pps and 30 pps.
A study in 15 paraplegics using conditional stimulation via an anal plug
electrode found 5, 10 and 20 pps stimulation-frequences to be equally effective9. Continuous stimulation of the dorsal
penile nerve using 1 and 5 pps was effective in eliminating hyperreflexic
contractions and increasing cystometris capacity3,4. Further studies are needed to optimize
stimulation parameters and substantiate the effect of repeated conditional
stimulation cystometries.
Acknowledgement
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