Re: The Artificial Somato-Autonomic Reflex Arch Does Not
Improve Lower Urinary Tract Function in Patients with Spinal
Cord Lesions
M. M. Rasmussen, Y. F. Rawashdeh, D. Clemmensen, H. Tankisi,
A. Fuglsang-Frederiksen, K. Krogh and P. Christensen
J Urol 2015;
193:
598
e
604.
To the Editor:
As the inventor and promoter of the Xiao procedure, I was disappointed in the
10 of 10 negative results in this trial from Denmark. However, I was not at all surprised due to
my experience in trying to convince other research teams to test the Xiao procedure in the right
way. When I read of the negative results in the abstract, I believed that there must be something
fundamentally wrong in the trial. I know now that the authors continued anticholinergic
treatment following the reinnervation procedure. As noted previously, this treatment can
result in failure of the somato-autonomic reflex pathway.
1
The authors note my recommendation
regarding “rigorous patient selection criteria
.
[including] preoperative and perioperative
electrophysiological evaluation, patient education, discontinuation of anticholinergics,
maintenance of less than 700 ml bladder capacity and a suprapubic catheter left in situ until
reflex arch voiding is established.” They report that most criteria were met, save the upper limit
of bladder capacity and cessation of anticholinergics, as they judged the medication essential for
patient well-being throughout the 18-month study. They state, “As reinnervation occurs at the
level of the preganglionic (nicotinic) receptors, and anticholinergics mainly target postganglionic
(muscarinic) receptors, we cannot exclude
.
that treatment may have diminished the reflex
.
[but] we do not believe that it would have abolished the reflex completely.”
Anticholinergics and clean intermittent catheterization have been the gold standard treat-
ment for neurogenic bladder caused by spinal cord injury (SCI) for more than half a century in
developed counties. This approach aims to block the neural connection between postganglionic
nerves and detrusor, paralyze the detrusor, inhibit the bladder contraction and make the bladder
a low pressure storage tank for clean intermittent catheterization. However, the goal of the Xiao
procedure is to reestablish neural control of the lower urinary tract via somato-autonomic
reinnervation to allow voluntary voiding. The postganglionic nerve to detrusor connection is
the last and most important leg of the somatic-central nervous system-autonomic reflex arch,
and if this leg is blocked by anticholinergics continuously, the newly established reflex arch could
never be activated to initiate detrusor contraction and voiding, as is the case in this report.
This trial is well designed and rigorously carried out by an outstanding team with credible
expertise in multiple specialties related to SCI. However, the anticholinergics issue is a funda-
mental scientific error, which is unfortunate and likely makes all of the results meaningless.
For example the baseline as well as postoperative urodynamic test results are influenced by
anticholinergic treatment and do not reflect the real reflex activity of the bladder. With the
anticholinergic medication the results should be the same, and, indeed, they were the same.
Moreover, antimuscarinics not only block the bladder response to reflex activation, but also
may suppress development of the new reflex pathway by interfering with the mechanisms of
reinnervation. For example reinnervation may depend on release of neurotrophic factors in the
bladder, and suppression of bladder activity by the drugs may reduce neurotrophic factor
production. Why was decreased leakage the only statistically positive result? It is because the
external urethra was simultaneously reinnervated by somatic motor axons and became func-
tional, which cannot be blocked by anticholinergics.
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Dochead: Letters to the Editor/Errata COR 5.4.0 DTD

JURO12723_proof
3 September 2015
2:59 am
EO: JU-15-1098
0022-5347/15/1946-0001/0
THE JOURNAL OF UROLOGY
®
2015 by A
MERICAN
U
ROLOGICAL
A
SSOCIATION
E
DUCATION AND
R
ESEARCH
,I
NC
.
http://dx.doi.org/10.1016/j.juro.2015.06.083
Vol. 194, 1-2, December 2015
Printed in U.S.A.
www.jurology.com
j
1


Nonetheless, this study should not be the end of the Denmark trial. I am confident regarding
the success of neural microanastomosis performed by skilled neurosurgeons I met in China, and
the expertise of the electrophysiology and urodynamic staff as shown in the article. I am also
confident that the somato-autonomic reflex arch has been established and can be activated
for voiding after discontinuation of anticholinergics. I suggest that the authors discontinue
anticholinergics for 2 months and then repeat the postoperative assessment as designed.
Discontinuation of anticholinergics for a few months under close watch will not affect “patient
well-being,” but may prove that anticholinergics are no longer necessary, as many other centers
have reported. Finally, I would advise anyone who may try the Xiao procedure not to do it if they
are determined to keep using anticholinergics.
Respectfully,
Chuan-Guo Xiao
Institute of Neurourology
CG Xiao Hospital
Shenzhen, China
e-mail: cgxiao_hospital@163.com
1. Xiao CG: Xiao procedure for neurogenic bladder in spinal cord injury and spina bifida. Curr Bladder Dysfunct Rep 2012;
7:
83.
Reply by Authors:
An effect of anticholinergic treatment on the results of the procedure cannot
be completely excluded. However, it will probably only reduce and not eliminate a reflex
response as it targets the postganglionic neurons, whereas nerve reinnervation will be pre-
ganglionic in the bladder. Furthermore, and most importantly, when interpreting our data, only
4 of 10 patients included received anticholinergic treatment at baseline and 3 continued on
followup. There was no effect of treatment in the patients not receiving anticholinergics.
Therefore, anticholinergic treatment cannot explain the observed lack of effect of the somato-
autonomic reflex arch on neurogenic bladder dysfunction. Furthermore, data on bowel function
from the same patients have recently been published and revealed similar disappointing
results.
1
Finally, our findings of diffuse electrophysiological changes in nerve root function
should be a concern for all surgeons using operative interventions targeting nerve reinnervation
in patients with SCI.
2
1. Rasmussen MM, Krogh K, Clemmensen D et al: The artificial somato-autonomic reflex arch does not improve bowel function in subjects with spinal
cord injury. Spinal Cord 2015; Epub ahead of print.
2. Tankisi H, Pugdahl K, Rasmussen MM et al: Peripheral nervous system involvement in chronic spinal cord injury. Muscle Nerve 2015; Epub ahead of
print.
2
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Dochead: Letters to the Editor/Errata DIS 5.4.0 DTD

JURO12723_proof
3 September 2015
2:59 am
EO: JU-15-1098