Urological Outcome of the Xiao Procedure in Children
with Myelomeningocele and Lipomyelomeningocele
Undergoing Spinal Cord Detethering
Gerald F. Tuite,* Yves Homsy, Ethan G. Polsky, Margaret A. Reilly,
Carolyn M. Carey, S. Parrish Winesett, Luis F. Rodriguez,
Bruce B. Storrs, Sarah J. Gaskill, Lisa L. Tetreault, Denise G. Martinez
and Ernest K. Amankwah
From the Division of Pediatric Neurosurgery, Neuroscience Institute (GFT, CMC, LFR, BBS), Department of Occupational
and Physical Therapy (MAR), and Clinical and Translational Research Organization (LLT, DGM, EKA), Johns Hopkins
All Children¡¯s Hospital, Saint Petersburg and Division of Pediatric Neurosurgery, Department of Neurosurgery and
Brain Repair (GFT, CMC, LFR, BBS, SJG), Division of Pediatric Neurology, Department of Pediatrics (SPW) and
Department of Urology (YH, EGP), University of South Florida, Tampa, Florida, and Department of Pediatrics,
Johns Hopkins Medicine, Baltimore, Maryland (GFT)

Abbreviations
and Acronyms
BAM ¼ bladder active medication
CIC ¼ clean intermittent
catheterization
DT ¼ detethering only
DTtX ¼ detethering plus Xiao
LPP ¼ leak point pressure
QOL ¼ quality of life
TBC ¼ total bladder capacity
UDC ¼ uninhibited detrusor
contraction
XP ¼ Xiao procedure

Purpose: Although previous studies have revealed high success rates (70% to
85%) after an intradural somatic-to-autonomic nerve transfer procedure in
children with spinal dysraphism, no study has had a control group or blinded
observers. We report a rigorously designed study to investigate the effectiveness
of the Xiao procedure.
Materials and Methods: Children with neurogenic bladder dysfunction related
to myelomeningocele or lipomyelomeningocele who required spinal cord detethering
were randomized to 2 groups at surgery, with half undergoing only
spinal cord detethering and half undergoing the Xiao procedure in addition to
detethering. Double-blind evaluations were performed at regular intervals during
the 3-year followup.
Results: A total of 10 patients underwent spinal cord detethering only and 10
underwent detethering plus the Xiao procedure. The Xiao procedure did not
result in voluntary voiding or continence in any patient, but patients undergoing
spinal cord detethering plus the Xiao procedure were more likely to have greater
improvements in total bladder capacity, bladder overactivity and overall quality
of life than those who underwent detethering only. By the end of the study no
participant or evaluator was able to accurately predict to which group the patients
had been assigned.

Accepted for publication May 31, 2016.
No direct or indirect commercial incentive associated with publishing this article.
The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional
review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics
committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees
of confidentiality; IRB approved protocol number; animal approved project number.
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. This
work was financially supported primarily by a research grant from the All Children¡¯s Hospital Foundation. Additional financial support was
provided by the AANS/CNS Joint Section on Pediatric Neurosurgery and the AANS/CNS Joint Section on Disorders of the Spine and Peripheral
Nerves.
* Correspondence: Institute for Brain Protection Sciences, Division of Pediatric Neurosurgery, Johns Hopkins All Children¡¯s Hospital, 601 5th
St. South, Suite 511, Saint Petersburg, Florida 33701 (telephone: 727-767-8181; FAX: 727-767-8030; e-mail: gtuite1@jhmi.edu).
See Editorial on page 1608.

Conclusions: The results of this randomized controlled trial are in agreement with recently published
similarly poor results of the Xiao procedure in patients with spinal cord injury. Improvements in bladder
parameters observed in this study may be related to sacral nerve root section, a necessary portion of the Xiao
procedure, instead of reinnervation. Confirmatory animal studies are recommended before further clinical
trials of the Xiao procedure are performed in humans.
Key Words: nerve transfer, neural tube defects, spinal dysraphism, urination

THE Xiao procedure, which creates a ¡°skinecentral
nervous systemebladder¡± reflex through an intradural
lumbosacral nerve transfer, has been reported
to result in voluntary voiding in patients with
neurogenic bladder dysfunction related to spinal
cord injury and spina bifida.1e6 However, recent
studies of the Xiao procedure in patients with spinal
cord injury have not resulted in measurable benefit
to patients, raising concern about the reproducibility
of the results.7e10
Our group recently published the initial results
of a randomized, prospective, double-blind trial
of the XP in 20 children undergoing spinal cord
detethering.11 All patients remained incontinent,
wore pullups or diapers, and were unable to initiate
or control their own urination in a meaningful way
before and at all intervals during the 3-year followup.
Urodynamic bladder contractions (detrusor
pressure greater than 10 cm H2O) in response to
scratching occurred in many patients who underwent
XP, as well as those who did not undergo the
procedure. No patient who underwent XP had reliable,
reproducible, scratch initiated bladder contractions
or controlled voiding postoperatively.11 We
report our findings pertaining to urological outcomes
and perception of patients regarding their
results.
METHODS
Methodological details and initial results of the study
have been reported previously.11 The study received
institutional review board approval (No. 09-0153). Patients
were eligible for enrollment if they were younger
than 21 years, had neurogenic bladder dysfunction
related to spina bifida and were scheduled to undergo
spinal cord detethering for the usual reasons. Patients
underwent detailed evaluations at regular intervals
throughout the 3-year followup. All patients and evaluators
were blinded throughout the study to the surgical
procedure that was performed.
Urodynamic testing was done with retrograde filling
and patch electromyography in accordance with the International
Children¡¯s Continence Society guidelines,12
using the Aquarius TT system. All urodynamic evaluations
were performed by a urodynamics technologist along
with the study nurse coordinator (LLT). A rectal catheter
was used to measure abdominal pressure. The bladder
was filled 10 to 15 cc per minute to total bladder capacity,
which was determined by a sensation of fullness or
discomfort, signs of autonomic dysreflexia, a significant
leak around the catheter or a major sustained spike in
bladder pressure. Once the TBC was reached, 20% of the
volume was released and systematic scratching of the
lower extremities ensued. Patients underwent urodynamic
assessment preoperatively and at 6, 9, 12, 18, 24
and 36 months postoperatively. We report results at
1-year intervals because they are similar to the results at
the other time intervals.
All patients completed the same questionnaires used
by Peters et al in their previous study of the Xiao procedure
in patients with spina bifida.4,5 CIC and all BAMs
(anticholinergics, antimuscurinics, antispasmodics) were
discontinued 2 weeks before the procedure and were
reinstituted during the 3-year followup only if the upper
tracts were at risk, as defined by the protocol outlined in
supplementary Appendix 1 (http://jurology.com/). After
completion of the entire study each patient, both study
urologists and the research coordinator tried to predict
the group to which the patient had been randomized.
Decisions about reinstitution of CIC and BAMs after
completion of the study were made based on typical clinical
parameters. Management of bowel function was
directed by the usual caregivers and health care providers,
and not by a specific protocol.
RESULTS
Baseline Characteristics and Surgical Details
Of the 20 patients enrolled in the study 10 underwent
DT and 10 underwent DTtX (supplementary tables 1
and 2, and supplementary Appendix 2, http://
jurology.com/). The distribution of baseline characteristics
between the 2 groups was similar, except
that patients undergoing DTtX were younger and
less likely to be using CIC or taking BAMs preoperatively
compared to those undergoing DT. DTtX
donor roots consisted of L5 in 5 cases, L4 in 2, S1 in 2
and T12 in 1. Recipient roots in DTtX consisted of
S3/4 in 7 cases, S2/3/4 in 1, S3 in 1 and S2 in 1. Nerve
grafts were used in 2 patients.11 Five patients in the
DTtX group had worsening urological symptoms as
the primary indication for detethering, of whom 3
displayed LPP greater than 40 cm H2O and 2 had a
decrease in TBC associated with frequent UTIs and
leaking between catheterizations.

Urge to Urinate, CIC and Bladder Active
Medications
Preoperatively 20% of DTtX patients and 50% of
DT patients experienced the urge to void (fig. 1,
supplementary Appendix 2, http://jurology.com/). By
1 year postoperatively 2 additional patients in both
groups experienced the urge to void. Of patients
who did not experience the urge to urinate preoperatively
3 of 8 (37%) in the DTtX group and 2 of
5 (40%) in the DT group experienced to the urge to
urinate at study completion.
CIC was used preoperatively in 40% of DTtX
patients and 70% of DT patients. Most patients
were able to stay off CIC throughout the study.
After study completion when patients and their
urologists made decisions about catheterization
based on clinical symptoms, 5 of 9 (56%) in the
DTtX group and 5 of 8 (62%) in the DT group chose
to use CIC.
Preoperatively BAMs were used in 40% of DTtX
patients and 50% of DT patients. Most patients in
both groups were able to safely stay off BAMs during
the study period. However, by the end of the
study 2 patients in both groups chose to return to
BAM use. There were no statistically significant
differences in urge to urinate, use of CIC or use of
BAMs when comparing the DTtX and DT groups at
any point in the study.
Total Bladder Capacity
Baseline TBC was lower in DTtX patients
compared to DT patients (median 136 cc vs 188 cc,
p ¼ 0.17, fig. 2 and supplementary table 2, http://
jurology.com/). Median TBC when compared to
baseline increased more in DTtX patients than in
DT patients (median 59 cc vs 36 cc at 1 year,
p ¼ 0.36; 107 cc vs 78 cc at 2 years, p ¼ 0.42; 100 cc
vs 66 cc at 3 years, p ¼ 0.22). Overall there were no
significant differences in TBC between the groups at
the different time points. However, 2 patients in the
DTtX group had large increases in TBC compared
to baseline (179 cc and 356 cc), while the TBC
decreased for 3 patients in the DT group by the end
of the study. Patient 5 (DTtX) did not have the TBC
included in the 2 and 3-year analyses because she
had undergone bladder augmentation at age 18
months. By comparing the actual change in TBC to
the age related increase in TBC predicted by the
Hjalma € ˚s formula (30 t age in years 30), there
were greater improvements in TBC in the DTtX
group than in the DT group (p ¼ 0.14).13
Leak Point Pressure
Preoperatively 3 patients in each group had LPP
greater than 40 cm H2O and 1 patient in each group
did not leak at all during bladder filling
(supplementary Appendix 3, http://jurology.com/).
By 1 year LPP increased in 4 patients in the DT
group (from 40 cm H2O or less preoperatively to
greater than 40 cm H2O postoperatively), while no
patient in the DTtX group had a similar increase.
LPPs worsened with time in the DTtX group but
not as severely as in the DT group. By 3 years 90%
of patients in the DT group had no leak or an LPP of
greater than 40 cm H2O, compared to 5 of 9 (56%) in
the DTtX group. The bladders of 6 patients in the
DT group transitioned from an LPP of 40 cm H2O or
less preoperatively to either no leak or an LPP of
greater than 40 cm H2O postoperatively. However,
only 2 patients in the DTtX group had a similar
worsening of the LPP during 3 years of followup.
Uninhibited Detrusor Contractions
Preoperatively 90% of DTtX patients and 80% of
DT patients had UDCs greater than 15 cm H2O
(supplementary Appendix 3, http://jurology.com/).
By 1 year 2 of 9 DTtX patients (22%) had resolution
of the previous UDCs, while there was no
improvement in the DT group. By 3 years UDCs had
resolved in 2 of 9 DTtX patients (22%) and 1 of 8 DT
patients (13%).
Reactivity of Neurogenic Bladder
Preoperatively 80% of patients in each group were
considered to have overactive neurogenic bladders
(supplementary Appendix 3, http://jurology.com/).
During the 3-year study period patients in the DTtX
group more frequently experienced a decrease in
bladder contractility than those in the DT group.
Three of 8 patients with overactive bladder in the
DTtX group (38%) and 1 of 8 in the DT group (13%)
had normalized contractility at 3 years. Two patients
in both groups transitioned from underactive

Figure 1. CIC use before, during and after completion of study.
Most patients were able to stay off CIC and BAMs during
study (supplementary Appendix 2, http://jurology.com/), as
recommended by Xiao.6 Patients undergoing Xiao procedure
during spinal cord detethering were not more likely to stay off
CIC than those who underwent only detethering at most time
points

Figure 2. TBC postoperatively. When comparing actual TBC to expected TBC based on age, patients in DTtX group had greater
improvement in TBC than those who underwent only DT.

neurogenic bladder preoperatively to overactive
bladder by 3 years postoperatively.
Global Questionnaires Related to Strength,
Quality of Life, and Bladder and Bowel Function
Patient perceptions of the bladder, bowel and lower
extremity motor function throughout the study
were not statistically different when comparing
the 2 groups at every time point (fig. 3 and
supplementary Appendix 4, http://jurology.com/). Of
the DTtX patients 70% felt the ability to void had
improved by 1 year, compared to 50% of DT patients.
By 3 years 67% of DTtX patients felt voiding
had improved, compared to 40% of DT patients. By
3 years 3 of 10 patients in the DT group felt their
voiding ability had worsened, compared to 0 patients
in the DTtX group.
At 1 year half the patients in both groups felt the
ability to move their bowels had improved, without
significant change throughout the remaining 2
years. At years 2 and 3 a higher proportion of patients
in the DT vs DTtX group felt the ability to
move their bowels had improved. Patients in the DT
group felt the lower extremity leg strength had
decreased more than those in the DTtX group. By 3
years 4 patients in the DT group and 1 in the DTtX
group felt their legs were weaker than they were
preoperatively.
Improvement in overall QOL at the end of the
study was greater in DTtX patients than in DT
patients. At 1 year 80% of patients in the DTtX
group and 70% in the DT group felt their QOL was
better. By 3 years all patients in the DTtX group
felt their QOL was better than preoperatively,
compared to only 30% of patients in the DT group
(p ¼ 0.003). Review of the overall data for these 5
patients showed that 4 of 5 whose quality of life
worsened also had a decrease in their assessment of
lower extremity strength. It is noteworthy that all 4
patients were 13 years or older when they enrolled
in the study. All patients in the DTtX group were
9 years or younger at enrollment except for 1 patient,
who was 16 years.
Accuracy of Predicting Which Patients Underwent
Xiao Procedure
Ten of 18 patients (56%) and their parents thought
they had been assigned to DTtX. However, their
predictions were accurate only 44% of the time
(kappa ¼ -0.1, p ¼ 0.67, supplementary Appendix 5,
http://jurology.com/). The blinded urologists agreed
on the group assignment in only 6 of 20 cases (30%)
and each of them was correct only 55% of the time
(kappa ¼ 0.1, p ¼ 0.65). The research nurse, who
was most familiar with every aspect of the patient
assessment, correctly predicted the treatment arm
only 50% of the time (kappa ¼ 0, p >0.99).
Resumption of CIC and BAMs after Study
Completion
One patient in each group used CIC before the study
and did not need to use CIC after completion of the
study (supplementary Appendix 2, http://jurology.
com/). However, most patients in both groups who
were using CIC before the study chose to return to
CIC when the study was complete. Three DTtX

patients who did not use CIC before the study were
placed on CIC after the study was complete. At the
end of the study most patients resumed their prestudy
use or lack of use of BAMs. Two patients in
both groups who used BAMs before the study did
not resume them at the end of the study.
DISCUSSION
Xiao et al have published extensively on the
somatic-to-autonomic intradural anastomosis, taking
the concept from bench to bedside in a series of
studies involving animals, patients with spinal cord
injury and children with spina bifida.6,10,14e19 Their
results, which suggest an 86.2% rate of bladder
control,6 have not been reproducible by other
investigators.
Two well designed European studies of adults
with spinal cord injury failed to produce reflex
initiated bladder contractions or meaningful urination.7,8
In an editorial regarding the 2014 series
from Denmark that failed to demonstrate a positive
outcome Xiao attributed the lack of success by other
investigators to the use of BAMs popstoperatively.20
The present study involved little to no BAM use by
our patients postoperatively.9
Results of the procedure in patients with spina
bifida are predictably more difficult to interpret due
to the presence of partial bladder and bowel function
in most. In their study of children with spina
bifida who underwent the Xiao procedure Peters
et al found scratch initiated urodynamic contractions
more similar to the results of Xiao than of
ours.4,5 However, they failed to reproduce the dramatic
control of urination and continence described
by Xiao and others.
While the results of Peters et al4,5 were concerning
for a lack of duplication of the impressive
results of Xiao et al, many were still encouraged by
the findings. Our study revealed that many of the
results attributed to the performance of the Xiao
procedure may, in fact, have been related to spinal
cord detethering, placebo or the effect of sacral
rhizotomy.11 For example the greater increase in
TBC, the reduced likelihood of increased LPPs
developing and the more frequent resolution of uninhibited
detrusor contractions in DTtX patients
could all be related to the effect of the sacral rhizotomy
that is performed during the Xiao procedure
instead of the effect of reinnervation.21,22
Patients in the DTtX group had more signifi-
cant improvement in QOL at years 2 and 3, which
may be attributable to an outcome that we may not
have measured as part of our study. We believe
that the greater improvement in patients who underwent
the Xiao procedure is more likely attributable
to the younger age, less decrease in leg
function and/or greater improvement in TBC
following DTtX.
Although we used a randomized double-blind
methodology, our results are limited by the small
sample size and/or inclusion of only patients undergoing
detethering. The randomization of
younger patients to DTtX, although likely the
result of chance, also may have influenced our results.
The questionnaires that form the basis of the
subjective measures of outcome were the same as
those used by Peters et al,5 although the reliability
of these surveys has not been validated in separate
studies.
CONCLUSIONS
Performance of the Xiao procedure during spinal
cord detethering in patients with spina bifida was
more likely to lead to improvements in QOL, TBC,

bladder overactivity and leak point pressure, all of
which may be attributable to the effect of sacral
rhizotomy instead of bladder reinnervation. The
Xiao procedure did not result in voluntary voiding
or continence in any patient. These findings, in
combination with the results of other recently
published series, suggest that additional basic science/animal
studies need to be performed before
further clinical trials of the Xiao procedure in
humans.
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Figure 3. Patient and family responses to same global
questionnaires used by Peters et al.4,5 a, perceived changes in
foot and leg strength. b, perceived changes in overall quality
of life. There were no statistically significant differences in
responses to questionnaires, except for greater improvement
in quality of life for patients who underwent Xiao procedure
(p ¼ 0.003). Patients in DT group had greater worsening of
foot and leg strength than patients in DTtX group.