Vol.

48 (1): 31-51, January - February, 2022

REVIEW ARTICLE
doi: 10.1590/S1677-5538.IBJU.2020.0989

Management of neurogenic bladder dysfunction in children

update and recommendations on medical treatment
_______________________________________________
Cristian Sager 1, Ubirajara Barroso Jr. 2, 3, José Murillo B. Netto 4, 5, Gabriela Retamal 6, Edurne Ormaechea 7
1
Service of Urology, National Hospital of Pediatrics Prof. Dr. P. J. Garrahan, Buenos Aires, Argentina;
2
Departamento de Urologia, Universidade Federal da Bahia - UFBA, Salvador, BA, Brasil; 3 Escola
Bahiana de Medicina (BAHIANA), Salvador, BA, Brasil; 4 Universidade Federal de Juiz de Fora – UFJF,
Juiz de Fora, MG, Brasil; 5 Hospital e Maternidade Therezinha de Jesus da Faculdade de Ciências
Médicas e da Saúde de Juiz de Fora (HMTJ-SUPREMA), Juiz de Fora, MG, Brasil; 6 Service of Urology,
Hospital Roberto del Rio, Santiago, Chile; 7 Service of Urology, Italian Hospital, Buenos Aires, Argentina

ABSTRACT ARTICLE INFO

Introduction: Defective closure of the neural tube affects different systems and Cristian Sager
generates sequelae, such as neurogenic bladder (NB). Myelomeningocele (MMC) http://orcid.org/0000-0002-6884-8898
represents the most frequent and most severe cause of NB in children. Damage of the
renal parenchyma in children with NB acquired in postnatal stages is preventable given Keywords:
adequate evaluation, follow-up and proactive management. The aim of this document Urinary Bladder, Neurogenic;
is to update issues on medical management of neurogenic bladder in children. therapy [Subheading]; Child
Materials and Methods: Five Pediatric Urologists joined a group of experts and reviewed
Int Braz J Urol. 2022; 48: 31-51
all important issues on “Spina Bifida, Neurogenic Bladder in Children” and elaborated
a draft of the document. All the members of the group focused on the same system of
classification of the levels of evidence (GRADE system) in order to assess the literature _____________________
and the recommendations. During the year 2020 the panel of experts has met virtually Submitted for publication:
to review, discuss and write a consensus document. November 03, 2020
Results and Discussion: The panel addressed recommendations on up to date choice of _____________________
diagnosis evaluation and therapies. Clean intermittent catheterization (CIC) should be Accepted after revision:
implemented during the first days of life, and antimuscarinic drugs should be indicated December 27, 2020
upon results of urodynamic studies. When the patient becomes refractory to first-line _____________________
therapy, receptor-selective pharmacotherapy is available nowadays, which leads to a Published as Ahead of Print:
February 28, 2021
reduction in reconstructive procedures, such as augmentation cystoplasty.

INTRODUCTION sacral myelomeningocele (MMC) (1). Patients

with neurogenic bladder may present urinary
The most common etiology in neuroge- incontinence, urinary tract infections (UTI), ve-
nic bladder (NB) in children is spina bifida (SB) sicoureteral reflux (VUR) and eventually, renal
and the most frequent malformation is lumbo- scarring and renal failure.

31
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

Without treatment, up to 70% of patients including the year 2020. The documents that were
may develop urologic problems during the first not available in English or Spanish were excluded.
years of life, and less than 5% become continent The documents with a complete version that could
(2, 3). The main goals of treating the urinary tract not be recovered were also excluded. Each topic
are the preservation or improvement of renal of the review was analyzed independently by each
function, and the prevention of UTI and urinary author of the present document. The search strate-
tract deterioration. Until recently, there was con- gy is shown in Figure-1.
troversy over which approach was better for the All the members of the primary developer
initial management of NB: proactive or expectant group focused on the same system of classifica-
approach (4, 5), however, the balance seems to be tion of the levels of evidence in order to assess the
in favor of the first, since with a proactive appro- literature and the recommendations following the
ach there is a reduction in chronic renal disease GRADE system (modified) (9).
(CRD). The most proactive interventions with the
use of clean intermittent catheterization (CIC) and Main definitions and standardizations
pharmacotherapy have become the cornerstone of Neurogenic bladder is defined as any alte-
early management of NB (6), leaving the most in- ration of the physiologic function of the bladder
vasive procedures and reconstructive surgeries for due to a central or peripheral neurologic lesion.
older patients, even at ages reaching adolescence. Its most common cause in children is open spinal
The aim of the present document is to dysraphism, such as myelomeningocele (MMC).
update the main topics and subtopics discussed The functions of the lower urinary tract to
by international guidelines on the management store and periodically eliminate urine are regula-
of neurogenic bladder in children and to provide ted by a complex neural control system that coor-
useful medical recommendations on major issues dinates the activity of bladder and urethral outlet.
based on the best scientific evidence available. The Many neural circuits exhibit switch-like patterns
focus will be on diagnosis, evaluation and medical of activity that turn on and off in an all-or-none
treatment of children with neurogenic bladder. manner (10). A failure of the neurulation process
may induce different abnormalities called neural
MATERIAL AND METHODS tube defects (Figure-2).
Symptoms in the lower urinary tract
In order to adapt the guidelines analyzed (LUTS) are considered neurogenic only in the pre-
for the construction of the present document, the sence of a relevant neurologic disease. According
following instruments were used “Clinical practice to the International Continence Society (ICS), the
guidelines” (7) and “The Guideline Implementa- LUTS in neurogenic patients can be divided into
bility Appraisal (GLIA)” (8). In addition, research three groups considering the micturition phases
was done following suggestions made by interna- in which they are produced: storage, voiding, and
tional referents and by the International Children’s post micturition symptoms (11). ICS as well as the
Continence Society (ICCS). Furthermore, a tho- International Children’s Continence Society (ICCS)
rough literature search of systematic reviews on have published standardization documents on
different subtopics related to neurogenic bladder terminology for neurogenic LUTS (11) and non-
in children was carried out. With the purpose of -neurogenic LUTS (12) (Table-1). Most children
selecting the practical clinical guidelines and arti- with NB have a reduced bladder sensation or no
cles, the following inclusion criteria and parame- sensation at all, or are not aware of bladder filling
ters were used: Documents that contain in their or have no desire to void. Issues such as LUTS and
title or abstract at least one of the following MeSH enuresis, with different etiologies and approaches
(Medical Subject Headings) terms: “Spina Bifida, to neurogenic bladder will not be developed in the
Neurogenic Bladder in Children” were analyzed present manuscript.
and selected in Medline, Pubmed and Cochrane. Children with spinal dysraphism also
This search comprised articles published up to and present a neurogenic bowel, which is characte-

32
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

Figure
Figure 1 - The figure shows the1: Literature
search search
strategy of the strategy.
present review.
Identification

Records identified through Additional records identified

database searching through other sources
(n = 474) (n = 2 )

Records after duplicates removed

(n =5)
Screening

Records screened Records excluded

(n = 471) for not being in English or
Spanish (n = 78 )

Full-text articles assessed

for eligibility
Eligibility

(n = 393 ) Full-text articles excluded:

Case reports: 215
Duplicate data: 70

Studies included in
qualitative synthesis
(n = 107 )
Included

Studies included in
quantitative synthesis
(meta-analysis)
(n = 1 )

rized by severe constipation, fecal incontinen- births in the north of China (14). In South Ame-
ce, gastrointestinal motor dysfunction (13) and rica this prevalence is as high as 19.6 every
altered
From: visceral sensitivity.
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009).10.000 births.Items
Preferred Reporting These figures
for Systematic increase
Reviews and Meta- from 20
Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097
to 50 times when there is a sibling with spinal
Epidemiology and etiology dysraphism and 40 times if the mother suffers
For more information, visit www.prisma-statement.org.
Congenital defects of the neural tube from it (15). A reduction in the prevalence of
(CDNT) are common abnormalities that lead to CDNT has been observed during the last two
a neurogenic bladder in children. Their preva- decades especially due to the performance of
lence varies in the different continents and in early prenatal diagnosis, the subsequent inter-
regions within the same continent, from 1 every ruption of pregnancy and also the incorpora-
10.000 births in Alaska to 34.4 every 10.000 tion of folates in the diet (16, 17).

33
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

Figure 2 - Schematic drawing of the neurourological pathway in the bladder cycle: A: Bladder storage phase
and B): Bladder voiding phase.

34
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

Table 1 - Standardization of Terminology for Bladder Filling and Voiding Symptoms (adapted from referen-
ces 11 and 12).
Lower Urinary Tract Symptoms

Storage Symptoms
(Symptoms experienced during bladder filling)

Symptom Description

Urinary Frequency Increased frequency during daytime (> 7 micturitions daily)

Nocturia Waking up to void

Urgency Sudden and unexpected desire to void

Incontinence Stress: Urinary leakage on effort

Urgency: Urinary leakage following an urgency episode

Mixed: Urinary leakage associated with both, urgency and stress

Continuous: Constant urinary leakage during day and night

Enuresis: Incontinence during sleep

Impaired Mobility Incontinence: Inability to reach toilet in time to void due to a physical of
medical disability

Impaired Cognition Incontinence: Leakage that occurs in an individual with impaired

cognition without being aware of it

Bladder Sensation Normal: Individual is aware of bladder filling

Increased: Desire to void occurs earlier during filling phase and is more persistent

Reduced: Desire to void occurs later despite awareness that the bladder is filling

Absent: No sensation of bladder filling or desire to void

Abnormal: Sensations referred as “tingling”, “burning”, or “electric shock” during filling

Bladder Pain: Suprapubic or retropubic pain, pressure or discomfort that increases as

bladder fills

Voiding Symptoms
(Symptoms experienced during micturition)

Slow Stream Urinary stream slower than normal

Weak Stream Urinary stream is weak

Spraying Urinary stream passes as a spray or a split

Intermittency Urine flow that is not continuous, stopping and starting during micturition

Hesitancy Delay in initiating micturition

Straining to Void Need to make intensive effort (Valsalva or suprapubic pressure) to initiate or maintain
micturition

Terminal Dribble Slow flow that trickles/dribbles at the end of micturition

Dysuria Burning or discomfort during micturition

Post Micturition Symptoms

(Symptoms experienced immediately after voiding)

Feeling of Incomplete Emptying Bladder does not feel empty after micturition has ended

Post micturition Dribble/Leakage Urine loss after finishing voiding

35
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

MMC is the most common type of CDNT postnatally, is preventable with adequate assess-
and occurs with more frequency at the lumbosa- ment, follow-up and proactive management (27).
cral level (30-50%), followed by the lumbar and Renal and urinary tract ultrasound: They
thoraco-lumbar level (20-30%, respectively), with should be performed as early as possible after
less frequency at the cervical and thoracic level (0- birth. It helps detect hydronephrosis or other
5% and 5-10%, respectively) (18, 19). As to occult alterations of the upper urinary tract (26, 28).1C
spinal dysraphism, its incidence is unknown, espe- Strong recommendation: evidence of low or
cially due to underdiagnosis; however, it is known very low quality. The increased thickness of the
that approximately 40% of patients will present detrusor wall does not predict urodynamic fin-
urological symptoms at the time of diagnosis (14). dings. Regarding unfavorable videourodynamic
A lesion or injury in the spinal cord can findings, there are not significant differences in
also cause neurogenic bladder dysfunction in chil- bladder wall thickness measured at each maxi-
dren. This etiology represents between 3 and 5% of mum cystometric capacity, except for bladder
all lesions of the spinal cord (20). Its incidence in- trabeculation (29). 2B Weak recommendation:
creases with age, occurring in approximately 30% evidence of moderate quality.
of patients between 17 and 23 years of age and Voiding cystourethrography (VCUG): It
53% between ages 16 and 30 (21). After the age of offers anatomical information on the lower urina-
3, the incidence is greater in males (4:1) (20, 21). ry tract (26) and mainly on the presence or absen-
Of all the causes of neurogenic bladder, ce of VUR.
spinal dysraphism is responsible for up to 93% of Urodynamic evaluation: It assesses the
cases (open myelodysplasia: 85%, closed/occult filling and voiding phases of the bladder. It is
dysraphism: 8%), sacral agenesis, imperforate anus essential to carry out this evaluation since tre-
and lesion of the spinal cord represent 1% each, atments depend on a specific diagnosis of the
and cerebral palsy, 3%. Other less frequent causes type of neurogenic dysfunction (30). 1B Strong
are cerebral/spinal tumors and pelvic surgery (22). recommendation: evidence of moderate quality.
Neurogenic bladder is present in up to VCUG and urodynamic evaluation should be per-
98% of children with myelomeningocele (23). The formed at least 6 weeks after closure of the de-
prevalence of areflexia of the detrusor muscle va- fect, when it is expected that the spinal shock be
ries between 13 and 49.5% and hyperreflexia be- overcome (31, 32). If the closure of the defect was
tween 25 and 76% (24). In a group of 112 children intrauterus, it is not necessary to wait for 6 we-
with myelomeningocele who underwent urodyna- eks. VCUG and evaluation of the upper urinary
mic evaluation in 2015, Korzeniecka-Kozerska et tract should be repeated at regular intervals (26).
al. found a normal function of the bladder only Video-urodynamics combines in only one study
in 4 children (3.6%), 49.1% presented overactivity and instrumentation the data of the urodynamic
of the detrusor, 14.3% detrusor-sphincter dyssy- evaluation and VCUG, with the advantage of si-
nergia, 14.3% areflexia of the bladder, and 22.3% multaneity of the testing. It is recommended not
deficient compliance of the bladder (25). only in the initial evaluation but also during the
follow-up in children with VUR (33).
Initial evaluation The initial evaluation is useful to identify
All patients with MMC should undergo a subgroup of patients with a greater risk of de-
initial urologic evaluation, even those with no veloping nephro-urologic damage (34). Creatinine
neuro-orthopedic alteration. The initial evalua- estimation should be done after the seventh day
tion should provide information on the detrusor- of life (35). The urodynamic parameters of reduced
-sphincter status and define the type of dysfunc- bladder capacity and compliance and high detru-
tion (26). 1B Strong recommendation: evidence of sor leak point pressure (DLLP) are predictive fac-
moderate quality. The damage of the renal paren- tors of renal deterioration. In bladders with these
chyma in a child with MMC, which was acquired characteristics it is less likely that VUR will be re-

36
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

solved (26, 36). The presence of ureterohydrone- Proactive approach/expectant approach/risk

phrosis and VUR is correlated with a greater risk of groups
renal injury (31). All the patients with spina bifida It is necessary to know the factors that
should undergo Tc-99m DMSA renal scintigraphy may predict the appearance of renal lesion in chil-
during the first year of life, 1B Strong recommen- dren with MMC in order to implement preventi-
dation: evidence of moderate quality, and after 6 ve actions. Undoubtedly, the introduction of the
months of episodes of pyelonephritis. 1B Strong clean intermittent catheterization technique by
recommendation: evidence of moderate quality. Lapides et al. and the use of anticholinergic me-
Patients with a neurogenic bladder requi- dication have made a great difference in the tre-
re urologic control for life (26). The degree of atment of patients with neurogenic bladder (37).
severity in the renal damage conditions the fre- Nevertheless, when it is the best moment to apply
quency of urologic controls by imaging and uro- these measures is still subject to controversy.
dynamic evaluation. 1B Strong recommendation:
evidence of moderate quality. Early Treatment versus Expectant Treatment
This expert panel recommends: Renal and - Early Treatment
urinary tract ultrasound: every 3-4 months during It consists in starting treatment
the first year of life, every 6 months until age 2, before any signs of damage appear, such as UTI,
and then, yearly until age 5. Urodynamic evalu- hydronephrosis, renal scars, hypertension or de-
ation: yearly until puberty. VCUG and/or Video- creased estimated glomerular filtration rate (38).
-urodynamic evaluation: it will be repeated yearly This principle is based on the premise that high
in the patient with VUR prior to urologic surgery, pressures of the detrusor muscle (>40cm H20)
and as soon as possible in the case of patients who and pyelonephritis compromise renal function;
abandoned treatment and follow-up. For patients therefore, they should be avoided right after birth
who are neurologic and urologically stable, with (39). A comparative advantage attributed to the
adequate bladder continence, we recommend con- early start of CIC is a greater adherence and adap-
trol with renal and urinary tract ultrasound and tation of patients and members of the family.
annual evaluation of the residual urine (post CIC Anticholinergic drugs: The use of
or voluntary micturition, as applicable) (34). There anticholinergic medication reduces intravesical
exist different situations that make it necessary to pressure as well as the involuntary contractions
increase the frequency of urologic studies: Chan- of the bladder as shown on urodynamic studies
ges in urologic symptoms (36). (40). Although the use of oxybutynin has not been
Recurrent pyelonephritis episodes. Chan- approved in children younger than 5 years of age,
ges in the orthopedic and neurologic signs and/ there exists enough global experience on its bene-
or symptoms (36). fits. In a multicenter, retrospective study of chil-
Planning of treatments to improve or dren with spinal dysraphism, the mean end filling
achieve continence. detrusor pressure was reduced from 33 to 21cm
Neurosurgical complications (36). H2O. Over 80% of patients showed compliance
Pubertal development. greater than 70%. No serious adverse effects were
In the case of patients with changes in reported, although constipation and facial redness
the neurologic, orthopedic or urologic status, a were the major side effects. The oxybutynin dose
neurosurgical evaluation should be carried out indicated was: 0.2-0.6mg/kg/day given 2 or 3 ti-
in order to identify: symptomatic tethered cord, mes a day (41).
syringomyelia, increased intracranial pressure
caused by dysfunction of the valve system or - Expectant Approach
partial herniation of the cerebral trunk and cere- An “expectant approach” consists
bellum. 1B Strong recommendation: evidence of in adopting a vigilant behavior before initiating
moderate quality. any treatment. Advocates believe this approach

37
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

avoids the risks of UTI generated by CIC and the controlled prospective study, but unrandomized
side effects caused by the use of anticholinergic (49). A total of 35 (79.5%) out of 44 patients in
drugs, and it also helps reduce costs. When a tre- the observation group progressed to UUT dete-
atment is implemented, renal dilatation is reversi- rioration, whereas in the group that started treat-
ble in 92% of cases, according to Klose et al., and ment early, deterioration occurred in 3 out of 20.
in 69%, as reported in a study by Kaufman et al. Wu et al. performed a retrospective study with
(42, 43). However, the latter pointed out that com- a cohort of 46 children with dysraphism treated
pliance improved only in 42% of cases and almost before they were one year old and 52 children af-
half of the patients with renal dilatation required ter 4 years of age (50). These authors showed that
bladder augmentation. hydronephrosis persistence was similar in both
Some authors have argued that an groups (13% and 14%, respectively). However,
active vigilant approach performing ultrasound the rate of bladder augmentation was greater in
and urine and creatinine tests at short intervals the group of children older than 4 (11% compa-
(every 3-6 months) may help detect changes in red to 27%, respectively).
the upper urinary tract (UUT) early (44). These Keye et al. retrospectively evalu-
authors found deterioration of the UUT in 5% of ated 107 patients with spina bifida. The initial
cases. Nevertheless, as children with spina bifida treatment with CIC was performed by 39% of pa-
require multidisciplinary assistance, it is difficult tients and 61% were evaluated expectantly. Du-
to believe that a close follow-up could be kept ring the study period, 23% were changed from
over time. Other authors suggest that children be an expectant approach to starting CIC. The au-
evaluated taking into account the stratification thors observed that the patients who underwent
of risks for UUT (45). For instance, hydronephro- CIC were more prone to develop UTI (35.7%
sis, VUR, UTI and urinary retention were consi- vs. 18.5%, P=0.045), as well as VUR (54.5% vs.
dered risk factors of interest. In a study by Hopps 17.9%, P=0.015). As the minority group of pa-
et al., 79% of patients showed low risk at presen- tients underwent CIC, this was probably the
tation, and of these, 45% became cases of high group with more risk and, therefore, they develo-
risk. Only 1.2% progressed to renal failure (45). ped more infection (51).
No data about surgical and renal damage rates in In a retrospective study, Kaefer
the long term were informed in that report. et al. evaluated myelodysplastic patients with
bladder sphincter dyssynergia and high detrusor
- Comparative studies pressure (52). They compared 18 patients treated
Geraniotis et al. carried out a with an early approach (between 1985 and 1990)
prospective and randomized study of 21 patients with 27 patients treated with a conservative, ex-
with detrusor sphincter dyssynergia (46). Of the pectant approach (between 1978 and 1984). They
patients who kept urination (N=11), 6 presented concluded that the need to perform bladder aug-
deteriorated UUT compared with only one in the mentation was greater in the group treated ex-
group that were treated with CIC (N=10). pectantly (41% vs. 17%).
Kassabian et al. retrospectively In a retrospective study similar to
studied 26 patients with myelodysplasia treated Woo’s, Delair et al. used as a result the loss of re-
with CIC and oxybutynin, and 56 were treated nal function >15%. A total of 252 children were
expectantly in different moments of the evalua- assessed (53). They observed that the presence of
tion (47). The UUT deterioration rate was 8% and VUR and the start of CIC after one year of age
48%, respectively. were predictors of risk.
In a retrospective analysis of 144 Elzeneini et al. carried out a re-
patients, Dik et al. observed renal scarring in 6 trospective analysis of a group of 114 patients
(48). Of these, 5 had started CIC and received an- treated between 1997 and 2010 with an early
ticholinergics late. Edelstein et al. performed a proactive approach compared to another group

38
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

of 100 treated expectantly between 1985 and - Ultrasonography data

1994 (54). DMSA scans revealed renal scars in The high post void residual is a re-
19% and 39%, respectively. levant finding, since urine retention has been as-
sociated with UUT deterioration and it would be an
Risk factors indication to start CIC. However, there is no con-
- Urodynamic parameters sensus over which ratio of post void residual to
McGuire et al. were the first to bladder volume would be indicative to start CIC.
consider bladder pressure as a risk factor for re- Tanaka et al. measured the thick-
nal dilatation and VUR in children with myelo- ness of the bladder wall in 57 patients with MMC
dysplasia (39). Of a total of 42 patients analyzed, using ultrasonography and they compared their
22 presented end-filling detrusor pressure >40cm findings with urodynamic studies (58). Bladder wall
H2O and 20 had pressure <40cm H2O. In the case thickness was correlated to detrusor leak point pres-
of the group with lower pressure, no patient had sure >40cm H2O and end-filling detrusor pressure.
renal dilatation and only two showed ureteral di- Sekerci et al. studied 80 children
latation. In the group with higher pressure, 68% with myelodysplasia and they observed that in-
had vesicoureteral reflux and 81% had dilatation. creased bladder wall thickness correlated to uro-
Timberlake et al. studied parame- dynamic parameters, as well as to renal scarring
ters of ultrasound (US) and video-urodynamic stu- (59). Nevertheless, these data were not confirmed
dies that could be associated with renal scarring in the study by Kim et al. (29). In 52 patients exa-
on DMSA (55). Of interest, DMSA scans were per- mined, the thickness of the bladder wall as seen on
formed during the first 6 months of life and renal ultrasound did not correlate to video-urodynamic
scarring was observed in 24% of cases. The risk findings. These data were confirmed by a study
factors for renal scars were: trabeculation of the performed by Muller et al. (60).
bladder as shown on US, end-filling detrusor pres-
sure >40cm H2O, presence of residual urine >50%, This expert panel recommends
pressure >10cm H2O at the start of bladder filling, 1) All patients should be evaluated with ul-
and VUR on video-urodynamic studies. trasound after birth, (1C Strong recommendation:
Vesicoureteral sphincter dyssy- evidence of low or very low quality). For this test,
nergia (VSD) has also been identified as a risk the grade of renal dilatation and ureteral dilatation
factor of renal lesion (49, 56). In a retrospective should be taken into account. The measuring of bla-
study involving 312 patients with myelodyspla- dder wall thickness is controversial, nevertheless,
sia, Ozel et al. observed that VSD and invo- this panel advises to measure it (2B Weak recom-
luntary contractions were risk factors of renal mendation: evidence of moderate quality). This pa-
scars on DMSA scans. nel recommends that if the wall thickness is measu-
Other studies have not found association red with a full or semi-full bladder, it may provide
of urodynamic parameters and worse outcome (44, additional information for the interpretation of the
53). Nevertheless, some aspects deserve considera- general clinical status of the child. The cut-off value
tion. A high pressure bladder is more associated for this measure has not been established. In the pre-
with VUR and studies are consistent in showing sence of increased residual urine (>50% of expected
that VUR is a risk factor of deterioration of UUT. capacity for age) CIC is recommended (2B Weak re-
Furthermore, patients with high pressure bladders commendation: evidence of moderate quality).
began an early treatment with CIC and anticho- 2) Every patient should be evaluated with
linergic drugs, which may have favored a better urodynamic studies during the first 6 months of life
outcome. Finally, a study by Dudley et al. showed (1B Strong recommendation: evidence of moderate
that there exists a considerable variation between quality). The following data should be determined:
examiners in the performance of urodynamic stu- detrusor leak point pressure, end and start-filling
dies, which may render different results (57). pressure (Pdetmax), and bladder capacity.

39
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

3) Every patient should be evaluated with CIC is initiated even before evaluation with ul-
urinary cystourethrography and/or video-urody- trasound and urodynamic studies is carried out,
namic studies (Grade B recommendation). This and prior to the development of changes in UUT.
study helps define diagnosis and VUR classifi- Those who recommend it emphasize the fact that
cation, as well as identify signs of vesicoureteral it helps achieve better adherence, a reduction in
sphincter dyssynergia. the need of reconstruction of the urinary tract and
4) Every patient with spina bifida should a reduction in the risk of renal deterioration. The
undergo DMSA scan during the first year of life. recommendations by ESPU and ICCS in relation
(1B Strong recommendation: evidence of mode- to CIC are the following: The ESPU Guidelines on
rate quality) and after 6 months of having episo- the management of neurogenic bladder in chil-
des of pyelonephritis (1B Strong recommendation: dren and adolescents, Part I, 2019 (64), propose
evidence of moderate quality). a proactive management with early indication of
5) The early treatment with CIC helps pre- intermittent catheterization. They postulate:
vent UTI, VUR and renal scarring. Anticholiner- a) During the neonatal period, in the case of pa-
gic medication will be used if urodynamic results tients with spina bifida, each bladder should
show a need to (if there is overactivity and/or be considered with a potential development
filling pressures greater than 20cm H2O at expec- of overactivity and/or high filling pressure
ted capacity for age) (1B Strong recommendation: with deficient voiding, and CIC should be
evidence of moderate quality). Doses should be started soon, right after birth, since it con-
adjusted according to urodynamic results (36). tributes to diminishing renal complications
6) In children under CIC it is not advisa- and the need for later augmentation(64-66)
ble to indicate antibiotic prophylaxis (ATB) except (1B Strong recommendation: evidence of
during the first months of life until the parents moderate quality).
become familiar with the CIC technique and the b) CIC is much better accepted by patients and
initial evaluation is complete. It would only be in- parents if it is introduced early during the
dicated in the case of patients with VUR, hydro- first days of life.
nephrosis or UTI with recurrent fever (1B Strong c) In children with evident hypoactive sphinc-
recommendation: evidence of moderate quality). ter without overactivity, initiation of CIC
can be delayed. If CIC is delayed, then a clo-
Clean Intermittent Catheterization (CIC) se monitoring of UTI should be performed,
The introduction of CIC has helped impro- as well as ultrasound of the upper tract and
ve the management of patients with neurogenic urodynamic studies to evaluate the lower
bladders, when Dr. Jack Lapides showed its effi- urinary tract (1B Strong recommendation:
cacy in the long term in the 1970s (61, 62). It is a evidence of moderate quality).
fundamental tool in the treatment of patients with d) In the case of infants with spinal dysra-
alterations in bladder voiding and it contributes to phism, without any signs of outlet obstruc-
avoiding renal damage and to improving urinary tion as evidenced on urodynamic studies,
continence. CIC may be delayed, but a close follow-up
Indication for starting CIC: The right mo- should be kept.
ment to indicate CIC is still controversial. There The recommendations by ICCS for the ini-
exist two approaches: one expectant and one pro- tial diagnostic evaluation and follow-up in con-
active (63). With the expectant approach patients genital neurogenic bladder and bowel dysfunction
are periodically monitored in order to evaluate in children, 2012 (22), also propose a proactive
changes in UUT. CIC is indicated when there is management:
clinical deterioration or development of hydrone- a) Children with open spinal dysraphism that
phrosis, upon confirmation on urodynamic stu- cannot empty their bladders spontaneously
dies. With the proactive management of patients, should perform CIC until urodynamic stu-

40
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

dies can be done safely, in general during between prenatal versus postnatal closure on the
the first 2 to 3 months of life (67-69). need for CIC, the urinary incontinence rate, the
b) The presence of high grade VUR described need for reconstructive urologic surgery, or uro-
in cystourethrography/video-urodynamics dynamic parameters (78, 79).
requires management with CIC.
c) Patients with spinal cord lesion require ini- Training in CIC
tiation of CIC as soon as the initial clinical The person in charge of training parents
status is stabilized. If the patient presents or patients of an older age to use CIC should be a
spontaneous micturition, it is necessary to trained nurse. In a neonatal unit, the newborn will
know at which pressure this occurs. If voi- not be discharged until parents can complete their
ding and filling pressures of the detrusor are training in CIC. The clean technique includes hand
normal and the child empties the bladder washing with water and soap (it does not requi-
with synergia, CIC may be discontinued in re gloves or antiseptic products), and it should be
a safe way (70). If CIC is interrupted, perio- done 5 to 7 times a day.
dical evaluations of residual urine volume
should be done in order to ensure adequa- Age-related selection of the catheter diameter
te bladder function. If filling and voiding There exist different diameters and the
pressures are high due to vesicoureteral choice of catheter is related to the caliber of the
sphincter dyssynergia, then CIC should be urethra by age of the patient: between 0 and 2
continued (71). years of age, a 6 French (Fr) catheter is recommen-
ded, between 2 and 5, catheter 6 or 8 Fr, between
Variables to consider in CIC 5-10 years old, 8-10 Fr, between 10 and 16 years
In the case of patients with spinal dysra- old, 10 to 12 Fr, and for patients older than 16, ca-
phism it is important to indicate the use of latex- theters 12 to 16 Fr (80). Regardless of this descrip-
-free catheters, since this pathology is highly as- tion, the final selection is up to each individual.
sociated with allergy to latex (72).
Cochrane Revisions and recent studies Types of catheters
show that the incidence of UTI in patients with Although it has already been said that the
CIC is not affected by the use of a sterile or cle- ESPU Guidelines 2019 state that no final state-
an technique, coated or uncoated catheters, single ment can be made in relation to the best type of
(sterile) or multiple use (clean) of catheters, self- catheter to be used (64), it is important to know
catheterization or catheterization by others, or by which types there exist:
any other strategy (73-76). a) Uncoated catheters, made of polyvinyl
It is described that with the use of hydro- (PVC) or silicone, they require lubrication
philic catheters there is a tendency to reduce po- for its use.
tentially pathogenic agents (bacteria) and that b) Coated catheters with hydrophilic coatings.
they have a higher level of user satisfaction (77). When these catheters are exposed to water,
The investigation evidence on these issues is weak the outer layer attracts the water to the sur-
(75) and the ESPU Guidelines 2019 clarify that face of the catheters ensuring lubrication
on the basis of current data, no statement can be of the urethra. These catheters are useful
made regarding which type of catheter, technique to minimize discomfort, in the presence of
or strategy is better than others (64). urethral stenosis or catheterizable channel
For people using CIC, the selection of the stomas.
catheter will depend on personal preference, cost, c) Closed-catheters systems with pre-lubrica-
portability and how easy it is to use (75). ted products that are packaged as a sterile
In relation to the correction of in utero kit containing all the equipment required to
neural defect, there are no significant differences do aseptic catheterization.

41
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

There is an alternative catheter design to tomy (which uses cecal appendix), Yang-Monti
consider that can be useful: a catheter with a cur- tunneled channel (using reconfigured ileum), and
ved tip or Coudé tip to ease passage through a spiral Monti, which creates a longer tube that can
high neck bladder. be very useful in the case of obese patients (83).
In addition, it is worth mentioning the Fuji The ureter could also be used if the ipsilateral re-
catheter, made of silicone rubber, which preserves nal unit is excluded. The complications of these
its characteristics for a long time (12 to 14 months). reconstructive techniques include incontinence,
It is kept in a container with an antiseptic solution difficulty in catheterizing the channel and steno-
and a lubricant, which makes its preservation and sis of the stoma (5 to 57%) (84).
transportation easier. It is an ideal alternative for
school children performing self-catheterization. This expert panel recommends
1) CIC should be initiated soon, right after
Self-catheterization birth, since it contributes to diminishing
This is the technique by which patients renal complications and the need for subse-
perform their own bladder emptying. The patient quent bladder augmentation (35, 64, 65) (1B
should be mature and responsible enough to per- Strong recommendation: evidence of mode-
form a successful treatment and they should have rate quality.)
motor skills at least in one arm so that they can 2) CIC should be done 5 to 7 times a day, every
reach the urethra or stoma. An expert nurse should day after birth. Even before performing the
train these patients on CIC. The male patient may first urodynamic or video-urodynamic stu-
require time to know the correct positioning of the dies. (1B Strong recommendation: evidence
urethra during insertion of the catheter and the of moderate quality (36)).
female patient needs time to locate the urethral 3) In the case of those children with evident
meatus (they may use a mirror at first or digital hypoactive sphincter with no overactivity,
self-examination). For the patient, this is a great the initiation of CIC can be delayed. If CIC
step towards independence. is delayed, a close monitoring of UTI should
be performed, as well as ultrasound of the
Catheterizable channels upper tract and urodynamic studies to eva-
Surgically created channels can be used in luate the lower urinary tract. (1B Strong re-
the case of patients requiring CIC but whose ure- commendation: evidence of moderate qua-
thra is compromised or inaccessible. They can be lity).
indicated for several reasons (81): 4) The training program in CIC includes the
a) Difficult access to the perineum due to phy- necessary sessions for two adults responsi-
sical limitations or the use of a wheelchair; ble for the care of the child. Training starts
b) Presence of urethral sensitivity; in the intensive care unit and continues in
c) Surgery of bladder neck; the Urology unit (with necessary coordina-
d) Urethral pathology that makes access to tion between nurses of both sectors).
bladder difficult (urethra atresia, urethra 5) Self-catheterization should be encouraged
stenosis). upon evaluation of level of development
The creation of catheterizable channels can and maturity of each child.
improve quality of family life, since with this op- 6) The CIC diary constitutes one way of con-
tion the time allotted to positioning the patient and trolling adherence to CIC, and it should be
cleaning the insertion site of the catheter is reduced monitored in every visit to the Urology unit
(82). Also, training in the use of these channels is or the Spina Bifida Multidisciplinary group.
usually easier compared to training in CIC. 7) If possible, hydrophilic coated catheters
Among the channel techniques available should be used in the context of a painful
we can mention Mitrofanoff appendicovesicos- procedure, in the presence of urethral steno-

42
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

sis or in cases of stomas with catheterizable can be added with dose escalation, for instance
channels, such as Mitrofanoff. Tolterodine, doses: 4mg, 2mg every 12 hours or
0.25 - 1mg twice a day. The dose should be in-
Second-line pharmacological therapies creased until the symptoms disappear, intolerable
When first indications in the proactive side effects appear or until the maximum dose is
management, i.e. CIC and anticholinergic medi- reached (30mg of oxybutynin ER, 4mg of tolte-
cation, do not achieve optimal therapeutic effects rodine ER). If the minimum daily dose of 10mg
and there are adverse effects, the patient becomes oxybutynin ER is not well tolerated, it is replaced
refractory or intolerant to medication. This means by 4mg tolterodine ER.
there is a need to proceed to second-line therapies. In case there is a suboptimal response with
A patient is considered refractory if they the second anticholinergic drug (tolterodine 4mg
meet the following criteria: (1) previous medical ER) or the medication is not well tolerated, so-
therapies could not help improve urine inconti- lifenacin 5 to 10mg can be used. In a study of
nence, (2) there is absence of correctible neuro- patients with neurogenic and non-neurogenic
logical anomalies evaluated on nuclear magnetic bladder dysfunction with overactivity, Nadeau et
resonance (NMR), and (3) incomplete or non-sa- al. reported that mean micturition volumes, cysto-
tisfactory urodynamic response is shown despite metric bladder capacity and maximum pressure of
the use of optimized doses (without side effects) detrusor contractions improved significantly with
of anticholinergic drugs at the most tolerated hi- treatment with solifenacin. The number of incon-
ghest dose. tinence episodes per day diminished significantly
Once a patient becomes refractory, it is ne- from the beginning of therapy until the end of the
cessary to reevaluate the neurosurgical aspect in study (86).
order to rule out any active process in the central After the third month of each change of
nervous system that may be blocking the function medication or modification in the dosage, a cli-
of target organs: bladder, bowel and lower limbs. nical and urodynamic reevaluation is required
One of the most frequent entities of closed dys- to have an objective assessment. In addition,
raphism is lipoma and the possibility of having a blood samples and electrocardiograms should
tethered spinal cord. Although there exist contro- be obtained at the start of treatment and every
versy over the indication of surgery in the case of 6 months in order to detect potential toxicity
complex lipomas, Pang recommends total resec- with solifenacin.
tion for most complex lipomas with or without Even though the use of imipramine has
symptoms. With respect to asymptomatic chaotic been reported with promising results in cases of
lipomas, prophylactic resection is not currently patients refractory to anticholinergics with blad-
endorsed (85). der dysfunction of different etiologies, up to date
there is no solid evidence to recommend its use
Scheme of double oral anticholinergic therapy in pediatric populations. Furthermore, possible
The combination of two or more anticho- cardiac side effects have been reported and this
linergic drugs is a conservative option, although should not be disregarded (87).
adverse effects may be potentially additive. Ho-
wever, this alternative is worth considering, espe- ß3 adrenoceptor agonists
cially in a pediatric population, in which it is con- ß3 agonists, such as Mirabegron, are agents
venient to postpone more aggressive measures. with a different mechanism of action, since they
In other words, in the case of patients act on the ß3 receptors of the bladder producing
with persistent incontinence and incomplete uro- relaxation of the detrusor muscle and interacting
dynamic response to single-agent anticholinergic with receptors of other organs, such as the heart
therapy (oxybutynin 0.3mg/k/day or 15mg oxy- (88). Studies in phase 2 and 3 have reported that
butynin extended release (ER)), a second drug mirabegron significantly improves clinical symp-

43
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

toms of bladder overactivity in adults, which has bladder (Momper, 2014). Further studies should
led to its worldwide approval for this entity. focus on tests with a range of doses using objecti-
Blais et al. carried out a prospective study vely measured, clinically meaningful endpoints.
where they analyzed the clinical response to mira-
begron for the first time in a pediatric population Botulinum Toxin Type A
but with overactivity in non-neurogenic bladder. In children/adolescents with neurogenic
They included 58 patients refractory to behavioral bladder refractory to first-line therapy, injections
therapy or urotherapy and anticholinergic medi- with botulinum toxin-A (BTX) in the detrusor mus-
cation. They showed improvement in the voided cle should be considered in order to have a safe
volume, urinary incontinence and a reduction in bladder with adequate capacity at low pressure.
the side effect rates (89). Hascoet et al. performed a systematic re-
In 2018, JS Park et al. published their view in children with neurogenic bladder and
experience with mirabegron in the treatment of showed a wide range of results: continence could
neurogenic bladder in children. They recruited 66 be achieved in 32% to 100%, maximum detrusor
patients with NB as sequela of spina bifida who pressure decreased between 32% and 54%, maxi-
were refractory to anticholinergics. They excluded mum cystometric capacity increased between 27%
patients who had received botulinum toxin-A in- and 162%, and compliance improved between 28%
jection previously and they indicated mirabegron and 176%. OnabotulinumtoxinA (maximum doses
50mg/day. The results showed a significant incre- 300 IU injected into 20-30 different bladder sites)
ase in compliance and bladder capacity. Further- seemed to be more effective mainly in overactive
more, 37.1% of patients became completely dry cases, compared to hypertonic patterns (93).
after taking mirabegron and 9.1% reported adver- Some authors have reported that injec-
se effects (90). tions with botulinum toxin-A in patients with
Krhut et al. evaluated efficacy and safe- neurogenic bladder due to MMC can be ineffective
ty of mirabegron 50mg/day in the treatment of if the detrusor muscle is fibrotic, of low complian-
neurogenic overactivity of the detrusor in patients ce and with loss of contractility (94). Nevertheless,
between 18 and 65 years old with neurogenic we should not underestimate these findings, since
bladder as sequela of spinal cord injury or mul- some authors state that as there is increase in ca-
tiple sclerosis. They concluded that in the group pacity, there is also improvement in compliance.
of patients treated with mirabegron there was a It has been demonstrated that injections with BTX
significant increase in the volume during the first into the trigone seem to be safe regarding VUR
contraction, an improvement in compliance, a and the changes in the upper urinary tract (95).
non-significant increase in capacity and a ten- Among the main advantages of injections
dency to a reduction in urine leaks (91). with botulinum toxin-A we may mention: it is a
In children with neurogenic bladder re- minimally invasive method, it requires sedation
fractory to first and second-line therapies, mira- and a short hospital stay, it has very low adverse
begron, as an adjuvant, increases bladder capa- effect rates: mild hematuria and very few cases
city, reduces intravesical pressure and achieves of UTI reported (more related to cystoscospy). The
continence in a great number of patients. It is a main disadvantage is its transient effect, with no
well-tolerated drug, with no adverse effects, whi- more than 6 months of therapeutic effect, which
ch implies reducing or postponing the need for requires re-injections, and this is a problematic is-
bladder augmentation (92). sue when patients are in transition towards adult
centers (96) (2A Weak recommendation: evidence
The role of α-blockers of high quality).
Reports have shown that agents such as Injections of botulinum toxin-A into the
doxazosin, tamsulosin and alfuzosin do not modi- detrusor muscle in children who are refractory to
fy significantly DLPP in children with neurogenic antimuscarinic drugs have shown beneficial effects

44
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

in clinical and urodynamic variables. We evalua- tying has not been tested in controlled stu-
ted 26 children with neurogenic bladder refractory dies in children (36) (2C Weak recommenda-
to conventional treatment. After treatment with tion: evidence of low or very low quality).
repeated injections of intradetrusor onabotulinu- The use of bowel segments in bladder aug-
mtoxinA, urinary continence was achieved in up mentation has promoted important advances in
to 77%, the mean bladder capacity and the mean finding new ways to deal with patients with non-
maximum cystometric capacity increased. The -compliant bladders. Nevertheless, there is concern
mean detrusor pressure at the end of filling decre- regarding specific characteristics of the intestinal
ased, but only compliance after the first injection epithelium that can result in complications. Non-
improved significantly. Detrusor overactivity was -secretory bladder enlargement is considered as
attenuated, but did not disappear completely (97). one of these alternatives, as it does not present the
In the presence of patients refractory to characteristic disadvantages of the secretory and
antimuscarinic drugs, taking into account dosage absorptive function of the intestinal mucosa (98).
of each drug depending on body weight, and the
presentation of adverse effects, this panel of ex- The spina bifida multidisciplinary group
perts recommends the following possible plan: This group of experts considers it is ne-
1) Oxybutynin 0.2-0.6mg/k/day every 8 hours cessary to count on a multidisciplinary team for
or oxybutynin ER+Tolterodine (0.25-1mg a better management of patients with neurogenic
every 12h) or Tolterodine ER 4mg. bladder dysfunction.
2) Oxybutynin 0.2-0.6mg/k/day every 8 hours Every health care center will select the
or oxybutynin ER+Solifenacin 5 to 10mg a participants in a multidisciplinary team that must
day (for adolescents). very well know the commitment and responsibi-
3) Tolterodine 0.25-1mg every 12 hours or lity that the management of these patients requi-
Tolterodine ER 4 mg+Darifenacin 7.5, 15mg res. The specialties involved in such a team are:
a day (for adolescents). neurosurgery, neurology, urology, nephrology, pe-
4) Injections of botulinum toxin-A 6-10 IU/k: diatrics, gastroenterology, physiatry, orthopedics,
if there is overactivity or hyperreflexia (2A among others. In addition, we must mention nur-
Weak recommendation: evidence of high ses, physical therapists, occupational therapists,
quality). With or without plan 1, 2 and 3 psychologists, nutritionists and social workers.
as adjuvants. If after the first injection the- The so-called “Life Course Model” (99)
re are significant urodynamic and clinical describes the roles and milestones in the life of an
changes, repeat injection nine months after individual during childhood, school life, adoles-
the first injection. If there are no significant cence and adulthood focusing on medical assis-
changes, the following option should be tance with a multidisciplinary approach. At each
considered: stage in life there are objectives set and the health
5) Mirabegron 25 to 50mg a day, with or without care providers can monitor or intervene in a coor-
an agent from plan 1, 2 and 3 as adjuvants. dinated way in view of the goals to be achieved at
Example: Tolterodine 4mg+Mirabegron each step.
50mg day. Multidisciplinary groups of neurogenic
6) If after a clinical (CIC diary) and urodyna- bladder carry out different programs to manage
mic evaluation at least 3 months later with particular situations in several subgroups. One of
one of the previously mentioned options these subgroups with direct influence on neuro-
the patient remains refractory or resistant genic bladder is the neurogenic bowel subgroup.
to medication, bladder augmentation should Its treatment is fundamental for an adequate ma-
be considered. nagement of neurogenic bladder, especially at an
7) The use of α-blockers to diminish pressure early age, in order to avoid constipation and in-
in the exit tract and facilitate bladder emp- continence (64).

45
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

This panel of experts recommends: To ini- -EPI) creatinine-based formula and the updated
tiate an early adequate program of bowel mana- Schwartz “bedside” formula (CKiD 2009) for chil-
gement (1B Strong recommendation: evidence of dren (103, 104). Measuring the height in a patient
moderate quality). with spina bifida is a difficult task, since many
The nurse in the urology unit is usually patients cannot walk, but the estimation can be
the person who gets to know the socio-cultural done via measurement of the arms.
background of the patient better and they can In children, protein excretion of <100mg/
detect problems in adherence, thus they can ac- m2/day or <4mg/m2 /hour in a 24hr urine col-
tivate support networks to deal with issues such lection is considered normal. It is important to
as overweight (100), irregular behavior and bowel investigate proteinuria (up to 5mg/kg/day in
movement habits. Furthermore, they can counsel neurogenic bladder) as a marker of renal lesion,
the family and help them understand issues rela- as well as the protein/creatinine index (up to 0.2
ted to the rights of patients (101). in NB), the albumin/creatinine ratio (up to 30mg
The dynamics of the multidisciplinary in NB) and 24hr microalbuminuria (up to 30mg/
team will depend on the policy of each health day in NB).
care center, the availability of specialists in sha- DMSA, 99m Technetium Dimercapto-
red spaces and schedules, and, above all, the ma- -Succinic Acid renal scans, are ideal to confirm
nagement of the patient by the coordinated cir- renal scars in children with spina bifida. A his-
cuit of sectors. It is of vital importance to count tory of VUR and UTI is associated to abnormal
on a leader of the team, in general a pediatrician, findings on DMSA in follow-ups of patients ol-
who is in charge of encouraging necessary chan- der than 10 years of age with spina bifida (105).
ges and adjustments among specialties and sets Kanaheswari et al. identified 45 children with
priorities. Furthermore, it is necessary to address spina bifida who received multidisciplinary as-
the following issues: to have access to a physician sistance during at least 2 years. Of these, 78%
of reference in inland regions, and to count on showed evidence of having neurogenic bladder
counseling for the disability certificate and acces- and 35.5% developed renal failure with scarring.
sible integrated electronic registry. Most of the children were studied during the ne-
onatal period, but 35.6% showed remission after
Renal function in pediatric neurogenic bladder 6 months of age (106). A total of 36% of patients
The management of children with neuro- with MMC under follow-up for 5 years presented
genic bladder should be focused on the preserva- renal impairment (mainly renal disease grade I)
tion of the renal function with the prevention of with a proactive management. Of the ones with
renal scars, avoiding progression to chronic renal late initiation of treatment, 42% developed renal
disease (CRD). An early start of therapy leads to disease (Sager et al., 2020, data not published).
improve the preservation of the renal function in Despite advances in the understanding of Renin-
children with neurogenic bladder (102). Approxi- -Angiotensin-Aldosterone System (RAAS) as a
mately 10-30% of children are born with evidence participant in the mechanism of renal injury, the
of renal disease and this figure increases conside- analysis of its serum (ACE and ACE 2) and urina-
rably over time, with some even reaching renal ry (urinary ACE) markers was not significant in
compromise in about 50% of cases, as some re- patients with MMC with renal injury previously
ports describe (102). Therefore, accurate measures detected by renal DMSA scintigraphy (107).
of kidney function are essential to avoid glomeru-
lar and tubular compromise. Criteria for the definition of chronic renal dise-
It is recommended that the glomerular ase in children
filtrate rate (GFR) be estimated together with the A) Renal damage of more than 3 months of dura-
serum creatinine value using the Chronic Kid- tion defined by structural or functional altera-
ney Disease Epidemiology Collaboration (CKD- tions determined by imaging, laboratory analy-

46
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

ses (blood or urine tests), or renal biopsy, with bladder conditions. It has been demonstrated that
or without decrease in glomerular filtrate rates. clean intermittent catheterization and pharmaco-
B) Glomerular filtrate rate <90mL/m/1.73m²≥3 therapy should be implemented as early as possi-
months with or without signs of renal dama- ble in order to avoid deterioration or damage.
ge previously mentioned or using the updated If patients become refractory to first-line
Schwartz formula (108). medication, there are more selective second-line
therapies, such as beta agonists and botulinum to-
This panel of experts recommends xin-A that can delay cystoplasty, improve urinary
1) All patients with spina bifida should under- incontinence scores and maintain safe intravesical
go renal DMSA scintigraphy during the first pressures. This contributes to reducing the morbi-
year of life and after 6 months of presenting dity of reconstructive procedures and to enhan-
pyelonephritis episodes (1B Strong recom- cing quality of life and social inclusion.
mendation: evidence of moderate quality).
2) Evaluation of renal function with estimated CONFLICT OF INTEREST
clearance of creatinine (Schwartz formula)
or clearance measured in 24-hour urine col- None declared.
lection. It is recommended for those patients
with renal lesions as shown on DMSA and/
or with proteinuria. REFERENCES
3) Detection of 24 hr proteinuria (>5mg/Kg/
day: abnormal) and 24 hr microalbuminuria 1. Bauer SB, Labib KB, Dieppa RA, Retik AB. Urodynamic
(>30mg/day). Recommended for those pa- evaluation of boy with myelodysplasia and incontinence.
tients with renal lesions as seen on DMSA Urology. 1977; 10:354-62.
and/or with proteinuria. 2. Bauer S. Clean intermittent catheterization of infants with
myelodysplasia: the argument for early assessment and
CONCLUSION treatment of infants with spina bifida. Dialog Ped Urol.
2000;23:2‐3.
The aim of this document is to offer an 3. Sillén U, Hansson E, Hermansson G, Hjälmås K, Jacobsson
update on neurogenic bladder dysfunction in chil- B, Jodal U. Development of the urodynamic pattern in infants
dren and recommendations on the major topics with myelomeningocele. Br J Urol. 1996; 78:596-601.
related to the management of patients suffering 4. Snow-Lisy DC, Yerkes EB, Cheng EY. Update on Urological
from it. Management of Spina Bifida from Prenatal Diagnosis to
Neurogenic bladder dysfunction repre- Adulthood. J Urol. 2015; 194:288-96.
sents one of the main sequelae of defective closu- 5. Lee B, Featherstone N, Nagappan P, McCarthy L, O’Toole
re of the neural tube in children. The prevalence S. British Association of Paediatric Urologists consensus
of spina bifida is variable among regions and its statement on the management of the neuropathic bladder. J
most frequent type is myelomeningocele, which Pediatr Urol. 2016; 12:76-87.
produces severe sequelae for life. Multidisciplina- 6. Bauer SB. The management of the myelodysplastic child: a
ry groups of neurogenic bladder carry out diffe- paradigm shift. BJU Int. 2003; 92(Suppl 1):23-8.
rent programs to manage particular conditions, 7. Murad MH. Clinical Practice Guidelines: A Primer on
such as the neurogenic bowel subgroup. Development and Dissemination. Mayo Clin Proc. 2017;
One of the most affected systems is the 92:423-33.
urinary tract, with the potential compromise of 8. Shiffman RN, Dixon J, Brandt C, Essaihi A, Hsiao A, Michel
the renal parenchyma, which should be most ca- G, et al. The GuideLine Implementability Appraisal (GLIA):
red for. It is necessary to assess the anatomy and development of an instrument to identify obstacles to
function of the urinary tract in order to stratify guideline implementation. BMC Med Inform Decis Mak.
the risk of exposure of the renal mass to adverse 2005; 5:23.

47
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

9. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. 23. Torre M, Buffa P, Jasonni V, Cama A. Long-term urologic
GRADE guidelines: 1. Introduction-GRADE evidence profiles outcome in patients with caudal regression syndrome,
and summary of findings tables. J Clin Epidemiol. 2011; compared with meningomyelocele and spinal cord lipoma.
64:383-94. J Pediatr Surg. 2008; 43:530-3.
10. de Groat WC, Griffiths D, Yoshimura N. Neural control of the 24. Ruffion A, Castro-Diaz D, Patel H, Khalaf K, Onyenwenyi A,
lower urinary tract. Compr Physiol. 2015; 5:327-96. Globe D, et al. Systematic review of the epidemiology of urinary
11. Gajewski JB, Schurch B, Hamid R, Averbeck M, Sakakibara incontinence and detrusor overactivity among patients with
R, Agrò EF, et al. An International Continence Society (ICS) neurogenic overactive bladder. Neuroepidemiology. 2013;
report on the terminology for adult neurogenic lower urinary 41:146-55.
tract dysfunction (ANLUTD). Neurourol Urodyn. 2018; 25. Korzeniecka-Kozerska A, Porowski T, Bagińska J, Wasilewska
37:1152-61. A. Urodynamic Findings and Renal Function in Children with
12. Austin PF, Bauer SB, Bower W, Chase J, Franco I, Hoebeke Neurogenic Bladder after Myelomeningocele. Urol Int. 2015;
P, et al. The standardization of terminology of lower urinary 95:146-52.
tract function in children and adolescents: update report from 26. Tekgül S, Riedmiller H, Gerharz F, Hoebeke P, Kocvara R,
the Standardization Committee of the International Children’s Nijman R et al: Guidelines on paediatric urology. European
Continence Society. J Urol. 2014;191:1863-65.e13. Association of Urology, European Society for Paediatric
13. Preziosi G, Emmanuel A. Neurogenic bowel dysfunction: Urology. 2008; pp. 34-43.
pathophysiology, clinical manifestations and treatment. 27. González R, Ludwikowski BM. Tratamiento del reflujo
Expert Rev Gastroenterol Hepatol. 2009; 3:417-23. vesicoureteral en niños con mielomeningocele [The treatment
14. Giacomo GalliDidier Aubert. Epidemiology of Neurogenic of vesicoureteral reflux in children with myelomeningocele].
Bladder Dysfunction in Children.Pediatric Neurogenic Arch Esp Urol. 2008; 61:208-12.
Bladder Dysfunction. 2006; pp. 23-32. 28. Bauer SB: Vesicoureteral reflux in children with neurogenic
15. Scarff TB, Fronczak S. Myelomeningocele: a review and bladder dysfunction. In: Johnston JH (ed.), International
update. Rehabil Nurs. 1981; 6:26-9. perspectives in urology. Baltimore, Williams & Wilkins.
16. [No authors] Prevention of neural tube defects: results of 1984;10: pp.159-77.
the Medical Research Council Vitamin Study. MRC Vitamin 29. Kim WJ, Shiroyanagi Y, Yamazaki Y. Can Bladder Wall
Study Research Group. Lancet. 1991; 338:131-7. Thickness Predict Videourodynamic Findings in Children
17. Mourtzinos A, Stoffel JT. Management goals for the with Spina Bifida? J Urol. 2015; 194:180-3.
spina bifida neurogenic bladder: a review from infancy to 30. Bauer SB, Nijman RJ, Drzewiecki BA, Sillen U, Hoebeke P;
adulthood. Urol Clin North Am. 2010; 37:527-35. International Children’s Continence Society Standardization
18. Bauer SB, Labib KB, Dieppa RA, Retik AB. Urodynamic Subcommittee. International Children’s Continence Society
evaluation of boy with myelodysplasia and incontinence. standardization report on urodynamic studies of the lower
Urology. 1977; 10:354-62. urinary tract in children. Neurourol Urodyn. 2015; 34:640-7.
19. Netto JM, Bastos AN, Figueiredo AA, Pérez LM. Spinal 31. Arora G, Narasimhan KL, Saxena AK, Kaur B, Mittal BR. Risk
dysraphism: a neurosurgical review for the urologist. Rev factors for renal injury in patients with meningomyelocele.
Urol. 2009; 11:71-81. Indian Pediatr. 2007; 44:417-20.
20. Powell A, Davidson L. Pediatric spinal cord injury: a review 32. Stoneking BJ, Brock JW, Pope JC, Adams MC. Early
by organ system. Phys Med Rehabil Clin N Am. 2015; evolution of bladder emptying after myelomeningocele
26:109-32. closure. Urology. 2001; 58:767-71.
21. Parent S, Mac-Thiong JM, Roy-Beaudry M, Sosa JF, Labelle 33. Spinoit AF, Decalf V, Ragolle I, Ploumidis A, Claeys T, Groen
H. Spinal cord injury in the pediatric population: a systematic LA, et al. Urodynamic studies in children: Standardized
review of the literature. J Neurotrauma. 2011; 28:1515-24. transurethral video-urodynamic evaluation. J Pediatr Urol.
22. Bauer SB, Austin PF, Rawashdeh YF, de Jong TP, Franco 2016; 12:67-8.
I, Siggard C, et al. International Children’s Continence 34. Verpoorten C, Buyse GM. The neurogenic bladder: medical
Society’s recommendations for initial diagnostic evaluation treatment. Pediatr Nephrol. 2008; 23:717-25.
and follow-up in congenital neuropathic bladder and bowel 35. Bauer SB. Neurogenic bladder: etiology and assessment.
dysfunction in children. Neurourol Urodyn. 2012; 31:610-4. Pediatr Nephrol. 2008; 23:541-51.

48
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

36. Carol Burek, Liliana Campmany. Guías de atención pediátrica. 48. Dik P, Klijn AJ, van Gool JD, de Jong-de Vos van Steenwijk
GAP 2011. Manejo Urológico del mielomeningocele. [Internet]. CC, de Jong TP. Early start to therapy preserves kidney
Available at .<http://www.garrahan.gov.ar/PDFS/gap_historico/ function in spina bifida patients. Eur Urol. 2006; 49:908-13.
GAP2011-MANEJO-URO-MMC-VERSION-IMPRESA.pdf> 49. Edelstein RA, Bauer SB, Kelly MD, Darbey MM, Peters CA, Atala
37. Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean, intermittent A, et al. The long-term urological response of neonates with
self-catheterization in the treatment of urinary tract disease. myelodysplasia treated proactively with intermittent catheterization
Trans Am Assoc Genitourin Surg. 1971; 63:92-6. and anticholinergic therapy. J Urol. 1995; 154:1500-4.
38. Imamura M, Hayashi C, Kim WJ, Yamazaki Y. Renal 50. Wu HY, Baskin LS, Kogan BA. Neurogenic bladder
scarring on DMSA scan is associated with hypertension and dysfunction due to myelomeningocele: neonatal versus
decreased estimated glomerular filtration rate in spina bifida childhood treatment. J Urol. 1997; 157:2295-7.
patients in the age of transition to adulthood. J Pediatr Urol. 51. Kaye IY, Payan M, Vemulakonda VM. Association between
2018; 14:317.e1-317.e5. clean intermittent catheterization and urinary tract infection
39. McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic in infants and toddlers with spina bifida. J Pediatr Urol.
value of urodynamic testing in myelodysplastic patients. J 2016; 12:284.e1-284.e6.
Urol. 1981; 126:205-9. 52. Kaefer M, Pabby A, Kelly M, Darbey M, Bauer SB. Improved
40. Amend B, Hennenlotter J, Schäfer T, Horstmann M, Stenzl bladder function after prophylactic treatment of the high risk
A, Sievert KD. Effective treatment of neurogenic detrusor neurogenic bladder in newborns with myelomentingocele. J
dysfunction by combined high-dosed antimuscarinics Urol. 1999; 162(3 Pt 2):1068-71.
without increased side-effects. Eur Urol. 2008; 53:1021-8. 53. DeLair SM, Eandi J, White MJ, Nguyen T, Stone AR,
41. Lee JH, Kim KR, Lee YS, Han SW, Kim KS, Song SH, et al. Kurzrock EA. Renal cortical deterioration in children with
Eficácia, tolerabilidade e segurança do cloreto de oxibutinina spinal dysraphism: analysis of risk factors. J Spinal Cord
na bexiga neurogênica pediátrica com disrafismo espinhal: Med. 2007; 30 Suppl 1(Suppl 1):S30-4.
um estudo retrospectivo, multicêntrico e observacional. 54. Elzeneini W, Waly R, Marshall D, Bailie A. Early start of clean
Korean J Urol. Dezembro de 2014; 55: 828-33. intermittent catheterization versus expectant management in
42. Klose AG, Sackett CK, Mesrobian HG. Management of children with spina bifida. J Pediatr Surg. 2019; 54:322-5.
children with myelodysplasia: urological alternatives. J Urol. 55. Timberlake MD, Kern AJ, Adams R, Walker C, Schlomer BJ,
1990; 144:1446-9. Jacobs MA. Expectant use of CIC in newborns with spinal
43. Kaufman AM, Ritchey ML, Roberts AC, Rudy DC, McGuire dysraphism: Report of clinical outcomes. J Pediatr Rehabil
EJ. Decreased bladder compliance in patients with Med. 2017; 10:319-25.
myelomeningocele treated with radiological observation. J 56. Ozel SK, Dokumcu Z, Akyildiz C, Avanoglu A, Ulman I.
Urol. 1996; 156:2031-3. Factors affecting renal scar development in children with
44. Teichman JM, Scherz HC, Kim KD, Cho DH, Packer MG, spina bifida. Urol Int. 2007; 79:133-6.
Kaplan GW. An alternative approach to myelodysplasia 57. Dudley AG, Casella DP, Lauderdale CJ, Zhao S, Chen H,
management: aggressive observation and prompt Tanaka ST, et al. Interrater Reliability in Pediatric Urodynamic
intervention. J Urol. 1994; 152(2 Pt 2):807-11. Tracings: A Pilot Study. J Urol. 2017; 197(3 Pt 2):865-70.
45. Hopps CV, Kropp KA. Preservation of renal function in children 58. Tanaka H, Matsuda M, Moriya K, Mitsui T, Kitta T, Nonomura
with myelomeningocele managed with basic newborn K. Ultrasonographic measurement of bladder wall thickness
evaluation and close follow-up. J Urol. 2003; 169:305-8. as a risk factor for upper urinary tract deterioration in
46. Geraniotis E, Koff SA, Enrile B. The prophylactic use of clean children with myelodysplasia. J Urol. 2008; 180:312-6.
intermittent catheterization in the treatment of infants and 59. Şekerci ÇA, Işbilen B, Işman F, Akbal C, Şimşek F,
young children with myelomeningocele and neurogenic Tarcan T. Urinary NGF, TGF-β1, TIMP-2 and bladder wall
bladder dysfunction. J Urol. 1988; 139:85-6. thickness predict neurourological findings in children with
47. Kasabian NG, Bauer SB, Dyro FM, Colodny AH, Mandell myelodysplasia. J Urol. 2014; 191:199-205.
J, Retik AB. The prophylactic value of clean intermittent 60. Müller L, Abrahamsson K, Sillén U, Jacobsson B, Odén A,
catheterization and anticholinergic medication in newborns Hellström M. Ultrasound assessment of detrusor thickness
and infants with myelodysplasia at risk of developing urinary in children and young adults with myelomeningocele. J Urol.
tract deterioration. Am J Dis Child. 1992; 146:840-3. 2006; 175:704-8; discussion 708.

49
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

61. Fuentes I, Delgado JA, Crespi F, Blazquez J, Resel L: 74. Kiddoo D, Sawatzky B, Bascu CD, Dharamsi N, Afshar
Cateterismo vesical Intermitente. Clin Urol Complut. K, Moore KN. Randomized Crossover Trial of Single Use
2000;8:771-7. Hydrophilic Coated vs Multiple Use Polyvinylchloride
62. Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean, intermittent Catheters for Intermittent Catheterization to Determine
self-catheterization in the treatment of urinary tract disease. Incidence of Urinary Infection. J Urol. 2015; 194:174-9.
J Urol. 1972;107:458-61. 75. Prieto J, Murphy CL, Moore KN, Fader M. Intermittent
63. Snow-Lisy DC, Yerkes EB, Cheng EY. Update on Urological catheterisation for long-term bladder management.
Management of Spina Bifida from Prenatal Diagnosis to Cochrane Database Syst Rev. 2014, 10; 9:CD006008.
Adulthood. J Urol. 2015; 194:288-96. 76. Lindehall B, Abrahamsson K, Jodal U, Olsson I, Sillén U.
64. Stein R, Bogaert G, Dogan HS, Hoen L, Kocvara R, Nijman Complications of clean intermittent catheterization in young
RJM, et al. EAU/ESPU guidelines on the management females with myelomeningocele: 10 to 19 years of followup.
of neurogenic bladder in children and adolescent part I J Urol. 2007; 178(3 Pt 1):1053-5.
diagnostics and conservative treatment. Neurourol Urodyn. 77. Lucas EJ, Baxter C, Singh C, Mohamed AZ, Li B, Zhang J,
2020; 39:45-57. et al. Comparison of the microbiological milieu of patients
65. Kaefer M, Pabby A, Kelly M, Darbey M, Bauer SB. Improved randomized to either hydrophilic or conventional PVC
bladder function after prophylactic treatment of the high risk catheters for clean intermittent catheterization. J Pediatr
neurogenic bladder in newborns with myelomentingocele. J Urol. 2016; 12:172.e1-8.
Urol. 1999; 162(3 Pt 2):1068-71. 78. Clayton DB, Tanaka ST, Trusler L, Thomas JC, Pope JC
66. Dik P, Klijn AJ, van Gool JD, de Jong-de Vos van 4th, Adams MC, et al. Long-term urological impact of
Steenwijk CC, de Jong TP. Early start to therapy fetal myelomeningocele closure. J Urol. 2011; 186(4
preserves kidney function in spina bifida patients. Eur Suppl):1581-5.
Urol. 2006; 49:908-13. 79. Lee NG, Gomez P, Uberoi V, Kokorowski PJ, Khoshbin S,
67. Edelstein RA, Bauer SB, Kelly MD, Darbey MM, Peters CA, Bauer SB, et al. In utero closure of myelomeningocele does
Atala A, et al. The long-term urological response of neonates not improve lower urinary tract function. J Urol. 2012; 188(4
with myelodysplasia treated proactively with intermittent Suppl):1567-71.
catheterization and anticholinergic therapy. J Urol. 1995; 80. Newman DK, Willson MM. Review of intermittent
154:1500-4. catheterization and current best practices. Urol Nurs. 2011;
68. de Jong TP, Chrzan R, Klijn AJ, Dik P. Treatment of the 31:12-28.
neurogenic bladder in spina bifida. Pediatr Nephrol. 2008; 81. Strine AC, Misseri R, Szymanski KM, Kaefer M, Rhee
23:889-96. AC, Hillier K, et al. Assessing health related benefit
69. de Jong TP, Klijn AJ. Urodynamic studies in pediatric urology. after reconstruction for urinary and fecal incontinence
Nat Rev Urol. 2009; 6:585-94. in children: a parental perspective. J Urol. 2015;
70. Barkin M, Dolfin D, Herschorn S, Bharatwal N, Comisarow 193:2073-8.
R. The urologic care of the spinal cord injury patient. J Urol. 82. Chavarriaga J, Fernández N, Campo MAO, Bolivar J,
1983; 129:335-9. Patiño G, Perez J. Self-perception, quality of life and
71. Iwatsubo E, Iwakawa A, Koga H, Imamura A, Yamashita H, ease of catheterization in patients with continent urinary
Komine S. Functional recovery of the bladder in patients diversion with the mitrofanoff principle. Int Braz J Urol.
with spinal cord injury--prognosticating programs of 2020; 46:743-51.
an aseptic intermittent catheterization. Hinyokika Kiyo. 83. Casale AJ. A long continent ileovesicostomy using a single
1985; 31:775-83. piece of bowel. J Urol. 1999; 162:1743-5.
72. Hochleitner BW, Menardi G, Häussler B, Ulmer H, Kofler 84. Cain MP, Rink RC, Yerkes EB, Kaefer M, Casale AJ. Long-
H, Reider N. Spina bifida as an independent risk factor for term followup and outcome of continent catheterizable
sensitization to latex. J Urol. 2001; 166:2370-3. vesicocstomy using the Rink modification. J Urol. 2002;
73. Moore KN, Fader M, Getliffe K. Long-term bladder 168:2583-5.
management by intermittent catheterisation in adults 85. Pang D. Surgical management of complex spinal cord
and children. Cochrane Database Syst Rev. 2007, 17; lipomas: how, why, and when to operate. A review. J
4:CD006008. Neurosurg Pediatr. 2019; 23:537-56.

50
 IBJU | NEUROGENIC BLADDER DYSFUNCTION IN CHILDREN

86. Nadeau G, Schröder A, Moore K, Genois L, Lamontagne P, 98. Dantas RAF, Calisto FCFS, Vilar FO, Araujo LAP, Lima SVC.
Hamel M, et al. Double anticholinergic therapy for refractory Nonsecretory intestinocystoplasty: postoperative outcomes
neurogenic and nonneurogenic detrusor overactivity in of 25 years. Int Braz J Urol. 2019; 45:681-5.
children: Long-term results of a prospective open-label 99. Dicianno BE, Fairman AD, Juengst SB, Braun PG, Zabel TA.
study. Can Urol Assoc J. 2014; 8:175-80. Using the spina bifida life course model in clinical practice:
87. Cameron AP, Clemens JQ, Latini JM, McGuire EJ. an interdisciplinary approach. Pediatr Clin North Am. 2010;
Combination drug therapy improves compliance of the 57:945-57.
neurogenic bladder. J Urol. 2009; 182:1062-7. 100. Dosa NP, Foley JT, Eckrich M, Woodall-Ruff D, Liptak GS.
88. Dehvari N, da Silva Junior ED, Bengtsson T, Hutchinson DS. Obesity across the lifespan among persons with spina bifida.
Mirabegron: potential off target effects and uses beyond the Disabil Rehabil. 2009; 31:914-20.
bladder. Br J Pharmacol. 2018; 175:4072-82. 101. Dunleavy MJ. The role of the nurse coordinator in spina
89. Blais AS, Nadeau G, Moore K, Genois L, Bolduc S. bifida clinics. cientificWorldJournal. 2007, 26;7:1884-9.
Prospective Pilot Study of Mirabegron in Pediatric Patients 102. Kraus SR, Boone TB. Pediatric neurogenic bladder: etiology
with Overactive Bladder. Eur Urol. 2016; 70:9-13. and diagnostic evaluation; in Gonzales ET, Bauer SB (eds):
90. Park JS, Lee YS, Lee CN, Kim SH, Kim SW, Han SW. Efficacy and Pediatric Urology Practice. Baltimore, Lippincott Williams &
safety of mirabegron, a β3-adrenoceptor agonist, for treating Wilkins.1999; pp. 365-81.
neurogenic bladder in pediatric patients with spina bifida: a 103. Filler G, Gharib M, Casier S, Lödige P, Ehrich JH, Dave S.
retrospective pilot study. World J Urol. 2019; 37:1665-70. Prevention of chronic kidney disease in spina bifida. Int Urol
91. Krhut J, Borovička V, Bílková K, Sýkora R, Míka D, Mokriš J, Nephrol. 2012; 44:817-27.
et al. Efficacy and safety of mirabegron for the treatment of 104. Mian AN, Schwartz GJ. Medição e estimativa da taxa de
neurogenic detrusor overactivity-Prospective, randomized, filtração glomerular em crianças. Adv Chronic Kidney Dis.
double-blind, placebo-controlled study. Neurourol Urodyn. Novembro de 2017; 24: 348-56.
2018; 37:2226-33. 105. Shiroyanagi Y, Suzuki M, Matsuno D, Yamazaki Y. The
92. Sager C, Sanmartino M, Burek C, Gomez YR, Vazquez significance of 99mtechnetium dimercapto-succinic acid
Patiño M, Weller S, et al. Efficacy and safety of Mirabegron renal scan in children with spina bifida during long-term
as adjuvant treatment in children with refractory neurogenic followup. J Urol. 2009;181:2262-6; discussion 2266.
bladder dysfunction. J Pediatr Urol. 2020; 16:655.e1-655.e6. 106. Kanaheswari Y, Mohd Rizal AM. Renal scarring and
93. Hascoet J, Manunta A, Brochard C, Arnaud A, Damphousse chronic kidney disease in children with spina bifida in a
M, Menard H, et al. Outcomes of intra-detrusor injections of multidisciplinary Malaysian centre. J Paediatr Child Health.
botulinum toxin in patients with spina bifida: A systematic 2015; 51:1175-81.
review. Neurourol Urodyn. 2017; 36:557-64. 107. Do Amaral CMCA, Casarini DE, Andrade MC, da Cruz ML,
94. Tiryaki S, Yagmur I, Parlar Y, Ozel K, Akyildiz C, Avanoglu A, Macedo A Jr. Study of serum and urinary markers of the
et al. Botulinum injection is useless on fibrotic neuropathic renin-angiotensin-aldosterone system in myelomeningocele
bladders. J Pediatr Urol. 2015; 11:27.e1-4. patients with renal injury detected by DMSA. Int Braz J Urol.
95. Mascarenhas F, Cocuzza M, Gomes CM, Leão N. Trigonal 2020; 46:805-13.
injection of botulinum toxin-A does not cause vesicoureteral 108. Schwartz GJ, Work DF. Measurement and estimation of GFR
reflux in neurogenic patients. Neurourol Urodyn. 2008; in children and adolescents. Clin J Am Soc Nephrol. 2009;
27:311-4. 4:1832-43.
96. Palleschi G, Mosiello G, Iacovelli V, Musco S, Del Popolo
G, Giannantoni A, et al. Adolescence transitional care _______________________
in neurogenic detrusor overactivity and the use of Correspondence address:
OnabotulinumtoxinA: A clinical algorithm from an Italian Cristian Sager, MD
consensus statement. Neurourol Urodyn. 2018; 37:904-15. Combate de los Pozos 1881 (C 1245 AAM)
97. Sager C, Burek C, Bortagaray J, Corbetta JP, Weller Ciudad Autónoma de Buenos Aires (C.A.B.A.)
S, Durán V, et al. Repeated injections of intradetrusor República Argentina
onabotulinumtoxinA as adjunctive treatment of children with Fax: + 54 11 4122-6000
neurogenic bladder. Pediatr Surg Int. 2014; 30:79-85. E-mail address: cristian.sager@gmail.com

51