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T h e N e u ro g e n i c B l a d d e r :

An Update with
Management Strategies
f o r Pr i m a r y C a re
Physicians
a, b
Adam P. Klausner, MD *, William D. Steers, MD

KEYWORDS
 Neurogenic bladder  Urodynamics
 Bladder outlet obstruction

INTRODUCTION: THE MICTURITION REFLEX AND NORMAL VOIDING

To void in an efficient manner, there must be a finely coordinated reciprocal function-


ality of the urinary bladder and urinary sphincter. When the bladder contracts, the
external urethral sphincter must relax. Conversely, when the urinary bladder is relaxed,
the urinary sphincter contracts and maintains tone. The reciprocal coordination of
these 2 functional units within the lower urinary tract is mediated by a specialized
control center in the brain stem called the pontine micturition center.1
It is important to emphasize a few key concepts of urine storage. As the bladder fills
with urine, the intravesical pressure remains low until the threshold for micturition
is reached. This progressive increase in volumes with minimal increase in pressure
is termed compliance and is defined by the equation DVolume/DPressure.2 In a normal
50-year-old man, the typical cystometric bladder capacity is approximately 400 mL.3
During the increase in volume from 0 to 400 mL, it is expected that the pressure within
the bladder will increase to only about 10 cm H2O, resulting in a compliance of
40 mL/cm H2O. The compliance of the bladder is a function of its inherent viscoelas-
ticity, the ability of detrusor muscle cells to elongate while still maintaining efficient
contractility, and the neurally mediated suppression of signals that promote detrusor
contraction.4 A normally complaint bladder is essential for proper functioning of the
lower urinary tract.

a
Division of Urology, Department of Surgery, Virginia Commonwealth University School of
Medicine, PO Box 980118, Richmond, VA 23298-0118, USA
b
Department of Urology, University of Virginia School of Medicine, VA, USA
* Corresponding author.
E-mail address: apklausner@vcu.edu

Med Clin N Am 95 (2011) 111–120


doi:10.1016/j.mcna.2010.08.027 medical.theclinics.com
0025-7125/11/$ – see front matter Ó 2011 Published by Elsevier Inc.
112 Klausner & Steers

A patient with symptoms of or proven dysfunction of the lower urinary tract and
neurologic findings (or a known neurologic disorder) is said to have a neurogenic
bladder. Poor compliance is one consequence of neurogenic bladder dysfunction,
but compliance can only be determined during a formal urodynamic evaluation, in
which filling pressures and volumes are recorded simultaneously. Therefore, one of
the most important pieces of information that is obtained from a urodynamic evalua-
tion is a determination of the bladder compliance.
The micturition reflex is an autonomic process under voluntary control. In other
words, the reflex can be aborted midstream by inhibitory neural inputs from higher
cortical brain centers. Conversely, the reflex can be accelerated by neurologic
processes that affect or damage these areas that produce inhibitory inputs. Damage
to the cerebral cortex reduces inhibitory input to the pontine micturition center and
might cause urinary frequency, urgency, or even urge incontinence. Patients with
this type of reduced inhibitory control are those with Parkinson disease, cortical
strokes, brain tumors, normal pressure hydrocephalus, traumatic brain injury, or Alz-
heimer type dementia.5 Alternatively, patients with diseases such as multiple scle-
rosis, degenerative disk disease, or spinal cord pathology have neurologic lesions
caudal to the pontine micturition center but rostral to the sacral spinal cord. Typically,
lesions in this location result in a loss of coordination between the bladder and its
outlet, creating obstruction.5 In addition to often demonstrating detrusor overactivity,
these patients may exhibit either slowed external sphincter relaxation (eg, Parkinson
disease) or complete loss of coordination (eg, suprasacral spinal cord injury [SCI]).
Whether overactive bladder symptoms are merely caused by detrusor overactivity
or are the result of bladder outlet obstruction requires special physiologic testing of
the lower urinary tract termed urodynamics.

URODYNAMICS: INDICATIONS AND TECHNIQUE


Indications for Urodynamics
Multichannel pressure-flow urodynamics offers the most complete and useful eval-
uation of neurogenic bladder dysfunction. Urodynamic evaluation consists of
several tests used alone or in combination (multichannel). Tests include voiding
flow rate, cystometry, sphincter electromyography (EMG), and urethral pressure
profilometry. The goal of a urodynamic evaluation is to reproduce the patient’s
typical micturition cycle and associated urinary symptoms. It is crucial for the uro-
dynamicist to take a comprehensive history and be aware of the patient’s under-
lying neurologic status.

Urodynamic Technique
The cystometry portion of urodynamics is accomplished by infusing saline at room
temperature at the rate of 40 to 60 mL/min. Although faster than physiologic filling,
these rates have been chosen because of time constraints and to help unmask detru-
sor overactivity. During the filling phase, the urodynamicist asks the patient to identify
various sensory thresholds including the volumes at which the patient has the first
sensation of filling, the first desire to void, and a strong desire to void. The diagnosis
of increased bladder sensation is made when patients achieve sensory thresholds at
lower-than-expected volumes. Reduced or absent sensation is diagnosed when
patients achieve sensory thresholds at lower-than-expected volumes or not at all.
During the filling phase, any involuntary bladder contractions should be noted.
Although involuntary detrusor contractions (IDCs) are identified in up to 20% of
asymptomatic patients during cystometry,6,7 their presence is considered abnormal.
The Neurogenic Bladder 113

Thus, the presence of one or more IDCs during the filling phase allows the urodynam-
icist to diagnose detrusor overactivity. In the setting of known neurogenic bladder
dysfunction, the diagnosis is neurogenic detrusor overactivity as opposed to idio-
pathic detrusor overactivity. In addition, at a volume equal to about 50% of the known
or expected bladder capacity, filling is temporarily stopped and provocative maneu-
vers are sometimes performed to evaluate for the possibility of an incompetent
urethral sphincter closure mechanism, which is commonly found in patients with
stress incontinence.
Once the patient reaches cystometric capacity, the filling is discontinued and the
patient is given permission to void. Oftentimes, the patient is unable to wait and voids
involuntarily, which leads to the urodynamic diagnosis of detrusor overactivity incon-
tinence. During the voiding phase, the voiding flow rate is obtained using a flowmeter
that collects urine while calculating a urinary flow rate. Multichannel capability allows
flow and intravesical pressure to be graphed at the same time. This simultaneous
measurement of bladder pressure and urine flow is also called a pressure-flow study.
The pressure-flow study is the only test that can accurately determine whether phys-
iologic bladder outlet obstruction exists. A low peak voiding flow rate (<12 mL/s) may
suggest obstruction but cannot, in itself, exclude impaired detrusor contractility. The
diagnosis of bladder outlet obstruction is made only when elevated bladder pressures
and low urinary flow rates (ie, high pressure, low flow) are seen simultaneously. The
urodynamic criteria for obstruction in men has been clearly defined and can be
graphed on a standardized nomogram,8 whereas such a measure in women is some-
what controversial. Fluoroscopy performed simultaneously with multichannel
urodynamic evaluation (termed videourodynamics) allows the operator to note the
level of obstruction, such as the bladder neck, prostate, external sphincter, or distal
urethra.
EMG activity of the urinary sphincter is used to determine if the bladder and
sphincter are acting in a coordinated manner. In the setting of neurogenic bladder
dysfunction, obstruction often occurs because of a lack of neurally mediated coor-
dination of the sphincter and bladder, a process termed detrusor-sphincter dyssy-
nergia (DSD). It is crucial that the urodynamicist differentiate true dyssynergia
from dysfunctional voiding, a learned behavior or an artifact. The following cases
illustrate how urodynamics is used to diagnosis and treat patients with neurogenic
voiding dysfunction:

URODYNAMIC INTERPRETATION AND PATIENT MANAGEMENT


Case 1: Neurogenic Bladder Dysfunction Caused by Injury Above the Level of the
Pontine Micturition Center
An 82-year-old man complains of persistent urinary frequency and urgency with some
urge incontinence after having an ischemic cerebrovascular injury. His neurologic
examination reveals hemiparesis of the left side, and he has an enlarged prostate
on digital rectal examination. Are his symptoms caused by stroke or bladder outlet
obstruction from prostatic enlargement? Although empiric therapy can be attempted,
urodynamic testing is needed to exclude obstruction and document whether detrusor
overactivity exists.
During the filling phase of cystometry, he reports a strong desire to void at an
infused volume of 125 mL, associated with an IDC and involuntary leakage. His urinary
sphincter and bladder are reported to act in a coordinated manner based on the EMG
data, and he has no definitive evidence of bladder outlet obstruction. In this case, the
urodynamic diagnosis is neurogenic detrusor overactivity incontinence. The cause is
likely stroke-induced damage to inhibitory cortical inputs to the pontine micturition
114 Klausner & Steers

center, which clinically presents as a reduced warning time associated with urinary
urgency and urge incontinence.
This patient should first be treated with timed or prompted voiding, fluid manage-
ment, and urge suppression maneuvers. Diuretics should be avoided because
these will exacerbate his symptoms. Patients who do not fully respond to behav-
ioral modification may be managed with antimuscarinic medications. However,
many of these medications have inconvenient side effects such as dry mouth
and constipation, which limit their long-term efficacy, and some are associated
with short-term memory impairment, making them more risky for use in the elderly.9
Certainly, patients should be counseled that symptoms may improve spontaneously
in parallel with recovery of other motor and cognitive functions after an acute
stroke. Chronic symptoms that are severe, bothersome, and refractory to behav-
ioral modifications and medical therapy can be treated by sacral or tibial nerve neu-
romodulation or even with off-label usage of botulinum toxin injected into the
bladder muscle.10,11

Case 2: Neurogenic Bladder Dysfunction Caused by Suprasacral SCI


One year after a motor vehicle crash, a 26-year-old woman is paraplegic as a result of
an incomplete SCI at the T5 level. She complains of the need to urinate coinciding with
increased spasticity in her legs and associated with profuse sweating and facial flush-
ing. She wears adult diapers. During a urodynamic evaluation, she is noted to have
absent sensation of bladder filling but has a relatively normal cystometric capacity
(350 mL). At an infused volume of 300 mL, she develops a high-pressure sustained
IDC, with a maximum pressure of 110 cm H2O. She empties about 50% of her cysto-
metric capacity, but voiding is prolonged (4 minutes duration), comes in interrupted
spurts, and is associated with an increased EMG activity of the urinary sphincter.
Provocative maneuvers demonstrate no evidence of stress incontinence.
Based on the history and the data obtained from the urodynamic evaluation, it is
noted that this patient is not properly managing her bladder and is at high risk for renal
deterioration. Because her injury is below the pontine micturition center, the coordi-
nated reciprocal functionality of the urinary bladder and urinary sphincter is absent.
Clinically, the patient has DSD. DSD causes bladder outlet obstruction and inefficient
emptying. As a direct result of the obstruction, the patient’s voiding pressures are very
high. Typical unobstructed voiding pressures are at or less than 40 cm H2O; however,
this patient’s pressures are well above 100 cm H2O. The high pressures may over-
whelm the intrinsic valve mechanism of the ureters as they course through the bladder
wall and create reflux of high-pressure urine that is likely colonized by multiple bacte-
rial pathogens. This combination places the patient at significant risk for kidney
damage and other complications.
Treatment includes limiting fluid intake to less than 2 L/d to increase the time interval
between voiding events. In addition, antimuscarinic medications should be prescribed
and may need to be used at much higher doses than are typically recommended.12
Finally, the patient should be trained to perform intermittent catheterization using
a clean or sterile technique. The timing of catheterization should be adjusted to
keep the urine volumes less than the value at which high-pressure bladder contrac-
tions developed (<300 mL in this patient). A voiding diary or daily voiding log can be
used to help keep track of residual volumes. Because urodynamic evaluation indicates
a high detrusor leak point pressure, renal function should be monitored at 3- to 6-
month intervals using serum creatinine levels and renal ultrasonographys. The inability
to perform catheterization or lack of compliance with catheterization should prompt
discussion of more aggressive treatment options, including urinary diversion using
The Neurogenic Bladder 115

segments of bowel or botulinum toxin injections into the detrusor. Primary care
providers should recognize that patients such as these require lifelong urologic
management and should be referred to a urologist or other providers with training in
neurourology and urodynamics.

URODYNAMIC RISK FACTORS FOR KIDNEY DAMAGE AND OTHER UROLOGIC


COMPLICATIONS

The preceding cases illustrate many of the urodynamic risk factors for kidney damage
or upper urinary tract deterioration in patients with neurogenic bladder obstruction or
dysfunction. These risk factors include poor bladder compliance, bladder pressures
greater than 40 cm H2O, and the presence of DSD. Data supporting these risk factors
are discussed in the following sections.

Poor Bladder Compliance


Exact criteria to categorize bladder compliance in patients with neurogenic bladder
dysfunction do not exist. In a study by Hackler and colleagues,13 a compliance less
than 20 mL/cm H2O on urodynamic studies was considered as low. In their study,
69% of patients with low compliance were found to have renal damage on imaging
studies as compared with 21% of patients with normal compliance. In other investiga-
tions, cutoff value for poor compliance was set even lower at 12.5 mL/cm H2O and
high rates for renal damage and other urologic complications was demonstrated in
patients with values below this threshold.14

DSD
DSD is defined as the involuntary contraction or lack of relaxation of the striated
sphincter during a bladder contraction.5 DSD should exist only in patients who have
a neurologic abnormality below the brain stem and above the sacral spinal cord where
motor outflow to the bladder originates. In fact, nearly 75% of patients with suprasac-
ral SCI15 will have DSD, and patients with this type of neurologic injury should be
considered to have DSD until proven otherwise.
DSD is considered a risk factor for the development of renal damage. In a study of
male patients with SCI, Linsenmeyer and colleagues16 found that patients with pro-
longed voiding had the greatest risk of developing hydronephrosis. Patients with pro-
longed voiding, like the patient in case 2, may have both DSD and poorly compliant
bladders. Untreated DSD is clearly associated with the development of renal
damage,17 and 50% of patients with untreated DSD will develop significant urologic
complications, including vesicoureteral reflux, renal damage, urolithiasis, urosepsis,
and ureterovesical obstruction.18 Pharmacologic treatment with a-blockers may be
considered because these drugs work by reducing outlet resistance at the level of
the bladder neck; however, there is limited evidence that these agents actually
improve outcomes or decrease risk of complications in patients with DSD.19–22
Because of a-blockers and other types of pharmacotherapy lack efficacy, the main-
stay of treatment of DSD is performance of intermittent catheterization. Patients
should be counseled to time the catheterizations to keep the volumes of urine below
the threshold for the development of involuntary bladder contractions and/or below
the volume at which a detrusor leak point pressure of 40 cm H2O develops. In conjunc-
tion with fluid restriction, catheterization can often be accomplished every 4 to 6 hours.
However, some patients may need to catheterize far more frequently or may not be
willing or able to catheterize at all. In these more challenging situations, patients
can be offered botulinum toxin injection to paralyze the urinary sphincter, formal
116 Klausner & Steers

surgical sphincterotomy, or placement of a urethral stent (UroLume, American Medical


Systems Inc, Minnetonka, MN, USA) across the sphincter. All these methods are
designed to render the sphincter nonfunctional, leaving the patient safe but totally
incontinent. This option may be acceptable in men in whom urine leakage can be
effectively collected using a condom or Texas Catheter. However, in women, lack
of an effective external collecting device necessitates the need to use diapers or an
indwelling catheter. Studies have demonstrated the efficacy of botulinum toxin for
the treatment of DSD. However, at present, the therapy is not approved by the
Food and Drug Administration and requires repeat cystoscopic injections on every
6- to 9-month basis.23,24 In addition, sphincterotomy and urethral stenting have high
complication and/or failure rates.25 For these reasons, many individuals with DSD
and inability to perform self-catheterization are managed with urinary diversion using
sections of bowel or are maintained with indwelling urethral catheters.

Detrusor Pressures Greater Than 40 cm H2O


The value of urodynamic evaluations for patients with neurogenic bladder dysfunction
was demonstrated in studies by McGuire and colleagues26 in which more than 80% of
patients with myelodysplasia experiencing urine leakage at bladder pressures greater
than 40 cm H2O were found to have ureteral or renal dilation (hydronephrosis). This
cutoff value was dramatic in that only 10% of patients who had leakage at pressures
lower than 40 cm H2O had similar findings. Kim and colleagues27 followed up
55 patients with SCI managed with at least 1 sphincterotomy. These investigators
found that patients with bladder pressures greater than 40 cm H2O had the greatest
risk of renal damage and development of recurrent DSD. These studies were mainly
performed on patients with detrusor acontractility. However, studies in patients with
SCI and detrusor overactivity have found, similarly, that sustained bladder pressures
greater than 40 cm H2O are associated with greater risk of upper urinary tract deteri-
oration.28 Based on this, primary care physicians caring for patients with neurologic
diseases need to question whether the bladder pressures in their patients are safe.
The answer is provided by urodynamic studies demonstrating filling pressures less
than the critical threshold of 40 cm H2O.

SPECIAL SITUATIONS FOR THE MANAGEMENT OF NEUROGENIC BLADDER


DYSFUNCTION
The Indwelling Urinary Catheter
The long-term use of indwelling urethral (Foley) or suprapubic catheters is associated
with severe complications,29–31 including development of frequent urinary tract infec-
tions or sepsis,32 predisposition to renal failure and dialysis,33,34 formation of kidney or
bladder stones,35 shrinkage of the bladder with potential obstruction of the kidneys or
reflux of contaminated urine, and extremely high rates of invasive and potentially lethal
bladder cancer.36 If an indwelling catheter is to be used long-term, a suprapubic tube
is preferred to avoid creation of fistulous tracts from the urethra or the bladder to
the skin, damage to the sphincter muscles resulting in total incontinence, dilation of
the urethra with leakage around the catheter, urethral carcinoma, and erosion and
splitting of the penis called traumatic hypospadias.37 Serial upsizing of a urethral cath-
eter to prevent urine leakage in women is to be condemned.
Because of these severe complications, use of chronic indwelling catheters is
discouraged by urologists and other providers involved in the care of individuals
with neurogenic bladder dysfunction. In 1972, the treatment of individuals with neuro-
genic bladder dysfunction was revolutionized by the institution of a technique known
The Neurogenic Bladder 117

as clean intermittent self-catheterization (CISC) by Lapides and colleagues.38 CISC


involves placing a new or clean catheter into the bladder to drain urine at defined times
or at times when the individual feels a need to urinate. This method is much safer than
the use of indwelling catheters.39–41 Despite this advice, a large percentage of patients
with retention or incontinence caused by a neurogenic bladder are managed with
catheters. With close monitoring and aggressive treatment of symptomatic infections
and calculi, some think that chronic catheters can be more safely used. Review of
recent series on patients managed with suprapubic catheters demonstrates reduced
morbidity and risk of renal deterioration when compared with more historic reports.42

Urinary Tract Infections: to Treat or Not to Treat


Primary care physicians are encouraged to differentiate between chronic bacterial
colonization and symptomatic bacterial infection. In patients with neurogenic blad-
ders, only symptomatic infections (eg, worsening dysreflexia, malaise, fever, spasms)
or colonization with Proteus sp should be treated. Colonization with bacterial organ-
isms occurs universally within 30 days of catheterization,43 and attempts at eradica-
tion of asymptomatic bacteria are generally contraindicated. These practices
contribute to high rates of multidrug-resistant pathogens in patients with neurogenic
bladder dysfunction and a lack of effective antimicrobial agents in the case of truly
symptomatic infections or urosepsis. In addition, antibiotic prophylaxis is not indi-
cated before routine catheter changes, and studies demonstrate that low-dose
prophylaxis in patients with neurogenic bladder dysfunction does not reduce the
risk of symptomatic infection.44 Furthermore, there is no evidence that the use of cran-
berry tablets or oral methenamine reduces the incidence of complex urinary tract
infections in patients with neurogenic bladder dysfunction.45 Based on these data,
primary care physicians are encouraged to avoid obtaining routine urine cultures
and should avoid antimicrobial treatment in asymptomatic patients with neurogenic
bladders.

The Role of Fluid Restriction


Certainly, the blanket recommendation to “drink more water” to prevent urinary tract
infections or promote urinary health does not apply to many patients with neurogenic
bladder dysfunction. In fact, patients who experience high-pressure IDCs are often
managed with a combination of fluid restriction and antimuscarinic medications.
Patients are frequently told to limit fluids to less than 2 L/d. In theory, this recommen-
dation allows patients to empty their bladders using intermittent catheterization at
less-frequent and potentially safer, time intervals. However, there are limited data to
support the use of this fluid volume in the prevention of urologic complications. There-
fore, fluid management in patients with neurogenic bladder dysfunction needs to be
tailored to individual patient factors and should be considered after review of urody-
namic and other objective data.

The Role of Autonomic Dysreflexia


In patients with neurogenic bladder dysfunction caused by SCI, it is important to recog-
nize autonomic dysreflexia (AD). This condition is seen in patients with SCIs above the
T6 level, with much higher rates seen in patients with complete injuries than in those with
incomplete injuries. AD is a medical emergency associated with acute elevations of
blood pressure and a reflex bradycardia. Clinically, the disorder may be asymptomatic
or may be associated with symptoms including flushing, sweating, and headache as
displayed in case 2. Severe elevations in blood pressure can lead to cardiovascular
complications, cerebrovascular accidents, or even death. The pathophysiology is
118 Klausner & Steers

associated with unchecked sympathetic outflow triggered by noxious stimuli below the
level of injury. The bladder is the most common source of AD, and primary care physi-
cians who care for patients with neurologic conditions must be aware of this condition
and be ready to treat it aggressively. The first step is to eliminate the noxious stimulus. In
patients with SCI, this elimination can often be accomplished by emptying a distended
bladder through catheterization or irrigation of an obstructed catheter. Short-term treat-
ment of hypertension using nitroglycerine paste or sublingual nifedipine is often
required, and prevention with the use of oral a-blockers can be effective. In recurrent
episodes, a search for an occult urologic cause, such as a calculus or an improper
bladder management, should be initiated.46

SUMMARY

Patients with lesions of the central nervous system often have neurogenic bladder
dysfunction. Lifelong bladder monitoring and management in these patients is neces-
sary to prevent severe complications, including renal damage. The urodynamic test,
performed by neurourologists or other specially trained providers, is the definitive
test for diagnosis and management of neurogenic bladder dysfunction. This test
can help determine if a patient has a safe or an unsafe bladder, and primary care
physicians should refer patients for urodynamic testing as soon as neurogenic bladder
dysfunction in known or suspected.

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