Bladder Function and Dysfunction
after Neurologic Insult: Preventing
Secondary Conditions and
Improving Function
Suzanne L. Groah, MD, MSPH
National Rehabilitation Hospital
RRTC on Secondary Conditions after SCI
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Anatomy and Physiology
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Bladder - Anatomy
Neuroanatomy of Voiding
Neuroanatomy of Voiding
Frontal lobe
Micturition center
Sends inhibitory signals
Pons (Pontine Micturition Center)
Major relay/excitatory center
Coordinates urinary sphincters and the bladder
Affected by emotions
Spinal cord
Intermediary between upper and lower control
Peripheral Nervous
System
Somatic (S2-S4)
Pudendal nerves
Excitatory to external
sphincter
Parasympathetic (S2-S4)
Pelvic nerves
Excitatory to bladder,
relaxes sphincter
Sympathetic (T10-L2)
Hypogastric nerves to
pelvic ganglia
Inhibitory to bladder body,
excitatory to bladder
base/urethra
Normal Voiding
SNS primarily controls bladder and the IUS
Bladder increases capacity but not pressure
Internal urinary sphincter to remain tightly closed
Parasympathetic stimulation inhibited
Somatics (pudendal N) regulate
External urinary sphincter
Pelvic diaphragm
PNS
Immediately prior to PNS stimulation, SNS is suppressed
Stimulates detrusor to contract
Pudendal nerve is inhibited external sphincter opens
facilitation of voluntary urination
Innervation of the Lower
Urinary Tract
Function
Balance between suprasacral
modulating pathways, sacral cord
and the pelvic floor
Emptying phase: “Voiding
Reflex”
Series of coordinated events
involving outlet relaxation,
detrusor contraction
Storage phase: “Guarding
reflexes” constant afferent input
to maintain continence
Bladder Dysfunction
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Functional Classification
Failure to store
Because of bladder
Because of outlet
Failure to empty
Because of bladder
Because of outlet
Combination
Pathophysiology of
Voiding
Brain lesion above pons destroys master
control center
Ex – stroke, brain tumor, hydrocephalus, CP,
Shy-Drager
Result – urge incontinence, night incontinence,
coordinated sphincter
Spinal cord lesion, myelomeningocele, MS
Detrusor hyperreflexia
Spastic bladder
Areflexic bladder
Pathophysiology of
Voiding
Lumbosacral spinal lesion
Ex – spinal tumor, sacral SCI, herniated disc,
lumbar laminectomy, radical hysterectomy,
pelvic trauma
Result – areflexic bladder
Peripheral nerve injury
Ex – AIDS, diabetes, polio, GBS
Result – urinary retention
Medication Options
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Medications
Failure to store due to outlet
Alpha-adrenergic drugs
Location - Bladder neck receptors
Function - Increase bladder outlet resistance by
contracting the bladder neck
Example - pseudoephedrine
Medications
Failure to store due to outlet
Estrogen derivatives
Mechanism - Increases the tone of urethral
muscle by up-regulating the alpha-adrenergic
receptors in the surrounding area
Mechanism - Enhances alpha-adrenergic
contractile response to strengthen pelvic
muscles
Use in…Stress incontinence
Medications
Failure to store due to bladder
Anticholinergic drugs
Function - Inhibit involuntary bladder contractions
Adverse effects
• Blurred vision
• Dry mouth
• Heart palpitations
• Drowsiness
• Facial flushing
Ex. Pro-banthine, Levsin
Medications
Failure to store due to bladder
Antispasmodic drugs
Function - Relax the smooth muscles of the
urinary bladder
Function – Directly relaxes the smooth muscle of
the bladder
Adverse effects similar to anticholinergic agent
Impaired mental alertness and physical coordination
Ex. Ditropan, Detrol
Medications
Failure to store due to bladder
Tricyclic antidepressant drugs
Mechanism - Increase norepinephrine and
serotonin levels
Mechanism - Anticholinergic and direct
muscle relaxant effects on the urinary
bladder and bladder neck
Ex. imipramine
Medications
Failure to empty due to outlet/DSD
Botox
MOA
Inhibition of Ach release at neuromuscular junction
Relax spastic/overactive muscles
Relaxes sphincter when DSD present
Effect not permanent
DSD is often present with reflex voiding
Injection transurethrally or transperineally into the
urinary sphincter mechanism
Re-injection necessary as effect is lost after 3-6 months
Effect of Foods
Heightened urge incontinence
Spicy foods
Caffeine/chocolate
Citrus fruits
Carbonated beverages
Bladder Management Options
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Management Options
Type of Advantage Disadvantage
Management
Indwelling catheter Convenience Infection
Less caregiver ± Urethral damage
assistance ± Bladder cancer
Intermittent catheter ± Reduced infection Need anticholinergic
± Urethral damage
Assistance
Cost
Labor
Management Options
Type of Advantage Disadvantage
Management
Reflex voiding Non-invasive ± High pressure
± Continence
± High residuals
± Need for
sphincterotomy
Electrical stimulation + Improved bowel fxn Significant surgery
rhizotomy Reduced labor/cost Side effects- rhizotomy
Cosmetically appealing ↓ Reflex erection
↓ Reflex ejaculation
Management Options
Type of Advantage Disadvantage
Management
Surgical diversion May produce Significant surgery
continence Committed to
Continent pouch easier collection device/cath
for female to cath Risk of cancer
Electrical Stimulation
Electrical Stimulation and Posterior Sacral Rhizotomy
To produce effective voiding and reduce urinary tract infection
Electrodes surgically implanted on the sacral nerves
Stimulator placed under the skin of the abdomen or chest
Battery-powered remote control
Posterior sacral rhizotomy
Abolishes hyper-reflexia of the detrusor and sphincter
Increases bladder capacity and compliance
Reduces reflex incontinence
Reduces autonomic dysreflexia
Abolishes reflex erection, reflex ejaculation, sacral sensation, and
reflex defecation
1% risk of infection of the implant
1 fault per 20 implant-years
Electrical Stimulation
Consider in Evidence
↑ PVR ↓ Reflex incontinence
Chronic/recurrent UTI (post rhiz)
Problems with catheters ↑ Bladder capacity and
Reflex incontinence compliance
↓ need for anticholinergics
↓ bladder capacity and
↓ DSD
compliance
Intolerance of ↓ AD if posterior
anticholinergic rhizotomy
medication ↑AD if no posterior
DSD rhizotomy
AD
Bladder Augmentation
Procedure that increases bladder capacity using intestinal
segments
Ileum, colon, or stomach are used
Goals
Decreasing intravesicle pressure
Restore urinary continence
Preserve upper urinary tracts by alleviating reflux and
hydronephrosis
Can combine with a continent abdominal stoma
Consider in patients with
Intractable involuntary bladder contractions causing incontinence
Patients who are able and motivated to perform CIC
Reflex voiders wishing to convert to CIC
Females with paraplegia
Urinary Diversion
Diverts the urine flow from the bladder
Secondary form of bladder management when primary methods have
failed
Ureters transected just above the bladder and connected to a segment
of intestine (terminal ileum) which is in turn brought to the skin of the
lower abdominal wall
External appliance used as collection device
Considered if:
Lower urinary complications secondary to indwelling catheters
Urethrocutaneous fistulas, perineal decubitus ulcers
Urethral destruction in females
Hydronephrosis secondary to a thickened bladder wall and for
hydronephrosis secondary to vesicoureteral reflux or failed reimplant.
Bladder malignancy requiring cystectomy
Yet To Be Released PVA Guideline
Recommendations
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Recommendations from
the PVA Guidelines
Recommendation 1: Intermittent
catheterization is the preferable method for
bladder emptying for men and women who
have adequate hand function or a willing
caregiver to perform the catheterization and
have bladders that do not empty adequately.
Recommendation 2: Intermittent
catheterization should be ideally performed
every 4 to 6 hours to keep bladder volumes
below 400ccs.
Recommendations from
the PVA Guidelines
Recommendation 5: Consider sterile
catheterization for those individuals with
recurrent symptomatic infections occurring
with clean intermittent catheterization.
Rationale: Lower infection rates can be
achieved with sterile techniques and with
pre-lubricated self contained catheter sets
Recommendations from
the PVA Guidelines
Recommendation 5: Risk of symptomatic
infection is at least comparable and may be
less in individuals with indwelling catheters
than those managing their bladders with
clean intermittent catheterization.
Recommendations from
the PVA Guidelines
Recommendation 6: Patient should be
advised of long-term complications of
indwelling catheterization, including:
Bladder stones
Kidney stones
Urethral erosions
Bladder cancer
Epididymitis
Recurrent symptomatic urinary tract
infections
Genitourinary Assessment of
Function
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Assessment of Function
U/a and c & s
BUN & Cr
if compromised renal function is suspected
Postvoid residual urine
If high, the bladder may be contractile or
the bladder outlet may be obstructed
Renal/Bladder US
Mainstay of screening in many institutions
Advantages Disadvantages
Simple Low sensitivity for
Eval kidney, small stones
parenchymal loss, abnl Ureters not evaluated
echogenicity well
Eval for
hydronephrosis, stones
Nuclear Renal Scan
Advantages Disadvantage
Functional info Less anatomic info
No nephrotoxic Cannot detect stones
reactions
Low radiation
KUB
Historically, routinely used to detect renal
and bladder stones
Disadvantages
Poorly sensitive to stones
“KUB not justified in routine f/u of urinary
tract in SCI”
Tins et al. Spinal Cord 2005
Filling Cystogram
Bladder capacity
Bladder compliance
Presence of phasic
contractions
(detrusor instability)
Cystogram
Static Cystogram Voiding cystogram
Confirm the presence of Bladder neck and
stress incontinence urethral function (internal
Degree of urethral motion and external sphincter)
Presence of a cystocele during filling and voiding
phases
Intrinsic sphincter
deficiency
Urethral diverticulum
Urethral obstruction
Vesicovaginal fistula
Bladder diverticulum
Vesicoureteral reflux
Cystometrogram
Volume vs pressure graph
Evaluates
Detrusor compliance
Stability of detrusor
Urodynamics
Filling cystometry
Flow/pressure study
Detrusor pressure at maximum flow
Obstruction to passage of urine can be distinguished from a lack of
tone in the detrusor muscle
Electromyography
Coordinated or uncoordinated voiding
Detrusor sphincter dyssynergia
Videocystourethography
Combined x-ray or ultrasound
UD - Stable Bladder
Detrusor Hyperactivity
and Low Bladder Capacity
Cystoscopy
Bladder cancer
Bladder stone
Indicated in persistent irritative voiding
symptoms or hematuria
Selected Genitourinary Secondary
Conditions After Bladder
Dysfunction due to
Neurologic Disease
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Secondary Conditions
Increased risk of
Bladder infection
Kidney infection
Hydronephrosis
Urethral trauma/laxity
Urinary Stones and SCI
Higher incidence, especially in first 6 mos
3-6% upper tract
11-15% bladder
Etiology
Stasis
Calcium metabolism
Infection
Diagnosis
CT is gold standard
Bladder Cancer
Epidemiology
5th most common cancer
12th leading cause cancer mortality
Adjusted yearly incidence 17/100,000 py
54,400 new cases per year
Males at greater risk
Majority are transitional cell carcinoma
Risk Factors for Bladder
Cancer
Smoking
Male gender
Exposure to aromatic amines
Schistosomiasis infection
UTI
Is there a heightened risk of bladder
cancer after SCI?
If so, why?
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
The Evidence in SCI
Source “Incidence” Interpretation
Reported
Paraplegia, 1966 290/100,000 (.0029) Period prevalence
Unspecified time
Paraplegia, 1981 25/6744 (.0037) Prevalence/case series
Unspecified time
J Urology, 1991 8 cases, 1 year Case series
No population
denominator
Urology, 1999 130/33,565; (.0039) Appropriately reported
5 yr reporting period as prevalence
The Evidence in SCI
Source “Incidence” Interpretation
Reported
J Urology, 1981 10 cases/10,052 Case series
(.0009)
Unspecified time
J Urology, 1977 6 cases/62 (.097) Prevalence
Unspecified time
Urology, 2002 48 cases/43,561 Prevalence
(.0011)
Questionnaire data
J Urology, 1985 2/25 (.08) Case series/prevalence
Unspecified time
Recent Evidence
Groah SL. Arch Phys Med Rehabil 2002
3,670 subjects contributed 39,729 p-y
Stratified by bladder management method
Age-adjusted incidence
Indwelling catheter – 77/100,000 py
Mixed methods – 56.1/100,000 py
Non-indwelling catheter – 18.6/100,000 py
Retrospective Cohort
SCI > 1 year
Indwelling Non-Indwelling
Multiple
Catheter Use Catheter Use
Methods (Multi)
(IDC) (NIDC)
No No No
Bladder Bladder Bladder
Bladder Bladder Bladder
cancer cancer cancer
Cancer Cancer Cancer
Mortality Survival Mortality Survival Mortality Survival
Recent Evidence
Groah SL. Arch Phys Med Rehabil 2002
Using cox regression, only bladder
management method and age predicted disease
Cumulative Incidence of
Bladder Cancer
0.010%
0.009%
IDC
0.008%
Cumulative Incidence
NIDC
0.007%
0.006%
0.005%
0.004%
0.003%
0.002%
0.001%
0.000%
0 5 10 15 20 25 30 35 40 45 50 55 60
Years Post-SCI
Wilcoxan < 0.05
Cumulative Incidence of
Bladder Cancer
0.010%
0.009%
IDC
0.008%
Cumulative Incidence
NIDC
0.007%
0.006%
0.005%
0.004%
0.003%
0.002%
0.001%
0.000%
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Age
Wilcoxan < 0.05
Bladder Cancer Mortality
by Age
180
160
Mortality in 100,000 P-Y
140 IDC
120 SEER
100
80
60
40
20
0
0-9 10-19 20-29 30-39 40-49 50-59 60+
Age (years)
Proportional Mortality
Due to Bladder Cancer
100%
90%
IDC
80%
Proportion Surviving with BC
70%
60%
50%
40%
30%
20%
10%
0%
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39
Years post-SCI
Recent Evidence
Subramonian et al. BJU Int, 2004.
4 cases/1334 people followed
30.7/100,000 person-years
Reported as not statistically different from
general population and lower than reported in
other studies
Risk Factors for Bladder
Cancer
Source Results
Groah SL. JSCM 2003;26:339-44 Multiple risk factors (2 or more)
(mortality study) Catheter, tobacco
Hess MK. JSCM 2003;26:335-8 Gross hematuria present in 14/16
Vereczkey ZA. JSCM 1998;21:230- 19 RF and 12 interactions analyzed
9 Duration of indwelling catheter use
>10 years
Part 3 Design: Case-
control
Bladder Age at SCI
cancer Duration of SCI
survivors Age at BC
Level of SCI
ASIA
Method of bladder
Medical record
management
review Histology
Presentation
Controls Diagnosis
deceased Surveillance
due to Biopsy results
bladder Risk Factors
cancer
Presentation
70%
Survivor Control
60%
50%
40%
30%
20%
10%
0%
S/Sx H/O gross Gross hematuria Renal failure
hematuria
Potential Associated Risk
Factors
100%
Survivor Control
*
75%
*
50%
25%
0%
IDC use Tobacco use Calculi Pyelonephritis Prophylactic
antibiotic
Risk Factors
50%
Survivor
*
Control
*
25%
*
0%
0 RF 1 RF 2 RF 3 RF 4 RF
RF: IDC use, tobacco use, calculi, or pyelonephritis
Bladder Cancer
Surveillance
Survivor Control p value
Mean
number 7.8 16.8 .06
cystoscopies
Mean
number 1.6 3.6 > .1
biopsies
Genitourinary Surveillance
Supported by National Institute for Disability and Rehabilitation Research, Grant #
H133B031114
Surveillance Practices of
the MSCIS Centers
16 centers surveyed
13 responded
12/13 have a GU surveillance protocol
6/13 have a bladder cancer surveillance
protocol
Initial GU Surveillance
from the MSCIS Centers
1 2 3 4 5 6 7 8 9 10 11 12 13
U/A
C/S
Bun/Cr
Creat
Clear
US
VCUG
Renal
Scan
Initial GU Surveillance
from the MSCIS Centers
1 2 3 4 5 6 7 8 9 10 11 12 13
Cytol
IVP
CMG
UD
Bl US
KUB
CScope
Bladder Cancer
Surveillance from MSCIC
Protocols
If IDC, cysto at 5 yrs and yearly thereafter
Cysto every 5-10 years
Cysto if hematuria
Cysto for long-term IDC
Cysto if IDC + hematuria
Cysto at 10 years then yearly if IDC
Cysto yearly if IDC (2 centers)
Bladder Cancer
Surveillance
Yang CC. Spinal Cord 1999;37:204-7
Cysto if >10yrs catheter, smoker + cath (5yrs)
59 subjects had 156 cystos
No cancer diagnosed
4 other cases diagnosed during same period (2
did not meet criteria;1 not unit patient;1 had
screen 4 months prior)
Bladder Cancer
Surveillance
Groah SL. JSCIM 2003;26:339-44
8 survivors with bladder cancer compared with
13 deceased
Surveillance cystoscopy identified cancer in
14% survivors
11% deceased
Survivors had fewer surveillance cystoscopies
and biopsies than deceased group