Neurogenic Bladder

Dr Sumeet Singh
SR Neurology
GMC Kota
ES Abrams, P., Cardozo, L., Fall, M., et al., 2002. The standardisation of terminology of lower
urinary tract function: report from the Standardisation Sub-Committee of the International
Continence Society. Neurourol. Urodyn. 21, 167–178
NEUROLOGICAL CONTROL OF BLADDER
MICTURATION(VOIDING) REFLEX
BASIC FUNCTIONS OF BLADDER
• 1) STORAGE- During this phase, sympathetic and pudendal mediated
contraction of the internal and external urethral sphincters,
respectively, maintains continence. Inhibition of the parasympathetic
outflow prevents detrusor contractions

• 2)VOIDING- When it is deemed appropriate to void, the pontine

micturition center is no longer tonically inhibited. Relaxation of the
pelvic floor and external and internal urethral sphincters
accompanied by parasympathetic mediated detrusor contraction
results in effective bladder emptying.

Burks, J., Chancellor, M., Bates, D., et al., 2013. Development and validation of the actionable
bladder symptom. Int. J. MS Care 15, 182–192
Symptomatology
• Urinary symptoms may be related to either phase of bladder activity
(i.e. voiding or storage)
Micturition abnormalities

Retention : inability to pass/ no urine flow

Slow stream: decreased flow
Hesitancy : difficulty in initiating
Precipitancy: inability to stop midway
Dribbling: leak of small amount after
voluntary emptying
Incontinence : involuntary passage of
urine
TYPES OF URINARY INCONTINENCE

Sakakibara, R., Hattori, T., Uchiyama, T., et al., 2000. Micturitional disturbance in pure autonomic failure.
Neurology 54, 499–501.
DETRUSOR SPHINCTER DYSSYNERGIA
• Loss of the reciprocal
inhibition of the sphincter and
activation of the detrusor
following disconnection from
the pons results in detrusor
sphincter dyssynergia(DSD)

Sakakibara, R., Hattori, T., Yasuda, K., Yamanishi, T., 1996. Micturitional disturbance
and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases. J.
Neurol. Sci. 141, 105–110
Types according to level of bladder dysfunction
 Multiple sclerosis; PD, Parkinson disease; PVR, post void residual; SCI, spinal cord injury. From Panicker, J.N.,
Fowler, C.J., 2010. The bare essentials: uro-neurology. Pract Neurol 10, 178–185.
• UNINHIBITED (CORTICAL) BLADDER — Found in frontal lobe tumours,
parasagittal meningioma, dementia. There is urgency at low bladder
volume (like a child) with sudden uncontrolled evacuation of urine in
inappropriate time and place.

• BASAL GANGLIA LESIONS- Parkinson’s disease, MSA

• BRAINSTEM LESIONS- In brainstem strokes, lesions that resulted in

micturition disturbance usually were dorsally situated. The proximity
in the dorsal pons between the pontine micturition center and the
medial longitudinal fasciculus means that a disorder of eye
movements, such as an internuclear ophthalmoplegia, is highly likely
in patients with a pontine disorder causing a voiding difficulty.

Andersen, J.T., 1985. Disturbances of bladder and urethral function in Parkinson disease. Int. Urol. Nephrol. 17,
35–41
• SPINAL BLADDER—
a) Incomplete lesion :
(i) Precipitancy—Due to involvement of inhibitory fibers e.g., multiple
sclerosis.
(ii) Hesitancy—Due to involvement of facilitatory fibers e.g., incomplete
cord compression.

b) Complete lesion :
(i) Retention of urine with overflow incontinence -— Commonly seen in
‘neural shock stage’ of acute transverse myelitis. Evacuation of the
bladder is always incomplete.
(ii) AUTOMATIC BLADDER (UMN bladder)—The evacuation is always
complete. It is commonly seen when the ‘neural shock stage’ is over and
evacuation occurs by local reflex arc. The bladder is small, spastic and the
patient complains of frequency, urgency and urge incontinence
Araki, I., Kitahara, M., Oida, T., Kuno, S., 2000a. Voiding dysfunction : urodynamic abnormalities and urinary
symptoms. J. Urol. 164, 1640–1643.
• c) Lesion in the local reflex arc —
(i) Sensory paralytic bladder—There is loss of awareness of fullness of
bladder e.g., tabes dorsalis, diabetes mellitus, multiple sclerosis.
Large volume of urine collects in the bladder with a huge residual
volume.

(ii) Motor paralytic bladder—Inability to initiate and continue

micturition. It is commonly seen in pelvic neoplasm, trauma,
polyradiculopathy etc.

(iii) AUTONOMOUS BLADDER (LMN bladder)—Commonly seen in

cauda equina lesion, pelvic malignancy, spina bifida etc. There is no
sensation of bladder fullness but having continual dribbling. UTI is very
common.
Fowler, C.J., 1999. Neurological disorders of micturition and their treatment. Brain 122 (Pt 7), 1213–1231
DIAGNOSTIC EVALUATION
• HISTORY-
• Patients with storage dysfunction complain of frequency of
micturition, nocturia, urgency and urgency incontinence.
• Patients experiencing voiding dysfunction report hesitancy of
micturition, a slow and interrupted urinary stream, the need to strain
to pass urine
• Bladder Diary- It supplements the history taking and records the
frequency for micturition, volumes voided, episodes of incontinence,
and fluid intake over the course of a few days

Sakakibara, R., Hattori, T., Uchiyama, T., Yamanishi, T., 2001a. Videourodynamic and sphincter motor
unit potential analyses J. Neurol. Neurosurg. Psychiatry 71, 600–606.
• CLUES IN PHYSICAL EXAMINATION-
• In lesions of the conus medullaris and cauda equina findings may be
confined to saddle anesthesia and absence of sacral cord mediated
reflexes such as the anal reflex or bulbocavernosus reflex
• Akinetic rigidity, cerebellar ataxia, and postural hypotension should
raise the suspicion of MSA
• Examination for evidence of peripheral neuropathy (Eg-Diabetes
mellitus) is important
• Inspection of the lumbosacral spine- Congenital malformations of the
spine (dimpling, tuft of hair, sinus) can sometimes present with
bladder symptoms in adults

Sakakibara, R., Hattori, T., Uchiyama, T., et al., 2000. Micturitional disturbance in pure autonomic failure.
Neurology 54, 499–501.
 INVESTIGATIONS
• Screening for Urinary Tract Infections- Routine urine examination

• Ultrasonography abdomen with estimation of the post void residual

urine. A single measurement of a post void residual volume is often
not representative and if possible, a series of measurements should
be made over the course of 1 or 2 weeks. Normal PVRU should be
less than 100mL
• USG will also give evidence of damage such as upper urinary tract
dilatation or renal scarring.
• USG may also detect complications of neurogenic bladder dysfunction
such as bladder stones.
 URODYNAMIC STUDIES

• Non-invasive Bladder Investigations- Includes Uroflowmetry

• Investigations Requiring Catheterization- Includes

Cystometry during both filling and voiding,
Videocystometry

Dasgupta, R., Fowler, C.J., 2004. Urodynamic study of women in urinary retention treated with
sacral neuromodulation. J. Urol. 171, 1161–1164
 UROFLOWMETRY
• It consists of a commode or urinal into which the patient passes urine
as naturally as possible. In the base of the collecting system is a
spinning disk, and flow of urine onto this disk tends to slow its speed
of rotation
• The urinary flow (in ml/min) is calculated based upon the power
necessary to maintain the rotation speed and a graphic printout of
the urinary flow is obtained, and time taken to reach maximum flow,
maximum and average flow rates, and also the voided volume are
analyzed
• In men, a Qmax (maximum flow) >15 mL/s is considered
normal, whereas a Qmax <10 mL/s is considered abnormal.
• In women, Qmax > 20 ml/s is considered normal.
Dasgupta, R., Fowler, C.J., 2004. Urodynamic study of women in urinary retention treated with
sacral neuromodulation. J. Urol. 171, 1161–1164
 CYSTOMETRY
• Cystometry evaluates the pressure–volume relationship during
nonphysiological filling of the bladder and during voiding.

• The detrusor pressure is derived by subtraction of the abdominal

pressure (measured using a catheter in the rectum) from the
intravesical pressure (measured using a catheter in the bladder).

• The rate of filling is recorded by the machine, which pumps sterile

water or saline through the catheter in the bladder at rates of 50-100
ml per minute

Dasgupta, R., Fowler, C.J., 2004. Urodynamic study of women in urinary retention treated with sacral
neuromodulation. J. Urol. 171, 1161–116
• First sensation of bladder filling may be reported at around 100 mL
and full capacity is reached between 400 and 600 mL.
• In healthy subjects, the bladder expands to contain this amount of
fluid without an increase of pressure more than 15 cm H20. A bladder
that behaves in this way is said to be “stable.”
• Neurogenic detrusor overactivity- Involuntary detrusor contraction
during filling phase.
• During voiding phase we measure the detrusor pressor and urine flow
• Normal Detrusor pressure- <50cm water in males
<30 cm water in females
 SPHINCTER EMG
• Electromyography has been used to demonstrate changes of
reinnervation in the urethral or anal sphincter in a few neurogenic
disorders.

• EMG of the external anal sphincter demonstrating changes of chronic

reinnervation, with a reduced interference pattern and enlarged
polyphasic motor units (>1 mV amplitude) can be found in patients
with long-standing cauda equina syndrome

Allio BA, Peterson AC. Urodynamic and physiologic patterns associated with the common causes
of neurogenic bladder in adults. Transl Androl Urol 2016;5(1):31-38. doi: 10.3978/j.issn.2223-
4683.2016.01.05
• Pudendal Nerve Terminal Motor Latency (PNTML). The only test of
motor conduction for the pelvic floor is the pudendal nerve terminal
motor latency (PNTML).
• This technique records from the external anal sphincter. Prolongation
is considered evidence for pudendal nerve damage

• Pudendal Somatosensory Evoked Potentials. Pudendal somatosensory

evoked potentials can be recorded from the scalp following electrical
stimulation of the dorsal nerve of penis or clitoral nerve
Management of neurogenic bladder
Suprapontine (spastic) Infrapontine- suprasacral lesion Infrasacral(flaccid)
Behavior therapy- dietary by Pharmacological therapy- CIC- clean intermittent self
reducing caffeine and carbonated Anticholinergics - e.g. oxybutynin, catheterization
drinks tolterodine, solifenacin, darifenacin Increased fluid intake
Bladder training
biofeedback
Pharmacologic therapy- CIC- clean intermittent self Good hygiene
anticholinergics catheterization. Antibiotics
TCA
Surgical therapy-augmentation
cystoplasty

Fowler, C.J., 1999. Neurological disorders of micturition and their treatment. Brain 122 (Pt 7), 1213–
1231
 MANAGEMENT
• General Measures- Nonpharmacological measures are generally
effective in the early stages when symptoms are mild. A fluid intake of
around 1 to 2 liters a day is suggested, although this should be
individualized and it is often helpful to assess fluid balance by means
of a bladder diary
• Caffeine reduction may reduce urgency and frequency
• Bladder retraining, whereby patients void by the clock and voluntarily
“hold on” for increasingly longer periods, aims to restore the normal
pattern of micturition
• Pelvic floor exercises and neuromuscular stimulation may play a role,
if voiding dysfunction has been excluded, for ameliorating overactive
bladder symptoms.
 VOIDING DYSFUNCTION
• The mainstay of management of voiding dysfunction due to detrusor
areflexia is CIC (Clean Intermittent Self Catheterization) (usually done
if the post void residual urine is more than 150 ml)
• Intermittent catheterization is best performed by the patient
themselves, who should be taught by someone experienced with this
method such as a nurse continence advisor.
• Neurological lesions affecting manual dexterity, weakness, tremor,
rigidity, spasticity, impaired visual acuity, and cognitive impairment
may make it impossible for the patient to self-catheterize, in which
case it may be performed by the partner or care assistant.
• Alpha-blockers relax the internal urethral sphincter in men and there
is evidence that they improve bladder emptying and reduce post void
residual volumes. However, this is not consistently seen in clinical
practice unless there is concomitant bladder outlet obstruction.

• Botulinum toxin injections into the external urethral sphincter may

improve bladder emptying in patients with spinal cord injury who
have significant voiding dysfunction
 STORAGE DYSFUNCTION
Anti muscarinic medications

From Fowler, C.J., Panicker, J.N., Drake, M., et al., 2009. A UK consensus on the management of the
bladder in multiple sclerosis. J Neurol Neurosurg Psychiatry 80, 470–477. ER, Extended release; IR,
immediate release; bid, twice daily; qid, four times daily; tid, three times daily
• Adverse events arise due to their nonspecific anticholinergic action
and include dry mouth, blurred vision for near objects, tachycardia,
and constipation.
• These drugs can also block central muscarinic M1 receptors and cause
impairment of cognition and consciousness in susceptible individuals.
• This may be mitigated by medications which have low selectivity for
the M1 receptor, such as Darifenacin, or restricted permeability
across the blood brain barrier, such as Trospium.

• In many patients, there may also be underlying voiding dysfunction

and often it is the judicious use of anti-muscarinic medication with
clean intermittent self-catheterization which proves the most
effective management for neurogenic bladder dysfunction
 DESMOPRESSIN

• Desmopressin, a synthetic analog of arginine vasopressin, temporarily

reduces urine production and volume-determined detrusor
overactivity by promoting water re-absorption at the distal and
collecting tubules of the kidney.

• It is useful for the treatment of urinary frequency or nocturia in

patients with MS, providing symptom relief for up to 6 hours. It is also
helpful in managing nocturnal polyuria

Bosma, R., Wynia, K., Havlikova, E., et al., 2005. Efficacy of desmopressin in patients with multiple
sclerosis suffering from bladder dysfunction: a meta-analysis. Acta Neurol. Scand. 112, 1–5
 Botulinum Toxin
• Botulinum toxin type A injected into the detrusor muscle under
cystoscopic guidance has been shown to improve detrusor
overactivity, symptoms of an overactive bladder.
• The effect lasts 8 to 11 months, at which point the patient is eligible
for further injections
• There was no clinically relevant benefit in efficacy or duration of
effect between dosages of 300 U and 200 U, whereas the likelihood of
developing urinary retention requiring self-catheterization was dose
dependent
Kalsi, V., Gonzales, G., Popat, R., et al., 2007. Botulinum injections for the treatment of bladder
symptoms of multiple sclerosis. Ann. Neurol. 62, 452–457.
• Peripheral Nerve Stimulation- Electrical stimulation of peripheral
nerves such as the sacral nerve roots, posterior tibial nerve, pudendal
nerve and dorsal penile or clitoral nerves has been shown to be
effective in managing the overactive bladder

• Sacral Neuromodulation- An extra dural sacral nerve stimulator can

be highly effective in lessening detrusor overactivity refractory to
anti-muscarinic medications. For eg- Refractory neurogenic bladder in
MS
 SURGERY

Stohrer, M., Castro-Diaz, D., Chartier-Kastler, E., et al., 2009. Guidelines on neurogenic lower urinary
tract dysfunction. European Association of Urology Guidelines. European Association of Urology
• Permanent Indwelling Catheters- When the patient is no longer able
to perform self-catheterization, or when incontinence is refractory to
management
• Bladder stones and recurrent infections are also more likely in
patients with an indwelling catheter

• A preferred alternative to an indwelling urethral catheter is a

suprapubic catheter which is a better long term alternative to a
urethral catheter as it preserves urethral integrity, and helps to
promote perineal hygiene
 OTHER OPTIONS
• Beta-3-Receptor Agonists. The recent licensing of an oral beta-3-
receptor agonist, mirabegron, offers a new approach to the
management of the overactive bladder. ; it is a potentially attractive
option, being devoid of the central side effects that may be reported
with anti-muscarinics.
• Cannabinoids- In experimental stages
• Vanilloids- In experimental stages

Panicker, J.N., De Sèze, M., Fowler, C.J., 2010. Rehabilitation in practice: neurogenic lower urinary
tract dysfunction and its management. Clin. Rehabil. 24
MIRABEGRON
• Indications:
• Treatment of overactive bladder (OAB) with symptoms of
urgency, urge urinary incontinence and urinary frequency •
• Place in therapy: Patients unable to tolerate anticholinergic
agents for OAB and Patients for whom OAB significantly
impacts their quality of life
• Warnings/Precautions : May elevate blood pressure
• Use cautiously in patients with bladder outlet obstruction or
taking antimuscarinic agents for OAB
• Monitor patients taking concomitant CYP2D6 object drugs for
adverse reactions
• Cautiously initiate and titrate digoxin
Chapple, C.R., Cardozo, L., Nitti, V.W., et al., 2014. Mirabegron in overactive bladder: a review of efficacy, safety,
and tolerability. Neurourol. Urodyn. 33, 17–30
• Pregnancy: Category C
• Lactation: Predicted to found in human breast milk •
• Discuss discontinuing nursing or mirabegron to minimize
potential serious adverse effects to nursing infant

Chapple, C.R., Cardozo, L., Nitti, V.W., et al., 2014. Mirabegron in overactive bladder: a review of
efficacy, safety, and tolerability. Neurourol. Urodyn. 33, 17–30
• Pharmacology : Beta3 adrenergic agonist
• Agonizes beta3 receptors of the bladder detrusor muscle
leading to relaxation
• Minimal intrinsic activity on beta1 and beta2 receptors
• Pharmacokinetics :Bioavailability: 25-35%;
• Vd: 1670L; 70% protein bound •
Metabolism – Hepatic via dealkylation, amide hydrolysis,
glucuronidation, oxidation, CYP2D6 (minor) CYP3A4
Excretion – 55% urine (25% unchanged); 35% feces; t½:
• Common Adverse Effects Adverse Effect
• Hypertension
• Urinary Tract Infection
• Nasopharyngitis
• Headache
Price in India – Rupee 203 per 10 tablet
Case scenario#
• A 55‐year‐old Chinese woman k/c/o Parkinson disease since 2
years
• In the last three months, she complained of urinary dysfunctions
• as “she tried to urinate smoothly but it’s too hard for her” and
had to wear-and-take-off her pants to facilitate urination.
• UMN VS LMN ?
• After taking detailed history we get some clue
• Episodic
• Multiple
• These symptoms increase when patient missed her medication
This is a rare case of motor involvement of bladder in PD characterized by FOM.
Treatment – Dopaminergic drugs and bladder training.
 Summary

• For Detrusor hyperreflexia- Anti cholinergics are primary treatment

• For Detrusor areflexia- Best therapy is CIC
• For Detrusor sphincter dyssynergia- Anti cholinergics with alpha
blockers may be tried alongwith CIC.
Other references
• Bradley 8th edition.
• Continuum journal.
• The American journal of Urology.
• Localization in Clinical NeurologyPaul W. Brazis, Joseph C. Masdeu,
and José BillerThis material may be protected by copyright.
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