Neurogenic bladderNeurogenic bladder

Edmond

Neuropathway in micturitionNeuropathway in micturition

Sympathetic: (tone on internal sphincter)Intermediolateral column of T10-L2 preganglionic fibres sympathetic chains postganglionic sympathetic nerve fibres hypogastric nerve trigone, bladder vessels, smooth muscle of prostate and bladder neck (not much in female)

Parasympathetic: (Detrusor contraction)Intermediolateral column of S2-4 preganglionic fibres anterior primary rami of S2-4 nervi erigentes pelvic plexus parasympathetic ganglia post-ganglionic parasympathetic nerves pelvic and pudenal nerves 50% in adventitia + bladder base/ 50% within bladder wall

Afferent: (sensation) Ascend w/ parasympathetic neurons OR sympathetic neurons OR pudendal nerve back to the cord pontine storage and micturition centres and cerebral cortex. Local relays in cord

Motor & sensory innervations of bladder

Somatic motor & sensory innervation of the urethral sphincter: the distal sphincter mechanism: External sphincter: M: distal to Veru, F: mid urethra1. Outermost Extrinsic skeletal muscle: pubourethral sling, innervated by pudendal nerves (somatic), activated under stress & augments occlusion pressure2. Smooth muscle within urethral wall: cholinergic, tonically active, relaxed by NO3. Intrinsic striated muscle: rhabdosphincter, U shape, kink urethra rather by circumferential compress

Somatomotor: Onuf’s nucleus/ spinal nucles X (medial part of the anterior horn of spinal cord) preganglionic somatic fibres/ from S2-4 perineal branch of pudendal nerve external rhabdosphincter

Afferent: pudendal nerves dorsal root ganglia dorsal horn of S2-4 brainstem and cerebral cortex

Summary: motor

• Parasympathetic: (S2-4) voiding– Pelvic plexus detrusor muscle (contraction)– Bladder neck & urethra (relaxation)

• Sympathetic: (T10- L2) storage– Hypogastric plexus detrusor muscle (relaxation) – Bladder neck (internal sphincter in male) contraction– Less bladder neck innervation in female

• Somatic: (S2-4) Onufs nucleus : storage– Pudendal nerves– Pelvic floor muscle + external sphincter contraction

Summary: sensory

• Sensation of bladder fullness are convey to the spinal cord thru pelvic and hypogastric nerve

• At the dorsal root ganglion of S2-3, T11-L2• Ascend to the pontine micturition center & cerebral cortex• 2 types of fiber: • A fiber (myelinated) :

– Convey information about bladder filling (passive distension + contractions)

• C fiber (unmyelinated):– Noxious stimuli (chemical , temp)

• Afferent of trigone & urethra: run in hypogastric & pudendal nerve respectively

StorageStorage• During the storage of urine, bladder pressure remains low despite an

increase in volume1. Due to the visco-elasticity: detrusor muscle cell increase length wo change

in tension2. Due to the “gating mechanism” of parasympathetic system: Prevention of

transmission of activity from preganglionic parasympathetic neurons to post ganglionic efferent neurons

3. Inhibitory interneuron in spinal cord prevents transmission of afferent activity from sensors of bladder filling

4. sympathetic outflow in the hypogastric nerve to the bladder outlet (the bladder base and the urethra) and the pudendal outflow to the external urethral sphincter are stimulated

5. Sympathetic firing also inhibits contraction of the detrusor muscle and modulates neurotransmission in bladder ganglia.

6. A region in the rostral pons (the pontine storage centre) might increase striated urethral sphincter activity.

•Myelinated (A) axon – convey normal bladder distension and active contraction •Unmyelinated (C) axon – noxious stimuli like chemical irritation

VoidingVoiding• intense bladder-afferent firing in the pelvic nerve activates spinobulbospinal

reflex pathways (shown in blue) co-ordinated by the pontine micturition centre (PMC). (Barrington’ nucleus)

• Ascending afferent input from the spinal cord pass through parasympathetic to the periaqueductal grey (PAG) in pons, with input from other areas of the brain (e.g. limbic system, orbitofrontal cortex) PMC determine whether it is appropriate to start micturition

• Micturition:1. relaxing external urethral sphincter and pelvic floor 2. urine enters posterior urethra3. activates afferent neurons stimulate PMC activate detrusor

contraction4. inhibit Onuf’s nucleus further relax external sphincter

• +ve feedback maintain contraction until it is empty: bladder wall tension rises w/ detrusor contraction stimulate tension receptors further increases detrusor contraction

Neurotransmission

• Excitatory neurotrasmission in normal detrussor : cholinergic

• Relaxation of the urethral sphincter & bladder neck : nitric oxide

Autonomic DysreflexiaAutonomic Dysreflexia

Autonomic DysreflexiaAutonomic Dysreflexia

PathophysiologyPathophysiologyAfter stimulation, afferent nerves from the bladder travel

back to S2-4 nerve roots

Most nerves ascend to the brain via lateral

spinothalamic tracts & dorsal columns

Some interneurons reflexively excite pre-

ganglionic sympathetic neurones of the splanchnic

sympathetic outflow disordered sympathetic

activity

PathophysiologyPathophysiology

Mechanism: • Massive reflex sympathetic discharge• Sympathetic activity of the distal autonomous cord (below

level of SCI) vasoconstriction of the territory (below level of SCI) + compensatory vasodilatation of level above the SCI

Symptom:

1. Severe pounding headache

2. Profuse sweating (above level of SCI)

3. Flushing (above level of SCI)

4. Feeling of anxiety / agitation

5. Tightness in chest• In untreated case: convulsion , intracranial bleed, HT

encephalopathy & ultimate death

SignsSigns

ManagementManagementImmediate• Sit patient upright (induce postural hypotension) • Loosen tight clothes• Identify precipitating factors

(e.g. blocked Foley or distended bladder or fecal impaction)• BP/P q2-5min

If not resolved pharmacological treatments• “Bite & swallow” adalat (nifedipine) 10mg

o but potential of serious adverse effects such as MI or CVA, based on non-SCI patients

• Nitrates (TNG)o Make sure patient has not taken PDE5i within 24 hours

• Captopril 25mg sublingualo Initial reports suggest that it may be beneficial

ManagementManagement

ManagementManagement

Voiding dysfunction patternsVoiding dysfunction patterns

Suprapontine lesionsSuprapontine lesions

• Dementia, CVA, meningitis, brain tumors, Parkinson’s disease

• Reduced cortical inhibitory control of micturition reflex

• But micturition reflex is intact• Pontine micturition center not affected• Coordinated smooth and striated sphincter

muscle • Involuntary bladder contractions

Suprapontine lesionsSuprapontine lesions

• Safe low pressure bladders • No reflux / trabeculations o Voiding at inappropriate timeso Involuntary bladder contraction → incontinenceo Pseudodyssynergia

o patients would voluntarily contract the striated sphincter to prevent incontinence at the time of DO

Lesions at T6-S2Lesions at T6-S2

• Spinal cord segment of L5 = S2 • E.g. Suprasacral Spinal cord injury, MS

• Loss of higher detrusor inhibition and coordination• Normal spinal micturition reflex arc• Detrusor overactivity• Striated sphincter dyssynergia

o Functional obstructiono Loss of bladder sensations

o Typical: DO + DSD

Lesions at T6-S2Lesions at T6-S2

• Resulto Unsafe high pressure bladdero Low compliance bladdero Both storage and emptying problemo Uncontrolled reflex voiding with incontinenceo Incomplete bladder emptyingo High voiding pressure, infection, stone formation,

upper tract damage

Lesions below S2 + cauda equina + PN Lesions below S2 + cauda equina + PN • Below level of lesion

o Absent sensationo Depression of deep tendon reflexo Flaccid paralysis

• Detrusor areflexia• Post-void RU (AHCPR guidelines)

– Adequate bladder emptying < 50 ml– Inadequate emptying > 200ml

• Weaken sphincter • Smooth muscle sphincter: Competent but non relaxing • Striated sphincter: residual resting tone not under voluntary

control

Lesions below S2Lesions below S2

• Resulto Safe low pressure bladdero Attempt voiding by straining / Crede’s maneuvero Sometime possible low compliance > causing

Upper tract decompensation and damage

Lesions at peripheral reflex arcLesions at peripheral reflex arc

• Etiology, ?specific nerves involved • E.g. DM, radical pelvic surgery, prolapsed

lumbar disc, spinal stenosis, GBS• Similar to distal spinal cord injury

o Detrusor areflexiao Fixed tone striated sphincter

Lesions at peripheral reflex arcLesions at peripheral reflex arc

• Diabetic cystopathyo Peripheral + autonomic neuropathyo Impaired bladder sensation of fillingo ↓ Bladder contractilityo ↓ Flow rateo Painless urinary retention

What is DSD ?

• Involuntary contraction of the urethral or periurethral strated muscle simultaneously with a detrusor contraction

• Typical of a suprasacral neuro disorder

• Classical appearance on VCMG: 1. Saw-toothed appearance on the Pdet line

2. Sustained detrusor contraction > 5min & pdet of 80-90cmH2O

3. Hold up of contrast at the level of external urethral sphincter (like that of a PUV)

Spinal shockSpinal shock• Spinal shock : A period of decreased excitability of spinal cord at

and below level of lesion (all reflexes disappeared)• Suppression of autonomic activity as well somatic activity

– a brief period of tachycardia and hypertension– Followed by Neurogenic shock: prolonged bradycardia,

hypotension, reduction in cardiac output – Acontractile and areflexic bladder

• Absent of somatic reflex activity and flaccid muscle paralysis– Sphincter = residual tone – retention (catheter / SPC / CISC)

• Last 6-12 weeks

Spinal shockSpinal shock• return of the bulbocavernosus reflex (anal sphincter

contraction in response to squeezing the glans penis or tugging on the Foley) signifies the end of spinal shock,

• Bladder contraction: Last to recover• Majority of recovery in 1st 6 months• More subtle changes up to 2 -5 years?• Reflex recovery

– Reflex recovery1st = striated muscle of pelvic floor – If BCR present: sacral miturition center intact

History History

• Mechanism of SCI

• Urological symptoms (incontinence, UTI, stone passage)

• Bowel or sexual dysfunction

• Current bladder management (CIC)

• Urological surgery and medication

• Motivation, hand function

Physical examinationPhysical examination• Perineal sensation (pudendal afferent limb)• Anal sphinctor tone (distinguish suprasacral-increased/ sacral

lesion-reduced)• Lower extremeity spasticity• Bulbocavernosus reflex

– Test integrity of sacral micturition center S2-4, pudental afferent/efferent limb

– The S2 S4 reflex arc can be elicited by squeezing the glans in males or clitoris in females and looking for contraction of the anal sphincter S2-S4

• Traumatic hypospadia• Morbid obesity and mobility• Lack of adequate hand function• Palpable bladder

InvestigationsInvestigations

• Urinalysis / U&E + Cr / GFR?• USS - kidneys + FR + PVR• A bladder diary is kept for 3 days• After spinal shock or AUR resolved VCMG, but beware of autonomic

dysreflexia• Loss of compliance (normal < 12.5 cmH2O/cc)• Detrusor Leak Point Pressure

– Lowest detrusor pressure at which leakage occurs (against outlet resistence)

– In the absence of bladder contraction or increased abdominal pressure– DLPP > 40cm is prognostic indicator of upper damage

Upper tracing shows the variation of the uroflow rate with timeLower tracing shows the variation of the voided volume with timePost-void residual urine = 30 ml, maximum uroflow= 20.6ml/sec,

voided volume= 600ml

A.a 45-year-old gentleman who has suffered from compression fractureB. of the first lumbar spine after an industrial accident since 2 years ago

ImagingImaging

• Renal ultrasound (stones, hydronephrosis, scar)

• Serum creatinine

• Cystoscopy (on indwelling catheter for > 8 years)

• What are the UD findings? (2) • Name 3 treatment options for this condition (3)

Q64

• Neurogenic detrusor overactivity (1) & Detrusor sphincter dyssynergia (DSD) (1)

• Antimuscurinics with behavioral modification + CISC • External sphincterotomy• Urethral stent• Botox injection: for both bladder and sphincter• Augmentation cystoplasty and Mitrofanoff • Sacral anterior nerve root stimulator and dorsal

rhizotomy

Goal of bladder managementGoal of bladder management

• Protect upper tract (low pressure storage)

• Complete bladder emptying (prevent UTI and stone)

• Preserve continence

• Maintain quality living

Suprasacral injury

Behavioural therapyBehavioural therapy

o Pelvic floor muscle training with biofeedback e.g. vaginal cone

o Bladder training (voiding in fixed and gradually increasing schedule, urge inhibition)

o Decreasing caffeine intakeo Avoid abnormally high fluid intake and carbonated

beverageso Weight loss if obesity

Treatment of patients with suprasacral Treatment of patients with suprasacral spinal injury? NDO + DSDspinal injury? NDO + DSD

It is both a storage and voiding disorderI will start with some non-invasive treatment: To control storage problem: • Anti-cholinergic medication (oxybutynin, tolterodine)

– Reduce intravescial storage pressure– Improve detrusor compliance– Keep DLPP <40cm H20– Increase functional bladder capacity, reduce urgency and

urge incontinenceTo enhance emptying: • Intermittent catheterization

If the above failed?I will discuss with patient about the options of surgical treatment: To improve storage: • Botulinum Toxin

– Reduce intravesical pressure, improve compliance and capacity, improve continence, reduce anti-cholinergic dosage

– 300 units of Botox at 30 sites

– If for sphincter :Not as successful as in detrusor, Injected at 3,6,9 & 12 O O’clock clock

• Clam augmentation enterocystoplasty + CISCTo improve voiding:• External sphincterotomy• Urethral stent

– Memokath, Alloy of Ni Ti , Deploy hot water 55°C, Removal cold water 5°C

To abolished the autonoic desreflexia + coordinate muscle contraction: • Detrusor myectomy• SARS with dorsal rhizotomy – not suitable for patient who is still walking or

incomplete SCI

Antimuscarinic AgentsAntimuscarinic Agents• Tertiary (^lipophilicity, ^ Pass into CNS)

o Oxybutynin Ditropan® (XR form and transdermal form a/v – mixed action)

o Tolterodine Detrusitol® Detrol® (Relatively low lipophilicity, functional selectivity for bladder over salivary gland, XR form a/v)

o Atropine (if used, usu. Intravesical for neurogenic DO)o Propiverine Detrunorm® (mixed action and equal efficacy, fewer

S/E than oxybutynin)o Darifenacin Enablex® (only drugs is M3 selective)o Solifenacin Vesicare®

• Quaternary (less CNS effect)o Trospium Sanctura® (Non-selective)o Propantheline Pro-Banthine® (Non-selective)

(Antidepressants)(Antidepressants)• Actions:

o Central and peripheral antimuscuric effectso Blocking reuptake of neurotransmitterso Sedative

• Option: Imipramine (tricyclic)

External SphincterotomyExternal Sphincterotomy

• Current technique

o Colling’s electrocautery knifeo Anteromedian incision (12 o’clock)o Proximal part of verumontanum Corpus

spongiosum of the bulbous urethrao Plane of periurethral venous sinuseso Large bore catheter (24-48 hours)o Bladder irrigation

External SphincterotomyExternal Sphincterotomy

• Results

• 70% successful rate • Resolution of hydronephrosis / improved VUR• Reduced febrile UTIs• Reduced autonomic dysreflexia• Reduction in PVR• Reduction in mean voiding pressure

External SphincterotomyExternal Sphincterotomy

• Complication • Bleeding (clot retention)• Severe infection• Impotence• Reoperation (50%)• Laser sphincterotomy has better results• Not done often now – irreversible

Transurethral SurgeryTransurethral Surgery

• Botulinum A toxin injection

• Balloon dilatation• Endourethral stent

• Comparable outcomes• Less transfusion• Stricture formation• Encrustation / migration

Complication of Stents?

• Patient complete incontinent

• Need a Convent Shealth

• Stent may dislodge, block or encrusted

Sacral Anterior Roots Stimulation (SARS)Sacral Anterior Roots Stimulation (SARS)

• A type of Sacral Nerve Neuromodulation• Procedures to enhance detrusor contractility, usually

accompanied by with Dorsal Sacral Rhizotomy (abolish hyper-with Dorsal Sacral Rhizotomy (abolish hyper-reflexia )reflexia )

• Suitable for patient wheelchair bound and complete SCISuitable for patient wheelchair bound and complete SCI• Procedure

– Laminectomy from L3 to S2 vertebrae level– Intradural identification of S2-4 nerve roots– Rhizotomy of dorsal sensory roots (“sacral de-afferenation”)– Connection of anterior motor roots to implant slots and implant

(“The Finetech-Brindley bladder controller”) placed

What are the advantages and disadvantages of What are the advantages and disadvantages of SARS and dorsal rhizotomy?SARS and dorsal rhizotomy?

• Advantages1. Voiding is possible because the striated muscle of the

sphincter contracts and relaxes more rapidly than the smooth muscle of the detrusor (hence voiding occurs in spurts)

2. Minimal post-void residual so decreases UTI’s3. Convert the hyper-reflexic high pressure bladder into an

areflexic , low pressure one4. Increased bladder capacity5. Abolition of autonomic dysflexia

• Disadvantages1. Stress incontinence2. Loss of reflex erection / ejaculation / defaecation

Txn of infra sacral SCI

Treatment for infrasacral lesionTreatment for infrasacral lesion Detrusor underactivity• Intermittent catheterization• Indwelling catheter• Suprapubic catheter• Valsava manuever: contraindicated in VUR or

hydronephrosis• Reflex voiding

• Cholinergic agonist: no randomized trials have demonstrated efficay over placebo

• Incontinent ileovesicostomy• Continent catheterizable abdominal stoma

CICCIC

• GOLD standard for Mx of NLUTD (EAU guidelines)• Jack Lapides 1972

o Promoted & popularized CIC o First applying concept to large groups of pts with

voiding dysfunctiono Demonstrated safety & long term efficacy

• Most effective & practical means for attaining catheter free state in SCI

• Effective method for pts with emptying failure, esp after failed attempts ↑ Pves / ↓ outlet resistance

• Helps to prevent UTI & protect upper tract

CIC prerequisiteCIC prerequisite

• Cooperative, well-motivated pt / family• Adequate hand control• Adequate urethral exposure

• Complications o Urethral false passageo Bladder perforationo Silent deterioration of upper tracts o Bacteriuria common (not symptomatic infection )

• Atraumatic, non infecting manner • Clean Vs Sterile• Duffy et al evaluated cost-effectiveness in

a population of male residents of VA nursing homes comparing CIC and SICo similar outcome but ↓ cost for clean technique

Continuous catheterizationContinuous catheterization• Long term Indwelling urethral catheter

o ? Poorer outcome (upper / lower urinary tract Cx & QOL)

• Suprapubic catheter o More comfortable & ↓ urethral Cx in maleo DOES NOT

obviate urethral leakage with detrusor contractions Less leakage in sphincter incontinence

• Carcinoma controversy

No RCTs

Crede / Valsalva’s manoeuvreCrede / Valsalva’s manoeuvre

• Manual compression of bladder / abdominal straining • Can generate intravesical P ~ 50cm H20• Most effective

o ↓ bladder toneo Borderline / ↓ outlet resistance

• !! Upper tract deterioration (high intravesical pressure in filling phase) + incontinence

• EAU guidelines: “Crede manoeuvre: regretfully still applied”

• Relative C/I: VUR

Reflex voidingReflex voiding

• SCI / diseases with neurogenic DO• Manual stimulation of certain areas within

sacral / lumbar dermatomes may provoke reflex bladder contraction (Wein 1988)

• Triggers: pulling skin / hair of pubis, scrotum, thigh; squeeze clitoris, digital rectal

• Form of timed voiding

Pharmacological agentsPharmacological agents

1.Increase intravesical pressure & bladder contractility

2.Decrease outlet resistance

•Bethanechol chloride / distigmine bromide– Acetylcholine-like agent with relative selectivity on bladder & gut,

with little nicotinic action

• NO drug with evidence of efficacy for underactive detrusor

Incontinent Urinary DiversionIncontinent Urinary Diversion

Ileovesicostomy

o Low pressure conduit for preferential drainage (<10cmH2O)

o Native bladder as continent reservoiro Native ureterovesical junctiono Easy stoma care

Incontinent Urinary DiversionIncontinent Urinary Diversion

Ileovesicostomy

VUR in SCIVUR in SCI

• Incidence 25%• Contributing factor:

– Elevated intravesical pressure (filling and voiding)– Infection

• Persistent reflux can lead to chronic renal damage• Normalize lower urinary tract urodynamic

Pharmacotherapy, urethral dilatation, neuromodulation, augmentation cystoplasty, or sphincterotomy

• Injection of bulking substance (Deflux)