Neurourology

Physiology — Storage & Emptying

Filling (Storage)

1. Accommodation

• Compliance
  • Accommodation is primarily passive → intrinsic detrusor properties + parasympathetic quiescence
• Sympathetic stimulation
  • β₃ (and β₂) stimulation via the hypogastric nerve → direct detrusor relaxation → the pathway mirabegron targets
• Parasympathetic inhibition

2. Closed bladder outlet

• Sympathetic stimulation → increases involuntary smooth sphincter tone
• Onuf's nucleus stimulation → increases voluntary striated sphincter tone
  • Guarding reflex → spinal somatic reflex → gradual increase in striated sphincter activity during normal filling (rising urethral pressure, pudendal efferent firing, periurethral EMG)
  • Serotonin centrally inhibits micturition → duloxetine (serotonin–norepinephrine reuptake inhibitor) boosts sacral-cord sphincter drive during filling + damps the voiding reflex → helps stress urinary incontinence
• Detrusor afferent input to the CNS → reflex rise in urethral pressure during filling
  • Lost after orthotopic neobladder → isolated nocturnal incontinence
  • Preserved after radical prostatectomy → isolated nocturnal incontinence uncommon

Emptying (Voiding)

1. Open bladder outlet

• Relaxation of the pelvic muscle
• Sympathetic inhibition
  • Urethral smooth muscle relaxes → withdrawal of sympathetic excitation + parasympathetic nitric oxide release
• Onuf's nucleus inhibition
  • Striated sphincter relaxes → withdrawal of pudendal tone from Onuf's nucleus
  • First event in normal voiding → sudden, complete striated sphincter relaxation (falling urethral pressure, EMG silence) → seconds later detrusor contraction + vesical neck opening
  • Reversal of this order = detrusor–sphincter dyssynergia

2. Detrusor contraction

• Parasympathetic stimulation
• Sympathetic inhibition

Pathways & Receptors

• Central control by the pontine micturition center
  • Coordinates bladder + urethral reflex activity → suprasacral cord injury disconnects it from the sacral cord → detrusor overactivity + detrusor–external sphincter dyssynergia → upper tracts at risk
  • Glutamate = central transmitter that stimulates micturition → drives preganglionic parasympathetic neurons from the pontine micturition center
    • Acetylcholine acts at the ganglion + nerve–muscle junction
  • Central inhibition of the micturition reflex → serotonin, plus GABA and glycine pathways at the lumbosacral cord; GABA = most widespread inhibitory transmitter in the CNS
• M₂ is the predominant receptor, but M₃ is the primary (functional) receptor
  • M₂ outnumbers M₃ by at least 3:1
  • M₃ drives physiologic contraction → Gq/11 → phospholipase C → IP₃ (release of intracellular calcium) + L-type calcium channel influx
  • Obstructed and neurogenic bladders → contractile subtype shifts M₃ → M₂
  • M₃ selectivity gives little side-effect advantage → M₃ also mediates dry mouth and constipation

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Treatment Options — by Functional Category

Storage

A — Bladder related

• Behavioral → education, bladder training, timed voiding, pelvic floor
• Medication → antimuscarinic, β₃ agonist, Botox (presynaptic)
• Neuromodulation → sacral, posterior tibial
• Augmentation

B — Outlet related (sphincter)

• Behavioral therapy → bladder training, timed/fluid restriction, pelvic floor
• Sling procedure
• Artificial urinary sphincter

Voiding

A — Bladder related

• Credé maneuver
• Neuromodulation

B — Outlet related (sphincter / BPH / stricture)

• α-blocker
• Prostate surgery
• Urethral stricture repair
• Sphincterotomy
• CIC
• Indwelling catheter

EAU 16 (2025)

• EAU 16 (2025) discourages Credé / Valsalva / triggered reflex voiding:
  • They raise intravesical pressure and provoke reflex sphincter contraction → hazardous to the urinary tract unless UDS confirms pressures stay within safe limits.
• All assisted emptying requires low outlet resistance + close urodynamic surveillance.
• Triggered voiding can induce AD in lesions at or above T6.
• The penile clamp is absolutely contraindicated in NDO or low compliance.

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Evaluation

• Detailed history — including neurological and bowel history
• Physical exam — including sensory, reflexes, anal tone
• Voiding diary & QoL
• Labs & PVR
• Pad test & uroflow (optional)

→ After this, the patient is categorized as Low risk vs Unknown risk

Urodynamics — the only objective test of lower urinary tract function

• Video-urodynamics is the optimum invasive study in neurological patients; if unavailable → filling cystometry continuing into a pressure-flow study
• Frequency/urgency before lumbar laminectomy → cystometry first, which also sets a baseline against postoperative cauda equina compromise
• Man with hesitancy, straining, urgency and frequency after a stroke → full urodynamics before TURP or bladder neck incision, to exclude detrusor hyperactivity with impaired contractility

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Risk Stratification

Framework: AUA/SUFU 2021 NLUTD. Not present in EAU 16 (2025), which uses only an informal low- vs high-risk split.

Click the algorithm to open it full size.

• Low risk → no routine upper tract imaging, renal function testing, or UDS
• Not clearly low risk → unknown risk until worked up, which then reclassifies as moderate or high

The four goals in a spinal cord injury patient:

1. Preserve and protect the upper tracts
2. Minimize lower urinary tract complications
3. Treat incontinence
4. Produce a management plan that is both safe and compatible with quality of life

To assess the upper tracts: a renal scan is preferred, with renal ultrasound as the alternative.

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Patterns of LUT Following Neurological Disease

Key: I = impaired · OV = overactive · N = normal · S = synergic · D = dyssynergic · OP = open/incompetent · A = areflexia · CNR = competent, non-relaxing · F = fixed tone

Sensation is not tabulated above but is recorded for three: CVA — may be reduced · suprasacral cord injury — absent · tabes dorsalis — loss of sensation is the primary problem.

Pattern mnemonics — which disorders cluster where:

Causes of detrusor overactivity:

• Idiopathic
• Neurogenic
  • Supraspinal: stroke, Parkinson's, hydrocephalus, brain tumor, traumatic brain injury, MS
  • Suprasacral spinal: SCI, cord tumor, MS, myelodysplasia, transverse myelitis
  • Plus diabetes
• Non-neurogenic
  • UTI
  • BOO (men: BPH, bladder neck stricture; women: POP, post-incontinence surgery, primary bladder neck, stricture)
  • Bladder tumor
  • Bladder stones
  • Foreign body
  • Aging

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Cerebral shock — the early period after a stroke: urinary retention from detrusor areflexia, lasting 6–12 weeks and occasionally 1–2 years. The cerebral counterpart of spinal shock.

CVA beyond the acute phase

• Detrusor overactivity with synergic relaxation of both smooth and striated sphincters and an insignificant PVR.
• External sphincter contraction during DO = a normal voluntary guarding reflex — not DESD (suprasacral SCI) and not sphincter bradykinesia (Parkinson's)
• Cerebral cortex and/or internal capsule lesions → most cannot voluntarily contract the striated sphincter, so they leak; basal ganglia or thalamic lesions spare sphincter function
• True DSD does not occur with suprapontine lesions → the EMG sphincter flare on cystometry in 5–21% of brain-disease patients is pseudodyssynergia:
  • A voluntary external sphincter contraction attempting to inhibit an involuntary detrusor contraction

Cerebral palsy

• A non-progressive suprapontine brain injury
  • The pontine micturition center stays intact, so the usual UDS finding is detrusor overactivity (hyperreflexia) with coordinated sphincters.
• Striated sphincter dyssynergia, when present, probably reflects additional spinal cord damage.

Brain tumor

• The superior frontal lobe is the site most often associated with voiding dysfunction
• Incontinence is the usual picture, while retention is commoner with posterior fossa tumors.

Parkinson's disease

• Mainly detrusor overactivity, but a minority have acontractility, so TURP may not help.
• Motor onset precedes LUTS by about 3 years, so the patient is already known to have PD.
  • Exam answer: LUT dysfunction usually starts about 5 years after the PD diagnosis
• LUT dysfunction affects 35–70% of PD patients, with mainly storage symptoms; incontinence and large PVRs are more typical of MSA
• The DO comes with a synergic smooth sphincter; it probably reflects loss of the dopaminergic nigrostriatal pathway, which normally tonically inhibits the micturition reflex
• DO + urodynamic BPH obstruction (e.g., Pdet 88 cmH₂O, Qmax 7 mL/s, PVR 150 mL) → alpha-blocker first, before CIC or prostate surgery
  • Avoid antimuscarinics until emptying improves
  • Baclofen has no role — DESD is not seen in PD
• Advanced PD in retention with a low-pressure, low-flow study (detrusor underactivity) → suprapubic tube:
  • CIC and neuromodulation are hard to manage, and TURP is less likely to succeed

Parkinsonism is not only PD — it is the syndrome of tremor, rigidity and bradykinesia, also produced by multiple system atrophy, progressive supranuclear palsy and Lewy body dementia.

Tethered cord

• Often declares itself at a growth spurt
• Detrusor overactivity is the commonest urodynamic finding, which is the reverse of the usual spina bifida pattern.
• Adult with spina bifida and a tethered cord → DO is still the commonest finding, even though detrusor underactivity is common in spina bifida
• Adult symptoms frequently follow activities that stretch the spine; neurosurgical therapy is controversial and may not improve the condition

Lumbar disc disease and cauda equina syndrome

• Both cause retention.
• Lumbar disc — most commonly difficulty voiding with straining and a normally compliant areflexic bladder; detrusor areflexia in 26–27% of disc protrusions
• Most protrusions compress the roots at L4–L5 or L5–S1 → sensory loss in the perineum/perianal area (S2–S4) and/or lateral foot (S1–S2); LUT dysfunction in 27–68%
• Stable L4 vertebral injury → damages only the cauda equina (the sacral cord ends at about L2) → detrusor areflexia + denervation potentials on sphincter EMG
  • Because the intermingled roots also supply the external sphincter

Diabetic cystopathy

• Hits the sensory afferents first:
  • Impaired sensation and increased capacity, and only later decreased contractility and a raised residual.
• Yet detrusor overactivity is the most frequent urodynamic finding.
• Early, emptying preserved (e.g., 450 mL pre-void, 60 mL residual) → timed and double voiding to prevent overdistension + intensive diabetes therapy to slow progression

Multiple System Atrophy

• Urinary symptoms — urgency, frequency and urge incontinence — can precede the diagnosis by up to 4 years.
• The bladder neck is open.
• Treating the incontinence pharmacologically may worsen emptying, so the goal is to facilitate storage and use CIC
  • An indwelling catheter is considered only in advanced cases who cannot manage CIC.
• Desmopressin helps predominant nocturia.

Urogenital features favoring MSA over PD:

• Urinary symptoms, or erectile dysfunction, preceding or coinciding with the parkinsonism
• Urinary incontinence · high post-void residual · open bladder neck
  • Open bladder neck at rest on videourodynamics in a man with no prior prostate surgery, especially with erectile dysfunction, is highly suggestive of MSA and separates it from PD
  • Bladder neck dyssynergia instead keeps the neck closed during filling
• Striated sphincter denervation on EMG
• Worsening lower urinary tract function after urological surgery — unlike PD, where most patients do not deteriorate after surgery

TURP is an absolute contraindication in MSA (formerly Shy-Drager syndrome) — both smooth and striated sphincters are deficient, so prostatectomy removes the last outlet resistance → florid incontinence.

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Autonomic Dysreflexia

• Lesion above T6–T8 — an acute, massive, disordered sympathetic response to a noxious stimulus below the level of the lesion.
  • i.e., SCI at or above T6 — T6–T8 is the level of the sympathetic outflow
  • It occurs only after the spinal shock phase has passed and requires a viable, intact distal cord
    • The vasoconstriction is α₁-receptor mediated, and the lesion cuts descending inhibition in the lateral reticulospinal tracts.
• Mechanism — uninhibited sympathetic outflow below the lesion (splanchnic vasoconstriction) with reflex parasympathetic outflow above it.
  • Hypertension = arteriolar vasoconstriction (α₁); bradycardia = an intact vagal baroreflex response to it — the vagus arises above the lesion
• Commonest trigger is bladder distension.
  • Others: constipation, instrumentation, catheter change, stone, sexual activity, long-bone fracture pain, pressure sores.
• Pounding headache · hypertension · sweating and flushing above the lesion · cool skin below it · reflex bradycardia — though tachycardia or arrhythmia can occur instead.
• Urodynamics during an episode: detrusor overactivity + smooth sphincter dyssynergia + DSD.

Prophylaxis in an at-risk patient:

• Identify the at-risk patient and remove potential noxious stimuli beforehand (retention, constipation, pressure sores)
• Spinal anesthesia
• Nifedipine 10 mg, 30 minutes before the procedure — 20 mg before electroejaculation
• Labetalol · terazosin
• Routine BP + heart rate monitoring during urodynamics → early recognition; untreated AD can progress to cerebral hemorrhage or seizure

Treatment — the sequence matters:

1. Remove the noxious stimulus — stop the cystoscopy, check the catheter — then sit the patient up and loosen tight clothing. These steps alone may abort the episode.
   • During urodynamics: stop filling and empty the bladder first — AD from simple LUT instrumentation resolves quickly once the stimulus is withdrawn
2. Drugs come only after the bladder has been emptied.
3. Monitor observations every 2–5 minutes.
4. Topical 2% nitroglycerin paste above the level of the lesion — standard of care.
   • Alternatives: nifedipine 10–20 mg, or a beta- plus alpha-blocker.
   • Persisting after bladder emptying and catheter removal:
     • SBP > 150 mmHg → 2% nitropaste (½–1 inch)
     • SBP < 150 mmHg → look for fecal impaction (second commonest trigger)
   • Applied above the lesion because vasoconstriction below it impairs absorption; preferred as it can be wiped off if rebound hypotension occurs
   • Exam answer: nifedipine is discouraged for AD treatment or prophylaxis — rebound hypotensive crises have caused stroke and MI
5. Atropine 1 mg IV as needed for reflex bradycardia.
   • Exam answer: atropine does not treat the hypertension — it is not the drug step when BP stays high after the bladder is emptied
6. IV nitroprusside if still refractory.
   • IV hydralazine is the other option for hypertension unresponsive to transdermal or oral therapy — BP becomes labile (hypotension or rebound hypertension), so admit for monitoring

For dysreflexia refractory to oral agents, ablative options exist — sympathectomy, dorsal root ganglionectomy, sacral neurectomy, sacral rhizotomy, cordectomy.

• Sacral rhizotomy with CIC is the one usually favored, being moderately invasive and relatively low risk.

EAU

• EAU defines AD as an SBP rise > 20 mmHg from baseline, with headache, blurred vision, flushing/sweating above the lesion and pallor/cold skin below it.
• It is more common in cervical (60%) than thoracic (20%) SCI; bradycardia is typical, though only 23% were actually bradycardic in one series.
• Triggers: bladder/bowel distension, cystoscopy, urodynamics, any noxious stimulus (ingrown toenail, pressure sore), sexual stimulation.
• Drugs: 2% nitroglycerin paste above the lesion is first-line; sublingual nifedipine 10–20 mg works but is prohibited in many centers (rapid, non-reversible BP drop); IV nitroprusside if refractory.
• Prophylaxis: terazosin 1–10 mg daily.
• EAU (Strong): BP + HR monitoring is mandatory during UDS and other invasive procedures in at-risk patients; empty the rectal ampulla first.

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DSD — Detrusor Sphincter Dyssynergia

• Definition — a detrusor contraction concurrent with an involuntary contraction of the urethral and/or periurethral striated muscle
  • On urodynamics → EMG activity during the detrusor contraction
• Pathway — neurogenic DO + DSD = disruption of the reticulospinal tract, which carries pontine micturition center output to the sacral cord to inhibit the sacral reflex and coordinate sphincter relaxation with detrusor contraction
• Suprasacral SCI
  • DSD needs a lesion between the pontine micturition center (brainstem) and the sacral cord
    • Suprapontine lesions typically give DO with synergic sphincters
    • Sacral or more distal lesions give detrusor areflexia
  • An areflexic bladder facing fixed internal sphincter activity is normal — not dyssynergia
• MS (30–65%)
  • DSD after lumbar laminectomy → suspect undiagnosed MS:
    • The sacral cord begins at T12–L1, so disc herniation, cauda equina syndrome or laminectomy nerve injury are not associated with DSD
• Cerebral palsy (25%)
• Dyssynergia without a neurological lesion is not DSD → dysfunctional voiding, a learned behavior

Management

The goal is to lessen abnormal external sphincter activity or to circumvent it. Drugs used for detrusor overactivity do not relax the external sphincter — that is the central point.

1. CIC
   • CIC + antimuscarinics is the commonest DSD therapy. Not:
     • Alpha-blockers (no effect on the striated sphincter)
     • Intradetrusor onabotulinumtoxinA (lowers pressure, doesn't improve emptying)
     • A male sling (raises outlet resistance)
2. Sphincterotomy
3. Stent across the external sphincter
4. Botulinum toxin into the external sphincter
5. Continuous catheterization — urethral or suprapubic
6. Urinary diversion

By site of dyssynergia:

• Bladder neck → an alpha-blocker (tamsulosin)
• External sphincter → a skeletal muscle relaxant — baclofen, diazepam or dantrolene.

Indications for sphincterotomy:

• Autonomic dysreflexia caused by DSD
• DSD itself
• Risk of upper tract deterioration in a high-risk patient (DLPP > 40 cmH₂O)
• Difficulty performing CIC
  • DSD with hydronephrosis/VUR, a high detrusor LPP, febrile UTIs or AD, and CIC refused or not feasible → external sphincterotomy lowers outlet resistance and LPP, allowing condom catheter drainage
• High-pressure voiding with severe hydronephrosis or VUR
• To gain the patient independence

Recurrent UTIs after sphincterotomy + condom catheter (distended bladder):

• Urodynamics first — prostatic or sphincter regrowth, stricture or lost detrusor contractility causes high-pressure voiding or incomplete emptying
• Avoid antibiotic prophylaxis, especially before bladder function is evaluated — it breeds bacterial resistance

How to decrease the rate of bladder stones in SCI with a Foley catheter

• Long-term antibiotics
• Acidify urine
• Increase fluid intake
• Routine bladder lavage
  • Recurrent sediment and clogging of an indwelling catheter → urine culture first, for a urease-producing organism (e.g., Proteus mirabilis) whose biofilm drives encrustation
    • Irrigation or a larger suprapubic tube only temporizes
  • Urease producer found → treat it and look for bladder or upper-tract stones (cystoscopy, non-contrast CT) acting as a nidus for infection

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Fowler Syndrome

• Urinary retention with no neurological disease in a young female
  • Typically under 30, unable to void for a day or more
• Associated with PCOS
  • 50% have polycystic ovaries
• Capacity over 1 L with no urge sensation
• UDS → impaired sphincter relaxation
  • Abnormal external sphincter needle EMG + detrusor acontractility = diagnostic; true DSD and high-pressure, low-flow voiding are not seen
• Highly responsive to sacral neuromodulation — around 70% success, the best response of any indication
  • Treatment of choice — including after failed biofeedback when CIC is declined — because it restores volitional voiding rather than bypassing the retention
• Fails: alpha-blockers (relax bladder-neck smooth muscle, not the striated external sphincter) · hormone therapy · sphincter onabotulinumtoxinA; sphincterotomy is not indicated

Impaired sphincter relaxation is the concentric-needle EMG finding (decelerating bursts / complex repetitive discharges). The urodynamic finding is detrusor acontractility.

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CIC vs Indwelling Catheter

Benefits of CIC over indwelling catheter

• Improved quality of life
• Facilitates sexual activity
• Maintenance of bladder compliance — over 80% is lost with an indwelling catheter
  • Upsizing the catheter, changing it more often or switching to a suprapubic tube → unlikely to improve long-term compliance
  • Protect compliance / suppress DO instead → antimuscarinic or β₃ agonist, or intravesical Botox
  • Avoid prophylactic antibiotics in chronically catheterized patients
• Reduced risk of pyelonephritis
• Reduced risk of stones, upper and lower tract
• Reduced risk of prostatitis, epididymitis, orchitis and Fournier's gangrene
• Reduced risk of urethral stricture
• Reduced risk of traumatic hypospadias (both sexes) and the "lead-pipe" urethra in women

UTI in SCI on CIC

• Pyuria is unreliable — catheterization alone can cause it
• Increased spasticity + bacteriuria ≥ 100 cfu/mL → symptomatic UTI → antibiotics
• Spasticity persists after treatment → look for a physical injury below the lesion (obstipation, decubitus ulcer, ingrown toenail, developing syrinx) → then baclofen
• Recurrent symptomatic UTIs → UDS for elevated storage pressures

Bladder cancer in SCI with chronic catheter

• Incidence 1% → surveillance after 8 years

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Underactive Bladder (DUA)

• Difficult to diagnose — overlaps with OAB and is associated with BOO
• Diagnosis by urodynamics → measure BCI
  • DUA = ↓ contractile amplitude (low Pdet + low flow) + prolonged or incomplete emptying
  • High Pdet + low or normal flow → obstruction, not DUA

BCI = Pdet@Qmax + 5(Qmax)

• < 100 → underactive / acontractile bladder
• 100–150 → normal · > 150 → strong
• Unreliable when DUA and obstruction coexist (e.g. long-standing BOO)

Management

• Behavioral, timed voiding, pelvic physiotherapy
• CIC, indwelling catheter, urinary diversion
• Bladder outlet obstruction surgery
• Neuromodulation
• Bethanechol → essentially no reproducible urodynamic evidence supporting it in any patient group
  • Cholinomimetic side effects: flushing, GI cramps, bronchospasm, salivation, sweating

Neuromodulation — positive results found in

• Non-obstructive urinary retention
• DUA

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OAB

OAB = urgency, with or without UUI, usually with increased daytime frequency and nocturia, in the absence of UTI or other obvious pathology.

Evaluation

• Hx + physical exam + UA + PVR + QoL + voiding diary
• Urodynamics should be done if a neurological etiology is suspected
• Urodynamics & cystoscopy should be done when surgery for UUI is considered

Treatment Pathway

1. Behavioral, timed voiding, fluid restriction
   • Management is driven by bother → non-bothersome storage symptoms → reassurance + lifestyle changes, not drugs
   • ↓ Caffeine → improves urgency and frequency, not incontinence
   • 25% ↓ fluid intake → improves OAB symptoms, not UUI · warn of constipation and UTI
2. Pelvic floor muscle therapy
   • Urge suppression → don't rush to the toilet · sit still and contract the pelvic floor repeatedly to inhibit the detrusor until the urge passes → then walk at a normal pace
   • Giggle incontinence (complete emptying on laughing, LUT function otherwise normal) → biofeedback · more durable long-term response than methylphenidate
3. OAB medication (antimuscarinic / β₃ agonist)
   • AUA 2nd line → start here after failed behavioral therapy (UUI, negative UA + exam) · e.g. mirabegron · UDS premature · cystoscopy not indicated
   • Adequate trial → 4–8 weeks drug · 8–12 weeks behavioral → still symptomatic at 2 weeks with tolerable side effects → continue current treatment
   • Failure = no improvement after 4–8 weeks or intolerable side effects → only then switch or add another oral agent
4. Botox or neuromodulation
   • 3rd line → SNM, Botox, PTNS · only after 2nd-line (oral) drugs fail
5. Urinary diversion / augmentation

Tramadol

• ↑ Bladder capacity and compliance (animal reports) → can ease OAB symptoms
• μ-opioid effects → ↓ bladder sensation + ↑ sphincter tone → risk of postoperative urinary retention

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Management of MS for LUTS

• Hx + physical exam + voiding diary + QoL + UA + US KUB + PVR + UDS
  • Man with MS + DESD → renal US first — male MS patients with DESD are at greatest risk of upper tract deterioration
  • Known MS + DESD → spine MRI and videourodynamics unnecessary · TRUS unneeded — the dyssynergia, not the prostate, causes the obstruction
• High PVR → CIC
• Low PVR →
  • 1st behavioral therapy
  • 2nd OAB medication
  • 3rd Botox
  • 4th neuromodulation
  • 5th indwelling catheter
  • 6th augmentation

MS — LUT patterns

• 5% of previously undiagnosed MS present with urinary symptoms as the first manifestation
• Voiding dysfunction → 10% at onset · 75% after 10 years
• Demyelination most often in the cervical cord — lateral corticospinal + reticulospinal columns
• NDO 43–65% (most common finding) · DSD 35% · DUA 25%
  • Smooth sphincter generally synergic · striated sphincter dyssynergia coexists with DO in 30–65%
• Storage (frequency, urgency, nocturia) + voiding (hesitancy, intermittency, straining) symptoms → DO with DSD
• UDS pattern changes over time → approach irreversible treatments with caution
  • Upper tract damage is rare, even with severe disability

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Antimuscarinics

Divided into tertiary or quaternary.

A — Tertiary (lipophilic)

• Cross BBB → CNS side effects
  • BBB crossing favored by high lipophilicity, small molecular size and low electrical charge → in a cognitively impaired patient choose a drug with low lipophilicity
  • EEG → trospium no change · tolterodine occasional changes · oxybutynin consistent changes
• Hepatic metabolism → principally CYP3A4 and CYP2D6 (darifenacin, solifenacin, fesoterodine, tolterodine, oxybutynin)
• Oxybutynin (non-selective)
  • Most lipophilic → may worsen cognition in elderly women
• Tolterodine
  • Tissue selective (bladder > salivary gland) but no selectivity for muscarinic receptor subtypes
• Darifenacin (highest M3 selectivity)
  • Relatively selective M3 antagonist, but receptor selectivity ≠ tissue selectivity (salivary glands and gut also carry M3) → dry mouth and constipation remain its main adverse effects
• Solifenacin
• Fesoterodine

B — Quaternary (lipophobic)

• Safe on CNS
• Trospium (safe, but watch the renal profile)
  • Permanently charged quaternary amine → least BBB penetration → preferred in elderly cognitively impaired patients
  • Trade-offs → poor GI absorption (take on an empty stomach) · dose reduction in renal impairment
  • Antimuscarinic of choice in liver cirrhosis → not significantly metabolized by hepatic CYP450; eliminated mainly unchanged, actively excreted by the proximal convoluted tubules
  • Also avoids interactions with CYP3A4-substrate immunosuppressants after transplantation

Contraindications

• Urinary retention
• Closed-angle glaucoma — precisely: untreated narrow-angle; treated narrow-angle is not a contraindication
• Myasthenia gravis
• cognitive impairment

Side effects

• Constipation, dry mouth, blurry vision, headache, retention

Neurogenic detrusor overactivity (NDO)

• First-line for NDO → incl. leakage between catheterizations on CIC, or poor compliance with hydronephrosis
• Ladder → antimuscarinic → botulinum toxin A → augmentation only once less-invasive treatment has failed
• Failure of one antimuscarinic does not preclude another → higher doses or combinations may be used
• Oral route poorly tolerated → intravesical oxybutynin

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β₃ Agonist

• MoA → stimulates the β3-adrenoceptor → activates adenylyl cyclase → cAMP (second messenger) → detrusor relaxation during the storage phase
• Mirabegron (50 mg PO daily)
  • First β3-agonist approved worldwide; little β1/β2 activity
  • Increases bladder capacity without significantly changing micturition pressure, PVR or the voiding contraction
  • Men with BOO → no significant difference vs placebo in Qmax or detrusor pressure at Qmax; PVR rose ~30 mL only at the unapproved 100 mg dose
• Effect at 4 weeks to 3 months
• Contraindicated → severe uncontrolled hypertension
  • = systolic ≥ 180 and/or diastolic ≥ 110 mm Hg · coexisting diabetes is not a contraindication
  • Measure BP before starting mirabegron and during treatment → average trial rise only ~0.5–1 mm Hg, but postmarketing reports of hypertensive crisis and cardiac / cerebrovascular events
• Vibegron → more potent and more selective than mirabegron — no measurable β1/β2 activity
  • Not shown to affect BP (EMPOWUR) → urgency incontinence with memory decline + worsening hypertension → stop the antimuscarinic and use vibegron, not mirabegron
  • β3-agonists have no known cognitive effect

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OnabotulinumtoxinA (Botox)

• MoA → inhibits release of ACh at the presynaptic terminal
  • Cleaves SNAP-25 → SNARE complex inactivated → vesicles cannot fuse → muscle paralysis (presynaptic cholinergic motor nerve endings)
  • Subtype A → longest-acting of the seven botulinum toxin subtypes
• Indications → ① OAB with incontinence · ② decrease DLPP
  • After injection for high DLPP → repeat UDS: safe pressures → longer catheterization intervals + reinject in 6–9 months when symptoms return · pressures still high → consider bladder augmentation
• Efficacy → 30% complete resolution · 60% have a 50% reduction in symptoms
  • Retreatment often needed after 6 months
  • Do not reinject within 3 months
• Complications → UTI (most common), high PVR, transient retention requiring CIC
  • Retention in ~5% → worsening incontinence weeks after injection → check a PVR first to rule out overflow incontinence
• Contraindications → UTI, pregnancy, myasthenia gravis, not accepting catheterization

Steps

1. Map the bladder — except the trigone, don't inject it
2. 100 U / 10 mL → inject 0.5 mL × 20 sites
3. Increase to 200 U / 30 mL → inject 1 mL × 30 sites — for neurogenic overactivity
   • = the FDA-approved NDO dose

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Sacral Neuromodulation

• MoA → modifies the voiding reflex — stimulation of the S3 afferent nerve

2-stage procedure

1. Stage 1 → insertion of the electrode at the S3 root, test for 2–4 weeks; if symptoms improved →
   • S3 foramen → ~9 cm from the coccyx tip, level with the inferior sacroiliac joints (11 cm is an anal-verge distance; 13 cm from the coccyx lands near S2 or S1)
   • No preclinical factor (incl. urodynamics) predicts response → trial stimulation through a percutaneous or temporary lead is the best predictor of long-term response
2. Stage 2 → connection of the electrode to a subcutaneous generator

How to know if placement is accurate

• S3 → bellows = levator contraction · the great toe is ipsilateral · pulling sensation in the rectum, scrotum or vagina
• Sensation → S3 and S4 both give perianal tapping · S2 gives sensation several cm from the anal canal
• S2 → also gluteal contraction, leg rotation, foot rotation, heel rotation, calf cramping, buttock sensation → move the lead one foramen lower to S3 and re-test — changing depth won't help
• S4 → move one foramen up to S3 · switch to the contralateral side only if the ipsilateral S3 response is inadequate

Complications

• Pain → most common reason for reoperation and the leading adverse event (15% at 12 months)
  • Revision for an adverse event in 33% → includes relocating the generator for pocket-site pain
• Generator-site pain → turn the device off:
  • Pain persists → pocket-related (infection, waistline location, pocket too tight or too loose, seroma, erosion) → needs surgery, not reprogramming
  • Pain disappears → output-related → often fixed without surgery:
    • Switch unipolar → bipolar programming, or reprogram around a connector fluid leak (burning)
    • Revision only for intolerable symptoms
• Device infection (~3%) → pain, erythema, swelling or drainage over the generator — even if afebrile with normal labs
  • Remove generator + lead (biofilm contaminates the lead) · never reimplant at the same sitting
  • Reattempt only after complete healing, ≥ 6 weeks later
• Overall surgical removal → 8.5–18% of implanted patients

EAU 16 (2025)

• EAU 16 (2025) Strong: "Consider sacral neuromodulation in selected neuro-urological patients" (LE 1b) — MS with NDO are often good responders.
• MRI is no longer a barrier — current generators/leads are 1.5-T and 3-T conditional.
• SNM is not FDA-approved for neurogenic bladder (off-label) despite its efficacy — RCT success 76% on vs 42% off.
  • Exam answer: SNM, while an option, is not recommended in a known neurologic condition · after onabotulinumtoxinA, consider it only once an elevated residual has been ruled out

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Percutaneous Tibial Nerve Stimulation

• Insertion 5 cm cephalad to the medial malleolus and 2 cm posterior to the tibia
  • Exam answer: about 3–4 cm cephalad to the medial malleolus
• Stimulates S3 through the tibial nerve
  • Tibial nerve = branch of the sciatic nerve (L4–S3 fibers) → cross-talk with the sacral fibers to the bladder
• Proper placement → patient feels sensation at the bottom of the foot
  • = tickling of the sole (afferent) + great-toe flexion (efferent)
• Third-line OAB therapy (2019 AUA/SUFU)

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Polyuria

• Polyuria = > 40 mL/kg
• Nocturnal polyuria = 33% of the volume at night (NPI > 33%)

Evaluation

• Hx (DM, OSA, neuro) + physical + FVC (frequency-volume chart)

Click the algorithm to open it full size.

• Global polyuria (24-h output > 40 mL/kg) with NPI < 33% → overnight water deprivation test — not alpha-blockers or antimuscarinics (neither helps global polyuria)
  • Osmolality cutoff is 800 mOsm/kg; the renal concentrating capacity test is the diabetes insipidus workup

Treatment for nocturnal polyuria (NPI)

• Control the underlying cause
• Desmopressin — watch for hyponatremia
  • Contraindicated in:
    • CrCl < 50
    • Hyponatremia
    • vWD

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Spinal Shock

• Decreased excitability of cord segments at and below the lesion → areflexic, acontractile bladder; urinary retention is the rule
  • e.g. 1 week after SCI with an umbilical (T10) sensory level → large-capacity, low-pressure bladder in retention → catheterization required
• Duration → 6–12 weeks in complete suprasacral lesions; may last 1–2 years
  • So at 4 weeks spinal shock still persists → UDS shows the spinal-shock picture below
• Resolution → begins with return of the bulbocavernosus reflex, alongside return of lower-limb DTRs
• First UDS within 3 months of SCI (EAU); repeat after spinal shock resolves
• Bladder management meanwhile → CIC preferred (keep storage pressure as low as achievable)
• Do not perform irreversible interventions based on symptoms during this period

Urodynamics during spinal shock:

• Detrusor areflexia; radiologically a smooth-contoured bladder without trabeculation
• Synergic smooth sphincter; closed, competent bladder neck
• Reduced but still synergic external sphincter tone — no voluntary control, and the guarding reflex is absent
  • Maximum urethral closure pressure is lower than normal but maintained at the external sphincter zone
• Hypercompliance
• Absent sensation

Expected urodynamic findings by lesion:

• Vertebral level ≠ cord segment level — the sacral cord begins at about T12–L1 and ends in the cauda equina at about the L2 vertebral level
  • So a complete SCI at vertebral L2 is a sacral cord injury → competent bladder neck, but hypocontractile detrusor and no volitional external sphincter control
• Complete lesions above the sacral cord → usually DO + smooth sphincter synergy + striated sphincter dyssynergia
  • e.g. T8 SCI after spinal shock → DO, smooth sphincter synergia (T8 is below the sympathetic outflow), absent guarding reflex
  • Smooth sphincter dyssynergia can occur with SCI above T7 (T6 vertebral level) — the above-T6 row

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Radical Pelvic Surgery

The inferior hypogastric plexus, lying alongside the rectum and vagina, is the structure at risk.

Injury is permanent in 15–20%.

• Presentation — a combined storage and emptying failure: inability to empty, plus stress incontinence.
  • Permanent pattern = detrusor areflexia + stress incontinence — more obvious in women, as prostatic bulk masks the same urethral closure deficit in men
• Urodynamics — impaired detrusor contractility or areflexia · open smooth sphincter · fixed external sphincter (loss of voluntary control, obstructing) · reduced compliance, though it may be normal.
  • Persistent pattern after APR, low anterior resection or radical hysterectomy → compliance is usually decreased (fixed striated tone keeps raising outlet resistance → poorly compliant bladder)
  • The open smooth sphincter shows as an incompetent bladder neck
• Recovery takes 6–12 months. Avoid early intervention such as TURP, which can worsen the incontinence. Treatment is CIC.
  • Most post-APR dysfunction is transient → no prostatectomy unless clear outlet obstruction is proven
  • Retention with an acontractile detrusor after APR → continue CIC even with an enlarged prostate — TURP or Rezum risks incontinence (denervated bladder neck and membranous urethra)
    • Tamsulosin and finasteride don't help — the retention is from absent detrusor contraction, not BOO
    • End-fill Pdet 15 cmH₂O at 350 mL = mild compliance loss → upper tracts not at risk
• Mechanisms:
  • Denervation/decentralization
    • Detrusor areflexia after APR = injury to the pelvic nerves (nervi erigentes) — the preganglionic S2–S4 parasympathetic outflow running beside the rectum → bladder decentralized but not completely denervated (intramural ganglia survive)
  • Tethering or encasement of nerves in scar
  • Direct bladder or urethral trauma
  • Bladder devascularization.

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Storage Pressure & the Upper Tract

• DLPP = lowest Pdet at which leakage occurs without a detrusor contraction or raised abdominal pressure
• DLPP > 40 cmH₂O → hydronephrosis or VUR in 85%
  • A cut-off of 20 cmH₂O is more sensitive (91.5%) for upper tract damage
  • Aim for as low a pressure as reasonably achievable, well < 40 cmH₂O — the 40 figure is not a validated "safe" line
• Impaired compliance → < 20 mL/cmH₂O (no consistent definition; 10–20 range used)
• Continent after onabotulinumtoxinA ≠ safe storage pressure → repeat UDS now; a DLPP > 40 cmH₂O reflects lost compliance and raises upper tract risk

VUR in neurogenic bladder

• Incidence 17–25% in SCI; more common with suprasacral injury
• Driven by high storage/voiding pressures + infection — no discrete VUR pressure threshold is stated
• Best initial treatment → normalize urodynamics (lower storage pressure, lower outlet resistance) before considering surgical correction
• Upper tract deterioration 51% with urethral catheters vs lower with voiding/CIC
  • Chronically catheterized (e.g., tetraplegic) with new hydronephrosis → intravesical onabotulinumtoxinA (or antimuscarinics / β₃ agonists) best preserves the upper tracts → suppresses DO, maintains compliance

Risk factors for upper-tract damage in SCI:

• Bladder overdistension
• Loss of compliance
• High DLPP
• DSD.

Complications:

• VUR
• Infection (UTI, pyelonephritis)
• Stones, upper and lower
• Renal failure.

Six potentially dangerous UDS findings (usually need intervention):

• Detrusor–external sphincter dyssynergia
• Detrusor–internal sphincter dyssynergia
• Impaired compliance
• DLPP > 40 cmH₂O
• High-pressure DO throughout filling
• Poor emptying with high storage pressures.

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Bladder Augmentation

• Aim → low-pressure reservoir; improves compliance, abolishes/reduces NDO
• EAU (Strong): "Offer bladder augmentation in low bladder compliance and/or refractory neurogenic detrusor overactivity" — only when all less-invasive methods have failed
• Supratrigonal cystectomy → indicated with a severely thick, fibrotic bladder wall; CIC may become necessary
• Caution with pre-operative renal scars → metabolic acidosis
• Auto-augmentation (detrusor myectomy) → low surgical burden, does not preclude further intervention
• Transplantation into a defunctionalized bladder succeeds if capacity is > 100 mL and voiding pressure < 100 cmH₂O
• Extensive pelvic irradiation → augment with transverse colon — the colon segment least likely to have been irradiated
  • Irradiated bowel → anastomotic leaks, ureteroenteric strictures, poorly functioning reservoir
• Right colic artery most often arises directly from the SMA → can limit mobilizing the cecum/right colon into the pelvis; sometimes must be divided

Mitrofanoff appendicovesicostomy

• Flap valve → supple, small-caliber tube in a submucosal tunnel with firm muscular backing; rising reservoir pressure compresses it shut
  • Tunnel ≥ 2 cm · channel should accept a 10–14 Fr catheter
  • Flap valve grows more competent with filling; the same filling pressure tends to efface a nipple valve
• Appendiceal artery (must be preserved) → ileal branch of the ileocecal artery (an SMA branch) · anterior/posterior cecal branches → supply the cecum

Long-term complications

• Lifelong follow-up is essential — stabilizes renal function and prevents anatomical deterioration, but morbidity is significant
• Any bowel-segment reconstruction → annual history, physical, metabolic panel (electrolytes/acid-base), renal function, upper tract imaging (AUA/SUFU)

Incontinence after augmentation

• Years later, despite antimuscarinics + more frequent CIC, with negative urinalysis and normal ultrasound → videourodynamics next, not cystoscopy → assesses DO, compliance and outlet competence
• Stress incontinence on videourodynamics → outlet-enhancing procedure (e.g., sling) · DO → onabotulinumtoxinA into the native bladder or augment revision

Augment perforation

• Spontaneous perforation → most likely ischemic necrosis of the bowel segment from chronic overdistention; median ~4 years → immediate surgical repair
• Most occur in myelodysplasia → present late (impaired sensation) · risk doubles after bladder outlet procedures · recurrence up to 42%

Augment stones

• Driven by poor emptying + mucus; mostly struvite from chronic bacteriuria
• Abdominal-wall stoma → risk of incomplete emptying → best risk reduction = daily bladder irrigation + catheterization per urethra
• No proven benefit: antibiotics (may transiently lower bacteriuria, not stone risk) · thiazides · potassium citrate

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Follow-up & Surveillance

No high-level evidence; intervals are largely unspecified. Flagged as such rather than invented.

EAU 16 (2025)

• Interval between baseline and control investigations should not exceed 1–2 years; much shorter in high-risk
• High risk → upper tract ultrasound every 6 months
• High risk → physical exam + urine labs yearly
• UDS → mandatory baseline in high-risk, repeated at regular intervals — no numeric interval given
• Any significant clinical change → further specialized investigation (Strong)

AUA/SUFU 2021

• Low risk → no routine yearly surveillance unless symptoms, imaging, or renal function change
• Moderate / high risk → yearly history, physical, symptom check + yearly renal function + upper tract imaging every 1–2 years
• UDS → repeat for a change of symptoms or when clinically indicated — no fixed interval
• Stone history or high stone risk → imaging every 1–2 years

Renal function (GFR) estimate

• Low muscle mass (e.g., neonates with spina bifida) → serum cystatin C is the best GFR estimate — creatinine is made only by muscle → falsely low → overestimates renal function
• Neurogenic bladder children → cystatin C is more sensitive, not more specific than creatinine
  • Healthy children or non-neurogenic voiding dysfunction → normal muscle mass → similar sensitivity