CUA: Neurogenic Lower Urinary Tract Dysfunction (2019)

See Original Guideline

Definitions

• Definition of neurogenic lower urinary tract dysfunction (NLUTD): lower urinary tract dysfunction due to disturbance of the neurological control mechanism
  • This broad definition is used to describe a multitude of conditions of varying severity

Causes of NLUTD

• Neurological conditions commonly associated with LUT dysfunction (3):
  1. Multiple sclerosis (MS)
  2. Spina bifida (SB)/myelomeningocele
  3. Spinal cord injury (SCI)
• Other causes include (9):
  1. Parkinson’s disease
  2. Cerebrovascular accidents
  3. Traumatic brain injury
  4. Brain or spinal cord tumour
  5. Cauda equina syndrome
  6. Transverse myelitis
  7. Multisystem atrophy
  8. Pelvic nerve injury
  9. Diabetes

Classification

• Based on whether the primary lesion is (3):
  1. Suprapontine
  2. Spinal (infrapontine-suprasacral)
  3. Sacral/infrasacral
     • These systems provide a general idea of how the lower urinary tract is likely to behave in SCI patients with more complete injuries

Location of lesion	History	Ultrasound	Urodynamics	Sphincter
Suprapontine	Predominantly storage symptoms	Insignificant PVR	Detrusor overactivity	Normal
Spinal (infrapontine-suprasacral)	Storage and voiding symptoms	Usually elevated PVR	Detrusor overactivity Detrusor sphincter dyssynergia (DSD) Lesions between brainstem and T6 may have autonomic dysreflexia and smooth sphincter dyssynergia	Overactive
Sacral/infrasacral (below S2)	Predominantly voiding symptoms	Usually elevated PVR	Underactive (hypocontractile or acontractile) detrusor	Normal or underactive

Risk classification for urological morbidity in NLUTD

Risk group	Description
High-risk	Underlying high-risk disease (SCI, spina bifida, advanced MS) OR select other neurogenic diseases with evidence of significant urological complications or morbidity With any high-risk feature(4): Bladder management technique: Valsalva/crede/reflexive voiding; or UDS: Known high-risk features on UDS without confirmation of appropriate attenuation after treatment (DSD, NDO, impaired compliance [<20 ml/cm H2O], DLPP >40 cm H2O, vesico-ureteral reflex); or Imaging: new/worsening renal imaging (hydronephrosis, atrophy, scarring); or Renal function: new/worsening renal insufficiency
Moderate-risk	Underlying high-risk disease (SCI, spina bifida, advanced MS) OR select other neurogenic diseases with evidence of significant urological complications or morbidity With ANY feature such as: Bladder management technique: clean intermittent catheterization, spontaneous voiding, indwelling catheter or UDS: Prior history of high-risk features on UDS (see above) that have been appropriately optimized; or Imaging: no significant change or Renal function: no significant change
Low-risk	No evidence of high-risk disease/features on initial evaluation

• Other indicators of potentially higher risk of urological morbidity in NLUTD patients (3):
  • Imaging demonstrating
    • Stone disease
    • Abnormal bladder morphology
  • SCI patients with autonomic dysreflexia associated with bladder dysfunction
• Patients with SCI, spina bifida, or advanced MS without high-risk features are considered moderate-risk

Urologic Complications of NLUTD

• SIRI OU

1. Stones
2. Infection
3. Vesicoureteral Reflux
4. Incontinence and urethral damage
5. Ureteric Obstruction
6. Upper urinary tract deterioration (UUTD)

Infection

• Sepsis
• Urinary Tract Infections
  • Pathogens
    • The Enterobacteriaceae family represents the most commonly isolated organism in the NLUTD population, with E.coli comprising 50% of all strains.
      • This is a lower than non-neurogenic UTIs, partly explained by the increased incidence of Pseudomonas, Acinetobacter, Enterococcus, and fungi such as Candida
  • Diagnosis and Evaluation
    • The accepted definition of UTI in persons with NLUTD requires the presence of (3):
      1. Leukocyturia
         • Consensus cut-off for leukocyturia is 100 leukocytes/mL or any leukocyte esterase activity on dipstick
      2. Bacteriuria
         • No evidence-based cut-off values for bacteriuria; generally accepted guidelines:
           • Any detectable concentration for suprapubic aspirate
           • >102 cfu/ml (clean catheterized sample)
           • >104 cfu/ml (clean voided)
      3. Clinical symptoms
         • Signs and symptoms of UTI in SCI
           1. Fever
           2. Cloudy urine
           3. Malodorous urine
           4. Dysuria
           5. Urinary incontinence/failure of control or leaking around catheter
           6. Increased spasticity
           7. Malaise
           8. Lethargy or sense of unease
           9. Back pain
           10. Bladder pain
           11. Autonomic dysreflexia
    • Urine cultures should always be obtained prior to antimicrobial therapy due to the increased risk of nosocomial and multidrug-resistant microorganisms
  • Management
    • 7-day course of antimicrobials is recommended for patients with prompt clinical response and 10–14 days for those with significant infection or a delayed response
    • Prevention of UTI
      • Bladder management
        • When possible, CIC should be used over other methods
          • Risk of UTI: Transurethral indwelling catheterization carries >5x risk of recurrent UTIs when compared to suprapubic catheterization and CIC. Risk of UTI comparable between suprapubic, condom catheter, and CIC.
            • Condom catheters are effective and safe in select NLUTD patients (low PVRs and bladder storage pressures) but are significantly associated with Pseudomonas and Klebsiella bacteriuria and an incidence of UTI comparable to CIC.
          • Risk of stones: CIC and condom catheter lower risk than indwelling transurethral or suprapubic
        • Indwelling catheters should be changed every 2–4 weeks, with monthly being the most common interval
      • Antimicrobial prophylaxis
        • Routine antimicrobial prophylaxis for NLUTD UTI is not recommended for most patients
    • Screening and treatment of asymptomatic bacteriuria in persons with NLUTD should be avoided as it promotes microbe resistance and can increase the likelihood of symptomatic UTI
      • Exceptions to treat asymptomatic bacteriuria include pregnancy and prior to urological interventions where mucosal bleeding is expected

Ureteric obstruction

• In some cases, high storage pressure results in prolonged compression of the ureteric orifices, leading to obstructed urine outlet during a prolonged period and, consequently, renal damage.

Incontinence and urethral damage

• Urinary incontinence is commonly observed in patients with neurogenic bladder
• Freedom from indwelling catheters is a priority in the management of neurogenic bladder
• Reports on urethral complications from indwelling catheters are scarce, but more common than for patients on CIC
• Complications related to an indwelling catheter include:
  • Males:
    • Urethral strictures
    • False passages
    • Diverticuli
    • Periurethral abscesses
    • Urethrocutaneous fistula
    • Iatrogenic traumatic hypospadias
  • Females:
    • Urethral dilation
    • Urethral erosion
    • Urethral destruction
  • Potentially serious secondary consequences, such osteitis pubis or non-healing decubiti ulcers can occur from continued urinary leakage
• Urethral urinary leakage (catheter bypassing) should be addressed by (3):

1. Ruling out bladder stones and infection
2. Avoiding increasing the catheter size
3. Aggressively treating with oral medications or onabotulinumtoxinA injections

• Patients with indwelling urethral catheters should be offered conversion to a suprapubic catheter in the setting of significant urethral damage and ideally before the urethra has been irreversibly damaged and there is a risk of stress incontinence.
• Sexuality is adversely affected. Side effects from medications and surgeries to treat urinary incontinence may also secondarily cause sexual dysfunction

Upper urinary tract deterioration (UUTD)

• CKD rates vary from 0.6–3.3% for MS, 1.3–5.6% for SCI, and up to 8% for SB patients, which is higher than that of the general population
• The pathophysiology of CKD in neurogenic bladder is not well-understood
• Potential risk factors for UUTD in NLUTD (5):
  1. Bladder outlet obstruction
  2. Ureteric obstruction
  3. UTIs
  4. Stones
  5. Persistent high intravesical pressures (most important)
     • High pressures could be from NDO, poor bladder compliance, DSD, ureteric obstruction, or a combination, and can cause subsequent VUR and UUTD.
       • VUR may appear as hydroureteronephrosis on imaging.
     • Symptoms of high intravesical pressure (e.g., leakage between CIC) are rarely present and UDS are required to properly identify it
     • Since VUR and hydroureteronephrosis may be manifestations of high bladder pressures in neurogenic bladder, treatment should focus first on ensuring low storage pressure.
       • Anti-reflux surgery or double-J ureteral stenting should be avoided in these cases.
• CIC is superior to chronic suprapubic or urethral catheterization for preserving bladder compliance
  • Despite the fact that patients with a chronic indwelling catheter have an empty bladder most the time, they still warrant follow-up for urological complications and hydronephrosis
• Overall, patients at higher risk of UUTD are SB, suprasacral SCI, and men with MS. Clinically stable MS patients have lower rates of UUTD
• Lifelong upper tract surveillance of UUTD is recommended
  • Renal function decline can occur up to 45 years after injury

Diagnosis and Evaluation

• Mandatory in all patients (3):
  1. History and physical exam
  2. Urinalysis
  3. PVR
• If SCI, SB, or advanced MS with specific features, should also have (3)
  1. Baseline UDS
  2. Renal ultrasound
  3. Measurement of renal function
     • SCI, SB, or advanced MS patients are at higher risk of serious sequela from bladder dysfunction
     • Selected patients with NLUTD due to other diagnoses may undergo these investigations when referred for specific urological concerns such as:
       1. Clinically significant PVR
       2. Frequent UTI
       3. Bothersome incontinence
       4. Use of catheters for bladder management
       5. Known high-risk features
       6. Considering more invasive treatment options
• See Figure 2 (Initial investigations and risk stratification for neurogenic lower urinary tract dysfunction (NLUTD) patients) from Original Guideline

History and Physical Exam

• History
  • History of the neurological disease
    • SCI: Year and level/completeness of lesion (ASIA level), frequency of autonomic dysreflexia, level of spasticity, mobility/transfers
    • MS: Year and type of MS (primary progressive, secondary progressive, relapsing remitting), mobility level (or Expanded Disability Status Scale)
    • Spina bifida: Type (i.e., ambulatory lipomyelomeningocele), caregiver, VP shunt, latex allergy, prior reconstructive surgery
  • Bladder management history
    • Use of catheters (CIC, indwelling [size and frequency of changes], condom), crede/straining/reflexive bladder emptying, bladder medications, and prior urological surgery history
  • Storage & voiding symptoms
    • Storage: frequency, urgency, nocturia, incontinence
    • Voiding: weak stream, intermittency, straining, incomplete emptying
  • NLUTD complications
    • UTIs (symptoms, culture status, associated sepsis/fever, response to antibiotics/antibiotic resistance, triggers, hospital admissions)
    • Sequela of incontinence (skin breakdown, ulcers, pad usage, bother)
    • Bladder or renal stone disease
    • Catheter complications (urethral loss in women; urethral erosion, false passages, strictures in men, encrustation/sediment)
    • Renal function deterioration (imaging results, renal function)
  • Review of relevant systems
    • Bowel function
    • Sexual function
    • Coexisting non-NLUTD dysfunction (prostatic enlargement, stress incontinence)
    • Gross hematuria
    • Gynecological/pregnancy history
    • Genitourinary/pelvic pain
    • Motor abilities (hand function, ability to transfer)
    • Cognitive function
    • Support systems/caregivers
  • General components
    • Allergies, medications, alcohol/drug use/smoking
• Physical Exam
  • General
    • Body habitus
  • Abdomen
  • Genitals
  • Rectal exam
  • May include a focused screening neurological exam (such as lower limb sensory, motor, and reflex function), especially when there is a suspicion of NLUTD without a confirmed neurological disease.

Labs

• Urinalysis
  • Rule out infection, microscopic hematuria, and unexpected pyuria or proteinuria
    • Proteinuria is a marker of renal damage which can be screened for and warrants a nephrology referral
• Renal function
  • Serum creatinine
    • can be used to assess renal function
    • Has been criticized as a reliable early marker of renal function in patients with NLUTD, as patients often have muscle atrophy from disuse and denervation.
  • Renography and 24-hour urine creatinine clearance may be preferred to sequentially assess renal function in neurogenic bladder patients.

Imaging

• Renal and bladder imaging
  • Necessary to identify (4):
    1. Hydronephrosis (a late but potentially reversible sign of bladder dysfunction in NLUTD)
    2. Renal/bladder stone disease
    3. Abnormal bladder morphology (for example, thickened bladder wall, diverticula)
    4. Renal atrophy and degree of scarring

Other

PVR

• To address potential UTI risk and overflow incontinence; may prompt screening for upper tract deterioration
• In the non-NLUTD population, a value >300 mL is used to define chronic urinary retention.
• The need to treat PVR should be based on patient symptoms rather than an absolute number.

Urodynamics

• Gold standard for evaluating NLUTD
• Necessary due to the absence of normal lower urinary tract sensation and the poor ability of symptoms to predict high-risk features.
• VideoUDS are preferred, as the additional correlation with imaging allows assessment of (3):
  1. VUR
  2. Abnormal bladder morphology
  3. Behaviour of the urinary sphincters during voiding
  • The availability of videoUDS is not universal; a voiding cystogram is an acceptable alternative in some cases
• Urodynamic findings associated with increased risk of urological complications (such as renal dysfunction, urinary infections, and incontinence) (4):
  1. Neurogenic detrusor overactivity (NDO)
     • Duration of the NDO contraction may predict renal deterioration
  2. Impaired compliance
  3. Reduced bladder capacity
  4. High detrusor leak point pressure (DLPP)
     • DLPP: defined as the lowest detrusor pressure at which urine leaks from the bladder in the absence of a detrusor contraction or increased abdominal straining
       • A DLPP of >40 cm H2O has traditionally been cited as the cutoff above which a patient has a high risk of renal deterioration; however, this is based on a historical study of children with SB, and may not be applicable to adult NLUTD.
       • As DLPP increases, so too does the risk of renal dysfunction due to an increased resting pressure in the bladder being transmitted to the kidneys.
       • If a high DLPP only occurs at a volume greater than the usual capacity during the normal daily voiding pattern, then this DLPP may not be physiologically relevant.
       • A low DLPP maintains low pressure drainage from the kidneys, however, this often results in urinary incontinence.

Voiding diaries

• Should be considered for all patients
• Allows the patient to self-reflect on their urinary habits and the physician to measure changes over time in a non-invasive manner and interpret urodynamic findings in the context of the patient’s day-to-day urinary patterns.

Validated questionnaires

• Optional
• Generally used for research purposes in the NLUTD population

Cystoscopy

• Should be reserved for situations where there is a clinical indication to assess either the urethra or bladder (such as suspicion of urethral strictures or false passages, bladder stones, or bladder cancer)

Timing

• Depends on the severity of symptoms, underlying risk of serious urological complications, and the etiology of the neurogenic bladder.
  • SB and SCI have a significant risk of renal dysfunction and are acquired at birth (SB) or often as young adults (SCI); this makes patients particularly susceptible to renal dysfunction in their lifetime. This contrasts with slowly progressive diseases, such as relapsing-remitting MS, or the predominately elderly population with Parkinson’s disease or dementia.
  • The urological evaluation of a patient with a newly acquired SCI should occur within 3–6 months of the SCI.
    • Significant bladder dysfunction can appear early after SCI. Efforts should made to assess patients with urological complications or concerns as soon as possible after the acute SCI.

Management

• The treating clinician should identify patients as either being high-, moderate-, or low-risk, offer the patient appropriate initial therapy, and consider a urological surveillance program as outlined below

Assisted bladder drainage

• CIC or condom-catheter preferred
  1. Non-catheter mechanisms
     • Rely on involuntary emptying that is either induced or spontaneous
     • Some bladder methods (reflex triggering and Valsalva or Credé manoeuvres) should be strongly discouraged due their associated risk of upper tract injury.
       • The Crede manoeuvre (external pressure on the bladder) and Valsalva voiding induces bladder drainage via an increase in abdominal pressure that can overcome the external urethral sphincter. It can be inefficient and risk high pressures and cause hemorrhoids, hernias, and VUR.
     • Condom catheter drainage is often used to collect urine in these non-catheter methods
  2. Catheter mechanisms
     • Options (3): CIC (preferred), indwelling urethral and suprapubic catheter
       • CIC associated with reduced risk of infection, reduced risk of stones, and preservation of bladder compliance compared with indwelling urethral or SP catheter
     • Until evidence can confidently demonstrate that multiple use is as safe as single-use catheters, healthcare providers should advocate a single use of catheters in individuals with SCI.

Oral therapy

Options (2):

• Anticholinergics
• Beta-3 agonists

Anticholinergics

• First-line pharmacological treatment for patients with NLUTD
• Indications
  • Should be offered to people with urodynamic findings of NDO or those with SCI and symptoms of overactive bladder (OAB)
  • Should be considered whether or not patients are using assisted bladder drainage.
    • Absence of its usage has been shown to be a risk factor for upper tract deterioration
• Use improves OAB symptoms and NDO, decreases urgency urinary incontinence, and lowers detrusor pressures
• Do not alter the detrusor or abdominal leak point pressures since they do not act on the external urethral sphincter
• Studies that compared one medication to another (usually oxybutynin IR) did not reveal statistically significant differences. The optimal drug dosage was not identified.
• Supratherapeutic dosages may be considered according to tolerability but should be used cautiously.
• Combining antimuscarinics may be beneficial for patients who are refractory to dose escalation antimuscarinic monotherapy
• There is very limited data supporting the use of transdermal oxybutynin in NLUTD

Beta-3 adrenergic agonist

• Mirabegron may be a useful alternative to anticholinergics for patients with symptoms of OAB and NLUTD, but further evidence of urodynamic changes are needed in this population
  • There is very limited data supporting the use of mirabegron in NLUTD

Intravesical therapy

Options (2):

• Botox
• Oxybutynin

Botox

• Ona-botulinum toxin A injection (200 units) in the detrusor is an effective, minimally invasive treatment that can achieve continence, improve bladder function, and diminish NDO in individuals with SCI or MS who have an inadequate response to or are intolerant of an anticholinergic medication
• Abo-botulinum toxin A is also effective in NLUTD, with the optimal dose of 750 units
• Sustained efficacy in terms of reduced incontinence episodes, enhanced bladder function, as well as substantial improvements in key urodynamic parameters and QoL
• UTIs and large urine residual or urinary retention are the most frequent adverse events. Therefore, the likelihood of future need of CIC is increased

Oxybutynin by CIC

• A safe alternative approach to managing NDO and NLUTD in patients who are doing CIC; safe and effective short-term therapy in patients suffering from NDO who remain incontinent or are intolerant of oral anticholinergic medication
• Results in significant increase in bladder capacity
• This approach avoids systemic side effects compared to oral oxybutynin

Neural stimulation and neuromodulation therapy

• Current data supporting the use of sacral neuromodulation (SNM) and peripheral tibial nerve stimulation (PTNS) are limited; remains unclear which subgroups of neurogenic voiding dysfunction and which underlying neurological disease will respond best to these different therapies.
  1. SNM could be considered for the treatment of NDO or non-obstructive urinary retention in carefully selected individuals with NLUTD, as it can be a safe and effective option. It should be preceded by an adequate testing phase and may not be a good alternative to decrease detrusor pressures or improve bladder compliance.
  2. PTNS can be effective in NLUTD resulting from MS, but requires initial frequent weekly visits. PTNS appears to be well-tolerated and effective in small studies, with minimal reported adverse events, mainly mild to moderate pain at the puncture site
• Dorsal rhizotomy (sacral deafferentation S2-S4/5) and sacral anterior root stimulation by an implantable device can achieve safe storage detrusor pressure and voluntary emptying of bladder and bowel in patients with complete SCI. Furthermore, it diminishes autonomic dysreflexia. This technique has good variable success rates in specialized centres, but comes with long-term complications and a very high rate of surgical revisions

Surgical management of LUTD

Indications

• When conservative measures, medical therapy, and minimally invasive interventions alone fail to achieve the objectives of:
  1. Protecting kidney function and mitigating autonomic dysreflexia by maintaining bladder storage at safely low pressures
  2. Ensuring adequate and timely bladder emptying to mitigate the risks of overflow incontinence, recurrent UTIs, bladder stones, and kidney damage
  3. Preventing the adverse effects of incontinence (e.g., dermatitis)
  4. Improving QoL by relieving bothersome symptoms of OAB and incontinence.

Options (5):

1. Bladder augmentation
2. Catherizable channel
3. External urethral sphincterotomy
4. Bladder neck closure with continent or incontinent channel
5. Incontinent diversion

Bladder augmentation

• Indications (2):
  1. Reduced compliance or NDO refractory to all other non-surgical treatments
  2. Reduced bladder capacity necessitating an indwelling catheter or CIC to be done too frequently

Catheterizable channels and continent cutaneous urinary diversion

• In cases where urethral catheterization is precluded, a catheterizable channel may be offered after careful consideration and multidisciplinary evaluation.
• The most commonly used tube is the appendix (Mitrofanoff appendicovesicostomy). Where the appendix is unavailable or unsatisfactory (must be 8–10 cm in length for adult patients), a segment of terminal ileum can be employed (Yang-Monti or Casale technique), albeit with slightly poorer outcomes.

External urethral sphincterotomy

• Contraindications (4):
  1. Female
  2. Unable to wear condom catheter
  3. Detrusor underactivity
  4. Patient wants to maintain fertility

Bladder neck closure combined with a continent or incontinent channel

• Indicated in cases of severe outlet damage

Incontinent urinary diversion (ileovesicostomy and ileal conduit)

• Last resort in managing the complications of NLUTD
• The bladder should be removed at the time of surgery to reduce the risks of pyocystis, chronic symptomatic cystitis, and malignancy

Surveillance studies for NLUTD patients in the community setting

Risk group	Suggested surveillance strategy
High/moderate-risk	Urological evaluation (history and physical examination): yearly Imaging: yearly Renal function: yearly UDS High-risk: yearly Moderate-risk: every 2-5 years VideoUDS or a cystogram should be performed in patients where further knowledge of the urinary tract anatomy is needed
Low-risk	Evaluation with GP, physiatrist, neurologist, or urologist (history and physical examination with attention to general neuro-urological assessment outlined previously): yearly Imaging: yearly in select cases Re-referral for urological evaluation as suggested by: New-onset/worsening incontinence; or New frequent urinary infections; or New-onset catheter issues (for example, penile/urethral erosions, encrustation, bypassing) Renal-bladder imaging changes suggestive of upper or lower urinary tract deterioration (hydronephrosis, new clinically significant PVR, or significant increase in PVR) or new stone disease

• When children with SB transition to adulthood, they should be followed by an adult urologist as soon as it is practical to transition them.
• We support the use of cystoscopy for the assessment of suspected urethral or bladder pathology. We do not support routine surveillance cystoscopy for bladder cancer screening in NLUTD with or without augmentation cystoplasty

Autonomic Dysreflexia

Causes

• Typically occurs in patients with an injury at level T6 or above
• Caused by an exaggerated sympathetic nervous system response triggered by either a noxious or non-noxious stimulus originating below the level of the SCI

Diagnosis and Evaluation

• Signs and Symptoms (5):
  1. Acute onset hypertension
  2. Reflex bradycardia
  3. Sweating
  4. Headache
  5. Flushing above the level of the spinal cord lesion
  • If BP is > 120 mmHg and patient is symptomatic, presumed autonomic dysreflexia is present
    • The normal BP in para and quadriplegics is low, usually 90-110 mmHg systolic. Elevation with autonomic dysreflexia symptoms classically begin with a 20 mmHg rise above baseline, well within normal range for a neurologic intact individual.

Management

• An emergency in patients who have had a spinal cord injury
• Initial therapy should focus on the removal of inciting factors (e.g. emptying of the bladder and removal of all urodynamic catheters in an SCI patient experiencing autonomic dysreflexia during UDS)
• If symptoms persist and systolic pressure remains
  • < 150 mmHg, then evaluation for and treatment of fecal impaction, the second most common cause of AD after the bladder, is recommended.
  • > 150 mmHg after bladder emptying and catheter removal, then use of a rapid-onset, short-acting antihypertensive is recommended while the cause of AD is investigated.
    • Nitroglycerin
      • First-line drugs in the outpatient setting
        • Nitropaste 2% (preferred)
          • Applied 0.5-1 inch above the level of the lesion (vasoconstriction occurs below the level of the lesion and may interfere with the drugs absorption)
          • Preferred due to its ability to be wiped free if rebound hypotension occurs
        • Nitroglycerin 0.4 mg sublingually
      • Must make sure the patient has not used a PDE-5 inhibitor for erectile dysfunction in the past 24 hours, due to concern for rebound hypotension.
        • If a sildenafil agent has been used within 24 hours, Captopril 25 mg chewed or given sublingually becomes the drug of choice.
    • Nifedipine
      • Used to be recommended as primary treatment or prophylactic agent for AD
      • Because of several adverse, rebound hypotensive crisis resulting in stroke or MI after its use, the Joint commission for treatment of High Blood Pressure and National Spinal Cord Injury committees have discouraged its use and it has been banned for treatment or prevention of autonomic dysreflexia in some hospitals
• If the blood pressure remains elevated and does not respond to oral therapy I.V. hydralazine is an option
  • Patient will require hospital admission with further monitoring as BP may be quite labile after use of I.V. hydralazine with both hypotension and/or rebound hypertension
• In the outpatient setting, when autonomic dysreflexia is triggered and successfully treated, patient should be monitored for resumption of hypertension for a minimum of two hours.
  • If AD recurs, hospitalization with monitoring for 24 hours is recommended, if not, the patient can be discharged from the outpatient setting.

Prevention

• Recommendations to prevent autonomic dysreflexia preceding cystoscopy or urodynamic evaluations
  • Terazosin 5 mg the night before the exam
  • Prazosin 1 mg the night before the exam
  • Tamsulosin 0.8 mg the night before the exam
  • At the time of the exam place Nitropaste 2% .5 inch (if not on sildenafil)
  • Captopril 25 mg sublingually 10-15 minutes prior to exam.
• Recent data suggests that intravesical injection of onabotulintoxinA decreases the frequency and severity of AD episodes.

Questions

1. List conditions associated with neurogenic lower urinary tract dysfunction.
2. What is the expected history, urodynamic findings, PVR, and sphincter activity based on the location of the spinal cord lesion?

Location of lesion	History	Ultrasound	Urodynamics	Sphincter
Suprapontine
Spinal (infrapontine-suprasacral)
Sacral/infrasacral

2. What are considered high-risk features related to NLUTD?
3. What are potential risk factors for upper urinary tract deterioration in patients with NLUTD?
4. What are potential imaging findings associated with high bladder pressures in neurogenic bladder?
5. What are potential complications of long-term indwelling catheterization?
6. What is the most common pathogen responsible for UTI in NLUTD?
7. What is signs and symptoms are required for a diagnosis of UTI in patients with NLUTD?
8. What are signs and symptoms of UTI in a patient with SCI?
9. What are potential complications of NLUTD?
10. What spinal cord injury level is associated with autonomic dysreflexia?
11. What are the mandatory investigations in patients with NLUTD?
12. When should the urological evaluation of a patient with newly acquired SCI take place?
13. What is the first-line pharmacological treatment for patients with NLUTD?
14. What is the second-line pharmacological treatment for patients with NLUTD?
15. What is a potential treatment option to treat NDO in NLUTD patients who are doing CIC?
16. What are the objectives of treatment of NLUTD?
17. What are the surgical options in the treatment of NLUTD?
18. What is the recommended surveillance in patients with NLUTD?

Answers

1. List conditions associated with neurogenic lower urinary tract dysfunction.
   1. Multiple sclerosis (MS)
   2. Spina bifida (SB)/myelomeningocele
   3. Spinal cord injury (SCI)
   4. Parkinson’s disease
   5. Cerebrovascular accidents
   6. Traumatic brain injury
   7. Brain or spinal cord tumour
   8. Cauda equina syndrome
   9. Transverse myelitis
   10. Multisystem atrophy
   11. Pelvic nerve injury
   12. Diabetes
2. What is the expected history, urodynamic findings, PVR, and sphincter activity based on the location of the spinal cord lesion?

Location of lesion	History	Ultrasound	Urodynamics	Sphincter
Suprapontine	Predominantly storage symptoms	Insignificant PVR	Detrusor overactivity	Normal
Spinal (infrapontine-suprasacral)	Storage and voiding symptoms	Usually elevated PVR	Detrusor overactivity, DSD, (lesions between brainstem and T6 may have smooth sphincter dyssynergia and autonaumic dysreflexia)	Overactive
Sacral/infrasacral	Predominantly voiding symptoms	Usually elevated PVR	Hypocontractile or acontractile detrusor	Normal or underactive

2. What are considered high-risk features related to NLUTD?
   1. Bladder management technique: Valsalva/crede/reflexive voiding
   2. Known high-risk features on UDS without confirmation of appropriate attenuation after treatment (DSD, NDO, impaired compliance [<20 ml/cmH2O], DLPP >40 cmH2O, vesico-ureteral reflex)
   3. New/worsening renal imaging (hydronephrosis, atrophy, scarring)
   4. New/worsening renal insufficiency
3. What are potential risk factors for upper urinary tract deterioration in patients with NLUTD?
   1. High bladder storage pressures
   2. Bladder outlet obstruction
   3. Ureteral obstruction
   4. UTI
   5. Stones
4. What are potential imaging findings associated with high bladder pressures in neurogenic bladder?
   1. VUR
   2. Hydronephrosis
   3. Thick-walled bladder
   4. Abnormal contour bladder
5. What are potential complications of long-term indwelling catheterization?
   • Men: urethral strictures, false passages, diverticuli, periurethral abscesses, urethrocutaneous fistula, and iatrogenic traumatic hypospadias
   • Women: urethral dilation, erosion, and potentially destruction
6. What is the most common pathogen responsible for UTI in NLUTD?
   • E. Coli
7. What is signs and symptoms are required for a diagnosis of UTI in patients with NLUTD?
   1. Leukocytosis
   2. Bacteruria
   3. Presence of symptoms
8. What are signs and symptoms of UTI in a patient with SCI?
   • Fever, urinary incontinence/failure of control or leaking around catheter, increased spasticity, malaise, lethargy or sense of unease, cloudy urine, malodorous urine, back pain, bladder pain, dysuria, and autonomic dysreflexia
9. What are potential complications of NLUTD?
   1. UUTD
   2. UTI
   3. Stones
   4. Sepsis
   5. Ureteric obstruction
   6. Vesicoureteric reflux
   7. Sequela of incontinence (skin breakdown, ulcers, pad usage, bother)
   8. Catheter complications
10. What spinal cord injury level is associated with autonomic dysreflexia?
    • Above T6
11. What are the mandatory investigations in patients with NLUTD?
    • History, physical exam, PVR, urinalysis in all patients
    • In patients with MS, SB, or SCI, all should have baseline UDS, renal imaging, renal function assessment
    • In patients with other neurological conditions but specific features should also have baseline UDS, renal imaging, and renal function assessment. These features include:
      1. Clinically significant PVR
      2. Frequent UTI
      3. Bothersome incontinence
      4. Use of catheters for bladder management
      5. Known high-risk features
      6. Considering more invasive treatment options
12. When should the urological evaluation of a patient with newly acquired SCI take place?
    • Within 3-6 months of injury
13. What is the first-line pharmacological treatment for patients with NLUTD?
    • Oral anti-cholinergics or beta-3-agonists
14. What is the second-line pharmacological treatment for patients with NLUTD?
    • Intradetrusor botox
15. What is a potential treatment option to treat NDO in NLUTD patients who are doing CIC?
    • Intravesical oxybutynin
16. What are the objectives of treatment of NLUTD?
    1. Prevent UUTD
    2. Ensuring adequate and timely bladder emptying to mitigate the risks of overflow incontinence, recurrent UTIs, bladder stones, and kidney damage
    3. Preventing the adverse effects of incontinence (e.g., dermatitis)
    4. Improving QoL by relieving bothersome symptoms of OAB and incontinence.
17. What are the surgical options in the treatment of NLUTD?
    1. Bladder augmentation
    2. Catheterizable channel and continent cutaneous diversion
    3. Incontinent urinary diversion
    4. External urinary sphincterotoy
    5. Bladder neck closure
18. What is the recommended surveillance in patients with NLUTD?
    1. High/moderate risk:
       1. Yearly urological evaluation (history and physical examination)
       2. Yearly renal-bladder imaging
       3. Yearly renal function assessment
       4. UDS
          • High-risk: yearly
          • Moderate-risk: every 2-5 years
    2. Low risk:
       1. Yearly evaluation with GP, physiatrist, neurologist, or urologist (history and physical examination with attention to general neuro-urological assessment outlined previously)
       2. Yearly renal imaging in select cases
       3. Re-referral for urological evaluation as suggested by:
          1. New-onset/worsening incontinence; or
          2. New frequent urinary infections; or
          3. New-onset catheter issues (for example, penile/urethral erosions, encrustation, bypassing)
          4. Renal-bladder imaging changes suggestive of upper or lower UT deterioration (hydronephrosis, new clinically significant PVR, or significant increase in PVR) or new stone disease

References

• Kavanagh, Alex, et al. "Canadian urological association guideline: diagnosis, management, and surveillance of neurogenic lower urinary tract dysfunction–full text." Canadian Urological Association Journal 13.6 (2019): E157.