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FUNCTIONAL: NEUROMUSCULAR DYSFUNCTION OF THE LOWER URINARY TRACT

See 2019 CUA NLUTD Guideline Notes

Classification of Neuromuscular Dysfunction of the Lower Urinary Tract

Classified based on location of disease: suprapontine, spinal, sacral/infrasacral

Location of lesion	History	PVR	Urodynamics	Sphincter
Suprapontine	Predominantly storage symptoms	Insignificant	Detrusor overactivity	Normal
Spinal (infrapontine-suprasacral)	Storage and voiding symptoms	Usually elevated	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	Underactive (hypocontractile or acontractile) detrusor	Normal or underactive

Lesions above the brainstem (suprapontine)

Typically (with rare exceptions) associated with:
1. Involuntary bladder contractions (detrusor overactivity) with
2. Coordinated sphincter function (smooth and striated sphincter synergy)
- Coordinated voiding is regulated by neurologic centers above the spinal cord
- Urinary incontinence may occur owing to the detrusor overactivity
Sensation and voluntary striated sphincter function are usually preserved, but sensation may be deficient or delayed
Detrusor areflexia may, however, occur, either initially or as a permanent dysfunction

Complete spinal cord lesions

After recovering from a period of spinal shock, typically associated with:
1. Absent sensation
2. Involuntary bladder contractions (detrusor overactivity)
3. Smooth sphincter synergy but striated sphincter dyssynergia.
  - A diagnosis of striated/detrusor sphincter dyssynergia (DSD) implies a neurologic lesion that interrupts the neural axis between the pontine-mesencephalic reticular formation and the sacral spinal cord
  - Lesions above spinal cord level T6-T8 (the upper level of the sympathetic outflow) may be associated with smooth sphincter dyssynergia and autonomic hyperreflexia.
Incontinence may occur owing to detrusor overactivity; however, the outlet obstruction resulting from striated sphincter dyssynergia can also cause urinary retention and overflow incontinence.

Disease below S2 (sacral)

Typically associated with:
1. Lack of involuntary bladder contractions
2. After the period of spinal shock resolves, persistent detrusor areflexia is the rule.
3. Various forms of decreased compliance during filling (usually resulting from bladder wall fibrosis) may occur and will depend on the type and extent of neurologic insult.
4. An open smooth sphincter area may result
5. Various types of striated sphincter dysfunction may occur, but commonly an injury in this area is associated with a residual/fixed resting striated sphincter tone (not the same as dyssynergia) and striated sphincter activity is not under voluntary control.

Interruption of peripheral reflex arc

Processes that affect or interrupt the peripheral reflex arc (coordination among spine, bladder, and urethra) may cause storage or emptying dysfunctions that resemble those seen after distal spinal cord or nerve root injury.
- Detrusor areflexia often develops, and low compliance may result.
- The smooth sphincter may be relatively incompetent, and the striated sphincter may exhibit fixed residual tone that does not voluntarily relax.
- True peripheral neuropathy can be motor or sensory, and, at least initially, the usual sequelae can be expected.

See Table 75-1 for Most Common Patterns of Voiding Dysfunction seen with Various Types of Neurogenic Disease or Injuary

Diseases at or above the brainstem: CVA, dementia, TBI, brain tumour, cerebellar ataxia, NPH, cerebral palsy, Parkinson’s, MSA

Cerebrovascular accident

After an initial acute CVA, urinary retention from detrusor areflexia often occurs
The most common long-term expression of LUT dysfunction after CVA is phasic detrusor overactivity

Urinary incontinence within 7 days of a stroke is a more powerful prognostic indicator for poor survival and functional dependence than a depressed level of consciousness

Sensation is variable but most typically intact, and thus the patient has urinary urgency and frequency with detrusor overactivity.
- The appropriate response to detrusor overactivity is to try to inhibit the involuntary bladder contraction by voluntarily and forcefully contracting the striated sphincter. If this can be accomplished, only urgency and frequency result; if not, the result is urgency urinary incontinence
  - Patients with lesions in only the basal ganglia or thalamus have normal sphincter function.
  - The majority of patients with involvement of the cerebral cortex and/or internal capsule are unable to forcefully contract the striated sphincter under these circumstances, and may therefore have incontinence
Possible mechanisms for the incontinence associated with involuntary bladder contractions in patients who have sustained a CVA (2):
1. Impaired striated sphincter control
2. Lack of appreciation of bladder filling and impending bladder contraction
In general, the smooth sphincter is unaffected after CVA and remains synergic; true detrusor striated sphincter dyssynergia does not occur in this situation, although pseudodyssynergia (electromyographic sphincter “flare” during filling cystometry that is secondary to attempted inhibition of an involuntary bladder contraction by voluntary contraction of the striated sphincter) has been found to occur
The guarding reflex in these patients usually remains intact
Detrusor hypocontractility or areflexia may rarely persist after CVA; poor flow rates and high residual urine volumes in a man with LUTS before CVA usually indicate prostatic obstruction. However, a full urodynamic evaluation to exclude detrusor overactivity with impaired contractility as a cause of symptoms is advisable before committing such a patient to surgical reduction of bladder outlet obstruction.
In the functional system of classification (see Pathophysiology and Classification of LUT Dysfunction Chapter Notes), the most common type of LUT dysfunction after CVA would be characterized as a failure to store secondary to detrusor overactivity, specifically involuntary bladder contractions. In the International Continence Society classification system, the dysfunction would most likely be classified as overactive neurogenic detrusor function, normal sensation, low capacity, normal compliance, and normal urethral closure function during storage; regarding voiding, the description would be normal detrusor activity and normal urethral function, assuming that no anatomic obstruction existed.
Management
- In the absence of coexisting significant bladder obstruction or significantly impaired contractility, is directed at decreasing bladder contractility and increasing bladder capacity

Dementia

Urinary dysfunction doe
- s not consistently accompany dementia; when voiding dysfunction occurs the result is typically incontinence. It is difficult to ascertain whether the pathophysiology and considerations are similar to those in the stroke patient or whether the incontinence reflects a situation in which the individual has simply lost the awareness of the desirability of voluntary urinary control.
Therapy that inhibits muscarinic brain receptors may be contraindicated in Alzheimer disease if current theories about its cause are valid (cortical cholinergic loss).

Traumatic brain injury

There may be an initial period of detrusor areflexia when LUT dysfunction occurs.
With lesions above the PMC, detrusor overactivity and coordinated sphincter function are the most frequent manifestations of chronic LUT dysfunction.
In patients who have more isolated brainstem injuries with involvement below the PMC, additional findings may include detrusor striated sphincter dyssynergia.

Brain tumour

When LUT dysfunction occurs, it usually consists of detrusor overactivity and urinary incontinence
- Urinary retention has also been described in patients with space-occupying lesions of the frontal cortex, in the absence of other associated remarkable neurologic deficits.
- Posterior fossa tumors is usually associated with retention or difficulty voiding is the rule; incontinence rarely reported.
In general, smooth and striated sphincters are synergic

Cerebellar ataxia

LUT dysfunction typically manifests with incontinence, usually detrusor overactivity and sphincter synergy.
Retention or high postvoid residual urine volume may occur as well. When present, impaired emptying is most commonly caused by detrusor areflexia, but it may also be associated with detrusor striated sphincter dyssynergia, presumably a result of spinal cord involvement

Normal-pressure hydrocephalus

A condition of progressive dementia and ataxia occurring in patients with normal cerebrospinal fluid pressure and distended cerebral ventricles, but with no passage of air over the cerebral convexities on pneumoencephalography.
When voiding dysfunction occurs, it is usually incontinence secondary to detrusor overactivity with synergic sphincters

Cerebral palsy

A nonprogressive injury of the brain that typically occurs during the first year of life (but potentially up to 3 years of age) and produces neuromuscular disability and/or specific symptom complexes of cerebral dysfunction. In general, the cause is infection or a period of hypoxia. Affected children exhibit delayed gross motor development, abnormal motor performance, altered muscle tone, abnormal posture, and exaggerated reflexes.
Most children and adults with only CP have urinary control and what seems to be normal storage and emptying.
Some individuals with CP exhibit significant phasic detrusor overactivity and coordinated sphincters dysfunction

Parkinson disease

A neurodegenerative disorder of unknown cause that affects primarily the dopaminergic neurons of the substantia nigra
- Classic symptoms include tremor, skeletal rigidity, and bradykinesia
- The gold standard for the diagnosis of PD is the neuropathologic examination
LUT dysfunction occurs in 35-70% of patients with PD
- It has been hypothesized that dopamine modulates the normal micturition reflex, and therefore neurogenic degeneration in the nigrostriatal pathway leads to the significant LUT dysfunction associated with PD
- When LUT dysfunction does occur:
  - Symptoms usually consist of urgency, frequency, nocturia, and urgency incontinence.
- PET scanning shows brain responses with bladder filling.
- The time from onset of PD to initiation of LUTS is ≈5 years
TURP should not be contraindicated in patients with PD, because external sphincter acontractility is extremely rare in such patients. However, one must be cautious with such patients, and a complete urodynamic or video-urodynamic evaluation is advisable. Poorly sustained bladder contractions, sometimes with slow sphincter relaxation, should make one less optimistic regarding the results of outlet reduction in the male.

Multiple system atrophy

A progressive neurodegenerative disease of unknown cause; results from glial α-synucleinopathy
Symptoms encompass parkinsonism and cerebellar, autonomic (including urinary and erectile problems), and pyramidal cortical dysfunction in a multitude of combinations
The neurologic lesions of MSA consist of cell loss and gliosis in widespread areas and occur to a significantly greater degree than with PD. This more diffuse nature of cell loss probably explains why bladder symptoms may occur earlier and be more severe than in PD, and why erectile function may be affected as well
The initial urinary symptoms of MSA are urgency, frequency, and urgency incontinence, occurring up to 4 years before the diagnosis is made.
- As would be expected from the central nervous system (CNS) areas affected, detrusor overactivity is frequently found
- Decreased compliance may also occur, reflecting distal spinal involvement of the locations of the cell bodies of autonomic neurons innervating the LUT.
- As the disease progresses, difficulty in initiating and maintaining voiding may occur, probably from pontine and sacral cord lesions, and this usually is associated with a poor prognosis.
- Cystourethrography or video-urodynamic studies may reveal an open bladder neck (different than PD), and many patients exhibit evidence of striated sphincter denervation on motor unit electromyography.
Management

The treatment of LUTS caused by MSA is difficult
Treatment of detrusor overactivity during filling may worsen problems initiating voluntary micturition or worsen impaired contractility during emptying.
Patients usually have smooth and striated sphincter insufficiency predisposing females to sphincteric incontinence and making outlet-reducing procedures (prostatectomy) hazardous in males (different than PD)
Conversely, drug treatment for sphincteric incontinence may further worsen emptying problems.
In general, the goal in these patients is to facilitate storage, and CIC would often be desirable. Unfortunately, patients with advanced disease often are not candidates for CIC.
Some patients do respond well to desmopressin administration for predominant nocturia; however, the majority of the patients do not respond well to antimuscarinic or other types of therapy

Diseases primarily involving the spinal cord: MS, SCI, transverse myelitis, tabes dorsalis, pernicious anemia, spinal dysraphism, poliomyelitis

Multiple sclerosis

Primarily a disease of adults ages 20-50 years with a 2x predilection for women
The disease is believed to be immune mediated and is characterized by neural demyelination in the brain and spinal cord; it is characterized, in general, by axonal sparing. The demyelinating process most commonly involves the lateral corticospinal (pyramidal) and reticulospinal columns of the cervical spinal cord
Common symptoms include optic nerve dysfunction, pyramidal tract abnormalities (hyper-reflexia), ataxia, bowel dysfunction, neurogenic bladder, and bowel and sexual dysfunction
50-90% report voiding symptoms at some time; the prevalence of incontinence is cited as 37-72%
Urodynamic findings

Detrusor overactivity is the most common abnormality detected
In general, the smooth sphincter is synergic
Striated sphincter dyssynergia coexists with overactivity in 30-65% of patients
The prevalence of coexistent impaired detrusor contractility or areflexia ranges from 12-38%, a phenomenon that can considerably complicate treatment efforts
One must be careful to distinguish urodynamic pseudodyssynergia from true striated sphincter dyssynergia
Sensation is frequently intact in these patients

The most common functional classification applicable to patients with LUT dysfunction secondary to MS would be storage failure secondary to detrusor overactivity. This is commonly complicated by striated sphincter dyssynergia, with varying sequelae based on the patient’s ability to empty completely at acceptable voiding pressures. Other abnormalities, and especially combined deficits, are obviously possible
Progressive neurologic disease in patients with MS rarely causes upper urinary tract damage, even when severe spasticity and disability exist
Management

At present there is no consensus on optimal bladder management for patients with MS, and management is most commonly predicated on symptomatic and urodynamic findings.
Caution should be exercised in recommending irreversible therapeutic options, because a significant proportion of patients with MS, both with and without new symptoms, will develop changes in their detrusor compliance and urodynamic pattern.
- Surgical intervention for MS appears to be diminishing with improved pharmacologic management and the realization of the alternating neurologic picture of lower urinary dysfunction associated with MS

Spinal cord injury

The majority of SCIs occur at or above the T12 spinal column (vertebral) level, with injury to one of the 8 cervical segments accounting for the patients with tetraplegia and with patients with paraplegia having injury in the thoracic, lumbar, or sacral regions of the spinal cord.
Urologic complications of SCI (8):
1. UTI
2. Sepsis
3. Upper urinary tract and LUT deterioration
4. Urolithiasis
5. Sexual and reproductive dysfunction
6. Autonomic hyperreflexia (dysreflexia)
7. Skin complications
8. Depression (which can complicate urologic management)
Despite the strong correlation between neurologic and urodynamic findings, it is not perfect, and a neurologic examination is no substitute for a urodynamic evaluation in these patients when one is determining risk factors and treatment
Spinal shock

A temporary physiologic disorganization of spinal cord that may be expected after a significant SCI
Defined as the loss of motor, sensory, reflex, and autonomic neurologic function below the level of SCI
Classically starts within one hour after the neurologic injury.
Bladder is acontractile and areflexic. The bladder neck is usually closed and competent
The smooth sphincter mechanism appears to be functional. Some electromyographic activity may be recorded from the striated sphincter
The normal guarding reflex (striated sphincter response during filling) is absent and there is no voluntary control
Urinary retention is the rule, and catheterization is necessary to circumvent this problem
- Once the patient is medically stable and can regulate fluid intake, the indwelling catheter can be removed and clean intermittent catheterization should be started.
Spinal shock usually lasts 6-12 weeks in complete suprasacral spinal cord lesions but may last up to 1 or 2 years.
- May last a shorter period of time in incomplete suprasacral lesions and only a few days in some.
  - The exception is sacral SCI which has persistent detrusor areflexia
- Resolution of spinal cord shock classically begins with the initial return of the bulbocavernosus reflex followed by the eventual restoration of the deep tendon reflexes (DTR) below the level of spinal cord injury.
Initial urodynamics should be performed within 3 months of SCI onset regardless of spinal shock resolution and then repeated after spinal shock has resolved.
- The ideal time to perform initial urodynamics is after spinal shock has resolved, which can take up to 3 months in most cases.
  - Nearly two-thirds of patients had unfavorable urodynamic parameters (detrusor overactivity, vesicoureteral reflux and high detrusor filling pressures) within 40 days after SCI.
- Videourodynamics with fluoroscopy is the gold standard for urodynamic investigation in patients with neurogenic bladder.
- The Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction best practice policy on antibiotic prophylaxis during urodynamics recommends that patients with SCI receive a single antibiotic dose to avoid symptomatic UTI and bacteremia.

Suprasacral spinal cord injury

The characteristic pattern in a patient with a complete lesion above the sacral spinal cord is detrusor overactivity, smooth sphincter synergia (with lesions below the sympathetic outflow), striated sphincter dyssynergia, and absent sensation below the level of the lesion
- Lesions at or above the spinal cord level of T7 or T8 (the spinal column level of T6) may result in smooth sphincter dyssynergia as well

The striated sphincter dyssynergia causes a functional obstruction with poor emptying and high detrusor pressure.
Occasionally, incomplete bladder emptying may result from what seems to be a poorly sustained or absent detrusor contraction.

Neurologic examination shows spasticity of skeletal muscle distal to the lesion, hyperreflexic DTRs, and abnormal plantar responses. There is impairment of superficial and deep sensation
The guarding reflex is absent or weak in most patients with a complete suprasacral SCI. In incomplete lesions the reflex is often preserved but quite variable
From a functional standpoint, the voiding dysfunction most commonly seen in suprasacral SCI represents both a filling or storage and an emptying or voiding failure. Although the urodynamics are “safe” enough in some individuals to allow only periodic stimulation of bladder reflex activity, many will require some form of additional treatment.

Sacral spinal cord injury

Typically, a depression of DTRs below the level of a complete lesion with varying degrees of flaccid paralysis. Sensation is usually absent below the lesion level. Detrusor areflexia with high or normal compliance is the common initial result. However, decreased compliance may also develop
The classic outlet findings are described as a competent but nonrelaxing smooth sphincter and a striated sphincter that retains some fixed tone but is not under voluntary control. Closure pressures are decreased in both areas

Management

Although generally correct, the correlation between somatic neurologic findings and urodynamic findings in suprasacral and sacral SCI patients is not exact, especially in patients with paraplegia resulting from spinal cord lesions at column level T10 to L2.
If bladder pressures are suitably low or if they can be sufficiently and safely lowered with nonsurgical or surgical management, the problem can be treated primarily as an emptying failure. CIC can then be continued as a safe and effective way of satisfying many of the goals of treatment. The role of additive antimuscarinic administration is supported in this patient population.
- 2019 AUA Update on SCI: For indwelling catheters a suprapubic catheter is preferred over a urethral catheter as there is less risk of urethral erosion and epididymo-orchitis in men. However, there is no difference between the 2 catheters regarding risk of UTI, bladder stones or urinary incontinence from NDO.
- In the absence of bladder outlet obstruction there is currently no role for medication in treating urinary retention in these patients.
Alternatively, sphincterotomy, urethral stenting, or intrasphincteric injection of onabotulinumtoxinA can be used in males to lower the detrusor leak point to an acceptable level and render the patient incontinent, thus converting the dysfunction primarily to a storage failure (incontinence), which can be obviated either by timed stimulation or with an external collecting device. In the dexterous SCI patient, the former approach using CIC is becoming predominant.
Electrical stimulation of the anterior sacral roots with some form of deafferentation is also now a distinct reality. Although used sparingly, as with all patients with neurologic impairment, a careful initial evaluation and periodic, routine follow-up evaluation must be performed to identify and correct the following risk factors and potential complications: bladder overdistention, high-pressure storage, high detrusor leak point pressure, vesicoureteral reflux (VUR), stone formation (lower and upper tracts), and complicating infection, especially in association with reflux.
Potential risk factors and complications are those previously described, with particular emphasis on storage pressure, which can result in silent upper tract decompensation and deterioration in the absence of VUR. The treatment of such a patient is usually directed toward producing or maintaining low-pressure storage while circumventing emptying failure with CIC when possible.
Bowel management
- Approximately 60% of patients will have fecal incontinence and 40% will have constipation.
- The goal of a neurogenic bowel regimen is to accomplish complete evacuation of the rectum on a regular basis, thereby reducing the risk of fecal impaction. This goal is achieved with adequate fluid intake, balanced diet, appropriate physical activity and a regular bowel routine.
- In a systematic review of non-pharmacological therapies for chronic constipation, a transanal irrigation system appeared promising in decreasing constipation and fecal incontinence.
- If further therapy is needed, patients with SCI should be started on medications such as cisapride, prucalopride or neostigmine.

Autonomic hyperreflexia (dysreflexia) (See 2019 CUA NLUTD Guideline Notes)

Potentially fatal emergency unique to the SCI patient
Onset after injury is variable—usually soon after spinal shock, but it may occur up to years after injury, and distal spinal cord viability is a prerequisite.
Represents an acute massive disordered autonomic (primarily sympathetic) response in patients with SCI above the cord level of T6-T8 (the sympathetic outflow) to specific stimuli below the level of the lesion
Symptoms (5):

Pounding headache
Hypertension
Flushing and sweating above the level of the lesion
Bradycardia

Tachycardia or arrhythmia may be present

Hypertension

May vary in severity from causing a mild headache before voiding to life-threatening cerebral hemorrhage or seizure

The pathophysiology is that of nociceptive stimulation via afferent impulses that ascend through the cord and elicit reflex motor outflow, causing arteriolar, pilomotor, and pelvic visceral spasm and sweating. Normally, the reflexes would be inhibited by secondary output from the medulla, but because of the SCI this does not occur below the lesion level.
The stimuli for this exaggerated response commonly arise from the bladder or rectum and typically involve distention. Precipitation may be the result of simple LUT instrumentation, tube change, catheter obstruction, or clot retention, and in such cases the symptoms resolve quickly if the stimulus is withdrawn.
Ideally, any endoscopic procedure in susceptible patients should be done using spinal anesthesia or carefully monitored general anesthesia.
Acutely, the hemodynamic effects of this syndrome may be managed with β- and/or α-adrenergic blocking agents.
- Sublingual nifedipine is capable of alleviating this syndrome when given during cystoscopy (10 to 20 mg) and of preventing it when given orally 30 minutes before cystoscopy (10 mg)
- No consensus on the acute pharmacologic management of autonomic dysreflexia when necessary;

Vesicoureteral reflux

Incidence between 17-25% in SCI patients, more common in those with suprasacral SCI.
- Persistent reflux can lead to chronic renal damage and may be an important factor in the long-term survival of SCI patients.
Contributing factors include:
1. Elevated intravesical pressure during filling and emptying
2. Infection
Management
- The best initial treatment for VUR in a patient with voiding dysfunction secondary to neurologic disease or injury is to normalize LUT urodynamics (i.e., decrease storage pressures and decrease outlet resistance) as much and as quickly as possible.
  - Depending on the clinical circumstances, this may be achieved by pharmacotherapy, urethral dilatation (in the myelomeningocele patient), neuromodulation, deafferentation, augmentation cystoplasty, or sphincterotomy

Urinary tract infection

Relatively common in patients with SCI.
Bacteriuria should be treated only when the patient has signs or symptoms of a UTI
Risk factors for symptomatic UTIs in patients with SCI:
- Bladder overdistention
- Increased bladder filling pressures
- Vesicoureteral reflux
- Bladder stones

Sexual dysfunction in males
- After SCI most men have erectile and ejaculatory dysfunction.
  - Rates of successful intercourse after SCI in men range from 5% to 75%, and only 10% with SCI can ejaculate.
- Erectile dysfunction in men can be managed using the same options available to the general population.
- Only 10% of men with SCI are able to achieve natural conception. Infertile men with SCI can achieve fertility with medical intervention that restores ejaculatory function and normal semen quality.
Spinal cord injury in women

Management complicated by lack of an appropriate external collecting device
Surgical intervention for SUI in this population may be beneficial in well-selected patients
Fertility is not impaired in most women with SCI

Spinal cord injury and bladder cancer

Strong association between the development of bladder cancer (squamous cell carcinoma) and long-term indwelling catheterization
- Some patients have no obvious tumors visible at endoscopy, and the diagnosis is made by bladder biopsy

Follow-up

See 2019 CUA NLUTD Guideline Notes

Transverse Myelitis

Acute transverse myelitis is a rapidly developing condition with motor, sensory, and sphincter abnormalities, usually with a well-defined upper sensory limit and no signs of spinal cord compression or other neurologic disease
May result from a variety of mechanisms: parainfectious, autoimmune, vascular, or demyelinating
Presentation
- Bladder dysfunction may occur simultaneously with the motor dysfunction or more commonly follows it
- Most common urinary symptom is urinary retention
- Most common urodynamic finding in the acute phase is areflexia or detrusor underactivity
- After resolution of spinal shock, the urodynamic patterns identifiable are detrusor overactivity (59-90%), decreased compliance (47%), DSD (17-80%), and detrusor leak point pressure > 40 cm H2O
- The condition usually stabilizes within 2-4 weeks and is not progressive afterward; however, recovery may be variable and some residual neurologic deficits are possible. Although recovery is more variable, and the prognosis, in general, is favorable, the development and nature of voiding dysfunction have been reported to be similar, level by level, to those of SCI

Neurospinal dysraphism

See Pediatrics: Neuromuscular Disorders of the Lower Urinary Tract Chapter Notes
LUT dysfunction occurs in 90% of patients.
LUT dysfunction secondary to occult spinal dysraphism may not manifest in childhood, and such patients may be referred as adults for symptoms as commonplace as urinary incontinence or recurrent UTIs.

The level(s) of the lesion correlate(s) poorly with urodynamic findings.
The “typical” myelodysplastic patient shows an areflexic bladder with an open bladder neck.
- The bladder usually fills until the resting residual fixed external sphincter pressure is reached, and then leakage occurs.
- Stress incontinence may also occur owing to changes in intra-abdominal pressure.
- A small percentage (10-15%) of patients demonstrate DSD, but these individuals show normal bladder neck function that, if detrusor reflex activity is controlled, may be associated with urinary continence.
The neurologic exam does not predict urodynamic behaviour
Management

Regardless of the pattern of LUT dysfunction in the adult, the main goal of therapy is the avoidance of high storage pressures
The urologic rehabilitation of patients with spinal dysraphism relies primarily on medical management and intravesical injection of onabotulinumtoxinA, with the selective use of augmentation enterocystoplasty or urinary diversion if failure occurs.
The treatment strategy in women is to increase urethral sphincter efficiency without causing an increase in urethral closing pressure significant enough to result in a change in bladder compliance.

Periurethral injection therapy may be a safer option than the pubovaginal sling and artificial urethral sphincter in this case.

SUI in men with myelodysplasia may follow similar general rules as in women, and bulking agents may give good results in this group as well.
- When the urethra is very widely dilated and somewhat rigid, and neither procedure alone will provide sufficient coaptation, it may be possible to combine a “prostatic sling” with periurethral bulking.
- Continent individuals will remain on CIC.

Tethered cord syndrome
- Defined as a stretch-induced functional disorder of the spinal cord with its caudal part anchored by inelastic structures and restricting vertical movement.
- Children often develop symptoms of tethered cord after growth spurts; in adults the presenting symptoms often follow activities that stretch the spine, such as sports or motor vehicle accidents
- Cord tethering can affect both bowel and leg function, as well as bladder function. Usually, there is no bladder dysfunction, and treatment must be based on urodynamic evaluation.
  - Despite efforts at improved radiographic visualization of the spinal cord, imaging does not correlate with physical findings or connote overall responsiveness to surgical intervention because detethering remains a critical aspect of management and control of tethered cord.
  - Urodynamics is improved by detethering, and this parallels functional improvement in those individuals who have undergone the surgical procedure
Follow-up
- Includes annual surveillance for early identification of urinary tract deterioration.
  - These assessments should include renal and bladder ultrasonography and urodynamics when indicated (by symptomatic change or clinical physical examination finding).
  - In addition, serum creatinine and renal scintigraphy may be performed when upper tract changes are suspected.

Tabes dorasalis (late neurosyphilis)

Syphilitic myelopathy is rapidly disappearing as a major neurologic problem
Involvement of the spinal cord dorsal columns and posterior sacral roots can result in a loss of bladder sensation and large postvoid residual urine volumes and therefore can be a cause of “sensory neurogenic bladder”

Pernicious anemia

Disease caused by impaired uptake of vitamin B12 resulting from the lack of intrinsic factor in the gastric mucosa.
Now uncommon
A spinal cord cause of the classic “sensory bladder” caused by subacute combined degeneration of the dorsolateral columns of the spinal cord

Poliomyelitis

Although not always present, when voiding dysfunction is seen in patients with polio it is that of a typical “motor neurogenic bladder”, with urinary retention, detrusor areflexia, and intact sensation.

Diseases distal to the spinal cord

Disk disease

Spinal Cord Anatomy
- In the adult, the sacral spinal cord begins at spinal column (vertebral bodies) levels T12 to L1 and terminates in the cauda equina at spinal column level L2
  - In this distal end of the spinal cord (conus medullaris), the spinal cord segments are named for the vertebral body at which the nerve roots exit the spinal canal.

Thus, although the sacral spinal cord segment is located at vertebral segment L1, its nerve roots run in the subarachnoid space posterior to the L2 to L5 vertebral bodies until reaching the S1 vertebral body, at which point they exit the canal.
Therefore, all of the sacral nerves that originate at the L1 and L2 spinal column levels run posterior to the lumbar vertebral bodies until they reach their appropriate site of exit from the spinal canal. This group of nerve roots running at the distal end of the spinal cord is commonly referred to as the cauda equina.
Conus medullaris vs. cauda equina
- The most distal bulbous part of the spinal cord is called the conus medullaris, and its tapering end continues as the filum terminale. Distal to this end of the spinal cord is a collection of nerve roots, which are horsetail-like in appearance and hence called the cauda equina (Latin for horse's tail)§

Usually, disk prolapse is in a posterolateral direction, which does not affect the majority of the cauda equina. However, in 15% of cases, central disk prolapse occurs and compression of the cauda equina may result.
- Thus, disk prolapse anywhere in the lumbar spine could interfere with the parasympathetic and somatic innervation of the LUT, striated sphincter, and other pelvic floor musculature, and afferent activity from the bladder and affected somatic segments to the spinal cord.
- Most disk protrusions compress the spinal roots in the L4 to L5 or L5 to S1 vertebral interspaces.
  - DESD does not occur as the injury is infrasacral
When LUT dysfunction is present, it typically occurs with the usual clinical manifestations of low back pain radiating in a girdle-like fashion along the involved spinal root areas. The most characteristic findings on physical examination are sensory loss in the perineum or perianal area (S2 to S4 dermatomes), sensory loss on the lateral foot (S1 to S2 dermatomes), or both.
Detrusor areflexia occurs in 27% of patients with lumbar disk disease
The most consistent urodynamic findings are:
- Normal compliance
- Areflexic bladder associated with normal innervation or findings of incomplete denervation of the perineal floor musculature.
- Occasionally, patients may show detrusor overactivity, attributed to irritation of the nerve roots
Laminectomy may not improve LUT function in many cases, and prelaminectomy urodynamic evaluation is prudent because it may be difficult postoperatively to separate causation of voiding dysfunction resulting from the disk sequelae from changes secondary to the surgery.
Cauda equina syndrome is a term applied to the clinical picture of perineal sensory loss with loss of voluntary control of both anal and urethral sphincter and of sexual responsiveness. Patients undergoing surgery are found to have an acontractile bladder and no bladder sensation. This can occur not only secondary to disk disease (severe central posterior disk protrusion) but also to other pathologic processes affecting the spinal canal.

Spinal stenosis

May occur without disk prolapse
Urodynamic findings are dependent on the level and the amount of spinal cord or nerve root compression
Because there is no consistent pattern of dysfunction with any type of spinal stenosis, urodynamic studies again should serve as the cornerstone of therapy

Radial pelvic surgery

The inferior hypogastric plexus (pelvic plexus) which innervates the viscera of the pelvic cavity is a paired structure located on the side of the rectum in males and at the sides of the rectum and vagina in females.
LUT dysfunction after pelvic plexus injury occurs most commonly after abdominoperineal resection (APR) and radical hysterectomy.

The injury may occur from denervation or neurologic decentralization, tethering of the nerves or encasement in scar, direct bladder or urethral trauma, or bladder devascularization.
Adjuvant treatment, such as chemotherapy or irradiation, may compound the damage.
Other dysfunctions related to sexual activity, ejaculatory dysfunction in men, and vaginal dryness and dyspareunia in women are also commonly associated with APR

≈1/3 of patients have some element of urinary tract dysfunction (urinary frequency, urgency, and/or poor detrusor contraction resulting in retention and incomplete emptying). The type of LUT dysfunction that occurs is dependent on the specific nerves involved, the degree of injury, and any pattern of reinnervation or altered innervation that occurs over time
When permanent LUT dysfunction occurs after radical pelvic surgery, the pattern is usually one of impaired bladder contractility or a failure of the bladder to voluntarily contract.
- UDS may show
  - Residual fixed striated sphincter tone, which is not subject to voluntarily induced relaxation, may result in obstruction
  - Often, the smooth sphincter is open and nonfunctional.
  - Decreased compliance is common in these patients, and, with the “obstruction” caused by fixed residual striated sphincter tone, may result in both storage and emptying failure.
  - These patients often experience leakage across the distal sphincter area and are unable to empty the bladder, because, although intravesical pressure may be increased, they cannot mount a true bladder contraction. The patient often has urinary incontinence that is characteristically and most commonly initiated with increases in intra-abdominal pressure. This is usually most obvious in women, because the prostatic bulk in men often masks an equivalent deficit in urethral closure function. Alternatively, patients may have variable degrees of urinary retention.
Management
- Upper tract risk factors are related to intravesical pressure and the detrusor leak point pressure, and the therapeutic goal is always low-pressure storage with periodic emptying.
- In men, the temptation to perform a prostatectomy should be avoided unless a clear bladder outlet obstruction is demonstrated at this level. Otherwise, prostatectomy simply decreases urethral sphincter function and thereby may result in the occurrence or worsening of sphincteric urinary incontinence.
We strongly urge caution in the early postoperative period, because the temptation to “do something” other than perform CIC initially after surgery in these patients is often strong, especially in those patients with little or no preexisting voiding dysfunction.
- Most of these dysfunctions will be transient, and patients can be discharged on CIC with full urodynamic evaluation at a later date.
- Frequently, 6-12 months may elapse before detrusor function returns to an acceptable level
Questions remain as to whether nonradical pelvic surgery such as simple hysterectomy can be ultimately responsible for storage or emptying abnormalities on the basis of neurologic damage. At this time there is no consensus opinion,
There is, as yet, no clear consensus as to the independent effects of childbirth and hysterectomy on LUT function. The debate regarding cesarean section as an alternative to spontaneous vaginal delivery and impact of each on the LUT also continues.

Simple and radical hysterectomy

Women who undergo hysterectomy by the vaginal approach may be more likely to have micturition symptoms as compared with abdominal approach patients
As compared with simple hysterectomy, radical hysterectomy may have more debilitating effects on bladder and bowel function

Diabetes

Most common cause of peripheral neuropathy in Europe and North America.
5-59% of patients with diabetes report symptoms of LUT dysfunction
Diabetic cystopathy
- Term to describe the involvement of the LUT by this disease.
- Current evidence points to both a sensory and a motor neuropathy as being involved in the pathogenesis, with the motor aspect contributing to the impaired detrusor contractility
  - The classic description is that of a peripheral and autonomic neuropathy that first affects sensory afferent pathways, causing the insidious onset of impaired bladder sensation.
  - As the classic description continues, a gradual increase in the time interval between voiding results, which may progress to the point at which the patient voids only once or twice a day without ever sensing any real urgency. If this continues, detrusor distention, overdistention, and decompensation ultimately occur. Detrusor contractility, therefore, is classically described as being decreased in the end-stage diabetic bladder.
Urodynamics

More recently, detrusor overactivity has been cited as the most frequent urodynamic finding.
- This could be a result of a difference in the time of diagnosis with reference to the natural history of the effects of diabetes on the LUT.
Other classic urodynamic findings include impaired bladder sensation, increased cystometric bladder capacity, decreased bladder contractility, decreased flow, and, later, increased residual urine volume
At least in men, the main differential diagnosis is bladder outlet obstruction, because both conditions commonly produce a low urinary flow rate; however, pressure-flow urodynamic studies easily differentiate the two.
Smooth or striated sphincter dyssynergia usually is not seen in classic diabetic cystopathy

Early institution of timed voiding will avoid some of the impaired detrusor contractility from chronic distention and detrusor decompensation. intensive therapy for diabetes can slow its progression and slow the development of abnormal autonomic tests.

Guillain-Barre syndrome

An inflammatory demyelinating disorder of the peripheral somatic and autonomic nervous system
Triggered by a preceding bacterial or viral infection, with the immune responses directed toward the infecting organisms cross-reacting with neural tissues.
Characterized by potentially life-threatening rapidly evolving ascending paralysis, symmetrical limb weakness, loss of tendon reflexes, absent or mild sensory signs, and variable autonomic dysfunctions
Autonomic neuropathy is a common complication. Cardiac arrhythmia, hypertension and hypotension, and bowel, bladder, and sexual dysfunction may occur. The prevalence of LUT dysfunction ranges from 25% to over 80%
The most common urinary findings include increased postvoid residual volume, followed by decreased bladder sensation, detrusor overactivity, diminished bladder compliance, and underactive detrusor contraction, as well as sphincteric dyssynergia. These findings underscore the difficulty in prediction of LUTS based on condition diagnosis only
Management

Voiding dysfunction is usually reversible with resolution of the disorder and should therefore be managed by reversible therapy (e.g., CIC, anticholinergic therapy) pending resolution

Herpesvirus infections

Invasion of the sacral dorsal root ganglia and posterior nerve roots with herpes zoster virus may produce urinary retention and detrusor areflexia days to weeks after the other primary viral manifestations
Urinary incontinence secondary to detrusor overactivity may also occur, but the pathophysiology is unclear.
Cystoscopy may reveal vesicles in the bladder mucosa similar to those seen on the skin. Spontaneous resolution usually occurs in 1 to 2 months.
Urinary retention has also been reported to occur in association with anogenital herpes simplex virus infection.

Miscellaneous neurologic diseases causing LUTD

Lyme disease
Hereditary spastic paraplegia
Tropical spastic paraparesis
Acute disseminated encephalomyelitis
Syringomyelia
Reflex sympathetic dystrophy
Systemic lupus erythematosus

Likely autoimmune origin in which there is widespread inflammatory change in the connective tissues and small vessels of the skin and systemic organs
LUT dysfunction seemed to have been related mainly to the myelopathy
Can have storage or voiding symptoms

Schistosomal myelopathy

Schistosomiasis may cause LUT dysfunction from bladder neck obstruction and impaired muscle contractility as a result of infiltration of the bladder smooth muscle itself

AIDS

Neuropathic bladder dysfunction is rare and mostly occurs in the late stages of the disease
Can have storage or voiding symptoms

Tuberculosis

Spinal tuberculosis has been associated with significant evidence of micturition disturbances including high postvoid residual volume and urinary symptoms.

Miscellaneous conditions definitely, probably, or possible related to neuromuscular dysfunction

Detrusor sphincter dyssenergia

Detrusor sphincter dyssynergia, unless specified otherwise, refers to dyssynergia of the striated sphincter and bladder
True DSD should exist only in patients who have an abnormality in pathways between the sacral spinal cord and the brainstem PMC.
- The diagnosis of DSD should be suspected in any patient with a neurologic lesion in this area.
Common causes include:
1. Traumatic SCI
2. MS
3. Transverse myelitis
- Conversely, in patients without such a lesion, this diagnosis should always be viewed with skepticism
It is important to remember that sphincter electromyographic activity that increases simultaneously with intravesical or detrusor pressure does not always indicate true DSD. These instances are referred to as pseudodyssynergia; common causes of pseudodyssynergia include:
1. Abdominal straining to either initiate or augment a bladder contraction or in response to discomfort
2. Attempted inhibition of a bladder contraction either because of its involuntary nature or because of discomfort
Without proper treatment, > 50% of men with DSD will develop significant complications, such as
1. VUR
2. Upper tract deterioration
3. Urolithiasis
4. Urosepsis
5. Ureterovesical obstruction
Therapy for DSD is designed to either eliminate or significantly minimize the abnormal sphincter activity or to bypass the sphincter itself.

Oral medical therapy directed toward the striated sphincter has not enjoyed wide success.
The most common treatment approaches currently are:
1. CIC (usually combined with therapy to control detrusor overactivity)
2. Sphincterotomy
3. Stent placement across the sphincter
4. Injection of onabotulinumtoxinA into the sphincter
5. Continuous indwelling catheterization
6. Urinary diversion

Dysfunctional voiding

Urodynamically appears to be involuntary obstruction at the striated sphincter level existing in the absence of demonstrable neurologic disease
Very difficult to prove urodynamically; unequivocal demonstration of this entity requires pressure-flow electromyographic evidence of bladder emptying occurring simultaneously with involuntary striated sphincter contraction in the absence of any element of abdominal straining, either in an attempt to augment bladder contraction or as a response to discomfort during urination

Bladder neck dysfunction

Defined as incomplete opening of the bladder neck during voluntary or involuntary voiding; has also been referred to as smooth sphincter dyssynergia
The dysfunction is found almost exclusively in young and middle-aged men, who characteristically report long-standing voiding and storage symptoms
These patients have often been seen by many urologists and have been diagnosed as having psychogenic voiding dysfunction because of a normal prostate on rectal examination, a negligible residual urine volume, and a normal endoscopic bladder appearance.
The differential diagnosis also includes:
- Anatomic bladder neck contracture
- Benign prostatic enlargement (BPE) or BPO
- Dysfunctional voiding
- Prostatitis
- Neurogenic micturition dysfunction
- Low pressure and low flow (anxious) bladder
Objective evidence of outlet obstruction in these patients is easily obtainable by urodynamic study. Once obstruction has been diagnosed, it can be localized to the level of the bladder neck by video-urodynamic study, cystourethrography during a bladder contraction, or micturitional urethral profilometry. The diagnosis may also be made indirectly by the urodynamic findings of outlet obstruction in the absence of urethral stricture, prostatic enlargement, and DSD.
The exact cause of this problem is unknown. Some have proposed that there is an abnormal arrangement of musculature in the bladder neck region, such that coordinated detrusor contractions cause bladder neck narrowing instead of the normal funneling.
The occurrence of this problem in young, anxious, and “high-strung” individuals, and its partial relief by α-adrenergic blocking agents, have prompted some to speculate that it may in some way be related to sympathetic hyperactivity.
Management

Although α-adrenergic blocking agents provide improvement in some patients with bladder neck dysfunction, definitive relief in men is best achieved by a bladder neck incision

Bladder outlet obstruction in women

Uncommon
Defined as radiographic evidence of obstruction between the bladder neck and the distal urethra in the presence of a sustained detrusor contraction of any magnitude which is usually associated with reduced or delayed urinary flow rate.

Obstruction at the level of the bladder neck is diagnosed when the bladder neck is closed or narrowed during voiding.
Obstruction of the urethra was diagnosed as a discrete area of narrowing associated with proximal dilatation.

Causes:
- Dysfunctional voiding
- Cystocele
- Prior incontinence surgery
- Urethral stricture
- Uterine prolapse
- Urethral diverticulum
- Rectocele
Management

Other than obvious pathology related to obstruction (cystocele, prior incontinence surgery, etc.), surgical treatment for bladder outlet obstruction in women should be approached with caution because sphincteric incontinence is a significant risk. Rather, pelvic floor therapy (biofeedback), behavioral modification, and the addition of pharmacotherapy should be used

Low-pressure and low-flow voiding in younger men – anxious bladder

When this occurs in a young man, it is usually characterized by frequency, hesitancy, and a poor stream. The entity is readily demonstrated on urodynamic assessment and with no coexisting endoscopic abnormality.
The patient usually notes marked hesitancy when attempting to initiate micturition in the presence of others, and some have therefore described this condition as an “anxious bladder” or a “bashful bladder.”
Psychologically, these men tend to be obsessional rather than anxious
Behavioral therapy should be attempted

Urinary retention: Fowler syndrome in women

Fowler syndrome refers specifically to urinary retention in young women in the absence of overt neurologic disease.
Potential causes or urinary retention are classically cited as neurologic, pharmacologic, anatomic, myopathic, functional, and psychogenic.
The typical history is that of a woman age < 30 who has found herself unable to void for a day or more with no urinary urgency but increasing lower abdominal discomfort.
A bladder capacity of over 1 L with no sensation of urgency is necessary for the diagnosis.
Concentric needle electrode examination of the striated muscle of the urethral sphincter may demonstrate impaired sphincter relaxation.
Urodynamic finding is detrusor acontractility.
Management: neuromodulation

Postoperative urinary retention

Incidence 4-25%
Contributing factors:
1. Diminished awareness of bladder sensation
2. Bladder overdistention
3. Decreased bladder contractility
4. Decreased micturition reflex activity
5. Traumatic instrumentation
6. Increased outlet resistance
7. Nociceptive inhibitory reflex
8. Pre-existent outlet pathology (e.g., BPH)
- Anesthesia and analgesia can contribute to factors 1-4

Hyperthyroidism

Can have incomplete emptying, frequency, straining

Schizophrenia

Can have involuntary bladder contractions

Gastroparesis
Isaacs syndrome
Wernicke encephalopathy

Caused by a deficiency in thiamine (vitamin B1)
The two major clinical manifestations of thiamine deficiency involve the cardiovascular and neurologic systems, with the latter manifesting in general as a peripheral neuropathy
Can have urgency incontinence
Management: thiamine replacement

Myasthenia gravis

Autoimmune disease caused by autoantibodies to acetylcholine nicotinic receptors. This leads to neuromuscular blockade and subsequent weakness in a variety of striated muscle groups.
Can have urinary incontinence from poor tone of sphincter or urinary retention from detrusor areflexia
- Increased risk of urinary incontinence even after a well-performed transurethral or open prostatectomy.

Systemic sclerosis (scleroderma)

Disease of the connective tissue characterized by thickening and fibrosis of the skin, abnormalities of the small arteries, and involvement of the gastrointestinal tract, heart, lung, and kidneys.
Can have storage and voiding symptoms

Ehlers-Danlos syndrome

Inherited abnormalities of connective tissue
Main clinical manifestations are skin fragility, skin hyperextensibility, and joint mobility
No characteristic pattern of dysfunction.

Corticobasal degeneration
Sacral coccygeal teratoma
Subacute combined degeneration
Willams-Beuren syndrome
Amyloidosis
Machado-Joseph disease
Radiation

Early radiation reaction most prominent at 4 to 6 weeks, with an incidence as high as 70%.
Storage symptoms are most common
Urodynamic studies have demonstrated:
1. Reduced volume at first desire to void
2. Reduced cystometric capacity
3. Reduced compliance
- These parameters tend to return to pretreatment values by 6 months.
Symptoms associated with later radiation effects are less common but may be progressive and intractable. Storage symptoms again predominate

Defunctionalized bladder

The previously normal defunctionalized bladder will often show decreased capacity and involuntary bladder contractions and/or decreased compliance.
Rehabilitation of a defunctionalized bladder is certainly possible and should definitely be attempted by cycling with progressively increasing volumes.

Congenital adrenal hyperplasia
Aging
Benign joint hypermobility syndrome
Attention-deficit/hyperactivity disorder.

Treatment of neurogenic lower urinary tract dysfunction: overview

Voiding dysfunction: goals of management:

Upper urinary tract preservation or improvement
Absence or control of infection
Adequate storage at low intravesical pressure
Adequate emptying at low intravesical pressure
Adequate control
No catheter or stoma
Social acceptability and adaptability
Vocational acceptability and adaptability

See 2019 CUA NLUTD Guideline Notes

Questions

Answers

References

Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 76
Mohapatra A, Chermanksy CJ. 2019 AUA Update on Acute and Chronic Urological Management of Spinal Cord Injury