The afferent and efferent peripheral pathways include the autonomic fibers traversing the pelvic (parasympathetic) and hypogastric (sympathetic) nerves, and the somatic fibers traversing the pudendal nerves (Figure 28-2 and Table 28-1). In healthy individuals the volume of the bladder and the normal voiding reflex is routed via the afferent Aδ fibers. In pathologic states, stimulation of capsaicin or vanilloid receptor subtype 1 (VR1) (receptors expressed by unmyelinated afferents in the bladder) lead to excitation of C-afferent fibers, possibly mediating bladder dysfunction as a result of inflammatory reactions. These receptors are cation channels, expressed almost exclusively by the primary sensory neurons involved in nociception and neurogenic inflammation, and can also be activated by noxious heat and changes in pH. In suprasacral neurogenic bladder disease these capsaicin-sensitive vanilloid receptors and C-afferent fibers have a major role in the pathogenesis of hyperactivity. Intravesical capsaicin and resiniferatoxin, which block transmission through C-afferent fibers for several months, have been used experimentally to treat hyperactivity when it does not respond to the usual pharmacologic agents.^20,²³

FIGURE 28-2 The parasympathetic, sympathetic, and somatic nerve supply to the bladder, urethra, and pelvic floor.

(Redrawn from Blaivas JG: Management of bladder dysfunction in multiple sclerosis, Neurology 30:12-18, 1980.)

Table 28-1 Bladder Afferent Pathways

Central Connections and Control

The reflex center for the bladder lies in the pons along with the other autonomic centers (Figure 28-3). Not shown in Figure 28-3 is a reflex with afferent axons originating from the bladder and synapsing on the pudendal nerve nucleus at S2, S3, and S4 (Onuf’s nucleus). This allows inhibition of pelvic floor activity during voiding. Another important reflex uses the local segmental innervation of the external sphincter with afferents from the urethra, sphincter, and pelvic floor and efferents in the pudendal nerve. Higher (voluntary) control over the pelvic floor is achieved through afferents that ascend to the sensory cortex. Descending fibers from the motor cortex synapse with the pudendal motor nucleus.⁶

FIGURE 28-3 The central connections of the bladder reflex are shown, with the afferents ascending possibly in the reticulospinal tracts or the posterior columns to the pontine mesencephalic reticular formation and the efferents running down to the sacral outflow in the reticulospinal tracts. The pontine center is largely influenced by the cortex but also by other areas of the brain, particularly the cerebellum and basal ganglia.

(Redrawn from Bradley WE, Brantley SF: Physiology of the urinary bladder. In: Campbell’s urology, ed 4, Philadelphia, 1978, WB Saunders.)

Bladder Function

Urodynamic studies in both healthy people and those with neurologic disease have yielded clinical insights into the normal and abnormal function of the lower urinary tract over the course of life(Figure 28-4).

FIGURE 28-4 Diagrams of external sphincter electromyography (EMG) and bladder pressure during filling and voiding in a 2-year-old boy (A), a normal male adult (B), and an elderly male (C). A, A bladder contraction occurs during filling, which the child attempts to suppress to stay continent by contracting his external sphincter. B, No contractions occur during filling. Voiding is initiated by relaxation of the sphincter before the bladder contracts. C, Contractions occur during filling, which the patient tries to suppress. The voiding contraction is low pressure and poorly sustained leading to incomplete emptying, a condition frequently found in elderly persons.

Infant and Young Child

Neonates and infants have reflex bladders that empty at approximately 50- to 100-mL volumes. Sometime after the first year of life, the child begins to show some awareness of bladder evacuation and can begin to delay urination for a brief period by contracting the voluntary sphincter. For normal control, the detrusor reflex has to be inhibited by the higher centers at the level of the pontine nucleus. By 5 years of age, approximately 90% of children have normal control. The remaining 10% have a more infantile or immature pattern, with detrusor activity between voluntary voidings that produces frequency, urgency, and occasionally urge incontinence and nocturnal enuresis. Most of these children gradually develop inhibition of the detrusor reflex by the onset of puberty.

Adult

With bladder filling, there is only a minimal increase in intravesical pressure (known as accommodation) together with an increase in recruitment of activity in the pelvic floor and voluntary sphincter. Normal voiding is initiated by voluntary relaxation of the pelvic floor with subsequent release of inhibition of the detrusor reflex at the pontine level. The detrusor contraction is maintained steadily throughout voiding, and the pelvic floor remains quiescent.

Elderly

Frequency, urgency, and incontinence with incomplete emptying are common in elderly persons. Urodynamic studies show that many elderly persons have bladder contractions during filling, producing frequency, urgency, and incontinence. These contractions are poorly sustained during voiding and result in incomplete evacuation. Elderly men can have prostatic obstruction, and women can have incontinence related to impaired sphincter activity or stress incontinence. In the absence of these mechanical factors, changes in bladder function in elderly persons have been ascribed to loss of cerebral control as a result of minor strokes and changes in the bladder wall caused by collagen deposition. Changes in bladder function can also result from polyuria secondary to reduced renal concentrating ability, diuretic use, lack of normal increase in antidiuretic hormone secretion at night, and mobilization of lower extremity edema during sleep.

Neurogenic Bladder Dysfunction and Classification

The neurogenic bladder has been classified in a variety of ways, beginning with the anatomic classification of Bors and Comarr.⁵ The first functional classification was based on cystometric findings, and five basic groups were described: (1) reflex, (2) uninhibited, (3) autonomous, (4) motor paralytic, and (5) sensory neurogenic bladders.³¹ Later a more anatomic classification system was proposed in which the neurogenic bladder was subdivided into types including supraspinal, suprasacral spinal, infrasacral, peripheral autonomic, and muscular lesions (Figure 28-5). At the same time others developed functional classifications, all of which were based on conventional urodynamic evaluations. This was an attempt to categorize the lower urinary tract according to the passive storage ability of the bladder and the activities and coordination of the detrusor and sphincter mechanisms (Table 28-2). In practice it is common to use a combination of both anatomic and functional classifications. Clinical management is based on functional changes demonstrated by urodynamic testing.

FIGURE 28-5 Anatomic classification of the neurogenic bladder.

Table 28-2 Functional Classification of the Neurogenic Bladder

Type of Failure	Bladder Factors	Outlet Factors
Failure to store	Hyperactivity
	Decreased compliance	Denervated pelvic floor
		Bladder neck descent
		Intrinsic bladder neck sphincter failure
Failure to empty	Areflexia
	Hypocontractility	Detrusor–sphincter dyssynergia (striated sphincter and bladder neck)
		Nonrelaxing voluntary sphincter
		Mechanical obstruction (benign prostatic hypertrophy or stricture)

Evaluation

History and Physical Examination

Although the symptoms associated with neuropathologic bladder processes are often misleading and correlate poorly with objective findings, relief of symptoms is one of the patient’s main concerns. It is often helpful to have the patient or attendant record fluid intake, output, and incontinence episodes over several 24-hour periods. A history of recurrent urinary tract infection (UTI) can indicate episodes of urinary retention. The patient’s ability to sense bladder fullness and note incontinence can also be useful. The history should help determine whether there were voiding symptoms before the causative neurologic event or any premorbid conditions such as diabetes, stroke, and previous urologic or pelvic surgery. The neurologic diagnosis, especially the level of the lesion and its completeness, is important in predicting the type of lower urinary tract dysfunction that might be expected.

The physical examination should assess mental status and confirm the level of the neurologic deficit (if present). Perineal sensation and pelvic floor muscle tone are particularly important. Reflexes are also important, but the bulbocavernous, cremasteric, and anal reflexes are sometimes difficult to elicit, even in neurologically intact patients. The skin of the perineum and the state of bladder support should be assessed. In women, a standard pelvic examination is warranted to assess for adequate estrogenization and any evidence of vaginal wall support defects. Good estrogenization is evidenced by a pink and moist vaginal mucosa with good rugae, whereas lack of estrogenization reveals a pale, dry, and smooth vaginal mucosa. Evidence of cystocele or pelvic organ prolapse can be seen in vaginal wall support defects. The prostate in males should be evaluated, but prostate size or consistency alone is not a good indicator of obstruction. It is also important to assess the patient’s motivation, lifestyle, body habitus, and other physical impairments including an assessment of upper limb function, lower limb function, and spine range of motion.

Diagnostic Tests

Indications

The extent of upper and lower urinary tract testing has to be individualized for each patient and each neurologic condition. The upper tracts need evaluation if there are symptoms suggestive of pyelonephritis or history of renal disease. Some neurologic conditions such as stroke, Parkinson’s disease, and multiple sclerosis rarely or only occasionally cause upper tract involvement. For these conditions, a simple baseline screening test such as renal ultrasonography (US) is sufficient. Conditions such as those involving a complete spinal cord lesion and myelodysplasia need more extensive and regular upper tract surveillance with both structural and functional tests. The lower urinary tract evaluation can be simple, from urinalysis to urine culture to measurement of postvoid residual. A full urodynamic evaluation might be necessary, however, especially if incomplete bladder emptying, incontinence, recurrent bacteriuria, or upper tract changes are present.

The bladder findings on urodynamic studies cannot be used alone to determine the level of neurologic lesion. For example, a suprasacral neurogenic bladder from a complete spinal cord injury can remain areflexic, and a conal or cauda equinal bladder can exhibit high pressures from poor compliance (Table 28-3). Although the anatomic level of the neurologic lesion can suggest to the clinician the most likely pattern of bladder dysfunction, urodynamic testing should be performed to confirm this. Functional bladder studies in traumatic spinal cord injury are best deferred until spinal shock has cleared.

Table 28-3 Urodynamic Definitions

Term	Definition
Bladder
Hyperactivity	Contractions of the detrusor during filling
Hypocontractility	Unsustained contractions causing failure to empty
Areflexia	Absent contractions with attempt to void
Compliance	Change in volume divided by change in baseline pressure with filling (<10 mL/cm H₂O abnormal; 10 to 20 mL/cm H₂O borderline if capacity reduced)
Outlet
*Detrusor–sphincter dyssynergia*
1. At bladder neck	Usually in high tetraplegic patients with autonomic hyperactivity
2. At striated sphincter	Uncoordinated pelvic floor and striated sphincter contraction with detrusor contraction during attempts to void
Nonrelaxing sphincter	Poor voluntary relaxation of voluntary sphincter in patients with areflexia attempting to void by the Valsalva maneuver
Decreased outlet resistance	Incontinence caused by damage to the bladder neck or striated sphincter, pelvic floor descent, or denervation

Upper Tract Tests

Lower Tract Tests

Urinalysis, Culture, and Sensitivity Testing

These tests are done routinely for all patients with neurogenic bladder disease and should be repeated as often as necessary or at the very least at routine follow-up annually. These would also be recommended before invasive procedures in cases of suspected UTI (i.e., with cloudy, foul smelling, or bloody urine) or with new lower urinary tract symptoms such as incontinence, frequency, etc. Bacteriuria should be treated before any invasive urologic procedure or test is performed.

Postvoid Residual

By itself, a low postvoid residual (PVR) of less than 20% of capacity is not indicative of a “balanced” bladder as it was once defined because high intravesical pressures can be present despite low PVR values. The PVR is simple to determine and clinically useful, especially when compared with previous recordings and considered in conjunction with the bladder pressure, clinical symptoms, and the appearance of the bladder wall. PVRs can vary throughout the day. A catheter insertion has been used for PVR in the past, but there are now simple US machines that noninvasively obtain the PVR.⁹

Cystography

This study is usually performed to test for the presence or absence of ureteral reflux, and it also shows the outline and shape of the bladder. The procedure is usually performed in the radiology department, and often with no control over the rate of bladder filling and without any monitoring of intravesical pressure. It is frequently helpful in planning management to know the level of intravesical pressure at which ureteral reflux occurred. Significant bacteriuria should be treated before the test is performed. Blood pressure should be monitored throughout the test in all patients with spinal cord lesions above T6 who are at risk for autonomic dysreflexia. In many cases a full videourodynamic study, which includes fluoroscopy of the bladder and monitoring of the intravesical pressure, is more clinically useful. This study is described later.

Cystometrography

Cystometrography (CMG) is a filling study and gives little information about the voiding phase of bladder function. Although carbon dioxide (CO₂) as a filling medium is convenient with the commercially available apparatus, this type of testing has shown considerable variability, poor reproducibility, and the presence of artifacts caused by leakage of CO₂ gas around the catheter. An advantage of the CO₂ CMG is that any size of catheter can be used because there is little resistance to flow and therefore no pressure artifact from the pump.

Water CMGs are best obtained with a two-channel catheter, with one channel used for filling and the other for pressure recording. A rectal pressure trace is also helpful in many patients to help distinguish intravesical pressure variations (resulting from intraabdominal transmission) from contractions of the detrusor itself. Reported filling rates vary but usually range from 25 to 60 mL/min. During filling, patients are asked to suppress voiding. Normal values include a capacity of 300 to 600 mL, with an initial sensation of filling at approximately 50% of capacity. The sensation of normal fullness is said to be appreciated in the lower abdomen with a sense of urgency in the perineum. The change in volume divided by the increase in baseline pressure during filling (i.e., in the absence of a detrusor contraction) describes the bladder’s compliance. This value should be greater than 10 mL/cm H₂O, and 10 to 20 mL/cm H₂O is considered borderline if the bladder capacity is reduced. The patient is asked to suppress detrusor contractions during this test. Any detrusor contraction during the test, usually defined as a phasic pressure change of more than 15 cm H₂O, is abnormal. If the patient is neurologically intact, these contractions are referred to as uninhibited. If the patient has a suprasacral or supraspinal lesion, these contractions are called hyperreflexic.² Overactive or hyperactive are terms now used to describe both types of contractions.

Although patients can be instructed to try to void at capacity, many are unable to generate a detrusor contraction. The presence of an easily obtainable involuntary detrusor contraction confirms the presence of hyperactivity in a patient with a suprasacral or supraspinal lesion, although the absence of a contraction does not necessarily imply true areflexia in a patient with an infrasacral lesion. The CO₂ CMG is a useful bedside test to monitor the return of a detrusor reflex in the spinal shock phase of spinal cord injury, and to confirm the presence of detrusor hyperactivity in patients with supraspinal or cerebral insult before pharmacotherapy is started.

Urethral Pressure Profiles

Urethral pressure profiles are obtained by withdrawing a measuring device (microtip transducer or perfused side-hole catheter) gradually down the urethra and measuring the centrally oriented forces. It has limited value except in determining whether a sphincter-active area is still present after a sphincterotomy, which can also be evaluated by videourodynamics.

Sphincter Electromyography

Sphincter electromyography (EMG) can be combined with the CMG or preferably with a full multichannel videourodynamic study.²⁸ Recordings have been made with a variety of electrodes (monopolar, coaxial needle, and surface electrodes) from the levator, perianal, or periurethral muscles. Because some authors claim there is a functional dissociation between these muscle groups, periurethral recordings are preferred. The integrated EMG is displayed on the same trace as the bladder pressure. EMG activity gradually increases as bladder capacity is reached during bladder filling, and then becomes silent just before voiding. Low levels of EMG activity with no recruitment during filling are a common pattern in complete spinal cord injury. When a reflex detrusor contraction occurs in these patients, the EMG activity in the sphincter can increase rather than decrease. With this detrusor–sphincter dyssynergia, voiding often occurs toward the end of the detrusor contraction because the striated sphincter relaxes more quickly than the smooth muscle of the bladder. This type of sphincter EMG does not display individual motor units and cannot be used for the evaluation of infrasacral denervation of the pelvic floor musculature (for which standard needle EMG is needed). Diagnostic integrated EMG recordings from the external urethral sphincter are difficult to obtain and are invasive and painful in patients who are sensate. The fluoroscopic appearance of the urethra is an alternative method of determining sphincter dysfunction and is preferred after distal sphincterotomy if recurrent distal sphincter dyssynergia is suspected (Figure 28-6).