Neurogenic Voiding Dysfunction

CHAPTER 14 Neurogenic Voiding Dysfunction

Leonard Glickman, MD and
George P. H. Young, MD, FACS

What are the pathways and influences involved in normal micturition?

Voluntary control is exerted by the cerebral cortex by release of tonic inhibitory signals to the pontine micturition center (PMC). The PMC initiates voiding by stimulation of parasympathetics at S2-S4 causing detrusor contraction. The PMC also inhibits sympathetic fibers T11-L2 causing relaxation of the bladder neck and proximal urethra. Finally, the PMC inhibits the somatic fibers of the pudendal nerve causing relaxation of the external sphincter.

Neurogenic control of the bladder in infants is by what part of the central nervous system also known as the primitive voiding center?

Sacral reflex center.

Where does the pudendal nerve originate?

Nucleus of Onuf. This nucleus is a collection of sacral somatic nerve cells that originate from the lateral border of the ventral horn of the sacral spinal cord (S2-S4).

Explain the functions of the pudendal nerve.

It controls the external urethral sphincter. The pudendal also innervates the penis as well as the ischiocavernosus and bulbocavernosus muscles. The pudendal and pelvic nerves also receive postganglionic axons from the caudal sympathetic chain ganglia.

Overstimulation of the pudendal nerve produces what urological problem?

Urinary retention.

What can cause overstimulation of the pudendal nerve?

Trauma to the suprasacral–infrapontine spinal cord.

What cord segment is evaluated with the bulbocavernosus reflex?

This test evaluates the integrity of the S2-S4 segments.

Briefly summarize the parasympathetic innervation of the bladder?

Parasympathetic efferents originate from the pelvic nerves S2-S4. The ganglions are located near the organ and the neurotransmitter is acetylcholine. The receptors are muscarinic (M2/M3) and stimulation results in bladder contraction.

Where are the parasympathetic postganglionic neurons located?

In the detrusor wall as well as the pelvic plexus.

What is the most common type of muscarinic receptor in the bladder?

The M2 type is the most common type as it accounts for approximately 80% of the bladder’s muscarinic receptors. Its exact function in the bladder is unknown, but it is thought to be involved with the neuromodulation of bladder compliance. The M2 receptors are primarily cardiovascular where they help mediate heart rate and cardiac output.

Which muscarinic receptor is most involved with cholinergic stimulation of the detrusor?

M3, even though it only represents about 20% of the total muscarinic receptors in the bladder. M1 receptors are primarily located in the central nervous system and salivary glands. They deal with cognition and saliva production. This is why a selective M3 antimuscarinic agent should theoretically have fewer central nervous system and dry mouth side effects than nonselective agents. The M5 receptors are primarily located in the ciliary muscle of the eye.

What is the pathway of the sympathetic innervation of the bladder?

Sympathetic preganglionic nerves exit from the lumbar spinal cord to synapse in the sympathetic chain ganglia. The postganglionic sympathetics then travel through the inferior splanchnic nerves to the inferior mesenteric ganglia. They finally travel in the hypogastric nerve to the pelvic plexus and the urogenital organs.

What is the role of sympathetic innervation of the bladder and outlet?

Together they promote bladder storage via the hypogastric nerve (T10-L2). Alpha (bladder base and prostate) and beta (bladder body) receptors exist on the bladder and alpha receptors are on the prostatic capsule. Beta activation results in inhibition of muscle contraction. Alpha activation results in increased outlet resistance.

What types of afferent fibers exist in the bladder?

Myelinated (AS) and unmyelinated (C) axons.

How do they differ?

• Aδ bladder afferents are finely myelinated axons located in the detrusor smooth muscle and sense bladder fullness (tension).

• C bladder afferents have unmyelinated axons, are located in the detrusor mucosa, and most are mechanoinsensitive (hence the term “silent C fibers”). These fibers can be recruited after injury/inflammation to form new functional afferent pathways (becoming mechanosensitive) that can cause pain and urge incontinence.

What is capsaicin?

A vanilloid, capsaicin stimulates and desensitizes unmyelinated C fiber axons to produce pain and release neuropeptides. Resiniferatoxin (RTX) is an ultrapotent analog of capsaicin.

How is capsaicin involved with spinal cord injuries?

Although normal micturition is associated with myelinated Aδ afferent fibers, after spinal cord injury a capsaicin-sensitive unmyelinated C fiber-mediated spinal reflex may develop, resulting in detrusor overactivity (DO).

What is the distinction between the smooth and the striated urinary sphincters?

The smooth sphincter refers to a physiological rather than an anatomic sphincter. It is located at the smooth musculature of the bladder neck and the proximal urethra. Control is involuntary. In contrast, the striated sphincter is anatomic and includes the skeletal muscle surrounding the membranous urethra in men and the middle segment of the urethra in females. This sphincter also includes the striated muscle surrounding the urethra in both men and women. The outer portion of this sphincter is under voluntary control.

The rhabdosphincter contains what specific type of muscle fiber?

Striated, slow-twitch (type 1) muscle fibers.

Which neurotransmitter is involved in urethral smooth muscle relaxation during voiding?

Nitric oxide (NO) has been identified as the neurotransmitter responsible for urethral smooth muscle relaxation. Pelvic parasympathetic nerves are responsible for mediating the release of NO.

According to Wein, what are the 3 factors necessary for (A) normal bladder and urine storage to occur, and (B) normal bladder emptying to occur?

The factors necessary for urine storage.

1. Accommodation of urine at low pressure with appropriate sensation.

2. A closed outlet at rest and one that remains so with increases of intra-abdominal pressure.

3. No involuntary bladder contractions.

Requirements for normal emptying.

1. A contraction of adequate magnitude and duration.

2. Lowering of outlet resistance when this contraction occurs.

3. No anatomic outlet obstruction.

What is the guarding reflex?

A reflex pathway that functions during the filling phase. As the bladder fills with urine, low-level vesical afferent activity via the pelvic nerve causes external sphincter contraction through somatic pathways. In turn, the somatic afferents from the sphincter inhibit parasympathetic efferent signals suppressing bladder activity and allowing urine to be stored in the bladder. It is thought that alterations in these primitive reflex pathways contribute to neurogenic bladder dysfunction.

What properties of the bladder allow for normal low pressure filling?

In general, the bladder contains viscoelastic properties that allow the bladder to maintain a low pressure of 10 cm H₂O throughout the filling phase. This property is known as compliance. Compliance (C ) is defined as the change in bladder volume divided by the change in intravesical pressure, C = Δ V/ΔP. Along with smooth muscle, approximately 50% of the bladder wall contains collagen and 2% elastin. As the collagen content of the bladder wall increases, the compliance decreases. Injury, denervation, and obstruction can all cause increases in collagen content of the bladder wall.

What is the order of processes in micturition?

Afferent activity from the bladder activates the PMC, which first acts to inhibit the spinal guarding reflex. The pudendal nerve mediates relaxation of the striated external sphincter. This is followed by relaxation of the bladder neck/proximal urethra by sympathetic fibers from T11-L2. Almost simultaneously the detrusor contracts and detrusor pressure rises via the S2-S4 parasympathetic efferents.

The first recordable event of the micturition reflex is?

Cessation of sphincter EMG activity.

Injury to which parts of the brain causes voiding dysfunction?

Voluntary voiding is dependent on intact neuronal pathways between the frontal cortex and the septal-preoptic region of the hypothalamus as well as intact connections between the paracentral lobule and the brainstem. Injury to these areas of the cortex results in increased bladder activity due to loss of cortical inhibitory signals.

How do bladder reflexes change from an infant to an adult?

It is important to remember that by definition the infant and the toddler will have DO. Children younger than 2 to 3 years of age lack the cerebral maturity to emit inhibitory signals to prevent voiding reflexes. As the infant’s bladder fills with urine and reaches its functional capacity the bladder will reflexively contract and empty. These neonatal pathways that cause detrusor overactivity do not disappear with age. They are, however, controlled by higher cortical function that develops with age. Neurologic disease and advanced age can cause these primitive reflexes to reemerge and cause urgency and urge incontinence.

Define “detrusor hyperreflexia” and explain how it differs from “detrusor instability.”

Detrusor hyperreflexia is defined as DO due to a disturbance of the neural control mechanisms. Without evidence of a relevant neurological disorder, the term “detrusor hyperreflexia” cannot be used, and instead the term “detrusor instability” is used.

What are the 3 hypotheses that explain DO?

1. Neurogenic—DO may arise from generalized, nerve-mediated excitation of the detrusor muscle from various sources. Cerebral damage can reduce suprapontine inhibition. Spinal cord lesions can damage axonal pathways allowing primitive spinal bladder reflexes to occur. New reflexes secondary to C fiber bladder afferent neurons can disrupt normal sacral activity. Over time, sensitization of peripheral afferents in the bladder can trigger DO.

2. Myogenic—DO contractions result from a combination of an increased likelihood of spontaneous contraction and enhanced propagation of activity between muscle cells. Patchy denervation commonly occurs in DO, which can affect smooth muscle cell spontaneous contractions, and ultimately propagation over a wider area of detrusor.

3. Peripheral autonomous activity—This hypothesis suggests that increased bladder sensation results from increased localized detrusor contraction and that DO is due to enhanced coordination of modular activity through the myovesical plexus.

What is overactive bladder (OAB)?

OAB is a symptomatic diagnosis that is usually secondary to DO. DO is a diagnosis that requires urodynamic testing. The quantification of OAB symptoms should be by frequency–volume chart and validated questionnaires.

From cranial to caudal, explain how neurological lesions typically effect voiding dysfunction.

• CNS lesions typically result in detrusor hyperreflexia. Normally, the CNS inhibits reflex contraction of the detrusor. Loss of this tonic detrusor inhibition (due to stroke, Parkinson disease [PD], multiple sclerosis [MS], and brain tumors) results in DO with normal coordination of detrusor and sphincter, and normal sphincter tone and sensation. (Please note MS can have ANY manifestation depending on the location of the lesion.)

• Pontine micturition center (PMC)—lesions above the PMC are described above, with coordinated DO. Below the PMC, the detrusor and external urethral sphincter become uncoordinated, resulting in detrusor–sphincter dyssynergia (DSD).

• Spinal cord lesions above S2 are upper motor neuron (UMN) lesions and result in DSD. All spinal cord injuries can result in spinal shock. Spinal cord injuries above T6 may result in autonomic dysreflexia.

• Neurological lesions below S2 can be due to spina bifida, MS, surgeries (APR), myelodysplasia, disc herniation, and results in an acontractile detrusor, and therefore retention.

In addition to anticholinergic agents, which class of oral medications can be used to treat DO?

The sympathetic efferents that effect bladder function are known to cause detrusor relaxation during the filling phase of the micturition cycle. It has been shown that β-3 adrenoceptor activation leads to detrusor relaxation. Therefore, a β-3 adrenoceptor selective agonist drug can be used to prevent detrusor activity.

What are the side effects and precautions in using this class of medication? Can it be used together with anticholinergics?

Mirabegron (Myrbetriq) is currently available. Side effects include an increase in blood pressure and there has been an increased incidence of urinary tract infection (UTI) noted with its use so far. Special precautions involve an increase in digoxin levels and 2D6 pathway issues. Use with anticholinergics is not currently recommended.

What is the bladder ice-water test?

A test that can be performed to check for the reemergence of primitive neonatal voiding reflexes. It is performed by instilling 100cc of sterile normal saline at 4°C in the bladder. In a normal adult a cold sensation will be felt but there will be no bladder instability. In an infant, or in an adult with voiding pathology, the cold saline will induce an involuntary detrusor contraction. The reflex is initiated by temperature-sensitive receptors that are supplied by unmyelinated c-fibers afferents.

The sacral spinal cord begins at what level and ends at which spinal cord level?

It is important to distinguish between spinal column segment (bone level) and the corresponding cord level. The sacral spinal cord actually begins at the column level of T12-L1. It terminates as the cauda equina at spinal column level L2.

After the cerebral shock phase wears off, what type of bladder condition is found most often?

Detrusor hyperreflexia with coordinated urethral sphincter activity. This occurs because the PMC is released from cerebral inhibitory control. Clinically, this causes frequency, urgency, and urge incontinence.

How is the above situation treated?

Foley catheter or intermittent catheterization during cerebral shock phase. Anticholinergic medications afterward.

Spinal shock typically lasts how long?

6 to 12 weeks.

What is the voiding pattern observed in a complete cord injury above the sacral reflex?

Most commonly, these lesions result in urge incontinence from detrusor hyperreflexia, absent sensation below the level of the lesion, smooth sphincter synergy, and striated sphincter dyssynergia. Lesions above the sympathetic outflow tract T7 or T8 (spinal column level of T6) may also result in smooth sphincter dyssynergia.

A diver suffers from a complete spinal cord injury at the level of T8. What pattern of voiding would be expected immediately following the accident?