Neurophysiology in Neurourology

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AANEM MONOGRAPH ABSTRACT: The bladder has only two essential functions. It stores and periodically empties liquid waste. Yet it is unique as a visceral organ, allowing integrated volitional and autonomous control of continence and voiding. Normal function tests the integrity of the nervous system at all levels, extending from the neuroepithelium of the bladder wall to the frontal cortex of the brain. Thus, dysfunction is common with impairment of either the central or peripheral nervous system. This monograph presents an overview of the neural control of the bladder as it is currently understood. A description of pertinent peripheral anatomy and neuroanatomy is provided, followed by an explanation of common neurophysiological tests of the lower urinary tract and associated structures, including both urodynamic and electrodiagnostic approaches. Clinical applications are included to illustrate the impact of nervous system dysfunction on the bladder and to provide indications for testing. Muscle Nerve 38: 815–836, 2008

NEUROPHYSIOLOGY IN NEUROUROLOGY

MARGARET M. ROBERTS, MD, PhD

AANEM, Illinois Urogynecology, LTD, Oak Lawn, Illinois, USA

Accepted 29 January 2008

The bladder has two essential functions: the storage than 26 billion dollars.1,63,154 This is similar to the and periodic elimination of liquid waste. It has a prevalence of diabetes in the United States6,140 and capacity in the range of 400–500 ml1,2,44,56 in an the total cost of health care for the entire country of average adult but is typically emptied 5–7 times a Switzerland.86 Urinary retention, though less preva- day,3,24 often at much smaller volumes. With an av- lent in the general population, is a common condi- erage urine flow time of less than 30 s,91 the bladder tion in patients with neurologic disorders. It has is actively emptying less than 1% of the time. Thus, been identified in more than 27% of patients admit- the predominant role of the bladder is that of a ted for rehabilitation, with 20% of cases both asymp- reservoir, storing urine at low pressures even during tomatic and unsuspected at presentation.160 Reten- filling to capacity. When necessary, the bladder is tion may be equally burdensome to the individual, also dynamic, responding to increased filling, infec- and untreated; it may result in devastating complica- tion, or even emotional stimuli with elimination at tions including renal failure and death. Until the essentially any volume, any time, as many times as 1970s, upper urinary tract disease was the leading necessary. cause of death in patients with spinal cord injury The significance of normal bladder function may (SCI) and myelomeningocele.57,75,128 be more readily apparent if one considers the impact While impressive for the sheer size of the num- of dysfunction. Urinary incontinence is readily ap- bers, statistics tend to be sterile and dry, failing to preciated as a prevalent and costly problem, affect- capture the human aspect of disease and impair- ing 17 million Americans at an annual cost of more ment. Consider the stigmatization, isolation, loss of self esteem, depression, and risk of institutionalization that occurs in those with bladder dysfunc- Abbreviations: ASIA, American Spinal Injury Association; BC, bulbocavern- tion.1,43 Failure to maintain continence is a major osus; CAR, clitoroanal reflex; DLPP, detrusor leak point pressure; DSD, de- 141 trusor sphincter dyssynergia; EAS, external anal sphincter; EDX, electro- factor for institutionalization, with more than half diagnostic; EMG, electromyographic; EUS, external urethral sphincter; IC, of those in nursing homes suffering from urinary ischiocavernosus; MUAP, motor unit action potential; NCS, nerve conduction 1,3,43 study; PAG, periaqueductal gray; PAR, peniloanal reflex; PMC, pontine mic- incontinence. Following hemispheric stroke, turition center; SCI, spinal cord injury; SEP, somatosensory evoked potential; urinary continence is the main determinant of dis- VLPP, Valsalva leak point pressure Key words: needle electromyography; nerve conduction study; urinary in- charge home within 6 months, independent of se- continence; urodynamic study; voiding dysfunction verity of hemiparesis.9 Correspondence to: M. Roberts; e-mail: [email protected]. The causes of storage and voiding dysfunction © 2008 Wiley Periodicals, Inc. Published online 14 June 2008 in Wiley InterScience (www.interscience.wiley. are myriad, diverse, and often multifactorial ranging com). DOI 10.1002/mus.21001 from a simple and reversible urinary tract infection

AANEM Monograph MUSCLE & NERVE July 2008 815 Table 1. Urinary incontinence. Symptoms and associated cough, laugh, sneeze, or other exertion which ele- conditions1 vates the intraabdominal pressure); urge inconti- Stress nence (which is accompanied by or immediately Inadequate pelvic support with urethral hypermobility preceded by urgency); or continuous leakage. Mixed Inadequate sphincter closure due to anatomic defect or urinary incontinence has features of both stress and functional impairment urge incontinence. While more descriptive, these Lower motor neuron injury categories still fail to define the underlying cause Retention (See text) Low compliance and any combination of these conditions may coex- Pharmacologic agents (adrenergic antagonists, e.g.) ist. In addition, leakage may be insensible and pa- Urge tients may not be able to characterize their urine Detrusor overactivity loss. Common conditions associated with these pre- Idiopathic sentations are indicated in Table 1. Voiding dysfunc- Neurogenic (upper motor neuron involvement) Continuous tion may result from impaired bladder contractility Fistula (due to sensory or motor defects), elevated outlet Ectopic ureter resistance, or a combination of the two. It is often Severe stress incontinence identified after a patient presents with urinary reten- Unrecognized detrusor overactivity tion and complaints of recurrent urinary tract infec- Retention (See below) Low compliance tion, urinary frequency, nocturia, or even incontinence, but patients with chronic urinary retention may be asymptomatic in spite of large volume retention (1,000 ml) and associated upper urinary tract injury.53,160 Some causes of urinary retention are to prostatic hypertrophy or cancer, urethral hyper- listed in Table 2. mobility with or without associated pelvic organ prolapse, pharmacologic effects, and neurologic dysfunction, anywhere along the neuraxis from the OVERVIEW OF NEURAL CONTROL brain to the spinal cord, or in the peripheral nerves Normal bladder function requires the integrity of or ganglia.36 extensive neurologic circuitry of the central and pe- Fortunately, neurourology, the study of the func- ripheral nervous systems supplied by the somatic and tion of the bladder, is a rapidly expanding field. autonomic nervous systems under both voluntary Since this monograph was originally written in and involuntary control.30 While many of the details 1977,35 more than 60,000 publications have ap- have not yet been elucidated, a sophisticated model peared on human bladder function/dysfunction in has been developed over the past eight decades with the English language. The explosion of interest and research with the concomitant emergence of tech- nology has provided new information on bladder function from the molecular level of the neuroepi- Table 2. Causes of urinary retention.1,53 thelium of the bladder wall to the cellular interac- Decreased contractility tion in the frontal cortex of the brain. It is the role of Lower motor neuron injury (cauda equina, radiculopathy neurophysiologists to elicit symptoms and clinical including herpes zoster or simplex, neuropathy) findings which are sometimes nonspecific or silent; Rapid overdistention such as with diuresis. Pharmacologic agents (e.g., anticholinergic) identify those patients in which neurological disease Decreased afferent function is potentially altering bladder function; and exam- Lower motor neuron injury (cauda equina, radiculopathy ine, diagnose, and ultimately ensure implementa- including herpes zoster or simplex, neuropathy) tion of optimal treatment. Analgesics (including alcohol) Outlet obstruction Prostatic hypertrophy (benign or malignant) BLADDER DYSFUNCTION Pelvic organ prolapse Stricture, stenosis, post-operative changes Urinary incontinence is defined by the International Stones Continence Society as “the complaint of any invol- Detrusor sphincter dyssynergia (upper motor neuron untary leakage of urine.”4 It may be a symptom, a dysfunction) sign, or a condition,1 but it is a nonspecific diagnosis Non-neurogenic neurogenic bladder (Hinman syndrome) or and fails to identify the underlying pathophysiologic pseudodyssynergia Pharmacologic agents (e.g., adrenergic agonists) process. It is sometimes categorized by the clinical Combined factors (e.g., diuresis and analgesia such as alcohol) presentation as stress incontinence (occurring with

816 AANEM Monograph MUSCLE & NERVE July 2008 supporting evidence drawn from experimentation in junction with the vascular supply of the area. Perti- animals, monitoring of normal human function, and nent effects of sympathetic stimulation include con- evidence drawn from clinical observation of patients traction of sphincter muscles, relaxation of smooth with neurologic lesions.7 muscle in the wall of hollow viscera, and constriction It is generally accepted that afferent information of blood vessels. The parasympathetic system has a regarding bladder filling is conveyed via the visceral more limited distribution, with no innervation of afferent fibers of the sympathetic and parasympa- somatic structures and no supply to blood vessels in thetic systems to neurons in the lumbar and sacral general.118 Parasympathetic stimulation results in re- spinal cord, and then to the periaqueductal gray laxation of sphincter muscles and contraction of (PAG).7,23,90 During urine storage the PAG main- smooth muscle in the wall of hollow viscera. In the tains input to an area of the ventral pons known as single instance of parasympathetic innervation of the L (lateral) region,7,23 which results in contrac- blood vessels, stimulation results in vasodilation of tion of the urethral sphincter and related muscula- vessels in the erectile tissue of the genitals and, ture to increase urethral closure pressure and main- hence, the pelvic splanchnic nerves may be referred tain continence.23,44 In contrast, at the appropriate to as nervi erigentes. level of filling and/or in the appropriate situation, Visceral afferent fibers supply the visceral perito- the PAG activates a region of the dorsomedial pon- neum, the pelvic organs, and the blood vessels. In tine tegmentum known as the M (medial) region, general, sympathetic afferent fibers mediate dull, analogous to the pontine micturition center (PMC) aching, poorly localized pain sensation, whereas or Barrington’s nucleus.7,23,90 This activates descend- parasympathetic afferent fibers convey visceral sen- ing pathways to excite parasympathetic neurons in sations including bladder distention, rectal fullness, the sacral spinal cord,90 resulting in increased intra- urge to urinate or defecate, and sexual sensations.28 vesical pressure while concomitantly stimulating in- However, parasympathetic fibers have been impli- hibitory interneurons which relax the urethral cated in mediating pain from all of the organs of the sphincter and facilitate flow.7,23,44 It is not clear what pelvis except the uterus.83,118 Both sympathetic and regulates the PAG.23,90 parasympathetic afferent fibers participate in vis- While the forebrain is not essential for the mic- ceral reflex activity. turition reflex, multiple forebrain structures are involved in the initiation of micturition. In particular, Sympathetic. The sympathetic efferent fibers to the the hypothalamus appears to have a role in activat- lower urinary tract originate in the intermediolateral 1,2 ing the PMC when the situation is deemed “safe” to cell column of the spinal cord at T10 to L2. They void. In addition, the cingulate gyrus and the pre- exit the spinal cord through the anterior root, inter- frontal cortex are thought to be involved in attention mingled with somatic efferent fibers forming the and response selection.23,25 spinal nerve and synapse in one of the nearby paravertebral ganglia of the sympathetic chain which join the anterior rami and continue peripherally with ANATOMY associated somatic segmental fibers to reach the pel- While the following discussion focuses on the lower vic floor. Alternatively, those fibers destined for the urinary tract, information regarding related systems bladder and urethra may pass directly through the is sometimes included due to common innervation paravertebral ganglia and exit as preganglionic vis- and interrelated symptoms, function, and examina- ceral or splanchnic nerves. These fibers may synapse tion. on one of the prevertebral or collateral ganglia on the anterior aspect of the aorta or internal iliac Peripheral Innervation. The bladder, the urethra, vessels such as the inferior mesenteric ganglia,2,118 and the associated striated musculature of the ure- before continuing inferiorly as the right and left thra and pelvic floor are innervated by three sets of hypogastric nerves which contribute to the pelvic peripheral nerves, each with efferent and afferent plexus. Other fibers pass through both the paraver- components. tebral and prevertebral ganglia before reaching the pelvic plexus, resulting in a dense complex of pre- Autonomic. The sympathetic system supplies both and postganglionic sympathetic and parasympa- somatic and visceral structures.118 In general, so- thetic fibers and ganglia. The pelvic plexus gives rise matic structures are innervated in a segmental fash- to multiple named and unnamed subsidiary plexi ion, along with the somatic spinal nerves to the area, and nerves including the vesical plexus to the blad- whereas visceral structures are innervated in con- der and the urethra38,118 and the cavernous nerves to

AANEM Monograph MUSCLE & NERVE July 2008 817 thetic system are typically microscopic and are located intramurally in the detrusor. Cholinergic excitatory transmission in the bladder is mediated via

muscarinic, primarily subtype M3, receptors. In addition, noncholinergic excitatory transmission is mediated by adenosine triphosphate acting on purinergic receptors.30 Postganglionic neurons innervating the bladder also contain neuropeptides, such as va- soactive intestinal polypeptide and neuropeptide Y and may modulate neurotransmission. Parasympa- thetic nerve fibers release nitric oxide which is in- hibitory to urethral smooth muscle.30,31 Sympathetic and parasympathetic afferent fibers are found in the hypogastric and pelvic nerves, respectively, as well as the many autonomic plexi of the pelvis, after originating in the proximal urethra and bladder2,15,38 As with all peripheral sensory nerves, the cell bodies are located in the spinal ganglia. The sympathetic fibers enter the spinal cord at T11 to L2 and the parasympathetic fibers enter at S2 to S4.38 FIGURE 1. The sympathetic, parasympathetic, and somatic path- Sensation from the bladder is carried predominantly ways of the pelvis. SPLN, splanchnic nerves; GR, gray rami; WR, in the parasympathetic system2,118 but there are white rami; BC, bulbocavernosus muscle; IC, ischiocavernosus some afferent fibers that travel in the hypogastric 32 muscle; SPH, sphincter. Adapted from de Groat and Steers in nerves to the spinal cord. Sensation from the prox- Roberts116 with permission from Lippincott Williams & Wilkins and Elsevier. imal urethra is also thought to be carried by both sympathetic and parasympathetic pathways.15 Somatic. The somatic efferent fibers to the pel- the urethral sphincter complex1,165 (Fig. 1). The vis originate from motor neurons in the anterior cell postganglionic fibers of the sympathetic nervous sys- column of the spinal cord at the lumbar, sacral, and tem produce excitation of the bladder base and coccygeal levels, with the sole purpose of innervating ␣ 114,118 urethra via 1-adrenoceptors or inhibition of detru- skeletal muscle. These fibers exit the spinal sor muscle via ␤-adrenoreceptors. Further, these fi- cord as the anterior root, form the spinal nerve with bers may inhibit bladder parasympathetic ganglia via the posterior root, and contribute fibers through the ␣ 2-adrenoreceptors, or facilitate bladder parasympa- anterior (or ventral) ramus to the lumbar and sacral ␣ 30,52 thetic ganglia via 1-adrenoreceptors. Based on plexuses. Anococcygeal nerves are formed from findings in animal studies, it appears that inhibition lower sacral and coccygeal anterior rami and spinal and facilitation occur at different firing frequencies, nerves. Somatic afferent fibers supply sensation to thus allowing the same mechanism to facilitate stor- the parietal layer of the peritoneum, as well as the age and emptying as appropriate.30 skin, muscles, tendons, and joints of the entire pelvis Parasympathetic. The parasympathetic efferent and perineum, including the outer urethra, vagina, fibers to the lower urinary tract originate as pregan- anus, and genitalia. These fibers travel proximally glionic neurons in the intermediolateral cell column along the same pathway to the posterior root and the of the spinal cord at S2, S3, and S4. As with the spinal ganglion containing the cell body before en- sympathetic fibers, they exit the spinal cord through tering the spinal cord through the lumbar, sacral, or the anterior roots, intermingled with somatic effer- coccygeal roots. These fibers convey pain, tempera- ent fibers forming the spinal nerves, continue in the ture, touch, vibration, and proprioception. anterior spinal rami, and finally travel via the pelvic Onuf’s Nucleus. A subgroup of closely packed, splanchnic nerves to ganglion cells in the pelvic atypical alpha motor neurons, collectively known as plexus, the subsidiary vesical plexus, cavernous Onuf’s nucleus (after the original description by nerves, and the wall of the bladder and ure- Onufrowicz) is located ventrolaterally within the an- thra38,52,118 (Fig. 1). Preganglionic synapses are nic- terior horns at S1 to S3 and provides innervation to otinic cholinergic, but they may be modulated by the urethral and anal sphincters and the levator muscarinic, adrenergic, purinergic, and peptidergic ani.2,143 The unique properties of these cells include input.30 The postganglionic fibers of the parasympa- anatomic features such as their uniformly smaller

818 AANEM Monograph MUSCLE & NERVE July 2008 size and dense dendritic bundling with extensive The detrusor muscle of the bladder is richly in- interconnections, as well as high numbers of norad- nervated by parasympathetic cholinergic nerve fibers renergic and serotonin terminals not seen in adja- with ganglion cells in the anterior portion of the cent cells. Their distinctive character is further sub- pelvic plexus (vesical plexus) as well as the bladder stantiated by their relative resistance to polio and wall itself. There are also sympathetic noradrenergic amyotrophic lateral sclerosis, both of which affect fibers to the detrusor but they are few in number and other anterior horn cells, and their selective involve- generally, though not exclusively, innervate the vas- ment in multiple system atrophy.15,88 cular supply.1,2,38,52 In contrast, the superficial tri- Pudendal Nerve. After forming on the posterior gone muscle has relatively few parasympathetic cho- aspect of the pelvis as part of the sacral plexus, the linergic nerves while sympathetic noradrenergic pudendal nerve exits the pelvic cavity below the fibers are prevalent. Sensory fibers have been iden- piriformis via the greater sciatic foramen. It reenters tified as a suburothelial plexus beneath the epithe- the pelvic cavity by curving around the sacrospinous lial lining of the bladder.2 It is somewhat sparse ligament just medial to the ischial spine and passing throughout the dome of the bladder, but becomes through the lesser sciatic foramen. Finally, it runs progressively denser approaching the trigone and forward along the lateral wall of the ischiorectal fossa bladder neck and extends into the urethra.38 in the pudendal (or Alcock’s) canal.2,118 There are The bladder neck, i.e., the internal urethral ori- three major branches of the pudendal nerve: the fice, is 3–4 cm behind the lower symphysis pubis. In dorsal nerve of the penis/clitoris that arises proxi- males the bladder neck rests on the prostate.2 At this mally and travels with the major trunk of the puden- level, smooth muscle forms a complete collar of dal nerve in the pudendal canal, continuing forward circular fibers surrounding the preprostatic urethra along the ischiopubic ramus to provide cutaneous to serve as an internal sphincter, with a well-defined supply to the clitoris/penis; the inferior rectal nerve adrenergic innervation which prevents retrograde which leaves the main trunk of the pudendal nerve ejaculation,1,2 but has an uncertain role in conti- within the canal and crosses the ischiorectal fossa to nence.2,38,52 In females the bladder neck is associated supply the lining of the lower anal canal, the exter- with the endopelvic fascia and supporting pubovesi- nal anal sphincter, and the skin around the anus; cal ligaments with smooth muscle extending from and the perineal nerve which divides into cutaneous the trigone and continuing obliquely or longitudi- branches to the posterior labia and lower vagina/ nally into the urethral wall. The circular smooth scrotum and ventral penis144 and distal urethra,2,15 muscle sphincter seen in the male is poorly devel- and muscular branches to the superficial and deep oped or absent1 and few adrenergic fibers are iden- perineal muscles, including the external urethral tified.38 In contrast to the male, the bladder neck of sphincter2 and parts of the levator ani.2,67,118 the female receives an abundant supply of cholinergic fibers.1,38,50 Bladder. The bladder is a muscular organ which resides in the pelvis when empty but expands into Pelvic Floor. The pelvic floor can be thought of in the abdominal cavity as it fills.1,2,118 It is composed of layers34 with the pelvic viscera and supporting en- an outer adventitial layer of connective tissue, an dopelvic fascia forming the first layer. The next layer inner mucosal layer consisting of transitional epithe- is the muscular diaphragm (Fig. 2) consisting of the lium (or urothelium) and submucosal lamina pro- levator ani and two muscles of the lower limb (piri- pria, and a middle muscular layer, the detrusor mus- formis and obturator internus). The piriformis arises cle.1,2,42 The muscle layer consists of circular smooth from the sacrum and the ilium and forms the pos- muscle situated between inner and outer layers of terolateral wall of the pelvis. The obturator internus longitudinal muscle, but large interlacing bundles of arises from the inner surface of the obturator fora- smooth muscle cells may travel between layers form- men, forming the anterolateral wall. Both attach to ing a meshwork.1,2,38 The trigone is a specialized area the greater trochanter.116,118 The levator ani is a of the bladder base extending from the two ureteric complex sheet of muscle arising from the posterior orifices to the internal urethral meatus. It is charac- aspect of the pubic bone, the inner surface of the terized by the presence of a superficial muscle layer, obturator fascia extending along the arcuate line to which is morphologically distinct from the deeper the ischial spine, and from the ischial spine it- trigonal detrusor, consisting of small diameter mus- self.115,118 Collectively, the fibers run down and back cle bundles which are continuous with those of the with varying degrees of obliquity to form a funnel intramural ureters above and the smooth muscle of which inserts into the anococcygeal ligament and the proximal urethra below.1,2,38,52 the coccyx posteriorly, while narrowing to encircle

AANEM Monograph MUSCLE & NERVE July 2008 819 FIGURE 2. Female pelvic diaphragm from above. Adapted from Mattingly and Thompson82 in Stenchever et al135 with permission from Lippincott Williams & Wilkins and Elsevier. and fuse with the urethra, the vagina (in females), sacrum and coccyx. In some cases it may be tendi- and the anal canal inferiorly.118 Although not well- nous rather than muscular.2 defined, several named regions are described, some- Just below the muscular diaphragm, the perineal times with variations in terminology between au- membrane, sometimes referred to as the urogenital thors. The pubococcygeus runs almost horizontally diaphragm, spans the anterior portion of the pelvic from the pubis to insert into the anococcygeal liga- outlet. It consists of striated muscles including the ment and the coccyx posteriorly. The most medial deep transverse perineal muscles as well as the com- fibers bordering the urogenital hiatus are often re- pressor urethrae and the urethrovaginal sphincter in ferred to as the pubovaginalis in the female and the the female.1,34,85 The urethral sphincter muscle in pubourethralis/levator prostate in the male. Posteri- the male is vertically oriented and does not contrib- orly, the muscle fibers encircle the anal canal, some- ute to the urogenital diaphragm.92 times blending with the longitudinal fibers of the The most superficial layer of the pelvic floor is rectal muscle. Inferiorly, muscle fibers from each the external genital muscles consisting of the bulbo- side unite with the contralateral fibers behind the cavernosus (BC) also referred to as the bulbospon- rectum to form a “sling” at the level of the anorectal giosus, the ischiocavernosus (IC) and superficial angle. This region of muscle, referred to as the transverse perineal muscles anteriorly, with the ex- puborectalis portion of the pubococcygeus muscle, ternal anal sphincter located posteriorly.34,118 In the maintains the anorectal angle which is critical for male the BC lies at midline anterior to the perineal anal continence.2,101 The iliococcygeus arises from body and runs forward with the contralateral sides the arcuate line and the ischial spine and runs pos- united by a median raphe. Its fibers encircle the bulb teriorly to join with fibers from the opposite side and of the penis and adjacent corpus spongiosum ex- form a raphe just superior to (and sometimes con- tending anteriorly to spread over the corpora caver- tinuous with) the anococcygeal ligament and the nosa. In the female the BC attaches to the perineal coccyx inferior to the attachment of the pubococcy- body and runs anteriorly on each side of the vagina, geus.2,118 The ischiococcygeus (sometimes referred covering the vestibular bulbs.2,118 to as a separate muscle, the coccygeus)118 is the most The levator ani is innervated on its pelvic surface posterior and superior portion of the levator ani, by small twigs arising directly from the S3, S4,101,118 arising from the ischial spine and running posteri- and sometimes S5 nerve roots.8 The anterior portion orly to insert on the lateral margins of the lower of the levator ani, particularly the puborectalis, may

820 AANEM Monograph MUSCLE & NERVE July 2008 FIGURE 3. Sagittal section of the male pelvis from the left. Adapted from Moore87 in Roberts116 with permission from Lippincott Williams & Wilkins and Elsevier. also receive some innervation from the pudendal three parts. Proximally, the urethral sphincter com- nerve,118 but the primary source of innervation for pletely encircles the smooth muscle of the urethral the puborectalis is direct branches of S3 and S4.8,101 wall, starting at the base of the detrusor and becom- The posterior portion of the levator, especially the ing fully developed in the middle one-third to two- ischiococcygeus, is thought to receive innervation fifths of the urethra, corresponding to the zone of from S5.115 The most superficial layer of pelvic floor maximal urethral closure pressure.1 More distally, at muscles (BC, IC, and transverse perineal) is inner- the level of the urogenital diaphragm, some of the vated on its inferior aspect by distal (perineal) muscle fibers surround both the urethra and the branches of the pudendal nerve.2,8,67,118 vagina as the urethrovaginal sphincter, while other fibers pass laterally to insert on the pubic rami form- Urethral Sphincter System. As indicated above, ing the compressor urethrae2,33,93 (Fig. 4). Again, there are differences between the male and female the periurethral sphincter is composed of the sur- urethral sphincter systems. In the male there is an rounding muscle fibers of the levator ani.2,38,51 internal sphincter composed of smooth muscle at The EUS is a striated muscle, composed almost the level of the bladder neck which is innervated by exclusively of small, type 1 fibers.2,26,38,51 While it may the sympathetic nervous system and functions pri- have a role in the maintenance of continence, it has marily to prevent retrograde ejaculation.1,2,38 The also been proposed as a sensory mechanism, providing external urethral sphincter (EUS), also known as the intramural sphincter or rhabdosphincter, consists of feedback to the bladder and periurethral muscle. This circularly oriented striated muscle surrounding the is particularly interesting, as the EUS is reported to be 2,38 smooth muscle of the urethral wall starting at the devoid of muscle spindles. The periurethral sphinc- base of the bladder and extending distally to the ter is a striated muscle, consisting of both type 1 and perineal membrane. It completely encircles this seg- type 2 fibers, but with a predominance of type 1 fi- ment of the urethra except where it is interrupted bers,38,51,123 making it well-suited for its role in the posteriorly by the prostate2,92 and corresponds to the maintenance of continence at rest, as well as during zone of peak urethral closure pressure1 (Fig. 3). As sudden increases in intraabdominal pressure. the urethra and EUS pass through the pelvic floor, The innervation of the urethra is surprisingly the adjacent fibers of the levator ani surround them complicated and controversial.26,67 The nerve supply as the periurethral sphincter.38,51 to the EUS is classically described as somatic fibers In the female no circular smooth muscle sphinc- from S2 to S4 that reach the EUS through the peri- ter can be identified.1,38 The EUS is composed of neal branch of the pudendal nerve.2,143 However,

AANEM Monograph MUSCLE & NERVE July 2008 821 FIGURE 4. Sagittal section of the female pelvis from the right. Adapted from DeLancey33 in Roberts116 with permission from Lippincott Williams & Wilkins and Elsevier. some investigators report that at least a portion,1,26 if branch of the pudendal nerve2,67,118 with significant not all,67 of these fibers take a separate intrapelvic crossover of the nerve supply occurring from one course, whereas others report that they travel side to the other.161 However, exceptions are com- through the pelvic plexus67 to the EUS. It is also mon, and perhaps even the rule. A ventral to dorsal claimed that parasympathetic fibers in the pelvic distribution of different branches of the pudendal plexus innervate the EUS.38 The innervation of the nerve, as well as spinal segments S2, S3, and S4, has smooth muscle of the urethra is autonomic, via the been described.46 Although the middle and dorsal pelvic plexus to the vesical plexus and cavernous portions of the EAS are supplied by the inferior nerves.1,52,143,165 The periurethral sphincter has gen- rectal nerve in the majority of cases, the pudendal erally been reported to be innervated by the perineal nerve itself, or its perineal branch, supplies the ven- branch of the pudendal nerve,16,38,118,130 but this tral portion up to 91% of the time.46 An appreciation must be further evaluated in light of mounting evi- of the variability in the innervation of the EAS is dence of nonpudendal innervation of the remainder important for the electromyographic (EMG) evalu- of the levator ani.8 ation of this muscle.

Anal Sphincter. The human external anal sphincter CLINICAL EXAMINATION (EAS) is an oval tube of striated muscle which surrounds the lowest portion of the anal canal.2,113 It is Although discussion of a complete neurologic exam- attached anteriorly to the perineal body and poste- ination is beyond the scope of this monograph, the riorly to the coccyx.2,118 It extends upward from the basic principles are familiar to all neurophysiolo- skin at the anal margin inferiorly to blend with the fi- gists. As always, adequate history is critical. In this bers of the puborectalis superiorly2,94,118,161 (Fig. 5). situation, in addition to routine questions used to The EAS is comprised of three anatomically distinct identify nervous system involvement, the intent is to layers: subcutaneous, superficial, and deep,94,118 but elicit symptoms of voiding dysfunction (hesitancy, the subcutaneous and superficial fibers are closely straining, incomplete emptying—perhaps with asso- associated, as are the deep EAS and the puborectalis. ciated daytime frequency and nocturia inconti- All four components are conjoined anteriorly in fe- nence, and/or frequent urinary tract infections) or males.94 The muscle is composed predominantly of incontinence (with stress symptoms such as leakage small (15 ␮m) type 1 fibers, as would be expected for with cough, laugh, sneeze, or with urgency, often a tonically active muscle.123 with associated daytime frequency and nocturia). The innervation of the EAS is classically de- Detailed questions regarding bowel and sexual func- scribed as being provided by the inferior rectal tion are also pertinent because of the common in-

822 AANEM Monograph MUSCLE & NERVE July 2008 FIGURE 5. Puborectalis and external anal sphincter from the right. Adapted from McMinn85 in Roberts116 with permission from Lippincott Williams & Wilkins and Elsevier.

nervation. Inquiry regarding autonomic dysfunc- ple, the presence of a dimple, hairy tuft, or abnormal tion, especially orthostatic hypotension, may also be gluteal cleft may indicate the presence of occult indicated. When possible, it is helpful to have the spinal dysraphism and should be further evaluated. patient complete a voiding diary indicating voided Finally, if possible, a postvoid residual should be volumes, as well as episodes of incontinence, for measured. Although bladder scanning is acceptable, several days prior to examination. the sterile specimen obtained with catheterization The basic physical examination of the nervous may be submitted for urinalysis and/or culture. system should be supplemented to include sensory testing of the lower abdomen, perineum, and prox- NEUROPHYSIOLOGIC TESTING imal lower extremities with correlation to findings in the lower extremities if abnormalities are identified. Urodynamic and EDX studies provide functional as- Pertinent reflex testing includes the anal wink and sessment of the lower urinary tract and its neural bulbocavernosus/clitoroanal reflex. Again, testing in control. As with any diagnostic test, these studies the lower extremities, such as the Achilles reflex, and must be ordered, performed, and interpreted in the flexor testing of the foot may be helpful to further context of the patient’s entire clinical picture. Eval- define the extent and type of lesion if identified. uation of the central nervous system should be com- Assessment of muscle function in the pelvic floor pleted when appropriate. Anatomic studies of the should include testing of perianal and perivaginal pelvis such as ultrasound, computerized tomography muscles (in females) with observation of initial rest- urography, and magnetic resonance imaging pro- ing tone, presence of contraction and lift of the vide complementary information and should be pelvic floor, as well as subsequent relaxation.114 Of used when indicated. In addition, functional testing course, the inability to contract may not indicate a of the lower gastrointestinal tract, such as colonic neurologic lesion. The patient may be uncomfort- transit testing with sequential lower gastrointestinal able or unfamiliar with testing. In addition, the im- films after ingestion of radiopaque markers, manom- pact of high resting tone, disuse and atrophy, or etry, and defecography may also provide relevant even muscle disruption should be considered as al- information. Finally, while the subsequent discus- ternative sources of weakness. Again, correlation sion focuses on testing of the bladder and muscles with the examination of other proximal and lower and nerves of the pelvis, other tests of autonomic extremity findings is essential. Inspection of the pa- function as well as nerve conduction studies (NCSs) tient’s lower spine may also be revealing. For exam- and EMG examination of the trunk and limbs may

AANEM Monograph MUSCLE & NERVE July 2008 823 be necessary to define the extent of abnormalities Most patients with neurologic impairment and should they be identified. lower urinary tract signs or symptoms should un- Prior to testing, these procedures should be fully dergo urodynamic testing to characterize the func- explained to the patient.109,116 If voiding is to be tion of the bladder, the urethra, the pelvic floor, and monitored the patient should be asked to avoid uri- their coordination.1,43,56,91,113 Indications include nating prior to arrival in the clinic. Otherwise, the central nervous system lesions such as stroke,119,120 patient should be given the opportunity to use a spinal cord injury,68,157 and multiple sclerosis,20,79 private toilet immediately prior to testing. After re- and peripheral nervous system disorders such as moving the undergarments, the patient should be cauda equina syndrome108 and diabetic neuropathy draped appropriately in a warm, secure room. A with cystopathy,27,64 as well as combined disorders urodynamics chair may accommodate both urody- such as myelodysplasia (e.g., in which testing is indi- namic and EDX testing. Alternatively, the patient cated within the first months of life to direct appro- may be positioned on his or her side or supine with priate management and prevent upper urinary tract the legs gently spread apart or placed in stirrups for injury).14,126 Exceptions are the few diseases in which EDX testing. If needle or wire EMG is planned, empirical, conservative therapy can be safely imple- anesthetic cream containing 2.5% lidocaine and mented56 (e.g., incontinence following cortical 2.5% prilocaine (EMLA cream by Astra, Westbor- stroke without associated urinary retention) with ough, Minnesota) may be applied periurethrally subsequent urodynamic testing if management is and/or perianally 20 min prior to needle insertion. unsuccessful. Of course, testing may also be helpful The ground electrode may be placed on the proxi- in identifying neurologic involvement. mal thigh. If a reference electrode is required, it may be placed on the mons pubis or on the ipsilateral Uroflowmetry. Uroflowmetry is a simple, noninva- proximal thigh. sive study of bladder emptying performed by measuring urine flow during voiding.1,91,122,137 Ideally, URODYNAMIC TESTING this study is done after a patient arrives with a com- fortably full bladder (with a minimum of 150–200 Urodynamic testing generally refers to any/all of a ml) because flow is influenced by the voided volume. series of functional tests used to assess lower urinary However, it is often impossible for patients to comply tract storage and/or emptying.1,56,62,113,137 Methods with this request due to urgency, frequency, and/or range from simple noninvasive procedures such as incontinence, and artificial filling may be required. uroflowmetry to highly sophisticated and invasive After uroflowmetry, the postvoid residual is deter- techniques such as videocystometrography. Testing mined with ultrasound or catheterization to deter- is tailored to the individual patient depending on mine adequacy of emptying and to allow calculation the nature of the clinical picture, much as various of the total volume in the bladder. The data are EDX tests are performed to investigate a patient’s usually displayed as a graph of urine flow in millili- nervous system. While urodynamic testing is indi- ters versus time in seconds. The normal shape of the rect, it documents various aspects of bladder and curve is a smooth, continuous, slightly asymmetric sphincter function, allowing inferences to be made bell curve which reaches its peak in the first third of regarding peripheral somatic and autonomic, as well flow (Fig. 6). Key measures include maximum and as central nervous system function in the context of mean flow rates, voided volume, and flow time. Re- the patient’s clinical picture. It is the best tool avail- sults are nonspecific because flow is determined by a able for the investigation of sacral parasympathetic combination of abdominal pressure, detrusor pres- activity.18 sure, and outflow resistance, but they provide a rea- The goal of urodynamic testing is to reproduce sonable screen of voiding function when normal. In the patient’s symptoms while monitoring the lower addition, this approach is most likely to document urinary tract to provide an objective description of its the patient’s typical flow pattern because the study function and/or dysfunction. Abnormalities are not can be performed before examination or instrumen- specific for a particular diagnosis, but facilitate iden- tation of any kind. It can then be compared with data tification of pathophysiology and contribute to diag- collected subsequently with catheters and other nosis, prognosis, and ultimately, implementation of monitors in place. optimum management.1,56,122,137 Unfortunately, the Patients with neurologic impairment may have nature of the study makes it prone to artifact and this reduced flow, due to impaired detrusor contractility must always be considered in the interpretation of or because of outlet obstruction such as detrusor results.62 sphincter dyssynergia (DSD). Flow may be irregular

824 AANEM Monograph MUSCLE & NERVE July 2008 water may be utilized to reproduce symptoms. Rapid filling at nonphysiological rates with cool filling me- dia may enhance detection of uninhibited detrusor contractions, but these maneuvers may also induce artifactual detrusor activity in patients with suprasacral injury and are used selectively. Graphic representation of the data as time in seconds versus fill volume in milliliters, vesical, ab-

dominal, and detrusor pressure in cmH2O and EMG activity allows analysis of related events, as well as identification of artifact (Fig. 7). Key measures include the bladder volume at first sensation of fill and normal and strong desire to void, the volume when uninhibited detrusor contractions appear (if present) and if they are detected by the patient, the compliance and capacity of the bladder, and the occurrence of incontinence. If there is incontinence with abdominal pressure elevation in the absence of a detrusor contraction, a diagnosis of urodynamic FIGURE 6. Normal uroflowmetry. Peak flow rate 44 ml/s. Mean 4 flow rate 23 ml/s. Flow time 14 s. Voided volume 340 ml. Vmic, stress incontinence is made and the Valsalva leak voided volume; Qura, flow rate. point pressure (VLPP) is determined. The VLPP is the minimum vesical pressure elevation sufficient to induce leakage4 and is a measure of continence. In due to abdominal strain voiding in the absence of contrast, if there is uninhibited detrusor activity detrusor function, fluctuating detrusor contractility, present, the detrusor leak point pressure (DLPP) is or variable outlet resistance as may also occur with determined. The DLPP is the minimum detrusor DSD or other sphincter and pelvic floor dysfunction. pressure sufficient to induce leakage and is a mea- Of course, abnormal waveforms with the same char- sure of storage pressure in the urinary tract. The acteristics may be observed in patients without neu- DLPP is also determined when leakage occurs in the rologic involvement and normal waveforms may be absence of increased abdominal pressure or a detru- produced via abnormal mechanisms in patients with sor contraction, as may occur with an underactive or neurologic disease.1,122,137 acontractile detrusor, when passive vesical pressure exceeds outlet resistance. Cystometry. Cystometry is the measurement of the intravesical pressure during filling and/or emptying Pressure Flow Studies. Pressure flow studies are the of the bladder.1,62,137 Because vesical pressure is the simultaneous recording of detrusor pressure and sum of the detrusor pressure and the abdominal urine flow during voiding. This combination allows pressure, detrusor pressure is calculated by measur- assessment of the voiding mechanism which is ing the abdominal pressure (in the rectum or va- not possible with uroflowmetry or cystometry gina) and subtracting from the vesical pressure. Si- alone.4,91,137 The addition of kinesiologic assessment multaneous recording of EMG activity from pelvic of the pelvic floor with monitoring of EMG activity floor muscles allows assessment of the pattern of enhances interpretation, particularly in the presence firing during filling and emptying. Activity is typically of obstructive flow patterns. It is helpful in any pa- recorded from the anal or urethral sphincter with tient with retention or suspected dysfunctional void- surface or wire electrodes. ing but is especially important in the presence of During filling, every attempt is made to repro- neurologic disease.1,62,113 Videourodynamic studies duce symptoms such as incontinence or pathological performed with fluoroscopy and the addition of a conditions, such as elevated detrusor pressure, while radiopaque contrast material to the filling medium the patient provides input. Information is collected may also be helpful in this setting. Normal voiding is regarding sensation, detrusor activity, compliance, initiated with relaxation of the external urethral capacity, and incontinence if it occurs. Depending sphincter and contraction of the detrusor muscle on the clinical picture and goals of the test, provoc- with subsequent onset of urine flow producing a ative measures such as coughing, straining, standing, smooth continuous waveform, as described above, bouncing on the heels, and listening to running followed by detrusor relaxation and resumption of

AANEM Monograph MUSCLE & NERVE July 2008 825 FIGURE 7. Filling cystometrogram documenting an uninhibited detrusor contraction and DSD. Pves, vesical pressure; Pabd, abdominal pressure; Pdet, detrusor pressure; VH2O, infused volume.

sphincter activity. Abdominal pressure rises mini- ELECTRODIAGNOSTIC TESTING 1,21,113,146 mally or not at all (Fig. 8). Key measures EDX testing generally refers to the combination of include the voided volume, maximum flow rate, and NCSs and EMG used in the physiological assessment detrusor pressure at maximum flow. Following com- of the peripheral nervous system. It may also provide pletion of the study the postvoid residual is deter- information regarding function of the central ner- mined to calculate the cystometric capacity. vous system, albeit indirectly in most applications. Patients with lower motor neuron dysfunction The following descriptions are limited to studies may have impaired sensation and an elevated capac- pertinent to the evaluation of lower urinary tract ity with high compliance, the detrusor may be un- function. deractive or acontractile, and there may be associ- In this context, EDX testing is indicated for the ated stress and/or “overflow” incontinence with an evaluation of urinary incontinence and/or voiding elevated residual. These findings are exemplified by dysfunction that may be attributed to a peripheral patients with diabetic cystopathy.27,44,64 Patients with nervous system lesion. Involvement may be sus- upper motor neuron dysfunction may also have im- pected on the basis of congenital abnormalities such paired sensation but the capacity is often low, com- as spinal dysraphism, trauma (including surgery) to pliance may be reduced, and (neurogenic) detrusor the pelvis or sacrum, or more widespread disease overactivity with incontinence is common. The resid- such as multiple system atrophy.88,162 Alternatively, a ual may be elevated in spite of high voiding pressures combination of clinical findings such as fecal incon- due to DSD.1,68,157 Essentially any combination of tinence, sexual dysfunction, and/or lower extremity these features may also occur. In each case, specific symptoms in addition to urinary incontinence or measures of function are clinically relevant, not only retention without an apparent cause may suggest an to direct symptomatic treatment, but also to avoid underlying neurological etiology.151 Patients with upper urinary tract deterioration which is associated unexplained urodynamic findings, particularly the with low compliance, DSD, and a DLPP of more than combination of an acontractile bladder and stress 20.76,84,126,157 40 cmH2O. incontinence, or urinary retention in a young wom-

826 AANEM Monograph MUSCLE & NERVE July 2008 FIGURE 8. Multichannel pressure ﬂow tracing documenting a typical void. Note detrusor contraction with mildly delayed muscle relaxation at onset of voiding followed by superimposed abdominal strain with associated increase in muscle activity nearing termination of voiding.

VH2O, infused volume; Pves, vesical pressure; Pabd, abdominal pressure; Pdet, detrusor pressure. an70 should also be evaluated. EDX testing is not stimulus and the response, defining the pathways indicated for the routine evaluation of patients with more precisely, and increasing the specificity of the incontinence or voiding dysfunction.149,151 Neither is data obtained, in addition to measuring the latency it useful as a screening tool for neuropathic le- and increasing the sensitivity of detection.22,158 sions.104 While current convention refers to all somatic reflexes as the bulbocavernosus reflex, this is nonspe- Nerve Conduction Studies. Sacral Reflex Testing. cific and sometimes misleading with multiple poten- Sacral reflexes are the contraction of the perineal tial stimulation and recording sites. No consensus muscles in response to stimulation of the perineum, has been reached, but nomenclature has been pro- urethra/bladder, or anus.145,151,152 Testing of the sa- posed which identifies the stimulating and recording cral reflexes assesses the integrity of the sacral spinal sites in the name.105 cord at S2 to S4 as well as the associated afferent and The sacral reflexes that have the most general efferent pathways.5,124,151 The afferent pathway of application in the EDX laboratory are the peniloanal the reflex may be somatic, sympathetic, or parasym- reflex (PAR) and penilobulbocavernosus reflex in pathetic, depending on the site of stimulation, but the male and the homologous clitoroanal reflex the efferent pathway is somatic and usually moni- (CAR) in the female. The urethroanal reflex and the tored in muscles innervated by the pudendal nerve. bladder (or vesico) anal reflex, sometimes referred Two of these reflexes are commonly used clinical- to as viscerosomatic reflexes, have potential utility in ly145,151: the bulbocavernosus reflex, elicited with patients with focal anatomic injury to the urethra, compression of the glans penis or clitoris, and the involvement of the bladder, and/or pelvic inju- anal reflex, elicited with pinprick of the mucocuta- ry,13,18,151 but have remained primarily limited to neous junction of the anus. In each case a response research thus far.151 The anal (or anoanal) reflex, may be observed or palpated in the bulbocavernosus which is a nociceptive reflex with wide variability in muscle or the anal sphincter. latencies, is not commonly used.151 Interestingly, a With electrical stimulation, sacral reflexes may be perineal response may also be observed during test- elicited from virtually any site in the lower sacral ing of the flexor response of the foot, or with poste- dermatomes or the lower urinary or gastrointestinal rior tibial nerve stimulation.58,99 This reflex provides tract.105 Recordings may be made from any of the an afferent pathway in an anatomically distinct re- perineal muscles or sphincters using surface or nee- gion which could be diagnostically useful, but it has dle electrodes. Thus, it is possible to isolate both the not been widely investigated or applied.

AANEM Monograph MUSCLE & NERVE July 2008 827 FIGURE 9. Clitoroanal reﬂex. Top trace with no stimulation. Second trace with volitional contraction. Third and fourth traces superimposed reﬂex responses with onset latency 50 ms and volitional response at 145 ms.

Peniloanal/Clitoroanal Reflex. The PAR/CAR uti- it.5,15,58,74,151,158 Finally, volitional responses may also lizes pudendal nerve afferent and efferent pathways, be recorded following the reflex response158 (Fig. 9). as well as the sacral roots and sacral spinal cord with Averaging is typically not used due to variation in suprasacral modulation during voiding.124 In the waveforms. The onset latency is recorded from each male the reflex is elicited by stimulating the dorsal side with typical mean latencies of 31–38.5 ms.147,151 nerve of the penis with either ring electrodes on the However, the range of reported latencies is wide in glans and shaft of the penis or with a standard bipo- individual normal subjects, with one report docu- lar stimulator at the base of the penis with the cath- menting latencies up to 102 ms.158 Also, it has been ode proximal. The response is recorded from the shown that latencies vary up to 2 ms with different EAS with a surface or needle electrode.19,145,152 It is recording sites within the same muscle152 and 2–7 ms also convenient to record with a surface electrode on from side to side.5,74,106 Therefore, disparities must an anal plug inserted into the anus to record from be interpreted cautiously. Krane and Siroky74 re- the anal sphincter.48 However, this electrode does ported lesion localization to the right or left and not allow for unilateral recording. The reflex may efferent or afferent pathways by virtue of the unilat- also be recorded from the BC muscle5,47,74,106,163 or eral afferent and bilateral efferent pathway of the the EUS.22,58,124,145,152 In the female the reflex is reflex. Others have corroborated this finding.18,47 It elicited with transcutaneous stimulation of the dor- has been debated by some authors,5 but Recht- sal nerve of the clitoris on either side of the base of hand112 nicely demonstrates the elicitation of a bi- the clitoris.155 The response is recorded from the lateral response in spite of unilateral dorsal nerve EAS with either needle or surface electrodes as indi- block. The PAR/CAR is inhibited during voiding41 cated above. and some,124 but not all,145 authors have found loss Adequate stimulation intensity is important to of inhibition to be a sensitive and specific indicator elicit the response and most laboratories report the of suprasacral lesions. use of 3–4 times the sensory threshold,47,112,158 but As with other NCSs, a supramaximal stimulus is responses are sometimes elicited at higher intensi- required to record the most robust response with the ties.5,111,148 Paired stimuli (2–5 ms apart) may also be shortest latency. However, as the stimulation inten- necessary to facilitate the response even in normal sity increases reflex contractions may be elicited in individuals and the response should not be consid- any of the perineal muscles. In addition, with high- ered absent with single stimuli.18,58,109,147,151 An ini- intensity stimulation there may be short latency re- tial, oligosynaptic response is recorded which is sta- sponses, at 5–13 ms, due to direct, rather than reflex ble and does not habituate. A second component stimulation of the nerve, and these responses may with a longer latency has also been described, but it initially be confusing.145,151,152 Because sacral re- is less consistently identified as a discreet response flexes are based on conduction (and not amplitude), and may require higher stimulation intensity to elic- they are not sensitive to incomplete lesions, whether

828 AANEM Monograph MUSCLE & NERVE July 2008 demyelinating or axonal. Thus, a normal response at 2–4 times the sensory threshold and cortical po- does not exclude a lesion.150,151 Finally, most authors tentials are recorded from CzЈ with reference to Fz report difficulty eliciting the sacral reflexes in some or Fpz. One hundred to five hundred responses are normal patients.15,145,148 averaged and then repeated to document reproduc- Sacral reflex testing may be helpful in evaluating ibility. The potential is readily elicited and consists of lower motor neuron/peripheral nervous system le- a positive peak, with amplitudes of 0.5–12 sions of the conus, sacral roots, plexus, or branches ␮V,138,147,148 designated as P1 or P40 (with a normal of the pudendal nerve.15,22,74,150,151,158 With a com- range of 30–49 ms)40,47,59,148,164 followed by a series plete lesion, the reflex is absent. An incomplete of additional waveforms which are more variable and lesion may be associated with a prolonged latency of uncertain significance.15,40,138,147,148,151 Ampli- and a diminished or absent response. However, to tudes have not been found to discriminate between reiterate, a normal response does not exclude a normal and pathologic responses.35,47,138 It should lesion. It is also important to note that even mark- also be noted that even experienced authors report edly prolonged latencies may be associated with nor- some difficulty recording bilateral responses in all mal bladder and sphincter function, as has been women.40,164 A spinal potential may be recorded in documented in patients with hereditary motor and men from T12 to L1 with reference to the iliac crest sensory demyelinating neuropathy.153 Finally, an un- or spine, but it is difficult to record in women, likely usually short latency has been documented in cases due to activation of small numbers of afferent fibers. of tethered cord syndrome and should not be disre- It is also difficult to record in obese male subjects garded.60 Thus far, sensitivity and specificity of sacral and it is not routinely performed.40,151 The some- reflexes have not been determined and clinical rel- what slower conduction in the pudendal response, evance has not been clearly demonstrated.147 compared to that in the tibial response, has been attributed to slower conducting spinal pathways.15 Somatosensory Evoked Potentials. Somatosensory Although this technique is technically feasible, evoked potentials (SEPs) are waveforms recorded and theoretically appealing, its utility in the evalua- from the peripheral and central nervous system after tion of urologic function is limited.109,151 For exam- activation of afferent nerve fibers.18,40,151 Large-di- ple, peripheral neuropathies which may affect the ameter myelinated afferent fibers from the urogen- bladder, particularly if there is small fiber involve- ital region and lower extremities generate impulses ment44 that could be expected to involve the puden- which enter the spinal cord and travel rostrally in the dal sensory fibers. In general, EDX studies are more ipsilateral dorsal columns, synapse in the nucleus appropriately performed in the limbs to make the gracilis, and cross to the contralateral brainstem to diagnosis of a neuropathy and urodynamic testing continue rostrally as the medial lemniscus and ter- provides more useful information regarding bladder minate in the ventral posterolateral thalamic nucleus function. Further, in patients with diabetic neurop- (VPL). Neurons in the VPL project to the somato- athy, abnormal tibial SEPs were correlated with both sensory cortex. An additional pathway in the spi- the presence of lower urinary tract symptoms and nomedullothalamic tract may also participate in urodynamic abnormalities, while abnormal puden- transmission of these impulses.40 The somatosensory dal SEPs were not.111 Central nervous system lesions region representing the urogenital region and lower in these pathways are also more likely to be identi- extremity is located along the medial aspect of the fied with tibial SEPs. Even in patients with multiple cerebral hemisphere. sclerosis and bladder symptoms, the tibial SEP is SEPs may be used clinically to investigate conduc- more likely to be abnormal than the pudendal tion in neural pathways extending from the periph- SEP.117 In patients with urologic complaints but no eral site of stimulation to the parietal sensory cortex. other neurologic symptoms and a normal neuro- The tibial SEP is a routine study with well-established logic examination, pudendal SEPs are unlikely to be techniques and normal values for evaluation of L4 to abnormal.35 S2(S3)2 pathways from the lower extremity and will In patients with acute, traumatic tetraplegic SCI, not be discussed here. The pudendal SEP with S2 to recovery of both bladder and urethral sphincter S4 pathways from the pelvis is sometimes used in an function correlate better with the American Spinal attempt to evaluate urologic function more specifi- Injury Association (ASIA) score and tibial SEPs than cally. It is elicited with stimulation of the dorsal with pudendal SEPs. However, if a pudendal SEP can nerve of the penis or the dorsal nerve of the clitoris be elicited, at least some recovery of bladder func- using ring or bar electrodes, as indicated above for tion can be predicted. In patients with acute para- the sacral reflexes.40,47,97 Stimulation intensity is set plegic SCI, ASIA scores, tibial and pudendal SEPs are

AANEM Monograph MUSCLE & NERVE July 2008 829 all predictive of recovery of urethral sphincter func- nerve terminal motor latency [PeNTML]) may also tion but not of bladder function. The pudendal be recorded from the urethral sphincter with a bi- SSEP appears more sensitive than the tibial SSEP in polar surface electrode mounted on a Foley cathe- this regard.29 SEPs have also been elicited from the ter.133 Typical latencies of 1.9 ms and 2.4 ms were urethra and bladder in an attempt to assess transmis- initially reported to the anal sphincter and urethral sion along small unmyelinated autonomic afferent sphincter, respectively,133 but the range reported in fibers.59 The proximal urethra or bladder is stimu- normal subjects is quite variable, from 1.4 to 5.6 lated with a bipolar surface electrode mounted on a ms77,96 to the anal sphincter and 1.7 to 3.8 ms to the Foley catheter. (Use of monopolar stimulation with urethral sphincter.96 As with all NCSs, the terminal the anode on the skin has been demonstrated to motor latency is determined by the fastest response stimulate somatic afferent nerves and the bipolar with axonal integrity. In this case, the stimulation site technique is used to minimize their activation.)59 is fixed (at the ischial spine) without measurement Cortical responses are recorded from CzЈ referenced of the nerve pathway in spite of differences due to to Fz. The most prominent and reproducible poten- patient size or position of the perineum. Further, the tial is a negative peak with a latency of Ϸ100 ms, distance between the stimulation site and pickup though earlier components may be identified. Am- changes as the examiner positions the electrode to plitudes are low, typically less than 1 ␮V, and config- obtain an optimal waveform. Latencies are not only uration is variable, making it difficult to identify even variable, but curiously short when compared to an- in some normal subjects.15,59,147,151 These factors, as tidromic sensory responses recorded with this tech- well as the requirement for placement of the ure- nique5 or to other motor conduction techniques thral ring electrode, which is somewhat uncomfort- using transperineal stimulation.100,152 In addition, able, particularly in men, have limited its use. How- the response may be absent or uninterpretable in up ever, if the response is present it may help exclude a to 30% of studies even in experienced laborato- subpontine lesion in patients with bladder dysfunc- ries.55,159 Due to local anatomy, it is not possible to tion.15 stimulate a second site; thus, a nerve conduction velocity cannot be obtained. Neither is it possible to Pudendal Nerve Conduction Studies. In 1984 Kiff localize focal changes in myelination if they are and Swash72,133 described a method for the transrec- present. tal stimulation of the pudendal nerve. The initial Anatomical factors which may be confounding reports were enthusiastically received. The tech- the technique include the proximity of the sacral nique was refined, commercially available electrodes nerve branches to the levator muscle near the ischial were produced, and studies were performed to de- spine where stimulation occurs.8 In addition, the velop normative data based on age, gender, and recording site is over multiple components of the parity.72,77,96 Prolonged pudendal nerve latencies sphincter mechanism, including the puborectalis were reported in obstetrical lesions, constipation, and all the layers of the EAS. Studies using sacral perineal descent, and fecal and urinary inconti- magnetic stimulation with needle recording elec- nence.67,71,72,127,129,131,132,134,136 Unfortunately, a trodes in each muscle of the sphincter mechanism number of issues related to this approach are now have documented the shortest latency to the pubo- apparent and the utility of the test has been ques- rectalis, with increasing latencies to the deep, super- tioned and found lacking.11,45,55,61,78,98,149,151 To perficial, and subcutaneous EAS with differences of 5.0 form the study, the St. Mark’s electrode (Dantec, ms or more from deepest to most superficial.121 Si- Skovlunde, Denmark) is affixed to the examiner’s multaneous recordings of latencies with surface elec- gloved hand with a bipolar stimulating electrode at trodes and needle electrodes may be similar, have the tip of the index finger and recording electrodes different responses, or even be present in one and at the base of the finger. The finger is inserted absent in the other.45 vaginally or rectally and the pudendal nerve is stim- The amplitude of the response, which would pro- ulated as it reenters the pelvis near the ischial spine. vide information regarding axonal integrity, has not The response of the inferior rectal nerve is recorded been reliable. This may be due to anatomic factors as from the anal sphincter with the electrodes at the above, but it is also likely influenced by positioning base of the index finger (or with surface electrodes of both the active and the reference electrodes over over the anal sphincter) as the pudendal nerve ter- the sphincter muscle. While the contribution of the minal motor latency (PNTML).72 Because the pu- reference electrode has not been systematically stud- dendal nerve branches distal to the stimulation site, ied, this configuration likely reduces the amplitude the response from the perineal nerve (perineal and may have other unrecognized consequences as

830 AANEM Monograph MUSCLE & NERVE July 2008 well.10 Finally, correlation with function has not eral unique features of which the EDX physician been demonstrated.45,98,142,159 must be aware. Normal MUAPs may have low ampli- Theoretically, in spite of these limitations, pu- tudes (with mean values of 300–600 ␮V but individ- dendal nerve stimulation could be useful in distin- ual units of 50–200 ␮V)18,21,37,54 and short duration guishing an upper motor neuron lesion from a lower (with mean values of 5–7 ms but individual units of motor neuron lesion if a response is obtained. It also 3ms)18,37,54,110 with complexity in as many as 15%– has potential utility in differentiating axonotmesis 30% of units examined with concentric needle from neurotmesis but clinical queries of this type are EMG.49,147,156 Thus, it may be difficult to identify uncommon. It has been used to optimize stimulator and/or differentiate changes reflective of myogenic placement during neuromodulation17 and it may (and/or neurogenic) involvement.115,139,149,151 Also, have a role in monitoring acute change, particularly normal sphincter muscles are tonically active15,21,37 for research purposes. However, routine use of this and most patients are unable to completely relax technique cannot be recommended.11,45,151 them, except during normal reflex inhibition of the pelvic floor during voiding.15,21,144 The combination Electromyography. As with muscles in other areas of of these factors may make it difficult to distinguish the body, EMG of the pelvic floor may be performed fibrillation potentials from MUAPs.88 with various surface electrodes, fine wire electrodes, The selection of muscles for examination follows or needle electrodes. Selection is determined pri- the principles common to all needle EMG studies marily by the type of information required and the and is determined with thoughtful consideration of ease and comfort of application, but other factors both the ease of examination and the amount of such as cost and examiner familiarity may also be discomfort to the patient, as well as the diagnostic considered. Surface electrodes are noninvasive and information to be gained. As all relevant pelvic floor easy to apply but not all muscles are accessible and muscles are innervated by several sacral nerve roots, specificity is limited by volume conduction. They are any normal muscle may suffice to exclude a diagno- useful for monitoring the presence or absence of sis of cauda equina syndrome if deemed a sufficient activity, and may provide kinesiologic data during sample based on the clinical setting. However, once urodynamic testing.1,116,151 Fine wire electrodes have an abnormality is identified, additional studies are the additional advantages of precise and stable place- required with evaluation of both pudendal- and non- ment, even during provocative testing for inconti- pudendal-innervated muscles to determine the ex- nence and voiding, with less susceptibility to volume tent of involvement. If only pudendal-innervated conduction, but they are more invasive. In addition, muscle is involved, consideration should be given to after placement, wires may not be relocated. Investi- evaluation of muscles innervated by the perineal and gation of specific muscle fiber and motor unit activ- the inferior rectal branches to further localize the ity, such as insertional and spontaneous activity, mo- site of the environment. Disparate findings have tor unit action potential (MUAP) morphology, and been well documented between the EUS and EAS as recruitment requires needle EMG. This approach well as other muscles of the pelvic floor.21,37,62,145,146 also allows accurate localization, with the option of Alternative strategies may be appropriate for the repositioning as needed. The application of quanti- selection of muscles in other clinical settings. For tative analysis to needle EMG provides automatic example, the EAS is often selected for the assessment measurement of amplitude, duration, area, number of sphincter involvement in atypical parkinsonism. of phases and turns, rise time and duration of neg- In contrast, the EUS must be included in the evalu- ative peak, and mean frequency of firing with calcu- ation of urinary retention in a woman with possible lation of thickness and size index.54,89,110,156 Single- Fowler’s syndrome.70 A protocol for the examination fiber EMG has also been used extensively72,130,136 to of the pelvic floor has been proposed by Podnar and determine fiber density as an index of reinnervation, Vodusek109 and may serve as a guide. but is primarily limited to research applications.151 Even with thorough investigation, it is not always All findings on needle EMG are nonspecific and possible to clearly define the site of injury, particu- must be interpreted based on the electrophysiology larly in proximal lesions, such as the cauda equina, of muscle, in the context of the patient’s clinical because paraspinal abnormalities are not present picture, to establish the most likely underlying pro- due to the lack of sacral innervation. The picture cess.39,69 Previous urethral or anal procedures, may be further complicated if multiple lesions exist sphincter defects, or obstetric trauma and repairs and/or confounding issues such as previous surgery should be noted. Interpretation of needle EMG find- or obstetric trauma coexist. In spite of these limita- ings in the sphincters is further complicated by sev- tions, needle EMG is the most informative tool in the

AANEM Monograph MUSCLE & NERVE July 2008 831 evaluation of focal lesions in this group of patients, ing the BC reflex.5,115,116 Examination of the BC documenting the integrity or involvement of the muscle is not routinely performed in women. peripheral nervous system, defining the severity, External Anal Sphincter. The EAS is easily acces- and contributing to the diagnosis and progno- sible and provides information about the integrity of sis.109,147,149,151 the sacral roots and plexus, the pudendal nerve, and External Urethral Sphincter. The EUS has a fun- the inferior rectal nerve branch (except anteriorly). damental role in maintenance of urinary continence While examination of the subcutaneous fibers is the- and in voiding. Assessment is critical in the diagnosis oretically adequate to evaluate the integrity of the of Fowler’s syndrome.70 Examination provides infor- conus medullaris and cauda equina,103,107 it provides mation about the integrity of the sacral roots and limited sampling, and the sensitivity increases 18% plexus, the pudendal nerve, and the perineal nerve with the additional examination of the “deeper” su- branch. perficial and deep EAS muscle.103 In addition, the In the female the EUS may be approached superficial and deep EAS muscles participate in transvaginally or periurethrally. The transvaginal sphincter function while the subcutaneous fibers do approach is theoretically less painful, as the vagi- not. Thus, their examination is particularly relevant nal wall has a relative absence of pain fibers and in patients with anal incontinence. Examination is specialized sensory nerve endings.80 However, performed with a 37- or 50-mm needle electrode while comparison of the two approaches docu- directed perpendicular to the skin 1 cm inside the mented higher pain scores with periurethral ex- mucocutaneous junction.107 The subcutaneous por- amination, patients reported mild to moderate tion of the muscle is encountered within the first 2–5 pain with both methods and the difference was not mm. The needle is then directed medially, toward significant.95 Furthermore, twice as many MUAPs the anal canal, and advanced until the superficial were identified using the periurethral technique. and deep muscles are entered at a depth of 1–5 In this approach, 20 min after the application of cm19,107,115 (Fig. 5). anesthetic cream, a 25-mm needle electrode is Levator Ani. The levator ani provides informa- inserted Ϸ5 mm anterior or lateral to the urethral tion about the integrity of the sacral roots and has meatus and advanced 10–20 mm while listening the distinction of nonpudendal innervation which for EMG activity21,37,80,95,115,116 (Fig. 4). may be helpful diagnostically. As this muscle is a In the male the EUS is usually examined with a continuum of ill-defined regions which generally transperineal approach. A 75-mm needle is inserted function as a unit, isolating separate portions may be in the midline, Ϸ4 cm anterior to the anus at the difficult, and in many instances unnecessary. The base of the penis and advanced toward the apex of levator is examined by inserting a 75-mm needle the prostate. Localization may be facilitated by pal- electrode 1–2 cm outside the anal mucocutaneous pation of the apex of the prostate in the rectum, but junction at the 3 to 4 o’clock or 8 to 9 o’clock the finger should be withdrawn as the needle elec- position (in dorsal lithotomy position) for the left trode is inserted21,37,115 (Fig. 3). and right sides, respectively. The needle is advanced Bulbocavernosus. The BC muscle is easily acces- until EMG activity is identified 2–5 cm from the skin sible in the male and provides information about the surface102,125 (Fig. 2). In females the pubococcygeus integrity of the sacral roots and plexus, the pudendal is accessible just inside the vaginal introitus. The nerve, and the perineal nerve branch. Thus, it may needle is inserted obliquely through the vaginal mu- serve as an alternative to the EUS in the appropriate cosa, while palpating the muscle with a digit of the setting. It may facilitate identification of muscle contralateral hand. Localization is facilitated if the membrane irritability, as it is not tonically active at patient activates the muscle by squeezing as if to rest.109 The muscle lies superficially behind the scro- delay urination.73,81 Alternatively, the ischial spine tum on either side of midline in the perineal region, may serve as a landmark with needle placement me- where it surrounds the bulb of the penis (Fig. 3). dial and caudal to the ischial spine through the The needle electrode is inserted through the perivaginal epithelium into the pubococcygeus/iliococ- neal skin about 1 cm lateral to the bulb of the penis cygeus.65,155,156 The puborectalis portion of the and advanced toward midline until EMG activity is pubococcygeus is particularly useful in the evalua- seen and heard. If the needle is inserted too far tion of patients who have fecal incontinence because laterally, the superficial transverse perineal muscle of the key role it plays in the maintenance of the may be entered. Localization may be confirmed by anorectal angle. A 50- to 75-mm needle electrode is having the patient cough or mimic terminal voiding. inserted 1 cm inside the mucocutaneous junction Alternatively, the muscle may be activated by elicit- between the 3 and 6 o’clock position on the left and

832 AANEM Monograph MUSCLE & NERVE July 2008 the 6 and 9 o’clock position on the right (in lithot- 8. Barber MD, Bremer RE, Thor KB, Dolber PC, Kuehl TJ, Coates KW. Innervation of the female levator ani muscles. omy position). The electrode is directed medially Am J Obstet Gynecol 2002;187:64–71. and cephalad, paralleling the long axis of the rec- 9. Barer DH, Mitchell JR. Predicting the outcome of acute tum. The needle is advanced through the EAS to stroke: do multivariate models help? Q J Med 1989;70:27–39. enter the puborectalis at a depth of 4–5 cm. In some 10. Barkhaus PE, Nandedkar SD. Tibial motor conduction study: reference electrode contribution to the CMAP. Mus- cases, there is a subtle decrease in the EMG activity cle Nerve 2005;32:396. between the two muscles which is helpful in confirm- 11. Barnett JL, Hasler WL, Camilleri M. American Gastroenter- ing location. Localization may also be facilitated by ological Association medical position statement on anorectal testing techniques. American Gastroenterological Associa- palpating the puborectalis sling posteriorly in the tion. Gastroenterology 1999;116:732–760. rectum to estimate the depth required12,72,115,116 12. Bartolo DC, Jarratt JA, Read MG, Donnelly TC, Read NW. (Fig. 5). The role of partial denervation of the puborectalis in idiopathic faecal incontinence. Br J Surg 1983;70:664–667. 13. Basinski C, Fuller E, Brizendine EJ, Benson JT. Bladder-anal CONCLUSION reflex. Neurourol Urodyn 2003;22:683–686. 14. Bauer SB, Hallett M, Khoshbin S, Lebowitz RL, Winston KR, In conclusion, urodynamic and EDX studies are Gibson S, et al. Predictive value of urodynamic evaluation in complementary tests of the neural pathways involved newborns with myelodysplasia. JAMA 1984;252:650–652. 15. Beck R, Fowler CJ. Clinical neurophysiology in the investi- in continence and voiding. 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