Neurophysiology of the neurogenic lower urinary tract disorders

Clinical Neurophysiology 118 (2007) 1423–1437 www.elsevier.com/locate/clinph

Invited review

Neurophysiology of the neurogenic lower urinary tract disorders Simon Podnar

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Institute of Clinical Neurophysiology, Division of Neurology, University Medical Center Ljubljana, SI-1525 Ljubljana, Slovenia Accepted 30 January 2007 Available online 26 April 2007

Abstract The nervous system structures involved in the control of the lower urinary tract (LUT) are usually divided using a neuroanatomical classification system into suprapontine, pontine, spinal and sacral. In all patients with LUT symptoms, after exclusion of local causes, a nervous system disorder needs to be considered. For the diagnosis of neurogenic LUT disorders, in addition to clinical assessment, neurophysiologic testing might be useful. Imaging and other laboratory studies (e.g., cystometry) often provide relevant additional information. Neurophysiologic tests are more useful in patients with sacral compared with suprasacral disorders. Although in patients with LUT disorders external urethral sphincter (EUS) electromyography (EMG) would seem the most appropriate, anal sphincter EMG is the single most useful diagnostic test, particularly for focal sacral lesions, and atypical parkinsonism. Another clinically useful method that tests the sacral segments, and complements EMG, is the sacral (penilo/clitoro-cavernosus) reflex. Kinesiologic EMG is useful to demonstrate detrusor sphincter dyssynergia (i.e., increased EUS activity during bladder contraction), which is particularly common in spinal cord disease. Somatosensory evoked potential (SEP) and motor evoked potential (MEP) studies (cortical and lumbar) may be useful to diagnose clinically silent central lesions. MEP, in addition, seems to be very promising in research into cortical excitability. Theoretically, cortical SEP on bladder/urethra stimulation would be much more useful than pudendal SEP because it tests thin nerve afferents from the pelvic viscera. However, the utility of this technique is limited by technical difficulties, which can be partially overcome by the concomitant recording of a palmar sympathetic skin response (SSR). SSR recorded from the saddle region is also useful for testing the lumbosacral sympathetic system. Although the technique of detrusor EMG has been recently described in humans, a clinically useful test for evaluating the sacral parasympathetic system, which is crucial for LUT functioning, is still lacking.  2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Electromyography; Lower urinary tract; Motor evoked potentials; Neurogenic bladder; Somatosensory evoked potentials; Sympathetic skin response; Voiding

1. Introduction The main function of the lower urinary tract (LUT) is to transform a continuous flow of urine produced by the kidneys into a controlled, intermittent evacuation. To achieve this, a reservoir that accommodates the urine temporarily, and then enables quick and efficient emptying, is needed. This function is undertaken by the urinary bladder. Furthermore, to enable retention of urine within the bladder during storage, and to release it to form a urinary flow during voiding, the assistance of a urinary sphincter is essen-

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Tel.: +386 1 522 1500; fax: +386 1 522 1533. E-mail address: [email protected]

tial. Therefore, the urinary bladder and urinary sphincter work in close cooperation – as a functional unit. For their effective function, precise coordination between the urinary bladder and sphincter is needed. This is accomplished by a control system that inhibits bladder and facilitates sphincter contraction during storage, and reverses its activity (facilitates bladder and inhibits sphincter contraction) during voiding. Such a switch control over the LUT is provided by the nervous system. All parts of the nervous system, including the brain with the brain stem, spinal cord and the peripheral (somatic and autonomic) lumbosacral nervous system, are involved (Table 1). For more detailed information on the nervous control of the LUT readers are directed to several specialized texts (Blok et al., 1997; Morrison et al., 2005).

1388-2457/$32.00  2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2007.01.022

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Table 1 Main neural structures involved in neuro-control of the lower urinary tract Neural structure

Animal experiments

Right inferior frontal gyrus Right anterior cingular gyrus

Stimulation produces bladder contraction (Gjone, 1966)

Right insula and operculum

PET studies in humans/ anatomy

Function

Activated during voiding (Blok et al., 1997)

Postulated to reach decision to void or not to void

Reduced activity during withholding of urine (Blok et al., 1997)

Postulated to facilitate either storage or voiding, according to decision Suppresses sensation of full bladder

Activated during bladder filling (Blok et al., 1998)

Activates sympathetic activity (Oppenheimer et al., 1992) – facilitates storage

Preoptic nucleus in hypothalamus

Stimulation produces bladder contraction (Gjone, 1966)

Periaqueductal grey in the midbrain

Stimulation results in complete voiding (Skultety, 1959)

Activated during voiding (Blok et al., 1997, 1998)

Activates the pontine micturition center

Pontine micturition center (Mregion) – a group of neurons in the dorsolateral pontine tegmentum

Stimulation produces bladder contraction (Holstege et al., 1986). Bilateral lesions result in inability to void (Barrington, 1925)

Activated during voiding (Blok et al., 1997, 1998)

Direct excitatory connections to the parasympathetic preganglionic nucleus in the intermediolateral column of the sacral spinal cord (Blok and Holstege, 1997)

Pontine storage center (Lregion) – a group of neurons ventrally and laterally to the M-region

Stimulation produces urethral sphincter contraction (Holstege et al., 1986)

Activated during withholding urine (Blok et al., 1997, 1973)

Direct projections to Onuf’s nucleus (Holstege et al., 1986)

Parasympathetic preganglionic nucleus in the intermediolateral column of the sacral spinal cord

Autonomic motor neurons innervating the bladder smooth muscle

Travel through the cauda equina and pelvic nerves to ganglia within the bladder wall

Facilitates bladder, and inhibits internal urethral sphincter contraction during voiding

Thoracolumbar sympathetic nucleus in the intermediolateral column of the spinal cord

Autonomic motor neurons innervating the internal urinary sphincter (smooth muscle of the bladder neck)

Travel through the hypogastric and pelvic nerves

Facilitates internal urethral sphincter, and inhibits bladder contraction during storage. Decreases mechanoreceptor output –decreases sensation of urge to void (Blok et al., 1998)

Onuf’s nucleus – a group of neurons in the upper sacral spinal cord

Somatic motor neurons innervating the pelvic floor and striated sphincter muscles (Schroder, 1981)

Travel through the cauda equina, levator ani nerves, and pudendal nerves

Facilitates external urethral sphincter contraction during storage

In the present review I will first introduce ‘‘neurogenic LUT’’ disorders using a neuroanatomical classification. A description of clinical neurophysiologic methods specific for evaluation of LUT (dys)function, and the use of these methods in the evaluation of patients with specific neurogenic disorders then follows. Finally, other uses of clinical neurophysiologic methods related to neurogenic LUT disorders, as well as future perspectives, will be discussed. 2. Neurogenic LUT disorders It is well documented that, apart from a lesion to the LUT itself, disturbed LUT function may also result from nervous system abnormalities. These are the so-called ‘‘neurogenic LUT’’ disorders, which may result from nervous system lesions at different levels. In fact, it is most convenient to divide neurogenic LUT disorders neuroanatomically into: • • • •

suprapontine (including extrapyramidal) pontine infrapontine–suprasacral (spinal) sacral (segmental).

Conveys decision on voiding to the pons (Blok et al., 1997)

Table 2 shows individual conditions causing neurogenic LUT dysfunction at different locations within the nervous system, together with their typical symptoms and urodynamic findings. 3. Clinical uro-neurophysiologic methods Neurophysiologic methods are well established in patients with neurogenic LUT disorders. In the following section methods of definite (i.e., electromyography (EMG), sacral reflex studies), and methods of probable value in the assessment of individual patients with neurogenic bladder [i.e., pudendal somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and sympathetic skin response (SSR)] will be described. This is followed by a description of other tests that currently do not have established clinical diagnostic value. In addition to methods that test the sacral nervous system specifically, a number of general neurophysiologic tests (tibial SEP, limb muscle MEP, etc.) are also useful in patients with suspected neurogenic LUT dysfunction.

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Table 2 Etiology, urinary symptoms and urodynamic findings of neurogenic lower urinary tract disorders according to their neuro-anatomic location Localization

Etiology

Urinary symptoms

Urodynamic findings

Suprapontine Particularly right anteromedial frontal lobe, its descending pathways, and the basal ganglia

Stroke Tumor Parkinsonism Dementia Normotensive hydrocephalus

Initial urinary retention usually gradually changes to voiding frequency, urgency, and urge incontinence

Initial acontractile detrusor and nonrelaxing urethral sphincter usually gradually changes to detrusor overactivity

Pontine

Stroke Multiple sclerosis Tumor

Urinary retention, frequency, urgency and incontinence

Bladder overactivity and underactivity, detrusor sphincter dyssynergia, and uninhibited sphincter relaxation

Infrapontine–suprasacral Spinal cord

Spinal injury Multiple sclerosis Spondylotic myelopathy Tumor Transverse myelitis

Initial urinary retention Changes to frequency, urgency, and urge incontinence Bladder emptying difficulties, double voiding, etc.

Initial acontractile detrusor gradually changes to detrusor overactivity with reduced bladder capacity Detrusor sphincter dyssynergia increased postvoid residuals increased bladder pressures

Sacral–segmental

Disc herniation Trauma Tumor Dysraphism Peripheral neuropathy

Bladder emptying difficulties, stress urinary incontinence

Underactive bladder and sphincter, increased post-void residuals, reduced detrusor capacity

Cauda equina, conus medullaris, sacral plexus, pudendal nerves

Uninhibited sphincter relaxation during detrusor contraction

3.1. Sacral neurophysiologic tests of the highest clinical utility

quantitative techniques are also available (i.e., measurement of the area under the rectified signal), which increase the validity of the findings (Reitz et al., 2003a). Utility. To demonstrate increased external urethral sphincter (EUS) EMG activity concomitant with detrusor contraction, both in neurologic patients (i.e., detrusor sphincter dyssynergia) (De et al., 2005), and in patients without any neurologic disorder (i.e., dysfunctional voiding) (Groutz et al., 2001).

3.1.1. Kinesiologic EMG of pelvic floor and sphincter muscles Aim. To assess the time course and intensity of the activity of individual muscles during various maneuvers (e.g., bladder filling and emptying). Technique. Surface or intramuscular (needle or wire) electrodes can be used at a single or multiple sphincter or pelvic floor muscle detection sites. For urethral sphincter recordings during cystometry, in addition to intramuscular electrodes, intraurethral ring electrodes can be used (Nordling et al., 1978), as well as electrodes mounted on an intravaginal sponge in women (Lose et al., 1985). After positioning of the electrodes various maneuvers are performed, during which EMG activity is recorded. Although either standard EMG equipment or EMG facilities contained within urodynamic systems can be used, better visual and audio control provided by the standard EMG equipment facilitate optimal electrode placement and improve recordings (De et al., 2005). Generally, the EMG signal is described only qualitatively. However,

3.1.2. Concentric needle EMG of pelvic floor and sphincter muscles Aim. To differentiate abnormally from normally innervated striated pelvic floor or sphincter muscle. Technique. Concentric or monopolar needle electrodes, and an advanced EMG system with quantitative template operated motor unit potential (MUP) analysis (e.g., multi-MUP), are ideal. The commonly used amplifier filter setting is 5–10 kHz. In women the EUS muscle can be examined using a perineal (Blaivas et al., 1977; Chantraine et al., 1973) or vaginal (Lowe et al., 1994) approach, the perineal technique being preferred due to the larger number of sampled MUPs (Olsen et al., 1998). Examination of this muscle is more difficult in men, in whom it is usually approached by needle insertion into the perineum, with guidance by the investigator’s finger in the rectum. In addition, insertion through the posterior rectal wall using the transrectal ultrasound biopsy channel has been described (Hasan et al., 1995). In contrast, the subcutaneous external

These tests, however, will not be covered in this part of the paper, but will be presented in the context of specific neurogenic LUT disorders. For more detailed information on these methods readers are directed to general neurophysiologic literature.

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anal sphincter (EAS) is easy to examine, and is regarded as the most practical muscle for needle EMG of the lower sacral myotomes (Podnar, 2003). It is reached by needle insertion about 1 cm from the anal orifice, to a depth of 3–6 mm (Podnar et al., 1999). As in the evaluation of other skeletal muscles, needle EMG of the sphincter and pelvic floor muscles is divided into observation of insertion and spontaneous activity, (quantitative) MUP assessment, and (qualitative) interference pattern assessment (Podnar and Vodusek, 2001). 3.1.2.1. Insertion activity and spontaneous activity. Due to the short duration of MUPs (Podnar et al., 2002c), and their continuous firing during relaxation (Podnar et al., 2002a) it is sometimes difficult to differentiate MUPs from fibrillation potentials in partially denervated sphincter muscles. In this situation, examination of the bulbocavernosus muscle is particularly useful, as it lacks ongoing activity of low-threshold motor units during relaxation. 3.1.2.2. MUP analysis. Three quantitative MUP analysis techniques (manual-MUP, single-MUP and multi-MUP), with similar sensitivities for detecting reinnervation changes, are available (Podnar et al., 2002c). Reference data for mean values and outliers for the EAS muscle have been published for each of these techniques (Del Rey and Entrena, 2002; Podnar et al., 2002c). In contrast, there are no good, consistent reference data for the EUS muscle (Eardley et al., 1989; Fanciullacci et al., 1987; Fowler et al., 1984). Template operated (e.g., multi-MUP) analysis is the fastest and easiest to use. In this technique the operator activates the computer acquisition of the previous (last) 5–10 s of the EMG signal. MUPs are then automatically extracted from the signal and sorted into several classes, each representing the average of consecutive MUP discharges. MUPs with an unsteady baseline (i.e., unclear beginning or end), or MUPs distorted by averaging, need to be recognized and deleted. Using template operated techniques, sampling of 20 MUPs (the standard number in limb muscles) from each subcutaneous EAS presents no problem in healthy controls (Podnar et al., 2002c), and in most patients (Podnar et al., 2002b). However, it is questionable whether it is possible to obtain a representative MUP sample in the EUS muscle as less than 10 MUPs were sampled in one study (Olsen et al., 1998). Traditionally, the MUP parameters of amplitude and duration were measured, and the number of phases was counted. However, for optimal diagnostic power (sensitivity and specificity) in the EAS muscle, the use of MUP area, duration, and number of turns is recommended (Podnar and Mrkaic, 2002). Criteria for possible, probable and definite neuropathic changes in the EAS muscle have also been proposed (Podnar, 2004). 3.1.2.3. Interference pattern analysis. The interference pattern can be quantitatively assessed using a number of automatic techniques, of which turn/amplitude analysis is the

most popular (Nandedkar et al., 1986). For turns/amplitude analysis in sphincter or pelvic floor muscles subjects contract muscles voluntarily or reflexly (e.g., by coughing), and the examiner indicates 0.5-s time intervals of the sharp EMG signal to be analyzed. Several interference pattern parameters are then measured automatically by the EMG system (Nandedkar et al., 1986; Podnar et al., 2002c). Although this approach is even faster than MUP analysis using the multi-MUP technique, its sensitivity for detecting neuropathic EAS muscles is only about half that of MUP analysis techniques (Podnar et al., 2002c). As a consequence, qualitative assessment of the interference pattern (reduction in the number of activated motor units firing at a high rate) has been recommended in sphincter and pelvic floor muscles to assess motor unit loss (Podnar and Vodusek, 2001). However, this is more difficult to evaluate than in limb muscles, because concomitant assessment of the muscle strength cannot be made. This approach can in principle also be used in the EUS muscle (Aanestad et al., 1998), but the validity of sampling such a small muscle is questionable. Alternatively, motor unit loss can be assessed by counting the number of continuously firing MUPs during relaxation (Podnar et al., 2002a). However, the sensitivity of this approach for the diagnosis of neuropathic lesions in the EAS muscle is low (Podnar et al., 2002a). 3.1.3. Single fiber EMG (SFEMG) of pelvic floor and sphincter muscles The SFEMG needle has a much smaller pick-up area than the CNEMG needle electrode (hemisphere radius: 300 and 2500 lm, respectively). It records individual muscle fiber action potentials as short biphasic positive– negative waves. In healthy muscles the SFEMG records potentials of only 1–3 single muscle fibers belonging to the same motor unit. Muscle fiber counts from 20-wellseparated intramuscular detection sites are usually performed during fiber density measurements. Increased mean fiber density (average number of muscle fiber signals per detection site) is a sensitive sign of collateral reinnervation (Stalberg and Trontelj, 1994). Utility. EMG is useful in diagnosing lower motor neuron lesions in the sacral segments (cauda equina or conus medullaris lesions, multiple system atrophy (MSA), etc.) by demonstrating denervation activity, reinnervation changes, and a reduced recruitment pattern. Although the EUS muscle would be the logical choice in patients with LUT dysfunction, its examination is hampered by technical difficulties, and small muscle bulk, which makes validity of quantitative analysis questionable (Olsen et al., 1998). Nevertheless, the EUS muscle has been used to diagnose sacral neurogenic lesions (Eardley et al., 1989; Fowler et al., 1984), although the technique remains poorly validated. The main indication for examination of this muscle is non-neurogenic urinary retention in young women, some of whom show pronounced pathologic spontaneous activ-

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ity (decelerating burst and complex repetitive discharges) accompanied by polycystic ovaries (e.g., Fowler’s syndrome) (Fowler et al., 1988; Fowler et al., 1985; Swinn et al., 2002). Although not providing information about the distal few centimeters of the pudendal nerve branch innervating the EUS, CNEMG of the subcutaneous EAS muscle is more useful for diagnosing neurogenic LUT dysfunction (Podnar and Vodusek, 2001). Although also being an established neurophysiologic technique in sphincter muscles, SFEMG is not recommended for use in clinical practice (Vodusek et al., 2005). 3.1.4. Sacral reflexes Aim. To test conduction along the sacral reflex arc, which is comprised of the somatic sensory fibers, spinal interneurons, and the somatic motor fibers. Technique. To elicit sacral reflexes, electrical (Amarenco and Kerdraon, 2000; Vodusek et al., 1983), mechanical (Amarenco et al., 2003; Podnar et al., 1997), or magnetic (Loening-Baucke et al., 1994) stimulation can be applied to the penis or clitoris. Mechanical stimulation is painless and is particularly suitable for testing children (Podnar et al., 1997). Magnetic stimulation is less useful due to the difficulty of stimulus localization. Using electrical stimuli, other skin areas within the lower sacral dermatomes, and (using a catheter-mounted ring electrode) the bladder neck/proximal urethra (Basinski et al., 2003; Hansen et al., 1990) can also be stimulated. To record reflex responses, needle, wire or surface electrodes are placed into or over the bulbocavernosus, EAS or EUS muscle. A twopart nomenclature of sacral reflexes (name: stimulation site–detection site) has been proposed (Podnar, 2006a). In sphincter muscles, but not in the bulbocavernosus muscle, continued MUP firing often obscures the onset of reflex responses. However, the bulbocavernosus (and EUS) muscles are more difficult to locate with the needle electrode than the EAS muscle. In addition to observing the elicitability of the response, currently the onset latency is the only measured parameter (Vodusek et al., 2005). The latencies of electrically and mechanically elicited penilo-cavernosus reflexes are similar (Amarenco et al., 2003; Podnar et al., 1997). In adults, values between 42 and 45 ms are used as the upper limit of normal latency (Amarenco et al., 2003; Vodusek et al., 1983), irrespective of body height (Nikiforidis et al., 1995). Two unilateral sacral reflex arcs have been demonstrated, with the upper normative limit for interside latency difference being 3 ms (Amarenco and Kerdraon, 2000). Utility. To detect damage to myelin and axons within the peripheral sacral reflex arc. Such studies are particularly useful in women, because clinical testing of the clitoro-cavernosus reflex is less reliable. In addition, changes in excitability of spinal interneurons (Kaiho et al., 2000), and an abnormally low position of the conus medullaris (Hanson et al., 1993) can be demonstrated. This test should be part of the diagnostic battery, of which needle EMG exploration of the sphincter and pelvic floor muscles is

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the most important component. The results, however, should be interpreted with caution, and always in the clinical context. A response of normal latency does not exclude the possibility of a partial axonal lesion, and abnormal latency of the response may not be clinically relevant. 3.2. Sacral neurophysiologic tests of moderate clinical utility 3.2.1. Pudendal somatosensory evoked potentials (SEPs) Aim. To test conduction in the somatosensory pathways from the sacral dermatomes. Technique. The pudendal SEP can be elicited by electrical (Delodovici and Fowler, 1995; Vodusek, 1990) or mechanical (Podnar et al., 1997) stimulation of the dorsal penile or clitoral nerves. Electrical stimulation, 2–4 times stronger than the sensory threshold, is usually applied. After computer averaging of 100 responses in healthy subjects, the first positive peak (P1 or P40) is usually clearly defined, and highly reproducible. The response is of highest amplitude (0.5–12 lV) at the central recording site (Cz’:Fz of the international 10–20 system of electrode placement) (Guerit and Opsomer, 1991). In one study, the latency of the response was 41 ± 2.3 ms (Vodusek, 1990), but the result depends on the body height (Nikiforidis et al., 1995). Utility. In theory, this technique allows for objective evaluation of the integrity of the sensory pathways from the periphery to the parietal cortex. It might be indicated in patients with a normal sacral reflex and abnormal sacral sensation, pointing to a suprasacral lesion. However, in patients with urogenital dysfunction pudendal SEP was claimed to be of no greater value than the neurologic examination (Delodovici and Fowler, 1995). Other studies have suggested tibial SEP to be more sensitive than pudendal SEP in diabetic cystopathy (Rapidi et al., 2006), and multiple sclerosis (Betts et al., 1994; Rodi et al., 1996). This finding might be partially explained by the inability to stimulate pudendal nerves unilaterally. Both techniques, in addition, assess only thick, but not thin, nerve fibers, which are more relevant for LUT function. Pudendal SEP might be theoretically more relevant than tibial SEP in patients with known neurologic disease in whom the reason for LUT dysfunction is sought. 3.2.2. Sacral central motor conduction studies – motor evoked potentials (MEPs) Aim. To test conduction along the sacral motor pathway from the cerebral cortex to the pelvic floor or sphincters. Technique. Magnetic or electrical stimulation can be used to stimulate the brain. In contrast to magnetic stimulation, cerebral electrical stimulation is painful and is nowadays only used in anesthetized patients during intraoperative monitoring (Inoue et al., 2002). During transcranial magnetic stimulation the coil is usually applied to the vertex (Brostrom, 2003). In healthy subjects MEPs can be recorded from a variety of sphincter and pelvic floor muscles (Brostrom, 2003). Instead of using a circular coil, which cannot elicit a response in all healthy women (Bro-

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strom, 2003), a coil with a figure eight configuration might be more effective. Due to concomitant activation of large gluteal muscles, detection of sphincter and pelvic floor muscles by needle electrodes is recommended (Brostrom et al., 2003b). As with measurements from limb muscles, only latencies are used in evaluating the response. When no facilitatory maneuver is used, the mean latencies are 20–30 ms, but slight voluntary contraction of the sphincter and pelvic floor muscles shortens the mean latencies to 17– 27 ms (Brostrom, 2003). By subtracting the latency of the MEPs obtained by stimulation over the scalp and at the L1 level, a central conduction time of approximately 16 ms without, and 13 ms with, facilitation, is obtained for pelvic floor and sphincter muscles (Brostrom, 2003). Utility. To demonstrate a lesion to motor pathways innervating the pelvic floor and sphincter muscles. In theory, MEPs might be useful to document some spinal cord lesions that are not demonstrated on clinical examination or imaging (e.g., of vascular or metabolic origin), although currently there is little evidence of this in the published literature. It has also been suggested that the diagnostic yield of the method is probably low because patients with abnormal findings on MEP measurement usually also have clinically recognizable spinal cord disease (Mathers et al., 1990). 3.2.3. Sacral sympathetic skin response (SSR) and other tests of thoracolumbar sympathetic function Aim. To test the function of myelinated sensory fibers, complex central autonomic connections, myelinated preganglionic and nonmyelinated postganglionic thoracolumbar sympathetic fibers innervating the perineal skin. Technique. To elicit the sacral SSR an electrical pulse delivered to a limb, or to the sacral region, can be used. The responses can be recorded from the genital region. Following stimulation of the median nerve at the wrist and recording from the penis, these responses have latencies of 1.5–2.3 s (Daffertshofer et al., 1994; Opsomer et al., 1993), and can be recorded in all control men. Similarly, SSR can also be recorded from the genital region in all control women (Secil et al., 2005). The SSR rapidly habituates and is critically dependent on a number of factors, including skin temperature. Responses are variable in shape, and only an absent SSR can be considered abnormal. SSR can also be recorded on bladder/urethra stimulation (Schmid et al., 2004), which in addition to central sympathetic pathways also tests thin afferent fibers from the pelvic viscera. In men, another approach to test lumbosacral sympathetic function is the neurophysiologic measurement of the dartos reflex obtained by cutaneous stimulation of the thigh. The dartos muscle is a sympathetically innervated dermal layer within the scrotum, distinct from the somatically innervated cremasteric muscle. A reliable and reproducible dartos reflex (i.e., scrotal skin contraction) of latency 5 s has been demonstrated in healthy men (Yilmaz et al., 2006).

Utility. The autonomic nervous system is the most relevant for LUT function. The SSR might be useful in the assessment of neuropathies involving unmyelinated nerve fibers (Ertekin et al., 1987), and thoracolumbar sympathetic function (Schmid et al., 2004). The utility of SSR on bladder/urethra stimulation (Schmid et al., 2004), and of the dartos reflex (Yilmaz et al., 2006) has not yet been established. 3.3. Sacral neurophysiologic tests of minor clinical utility 3.3.1. Pudendal nerve terminal motor latency (PNTML) test Aim. To test conduction of the fastest conducting distal sacral motor nerve fibers within the pudendal nerve. Technique. In the lower sacral segments recording of the M-wave is hindered by limited access to stimulation sites and difficulty in recording a supramaximal response. As a consequence, the only motor parameter that can be measured in the pelvic floor is the PNTML. Most often, a bipolar stimulating electrode fixed onto a distal gloved index finger, and the recording electrode pair placed 8 cm proximally on the base of the index finger – the ‘‘St. Mark’s electrode’’ (Kiff and Swash, 1984), is used. On insertion of the index finger into the rectum it was assumed that the pudendal nerve is stimulated close to the ischial spine and the response recorded in the EAS muscle. However, the latency of responses obtained by this approach is unusually short (around 2 ms) (Kiff and Swash, 1984) compared to monopolar intrarectal stimulation (3.7 ± 0.9 ms) (Lefaucheur et al., 2001). Thus it seems unlikely that the PNTML using the St. Mark’s electrode actually evaluates conduction along the last 8 cm of the pudendal nerve. Rather, the terminal pudendal nerve branches or pelvic floor muscles are probably stimulated near their motor points. Bipolar perianal stimulation and recording with a concentric needle electrode from the bulbocavernosus, EAS, or EUS muscles seems to be more reliable. Using this technique the PNTML is between 4.7 and 5.1 ms (Vodusek et al., 1983). Utility. To test for motor response in patients with suspected complete denervation of the sacral segments. 3.3.2. Proximal sacral motor conduction studies Aim. To test conduction in the lower sacral motor neurons distal to the cauda equina. Technique. Although both electrical and magnetic stimulation can be used (Brostrom, 2003), lumbosacral magnetic stimulation gives less reliable MEP. Stimulation can be delivered at different levels (e.g., L1-S3) (Brostrom et al., 2003b), with the sacral roots being stimulated at their exit from the lower spinal canal (Brostrom, 2003; Eardley et al., 1991). Such stimulation is nonselective and results in activation of all muscles innervated by lumbosacral segments; responses from the large gluteal muscles may contaminate surface recordings from the sphincter muscles (Vodusek and Zidar, 1988), and needle detection is necessary (Brostrom et al., 2003b). Recording

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from the EAS muscles is most common, although detection in the EUS or the bulbocavernosus muscles is also possible (Brostrom, 2003; Eardley et al., 1991; Lefaucheur, 2005b). Lumbosacral stimulation often evokes a large stimulus artifact that can be decreased by positioning of the ground electrode between the stimulating and the recording electrodes (Lefaucheur, 2005b). Typical mean latencies vary from 5 to 9 ms, depending mainly on the stimulation position (Brostrom, 2003). Recently, a technique for transcutaneous electrical stimulation of the S3 motor root has also been described (Pelliccioni and Scarpino, 2006). Utility. These tests may occasionally be helpful in patients without voluntarily or reflexly activated pelvic floor or sphincter muscles, but an absent response has to be evaluated with caution. By stimulating an individual root, its motor fiber function can be assessed before introducing therapeutic electrical stimulation (particularly implants) (Pelliccioni and Scarpino, 2006). 3.3.3. Dorsal penile nerve sensory studies Aim. To test conduction along the peripheral sensory axons in the lower sacral dermatomes. Technique. A pair of stimulating electrodes is placed across the glans and a pair of recording electrodes across the base of the penis. In healthy men, a low-amplitude (10 lV) sensory nerve action potential with a conduction velocity of 27–33 m/s can be measured (Bradley et al., 1984). Due to the changeable penile length, measuring the conduction distance is difficult. The antidromic method of stimulating the pudendal nerve transrectally using the St. Mark’s electrode and recording the sensory nerve action potential from the penis seems more reproducible (Amarenco and Kerdraon, 1999). Utility. Theoretically, a normal-amplitude sensory nerve action potential of the dorsal penile nerves in an insensitive penis distinguishes a sensory lesion proximal to the dorsal spinal ganglion (e.g., cauda equina, central pathways) from a lesion distal to the ganglion (e.g., sacral plexus, pudendal nerves). The test is not often used. 3.3.4. Peripheral sacral sensory conduction studies Aim. To test conduction in peripheral sacral sensory pathways. Technique. On stimulation of the dorsal penile nerves, and using surface recording electrodes at the level of the lower thoracic or upper lumbar vertebrae, particularly in slim men, a low-amplitude (<1 lV) monophasic negative potential with a mean peak latency of about 12.5 ms that does not correlate with the subject’s height (Nikiforidis et al., 1995) can be recorded. With epidural recording electrodes, sacral root potentials have been recorded in 59%, and postsynaptic cord potentials in 41% of men (Ertekin and Mungan, 1993). Intraoperatively, with the sacral roots exposed, SNAPs can be recorded more readily on stimulation of the dorsal penile and clitoral nerves (Huang et al., 1997).

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Utility. These studies have been helpful in preserving roots important for perineal sensation in spastic children undergoing dorsal rhizotomy, perhaps thereby decreasing the incidence of postoperative voiding dysfunction (Huang et al., 1997). No use for such recordings has been established outside of the operating room. 3.3.5. Cerebral SEP on stimulation of the bladder and urethra Aim. To test conduction along the sensory pathways from the bladder/urethra. Technique. Bipolar electrical stimulation applied to the bladder and urethra by catheters is required to obviate depolarization of somatic afferents (Hansen et al., 1990). These cerebral SEPs have been shown to be of low amplitude (61 lV) and of variable configuration, which makes their identification difficult, even in control subjects (Ganzer et al., 1991). They are of maximum amplitude over the head midline (Cz’:Fz). The typical latency of the most prominent negative potential (N1) is about 100 ms (Ganzer et al., 1991; Hansen et al., 1990). Instead of recording the cortical response, SSR can be recorded from the hand on bladder/urethra stimulation (Schmid et al., 2004). This approach tests peripheral and lower spinal afferents from the bladder/urethra. Utility. These responses are claimed to be more relevant to neurogenic bladder than the pudendal SEP, as the Adelta sensory afferents from the bladder, tested by these studies, accompany the autonomic fibers in the pelvic nerves and also participate in visceral reflexes. However, no clinical utility of this test has been established, mainly due to problems with recording the response. This deficiency may be at least partly obviated by recording the palmar SSR (Schmid et al., 2004). 3.3.6. Bladder smooth muscle EMG Aim. To provide information on parasympathetic innervation, and smooth muscle of the urinary bladder. Technique. Such studies are confronted with problems in discriminating between the very small extracellular membrane potential changes of bladder muscle cells, and the large electromechanical artifact caused by electrode movement as the tissue contracts. In the only study performed in humans, surface electrodes were placed on the abdominal skin, and bipolar signals in a horizontal, vertical and diagonal direction were recorded. It was claimed that voiding was accompanied by a slow voltage change that could be distinguished from striated muscle activity. Activity was related to bladder emptying and to the detrusor pressure (Kinder et al., 1998). The generators of these potentials, however, remain unknown, and the recordings have not been replicated. Utility. Although information on sacral parasympathetic function can, to some extent, be obtained by cystometry, this cannot directly demonstrate the neuropathic etiology of the bladder dysfunction. Neurophysiologic tests of sacral parasympathetic nerve function, such as detrusor

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EMG, would, in principle, constitute the most definitive indicator of neurogenic bladder involvement. However, further studies to improve and validate these tests are expected to clarify their place in research and clinical practice. 3.3.7. Assessment of LUT sensation Aim. To assess sensory function of the LUT. Technique. Electrical currents can be applied to the bladder, urethra or genital skin using appropriate cathetermounted or surface electrodes. The use of high frequency stimulation (>20 Hz), with a stimulus duration of 0.5 or 1 ms, has been suggested because it is more easily perceived in the LUT. Measurement of sensory thresholds obtained by such stimulation is highly reproducible, and normative data have been published (Wyndaele et al., 1996). To more objectively demonstrate sensations during cystometry, palmar SSR and perineal surface EMG recordings can be used. The activity of both appears and increases in parallel with the first sensation of bladder filling, and with the first desire to void, respectively (Reitz et al., 2003a). Utility. Although not a neurophysiologic test in its strict sense, measurement of the electrical thresholds adds clinically non-obtainable information on LUT sensory function (Wyndaele et al., 1996). To date it has been used in a few conditions (e.g., painful bladder syndrome (Fitzgerald et al., 2005)), although neurogenic LUT patients might also benefit from such testing. Recording of palmar SSR and perineal surface EMG during cystometry (Reitz et al., 2003a) might also be useful in neurogenic patients with impaired bladder sensation. Further studies using these methods are needed to establish their clinical utility. 4. Utility of clinical neurophysiologic methods in patients with neurogenic LUT disorders In patients with (suspected) neurogenic bladder disorders clinical neurophysiologic methods can be useful in: • diagnosis of patients with or without known neurologic disease, • evaluation of candidates for invasive treatments, • intraoperative mapping and monitoring, • research. The preceding description of individual sacral neurophysiologic methods will be followed by a discussion of their different uses. 4.1. Assessment of patients with suspected neurogenic LUT disorders Most LUT dysfunctions found in patients with neurogenic bladder can also be found in patients without any demonstrable neurologic lesion. They may arise due to local LUT pathology (e.g., benign prostate hypertrophy, cystitis, etc.), or the cause may not be identifiable. How-

ever, neurologic patients are also not immune to local LUT pathology. As a consequence, selected neurologic patients with LUT symptoms should be referred to urologists to exclude local pathologies as a possible cause of LUT dysfunction. To diagnose a ‘‘neurogenic LUT disorder’’ in addition to LUT abnormalities other signs of neurologic disease should be sought. 4.1.1. Position of neurophysiologic methods in the diagnosis of neurogenic LUT disorders Neurophysiologic tests are an extension of the clinical neurologic examination, but they are not useful for screening purposes (Podnar, 2005). They are helpful in evaluating selected patients with probable neurogenic bladder (Table 3). These studies might be relevant for assessing the prognosis and may affect decisions regarding therapeutic (including surgical) intervention. Neurophysiologic tests, however, also have limitations. They are uncomfortable, localization is difficult in patients with multifocal lesions and with proximal peripheral sacral lesions (paravertebral muscles are absent in the lower sacral segments), optimal timing of the investigation is limited (sensitivity of EMG studies is highest 3 weeks to several months after the onset of focal peripheral sacral lesions), and tests, in general, do not correlate well with LUT function. A recent international consensus statement proposed that sacral neurophysiologic studies are most useful in patients with suspected focal peripheral sacral lesions (i.e., conus medullaris, cauda equina, sacral plexus, and pudendal nerve lesions), in patients with MSA, and in women with urinary retention (Vodusek et al., 2005). In these patients an inability to empty the bladder and saddle sensory loss in particular are predictive of a peripheral sacral nerve lesion (Podnar, 2006b). Neurogenic LUT dysfunction can, of course, also be caused by a variety of other neurologic disorders, but the value of electrodiagnostic studies in the evaluation of these patients is probably less important (see below). 4.1.2. Other diagnostic methods To document and quantify the patient’s LUT complaints and to obtain additional data urodynamic studies (Schafer et al., 2002) may be considered. However, the physiologic investigations used in the evaluation of neurogenic bladder test LUT function, and do not directly reflect neurological lesions. As a consequence, neurologic examination and neurophysiologic tests are complementary and not an alternative to these tests. Similarly, neurologic examination and neurophysiologic tests are complementary to imaging studies (ultrasound, computerized tomography (CT) and magnetic resonance imaging (MRI)) of the LUT. These studies may reveal local morphologic abnormalities (e.g., abnormal position of the bladder neck, prostatic enlargement) possibly causing or contributing to LUT dysfunction. In addition, imaging studies may show structural changes in the brain, spinal

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Table 3 Diagnostic information provided by sacral neurophysiologic tests Information

Method

Finding

Documentation of integrity Central micturition pathways Lower motor neuron

Kinesiologic EMG EMG

Detrusor sphincter dyssynergia No denervation activity MUP firing during relaxation – sphincter muscles Preserved response* Dense interference pattern on reflex activation Normal penilo/clitoro-cavernosus reflex Dense interference pattern on voluntary activation Preserved response* Normal shape and latency of responses Preserved response Preserved cortical response* Preserved hand SSR

Sacral reflex arc Lower and upper motor neuron Sensory pathways – somatic Thoracolumbar sympathetic Sensory pathways – visceral Localization of lesions Root versus plexus or nerve

Lumbosacral stimulation EMG Sacral reflex response EMG MEP on cortical stimulation Pudendal SEP Sacral SSR SEP on bladder/urethra stimulation

EMG SNAP MEP on lumbosacral and cortical stimulation

Paravertebral denervation activity in neighboring myotomes Normal (penile) SNAP with impaired (penile) skin sensation Isolated cauda equina lesion – CMCT prolongation by the paravertebral stimulation. Additional central lesion – CMCT prolongation also by the F-wave latency

EMG Pudendal M-wave Sacral reflex response

Profuse denervation activity, absent MUPs No response* Penilo/clitoro-cavernosus reflex non-elicitable

Timing of lesions Acute or subacute vs. chronic

EMG

Profuse denervation activity Absent, subacute or chronic MUP changes

Progression of lesions Progressive vs. non-progressive

EMG

Denervation activity Subacute MUP changes

Type of lesion Conduction block vs. axonotmesis Axonotmesis vs. neurotmesis

EMG EMG

Absent or sparse denervation activity Appearance of nascent MUPs after complete muscle denervation

Isolated peripheral vs. central and peripheral

Severity of lesions Complete vs. partial Severe vs. moderate

CMCT – central motor conduction time; EMG – concentric-needle electromyography; MUP – motor unit potential; SEP – somatosensory evoked potentials; SNAP – sensory nerve action potential; SSR – sympathetic skin response. * Absent responses should be interpreted with caution.

canal or the pelvis relevant to sacral neurogenic dysfunction (Chuang et al., 2001; Kalita et al., 2002). In patients with suspected neurogenic LUT dysfunction neurologic examination would be best followed by urodynamic studies (Table 2). Based on the provisional neuroanatomic diagnosis established by data provided by these two studies, appropriate functional (neurophysiologic) and morphologic (imaging) studies would be performed. 4.1.3. Neurophysiologic studies in the diagnosis of neurogenic LUT disorders according to their location 4.1.3.1. Suprapontine disease. In most patients with suspected suprapontine LUT dysfunction (Table 2), in addition to neurologic examination imaging studies (i.e., brain MRI) are the most useful investigative tool. Neurophysiologic studies are useful primarily in patients with extrapyramidal disease. Kinesiologic EMG performed during urodynamic studies may document detrusor sphincter dyssynergia in some patients with Parkinson’s disease and

MSA (Sakakibara et al., 2000; Stocchi et al., 1997). Prolonged MUP duration in the sphincter muscles on concentric needle EMG (Libelius and Johansson, 2000; Palace et al., 1997; Stocchi et al., 1997; Tison et al., 2000) seems to be a particularly sensitive parameter of Onuf’s nucleus degeneration, which is typical of MSA (Mannen et al., 1982). Some controversy over the utility of this test was caused by negative studies (Giladi et al., 2000; Gilad et al., 2001), which, however, might be due to exclusion of late MUP components from the measurement of MUP duration (Podnar and Fowler, 2004). As late components seem to be a prominent feature and a sensitive sign of sphincter muscle denervation/reinnervation in patients with MSA (Palace et al., 1997), it was suggested that they be included in the measurement of MUP duration, at least in this condition (Podnar and Fowler, 2004). However, in MSA sphincter EMG may not be sensitive in the early phase of the disease (Stocchi et al., 1997; Yamamoto et al., 2005), and is probably not specific after 5 years of

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parkinsonism (Libelius and Johansson, 2000). The changes of chronic reinnervation in sphincter muscles may also be found in another parkinsonian syndrome, a progressive supranuclear palsy (Valldeoriola et al., 1995), with documented neuronal loss in Onuf’s nucleus (Scaravilli et al., 2000). Unilateral needle EMG of the subcutaneous EAS muscle, including quantitative MUP analysis (Libelius and Johansson, 2000; Palace et al., 1997; Stocchi et al., 1997; Tison et al., 2000), is clearly indicated in patients with suspected MSA (Podnar and Vodusek, 2001), particularly in its early stages when the diagnosis is unclear (Libelius and Johansson, 2000). If the test is normal, but the diagnosis remains unclear, it might be of value to repeat the test later (Stocchi et al., 1997; Yamamoto et al., 2005). In other suprapontine disorders causing LUT dysfunction neurophysiologic tests are of limited value. In particular, central conduction studies (MEP, SEP) contribute to the diagnosis in only the rare patient. 4.1.3.2. Pontine disease. Stroke in older patients and multiple sclerosis in younger patients are the most common causes of pontine disease causing LUT dysfunction (Table 2). Due to the proximity of the pontine micturition center to sensory pathways, the medial longitudinal fascicle and cerebellar connections, patients with LUT dysfunction due to lesions in this location may have concomitant sensory disturbances, abnormal eye movements (particularly internuclear ophthalmoplegia) (Pozzilli et al., 1992), and ataxia (Sakakibara et al., 1996), respectively. In evaluation of these patients, in addition to neurologic examination and imaging studies (e.g., MRI), some general neurophysiologic tests may be useful. Normal spinal and pathologic cortical median and tibial SEP responses may be obtained in patients with pontine lesions causing LUT dysfunction. Furthermore, the blink reflex and brainstem auditory evoked responses may also be useful in localizing lesions to the pons. In contrast, sacral clinical neurophysiologic tests seem less useful in this condition. 4.1.3.3. Infrapontine–suprasegmental (spinal) disease. A number of spinal cord diseases may also cause LUT dysfunction (Table 2). In such patients neurophysiologic methods can be used as an adjunct to the neurologic examination and imaging studies (Sakakibara et al., 2003). Of patients with voiding dysfunction those with a positive neurologic history and examination have the greatest diagnostic yield and are best suited to pudendal SEP testing (Klausner and Batra, 1996). Similar findings have led some authors to the conclusion that such testing is rarely useful in patients with normal neurologic examination of the lower limbs (Delodovici and Fowler, 1995). Although it might be indicated in patients with a normal sacral reflex and abnormal sacral sensation, pointing to a lesion above the sacral segments, tibial SEPs seem to be more sensitive in this situation (Rodi et al., 1996). For testing of the thin nerve fibers from the LUT, cortical SEPs

after bladder neck/posterior urethra stimulation might be more relevant than pudendal and tibial SEP. Unfortunately, the utility of this test is limited by the low amplitude of the response, which makes it unrecognizable in a proportion of controls (Ganzer et al., 1991). However, concomitantly recorded palmar SSR demonstrates continuity of the sensory pathways from the bladder neck/posterior urethra up to the cervical spinal cord level (Schmid et al., 2004). This test and perineal SSR may serve to assess function of the thoracolumbar spinal sympathetic, which is important for the function of the (smooth) internal urethral sphincter muscle (i.e., bladder neck competence) (Rodic et al., 2000). Due to significant discordance between the voiding cystourethrogram and kinesiologic EMG performed during cystometry, in order to increase the sensitivity of the diagnosis of detrusor sphincter dyssynergia, it has been suggested that both these investigations be performed (De et al., 2005). This might not be necessary if visual and audio guidance were used during insertion of the wire or needle electrodes into the EUS, which might increase the sensitivity of the EMG. In patients with multiple sclerosis (Brostrom et al., 2003a; Eardley et al., 1991), or other spinal cord disease (Jennum et al., 2001) and LUT dysfunction, a substantially prolonged MEP central conduction time on transcranial magnetic stimulation and EAS muscle detection demonstrates a lesion to the motor pathways innervating sacral myotomes. However, as for pudendal SEP, the diagnostic contribution of MEP is probably minor, because these patients usually have clinically evident spinal cord disease (Mathers et al., 1990). In contrast, MEP seems to be useful in patients with unclear localization of spinal lesions (Schmid et al., 2005). In patients with peripheral (e.g., cauda equina) lesions, a concomitant spinal cord lesion may be obscured clinically, but revealed neurophysiologically by prolongation of the central motor conduction time calculated using both lumbar magnetic stimulation, and the F-wave latency measurement, while patients without an additional spinal cord lesion only have central prolongation obtained by lumbar magnetic stimulation (Di Lazzaro et al., 2004). Clinically, suspected suprasacral spinal cord lesions can also be demonstrated by changes in the threshold, latency (both reduced), and amplitude (increased) of the penilo/clitoro-cavernosus reflex using a constant stimulus strength (Kaiho et al., 2000). Neurophysiologic studies (tibial SEPs) may also be useful in differentiating between lesions of the epiconus (normal cord and cauda potential), conus medullaris (only cauda potential), and cauda equina (no potential), which is often not possible by clinical examination (Restuccia et al., 1993). 4.1.3.4. Sacral disease. In our experience, compressive lesions to the cauda equina or conus medullaris are a common cause of neurogenic LUT dysfunction (Podnar et al., 2006), although more peripheral lesions may also cause sacral disease. Due to different neurophysiologic approaches it seems useful to divide sacral disease into

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focal lesions (of the conus medullaris, cauda equina, plexus, pudendal nerves), and generalized disorders (polyneuropathies also affecting the LUT and the perineum). Focal sacral lesions. In patients with suspected focal sacral disease, bilateral needle EMG of the EAS and sometimes of the bulbocavernosus muscle needs to be considered first (Podnar and Vodusek, 2001). Detection of spontaneous denervation activity, most appropriately in the bulbocavernosus muscle, is common in the interval from 3 weeks to several months after a lower motor neuron injury. Later, MUP analysis becomes more important for demonstrating reinnervation. Most of these lesions cause partial denervation, but a traumatic lesion to the lumbosacral spine or pelvis may also result in complete sphincter muscle denervation (Podnar, 2003). Eliciting an M-wave from the EAS muscle using perianal stimulation may be helpful in excluding a complete peripheral (axonal) lesion. Moreover, in small sphincter muscles with inefficient reinnervation after complete denervation, MUP area and duration may have values below the lower confidence limits (i.e., pseudomyopathic MUPs), even in a chronic situation (Podnar, 2003). In addition, neurophysiologic evaluation of the penilocavernosus reflex, when this is clinically absent or equivocal, and the clitoro-cavernosus reflex, are the neurophysiologic tests that may prove useful in patients with sacral lesions (Vodusek et al., 2005). In segmental lesions the penilo/clitoro-cavernosus reflex is useful for assessing the integrity of the sacral reflex arc. Separate testing of both reflex arcs improves the sensitivity of the test by unmasking unilateral disease, found in sacral plexopathy, pudendal neuropathy or asymmetric cauda equina lesions (Amarenco and Kerdraon, 2000). There are no validated techniques for distinguishing cauda equina lesions from more distal lesions. As pointed out above, an abnormally short reflex latency of the sacral reflex suggests either an abnormally low position of the conus medullaris characteristic of tethered cord syndrome (Hanson et al., 1993) or a suprasacral cord lesion (Kaiho et al., 2000). Neurophysiologic tests (EMG, sacral reflex studies, pudendal and tibial SEP) have also been suggested to be useful in the assessment of neurogenic lesions in children with spinal dysraphism (Torre et al., 2002; Tsai et al., 2001). Simultaneous recording of the lumbosacral and cortical SEPs with surface electrodes was claimed to be a reliable test for the detection of mild cauda equina abnormalities, but it could not differentiate between severe and complete cauda equina lesions (Lehmkuhl et al., 1988). Abnormal pudendal and normal tibial SEPs suggest a localized conus medullaris lesion (Rodi et al., 1996). Although focal involvement of the sacral nervous system (trauma or compression) usually involves both somatic and autonomic fibers, in some circumstances the autonomic system is affected in isolation. After hysterectomy for benign disease, SEP on bladder stimulation demonstrates deafferentation limited to the bladder in a proportion of women with normal neurologic examination (Everaert et al., 2003).

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Generalized sacral disorders. In patients with sacral dysfunction due to polyneuropathies, nerve conduction studies performed in the lower limbs are regarded as a more sensitive adjunct to clinical examination than sacral neurophysiologic studies (Hecht et al., 2001). However, some systemic disorders affect predominantly the autonomic nervous system (Hecht et al., 2001). Furthermore, in addition to diagnosing polyneuropathy affecting the longest nerve fibers obtained in the lower limbs, specific information on the condition of peripheral nerves relevant to LUT function (i.e., nerves to the pelvic organs, pelvic floor and sphincters) is needed to disclose the etiology of LUT symptoms. In diabetic patients urodynamic findings and tibial SEP, but not sacral reflex studies, pudendal SEP, or MEP on transcranial magnetic stimulation, correlated with LUT symptoms (Rapidi et al., 2006). In another study performed in patients with diabetic cystopathy bladder dysfunction (loss of bladder sensation, increased capacity and decreased contractility demonstrated by cystometry) was associated with abnormal SSR (Ueda et al., 1997). In patients with detrusor atonia, sensitivity of the bethanechol supersensitivity test, EMG of the EUS and sacral reflex latency were 90%, 88% and 78%, and the specificity 96%, 76% and 80%, respectively. The combined accuracy of all three tests to diagnose neurogenic lesion approached 100% (Sidi et al., 1988). 4.2. Application of neurophysiologic tests in invasive treatments of neurogenic LUT disorders 4.2.1. Surgery Several studies have demonstrated the utility of neurophysiologic studies in the assessment of surgical candidates with neurogenic LUT disorders. Abnormal tibial SEP recorded in the lumbosacral region was shown to predict patients with chronic high spinal cord injury in whom sphincterotomy failed to improve bladder emptying (Light et al., 1987); probably due to an additional peripheral lesion resulting in detrusor failure. An abnormal pudendal SEP was similarly reported to predict a poor surgical outcome after resection of a tight filum terminale (Selcuki and Coskun, 1998). Cerebral SEPs elicited by penile/clitoral stimulation may have value in intraoperative monitoring in patients in whom the cauda equina or conus medullaris is at risk during surgery (Vodusek et al., 1990). Other studies have also reported the utility of sacral neurophysiologic methods in intraoperative mapping of neural structures (Huang et al., 1997). 4.2.2. Neuromodulation In recent years sacral and pudendal neuromodulation has become increasingly important in the management of patients with neurogenic LUT disorders. In spite of wide clinical applications, the mechanism of neuromodulation remains unexplained, but according to a poor response in patients with complete spinal cord injury probable involve-

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ment of the suprasacral (probably spino-bulbo-spinal) pathways was postulated (Schurch et al., 2003). Pudendal SEP latency was also found to be significantly decreased by sacral neuromodulation, and this was proposed as a possible prognostic factor for clinical outcome (Malaguti et al., 2003). A very recent study also demonstrated that decelerating burst and complex repetitive discharge activity in the EUS of young women with non-obstructive urinary retention demonstrated by CNEMG (Fowler’s syndrome) is the only predictor of the long-term success of therapeutic sacral neuromodulation (De Ridder et al., 2007). Neurophysiologic guidance is also mandatory for placement of the lead for chronic pudendal nerve stimulation (Spinelli et al., 2005). Recently, a technique was described for percutaneous S3 spinal nerve stimulation, which enables non-invasive screening of candidates for chronic neurostimulation before the invasive peripheral nerve evaluation test (Pelliccioni and Scarpino, 2006). Adding neurophysiologic monitoring to the biologic monitoring was associated with a reduction in the percentage of patients denied implantation for sacral neuromodulation (from 50% to 20%) (Benson, 2000). 4.3. Application of neurophysiologic tests for research Neurophysiologic techniques have been widely used in research on patients with neurogenic LUT dysfunction. Although currently findings of such studies do not have direct clinical implications this might change in the future. Furthermore, these studies assist in the understanding of the (patho)physiology of the sacral nervous system. A description of only a few recent studies follows. The modulation of sacral motor neurons has been studied extensively. It has been shown that, in normal subjects, the amplitude of the penilo-urethral reflex increases with bladder filling, but the response disappears during voiding (Kaiho et al., 2004). Bladder distension, in contrast, reduced the H-reflex amplitude in patients with encephalopathy and controls, but not in patients with spinal cord lesions, which points to suprasegmental post-synaptic inhibition of the spinal motor neurons (Inghilleri et al., 2001). Similarly, pudendal stimulation 50 ms before lumbosacral magnetic stimulation inhibits the EUS contraction (Wefer et al., 2005). The effects of pudendal nerve stimulation were also studied in men with incontinence due to complete spinal cord injury. An increase in EUS pressure, with a latency of 27– 41 ms, and in bladder neck pressure, with a latency of 188–412 ms, was found. Phentolamine reduced the effect on the bladder neck, which supported the pudendal nerve somatic afferent neuromodulative effect on sympathetic thoracolumbar neurons at the spinal level, which seems to be at least partly responsible for bladder neck competence (continence) (Reitz et al., 2003b). Using transcranial magnetic stimulation, the duration of the cortical silent period and intra-cortical inhibition was found to be smaller for the EAS compared to hand muscles (Lefaucheur, 2005a).

5. Conclusion and recommendations Due to the limited utility of clinical examination, urodynamics and imaging studies to demonstrate a neurogenic etiology of the LUT dysfunction, the role of clinical neurophysiologic methods remains important. For evaluation of patients with neurogenic LUT dysfunction a number of neurophysiologic methods have been used. Of these, EMG of the EAS muscle is well standardized and ready to apply, particularly in patients with focal lesions of the peripheral sacral nervous system and atypical parkinsonism. Utility of the EUS EMG is limited by its small muscle bulk, and more difficult examination. Although the penilo/ clitoro-cavernosus reflex also seems to be useful in daily clinical practice, the method needs further standardization and validation. The potential of pudendal SEP and sphincter MEP studies is probably limited to revealing additional clinically silent lesions, and to assessing relevance of these lesions for LUT dysfunction. Further studies of cortical excitability, and other aspects of sphincter and pelvic muscle motor control using MEP, are encouraged. Although cortical SEP on bladder/urethra stimulation has not gained wide acceptance in clinical practice due to technical difficulties, its clinical utility may be increased by concomitant recording of hand SSR. However, in clinical neurophysiologic laboratories popularity of these studies may remain limited due to their relative invasiveness. Nevertheless, the method needs to be studied in well-defined patient populations. Similarly, several other available methods for evaluation of the lumbosacral sympathetic system seem promising, and need more attention, further research, and clinical application in the future. In contrast, our ability to evaluate the sacral parasympathetic system by clinical neurophysiologic methods is still very limited. However, because this system has a pivotal role in bladder function intense further research aimed at developing clinically useful methods is needed. Acknowledgements The author thanks Prof. David B. Vodusˇek for review of the manuscript, and Dr. Dianne Jones for language review. The writing of this paper was supported by the Republic of Slovenia Research Agency, Grant No. J3 7899. References Aanestad O, Flink R, Haggman M, Norlen BJ. Interference pattern in the urethral sphincter: a quantitative electromyographic study in patients before and after radical retropubic prostatectomy. Scand J Urol Nephrol 1998;32:378–82. Amarenco G, Kerdraon J. Pudendal nerve terminal sensitive latency: technique and normal values. J Urol 1999;161:103–6. Amarenco G, Kerdraon J. Clinical value of ipsi- and contralateral sacral reflex latency measurement: a normative data study in man. Neurourol Urodyn 2000;19:565–76. Amarenco G, Ismael SS, Bayle B, Kerdraon J. Dissociation between electrical and mechanical bulbocavernosus reflexes. Neurourol Urodyn 2003;22:676–80.

S. Podnar / Clinical Neurophysiology 118 (2007) 1423–1437 Barrington FJF. The effect of lesions of the hind- and mid-brain on micturition in cats. Q J Exp Physiol Cogn Med 1925;15:81–102. Basinski C, Fuller E, Brizendine EJ, Benson JT. Bladder-anal reflex. Neurourol Urodyn 2003;22:683–6. Benson JT. Sacral nerve stimulation results may be improved by electrodiagnostic techniques. Int Urogynecol J Pelvic Floor Dysfunct 2000;11:352–7. Betts CD, Jones SJ, Fowler CG, Fowler CJ. Erectile dysfunction in multiple sclerosis. Associated neurological and neurophysiological deficits, and treatment of the condition. Brain 1994;117:1303–10. Blaivas JG, Labib KL, Bauer SB, Retik AB. A new approach to electromyography of the external urethral sphincter. J Urol 1977;117:773–7. Blok BF, Holstege G. Ultrastructural evidence for a direct pathway from the pontine micturition center to the parasympathetic preganglionic motoneurons of the bladder of the cat. Neurosci Lett 1997;222:195–8. Blok BF, Willemsen AT, Holstege G. A PET study on brain control of micturition in humans. Brain 1997;120(Pt 1):111–21. Blok BF, Sturms LM, Holstege G. Brain activation during micturition in women. Brain 1998;121(Pt 11):2033–42. Bradley WE, Lin JT, Johnson B. Measurement of the conduction velocity of the dorsal nerve of the penis. J Urol 1984;131:1127–9. Brostrom S. Motor evoked potentials from the pelvic floor. Neurourol Urodyn 2003;22:620–37. Brostrom S, Frederiksen JL, Jennum P, Lose G. Motor evoked potentials from the pelvic floor in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2003a;74:498–500. Brostrom S, Jennum P, Lose G. Motor evoked potentials from the striated urethral sphincter: a comparison of concentric needle and surface electrodes. Neurourol Urodyn 2003b;22:123–9. Chantraine A, Leval J, Onkelinx A. Electromyographie des sphincters strie´s ure´tal et anal humains. Etude descriptive et analytique. Rev Neurol (Paris) 1973;115:396–403. Chuang TY, Cheng H, Chan RC, Chiang SC, Guo WY. Neurourologic findings in patients with traumatic thoracolumbar vertebra junction lesions. Arch Phys Med Rehabil 2001;82:375–9. Daffertshofer M, Linden D, Syren M, Junemann KP, Berlit P. Assessment of local sympathetic function in patients with erectile dysfunction. Int J Impot Res 1994;6:213–25. De EJ, Patel CY, Tharian B, Westney OL, Graves DE, Hairston JC. Diagnostic discordance of electromyography (EMG) versus voiding cystourethrogram (VCUG) for detrusor-external sphincter dyssynergy (DESD). Neurourol Urodyn 2005;24:616–21. Delodovici ML, Fowler CJ. Clinical value of the pudendal somatosensory evoked potential. Electroencephalogr Clin Neurophysiol 1995;96:509–15. Del Rey AP, Entrena BF. Reference values of motor unit potentials (MUPs) of the external anal sphincter muscle. Clin Neurophysiol 2002;113:1832–9. De Ridder D, Ost D, Bruyninckx F. The presence of Fowler’s Syndrome predicts successful long-term outcome of sacral nerve stimulation in women with urinary retention. Eur Urol 2007;51:229–34. Di Lazzaro V, Pilato F, Oliviero A, Saturno E, Dileone M, Tonali PA. Role of motor evoked potentials in diagnosis of cauda equina and lumbosacral cord lesions. Neurology 2004;63:2266–71. Eardley I, Quinn NP, Fowler CJ, Kirby RS, Parkhouse HF, Marsden CD, et al. The value of urethral sphincter electromyography in the differential diagnosis of parkinsonism. Br J Urol 1989;64:360–2. Eardley I, Nagendran K, Lecky B, Chapple CR, Kirby RS, Fowler CJ. Neurophysiology of the striated urethral sphincter in multiple sclerosis. Br J Urol 1991;68:81–8. Ertekin C, Mungan B. Sacral spinal cord and root potentials evoked by the stimulation of the dorsal nerve of penis and cord conduction delay for the bulbocavernosus reflex. Neurourol Urodyn 1993;12:9–22. Ertekin C, Ertekin N, Mutlu S, Almis S, Akcam A. Skin potentials (SP) recorded from the extremities and genital regions in normal and impotent subjects. Acta Neurol Scand 1987;76:28–36.

1435

Everaert K, De Muynck M, Rimbaut S, Weyers S. Urinary retention after hysterectomy for benign disease: extended diagnostic evaluation and treatment with sacral nerve stimulation. BJU Int 2003;91:497–501. Fanciullacci F, Kokodoko A, Garavaglia PF, Galli M, Sandri S, Zanollo L. Comparative study of the motor unit potentials of the external urethral sphincter, anal sphincter, and bulbocavernosus muscle in men. Neurourol Urodyn 1987;6:65–9. Fitzgerald MP, Koch D, Senka J. Visceral and cutaneous sensory testing in patients with painful bladder syndrome. Neurourol Urodyn 2005;24:627–32. Fowler CJ, Kirby RS, Harrison MJ, Milroy EJ, Turner-Warwick R. Individual motor unit analysis in the diagnosis of disorders of urethral sphincter innervation. J Neurol Neurosurg Psychiatry 1984;47:637–41. Fowler CJ, Kirby RS, Harrison MJ. Decelerating burst and complex repetitive discharges in the striated muscle of the urethral sphincter, associated with urinary retention in women. J Neurol Neurosurg Psychiatry 1985;48:1004–9. Fowler CJ, Christmas TJ, Chapple CR, Parkhouse HF, Kirby RS, Jacobs HS. Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome? Br Med J 1988;297:1436–8. Ganzer H, Madersbacher H, Rumpl E. Cortical evoked potentials by stimulation of the vesicourethral junction: clinical value and neurophysiological considerations. J Urol 1991;146:118–23. Gilad R, Giladi N, Korczyn AD, Gurevich T, Sadeh M. Quantitative anal sphincter EMG in multisystem atrophy and 100 controls. J Neurol Neurosurg Psychiatry 2001;71:596–9. Giladi N, Simon ES, Korczyn AD, Groozman GB, Orlov Y, Shabtai H, et al. Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson’s disease. Muscle Nerve 2000;23:731–4. Gjone R. Excitatory and inhibitory bladder responses to stimulation of ‘limbic’, diencephalic and mesencephalic structures in the cat. Acta Physiol Scand 1966;66:91–102. Groutz A, Blaivas JG, Pies C, Sassone AM. Learned voiding dysfunction (non-neurogenic, neurogenic bladder) among adults. Neurourol Urodyn 2001;20:259–68. Guerit J, Opsomer R. Bit-mapped imagine of somatosensory evoked potentials after stimulation of the posterior tibial nerves and dorsal nerve of the penis/clitoris. Electroencephalogr Clin Neurophysiol 1991;80:228. Hansen MV, Ertekin C, Larsson LE. Cerebral evoked potentials after stimulation of the posterior urethra in man. Electroencephalogr Clin Neurophysiol 1990;77:52–8. Hanson P, Rigaux P, Gilliard C, Biset E. Sacral reflex latencies in tethered cord syndrome. Am J Phys Med Rehabil 1993;72:39–43. Hasan ST, Hamdy FC, Schofield IS, Neal DE. Transrectal ultrasound guided needle electromyography of the urethral sphincter in males. Neurourol Urodyn 1995;14:359–63. Hecht MJ, Neundorfer B, Kiesewetter F, Hilz MJ. Neuropathy is a major contributing factor to diabetic erectile dysfunction. Neurol Res 2001;23:651–4. Holstege G, Griffiths D, de Wall H, Dalm E. Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat. J Comp Neurol 1986;250:449–61. Huang JC, Deletis V, Vodusek DB, Abbott R. Preservation of pudendal afferents in sacral rhizotomies. Neurosurgery 1997;41:411–5. Inghilleri M, Carbone A, Pedace F, Conte A, Frasca V, Berardelli A, et al. Bladder filling inhibits somatic spinal motoneurones. Clin Neurophysiol 2001;112:2255–60. Inoue S, Kawaguchi M, Takashi S, Kakimoto M, Sakamoto T, Kitaguchi K, et al. Intraoperative monitoring of myogenic motor-evoked potentials from the external anal sphincter muscle to transcranial electrical stimulation. Spine 2002;27:E454–9. Jennum P, Neerup Jensen L, Fenger K, Nielsen JE, Fuglsang-Frederiksen A. Motor evoked potentials from the external anal sphincter in patients with autosomal dominant pure spastic paraplegia linked to chromosome 2p. J Neurol Neurosurg Psychiatry 2001;71:561–2.

1436

S. Podnar / Clinical Neurophysiology 118 (2007) 1423–1437

Kaiho Y, Namima T, Uchi K, Nakagawa H, Aizawa M, Takeuchi A, et al. Electromyographic study of the striated urethral sphincter by using the bulbocavernosus reflex: study on change of sacral reflex activity caused by bladder filling. Nippon Hinyokika Gakkai Zasshi 2000;91:715–22. Kaiho Y, Namima T, Nakagawa H, Aizawa M, Uchi K, Ikeda Y, et al. Bulbocavernosus reflex during the micturition cycle in normal male subjects. Int J Urol 2004;11:33–7. Kalita J, Shah S, Kapoor R, Misra UK. Bladder dysfunction in acute transverse myelitis: magnetic resonance imaging and neurophysiological and urodynamic correlations. J Neurol Neurosurg Psychiatry 2002;73:154–9. Kiff ES, Swash M. Normal proximal and delayed distal conduction in the pudendal nerves of patients with idiopathic (neurogenic) faecal incontinence. J Neurol Neurosurg Psychiatry 1984;47:820–3. Kinder MV, van Waalwijk van Doorn ES, Gommer ED, Janknegt RA. A non-invasive method for bladder electromyography in humans. Arch Physiol Biochem 1998;106:2–11. Klausner AP, Batra AK. Pudendal nerve somatosensory evoked potentials in patients with voiding and/or erectile dysfunction: correlating test results with clinical findings. J Urol 1996;156:1425–7. Lefaucheur JP. Excitability of the motor cortical representation of the external anal sphincter. Exp Brain Res 2005a;160:268–72. Lefaucheur JP. Intrarectal ground electrode improves the reliability of motor evoked potentials recorded in the anal sphincter. Muscle Nerve 2005b;32:110–2. Lefaucheur J, Yiou R, Thomas C. Pudendal nerve terminal motor latency: age effects and technical considerations. Clin Neurophysiol 2001;112:472–6. Lehmkuhl LD, Dimitrijevic MR, Zidar J. Lumbosacral evoked potentials (LSEPs) and cortical somatosensory evoked potentials (SEPs) in patients with lesions of the conus medullaris and cauda equina. Electroencephalogr Clin Neurophysiol 1988;71:161–9. Libelius R, Johansson F. Quantitative electromyography of the external anal sphincter in Parkinson’s disease and multiple system atrophy. Muscle Nerve 2000;23:1250–6. Light JK, Beric A, Wise PG. Predictive criteria for failed sphincterotomy in spinal cord injury patients. J Urol 1987;138:1201–4. Loening-Baucke V, Read NW, Yamada T, Barker AT. Evaluation of the motor and sensory components of the pudendal nerve. Electroencephalogr Clin Neurophysiol 1994;93:35–41. Lose G, Tanko A, Colstrup H, Andersen JT. Urethral sphincter electromyography with vaginal surface electrodes: a comparison with sphincter electromyography recorded via periurethral coaxial, anal sphincter needle and perianal surface electrodes. J Urol 1985;133:815–8. Lowe EM, Fowler CJ, Osborne JL, DeLancey JO. Improved method for needle electromyography of the urethral sphincter in women. Neurourol Urodyn 1994;13:29–33. Malaguti S, Spinelli M, Giardiello G, Lazzeri M, Van Den Hombergh U. Neurophysiological evidence may predict the outcome of sacral neuromodulation. J Urol 2003;170:2323–6. Mannen T, Iwata M, Toyokura Y, Nagashima K. The Onuf’s nucleus and the external anal sphincter muscles in amyotrophic lateral sclerosis and Shy-Drager syndrome. Acta Neuropathol (Berl) 1982;58:255–60. Mathers SE, Ingram DA, Swash M. Electrophysiology of motor pathways for sphincter control in multiple sclerosis. J Neurol Neurosurg Psychiatry 1990;53:955–60. Morrison J, Birder L, Craggs M, De Groat W, Downie J, Drake M, et al. Neural control. In: Abrams P, Cardozo L, Khoury S, Wein A, editors. Incontinence. 2005 ed: Health Publications Ltd, 2005:363–422. Nandedkar SD, Sanders DB, Stalberg EV. Automatic analysis of the electromyographic interference pattern. Part II: findings in control subjects and in some neuromuscular diseases. Muscle Nerve 1986;9:491–500. Nikiforidis G, Koutsojannis C, Giannoulis S, Barbalias G. Reduced variance of latencies in pudendal evoked potentials after normalization for body height. Neurourol Urodyn 1995;14:239–51.

Nordling J, Meyhoff HH, Walter S, Andersen JT. Urethral electromyography using a new ring electrode. J Urol 1978;120:571–3. Olsen AL, Benson JT, McClellan E. Urethral sphincter needle electromyography in women: comparison of periurethral and transvaginal approaches. Neurourol Urodyn 1998;17:531–5. Oppenheimer SM, Saleh TM, Wilson JX, Cechetto DF. Plasma and organ catecholamine levels following stimulation of the rat insular cortex. Brain Res 1992;569:221–8. Opsomer RJ, Pesce F, Abi Aad A. Electrophysiologic testing of motor sympathetic pathways: normative data and clinical contribution in neurourological disorders. Neurourol Urodyn 1993;12:336. Palace J, Chandiramani VA, Fowler CJ. Value of sphincter electromyography in the diagnosis of multiple system atrophy. Muscle Nerve 1997;20:1396–403. Pelliccioni G, Scarpino O. External anal sphincter responses after S3 spinal root surface electrical stimulation. Neurourol Urodyn 2006;25:788–91. Podnar S. Electromyography of the anal sphincter: which muscle to examine? Muscle Nerve 2003;28:377–9. Podnar S. Criteria for neuropathic abnormality in quantitative anal sphincter electromyography. Muscle Nerve 2004;30:596–601. Podnar S. Critical reappraisal of referrals to electromyography and nerve conduction studies. Eur J Neurol 2005;12:150–5. Podnar S. Nomenclature of the electrophysiologically tested sacral reflexes. Neurourol Urodyn 2006a;25:95–7. Podnar S. Which patients need referral for anal sphincter electromyography? Muscle Nerve 2006b;33:278–82. Podnar S, Fowler CJ. Sphincter electromyography in diagnosis of multiple system atrophy: technical issues. Muscle Nerve 2004;29:151–6. Podnar S, Mrkaic M. Predictive power of motor unit potential parameters in anal sphincter electromyography. Muscle Nerve 2002;26:389–94. Podnar S, Vodusek DB. Protocol for clinical neurophysiologic examination of the pelvic floor. Neurourol Urodyn 2001;20:669–82. Podnar S, Vodusek DB, Trsinar B, Rodi Z. A method of uroneurophysiological investigation in children. Electroencephalogr Clin Neurophysiol 1997;104:389–92. Podnar S, Rodi Z, Lukanovic A, Trsinar B, Vodusek DB. Standardization of anal sphincter EMG: technique of needle examination. Muscle Nerve 1999;22:400–3. Podnar S, Mrkaic M, Vodusek DB. Standardization of anal sphincter electromyography: quantification of continuous activity during relaxation. Neurourol Urodyn 2002a;21:540–5. Podnar S, Oblak C, Vodusek DB. Sexual function in men with cauda equina lesions: a clinical and electromyographic study. J Neurol Neurosurg Psychiatry 2002b;73:715–20. Podnar S, Vodusek DB, Stalberg E. Comparison of quantitative techniques in anal sphincter electromyography. Muscle Nerve 2002c;25:83–92. Podnar S, Trsinar B, Vodusek DB. Bladder dysfunction in patients with cauda equina lesions. Neurourol Urodyn 2006;25:23–31. Pozzilli C, Grasso MG, Bastianello S, Anzini A, Salvetti M, Bozzao L, et al. Structural brain correlates of neurologic abnormalities in multiple sclerosis. Eur Neurol 1992;32:228–30. Rapidi CA, Karandreas N, Katsifotis C, Benroubi M, Petropoulou K, Theodorou C. A combined urodynamic and electrophysiological study of diabetic cystopathy. Neurourol Urodyn 2006;25:32–8. Reitz A, Schmid DM, Curt A, Knapp PA, Jensen K, Schurch B. Electrophysiological assessment of sensations arising from the bladder: are there objective criteria for subjective perceptions? J Urol 2003a;169:190–4. Reitz A, Schmid DM, Curt A, Knapp PA, Schurch B. Afferent fibers of the pudendal nerve modulate sympathetic neurons controlling the bladder neck. Neurourol Urodyn 2003b;22:597–601. Restuccia D, Di Lazzaro V, Valeriani M, Colosimo C, Tonali P. N24 spinal response to tibial nerve stimulation and magnetic resonance imaging in lesions of the lumbosacral spinal cord. Neurology 1993;43:2269–75.

S. Podnar / Clinical Neurophysiology 118 (2007) 1423–1437 Rodic B, Curt A, Dietz V, Schurch B. Bladder neck incompetence in patients with spinal cord injury: significance of sympathetic skin response. J Urol 2000;163:1223–7. Rodi Z, Vodusek DB, Denislic M. Clinical uro-neurophysiological investigation in multiple sclerosis. Eur J Neurol 1996;3:574–80. Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases. J Neurol Sci 1996;141:105–10. Sakakibara R, Hattori T, Uchiyama T, et al. Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation? J Neurol Neurosurg Psychiatry 2000;68:25. Sakakibara R, Hattori T, Uchiyama T, Kamura K, Yamanishi T. Uroneurological assessment of spina bifida cystica and occulta. Neurourol Urodyn 2003;22:328–34. Scaravilli T, Pramstaller PP, Salerno A, Egarter-Vigl E, Giometto B, Vitaliani R, et al. Neuronal loss in Onuf’s nucleus in three patients with progressive supranuclear palsy. Ann Neurol 2000;48:97–101. Schafer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, et al. Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn 2002;21:261–74. Schmid DM, Reitz A, Curt A, Hauri D, Schurch B. Urethral evoked sympathetic skin responses and viscerosensory evoked potentials as diagnostic tools to evaluate urogenital autonomic afferent innervation in spinal cord injured patients. J Urol 2004;171:1156–60. Schmid DM, Curt A, Hauri D, Schurch B. Motor evoked potentials (MEP) and evoked pressure curves (EPC) from the urethral compressive musculature (UCM) by functional magnetic stimulation in healthy volunteers and patients with neurogenic incontinence. Neurourol Urodyn 2005;24:117–27. Schroder HD. Onuf’s nucleus X: a morphological study of a human spinal nucleus. Anat Embryol (Berl) 1981;162:443–53. Schurch B, Reilly I, Reitz A, Curt A. Electrophysiological recordings during the peripheral nerve evaluation (PNE) test in complete spinal cord injury patients. World J Urol 2003;20:319–22. Secil Y, Ozdedeli K, Altay B, Aydogdu I, Yilmaz C, Ertekin C. Sympathetic skin response recorded from the genital region in normal and diabetic women. Neurophysiol Clin 2005;35:11–7. Selcuki M, Coskun K. Management of tight filum terminale syndrome with special emphasis on normal level conus medullaris (NLCM). Surg Neurol 1998;50:318–22, discussion 22. Sidi AA, Dykstra DD, Peng W. Bethanechol supersensitivity test, rhabdosphincter electromyography and bulbocavernosus reflex latency in the diagnosis of neuropathic detrusor areflexia. J Urol 1988;140:335–7. Skultety FM. Relation to periaqueductal gray matter to stomach and bladder motility. Neurology 1959;9:190–8. Spinelli M, Malaguti S, Giardiello G, Lazzeri M, Tarantola J, Van Den Hombergh U. A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: description of the method and preliminary data. Neurourol Urodyn 2005;24:305–9.

1437

Stalberg E, Trontelj JV. Single fiber electromyography: studies in healthy and diseased muscle. New York: Raven Press; 1994. Stocchi F, Carbone A, Inghilleri M, Monge A, Ruggieri S, Berardelli A, et al. Urodynamic and neurophysiological evaluation in Parkinson’s disease and multiple system atrophy. J Neurol Neurosurg Psychiatry 1997;62:507–11. Swinn MJ, Wiseman OJ, Lowe E, Fowler CJ. The cause and natural history of isolated urinary retention in young women. J Urol 2002;167:151–6. Tison F, Arne P, Sourgen C, Chrysostome V, Yeklef F. The value of external anal sphincter electromyography for the diagnosis of multiple system atrophy. Mov Disord 2000;15:1148–57. Torre M, Planche D, Louis-Borrione C, Sabiani F, Lena G, Guys JM. Value of electrophysiological assessment after surgical treatment of spinal dysraphism. J Urol 2002;168:1759–62, discussion 63. Tsai PY, Cha RC, Yang TF, Wong TT, Huang PH, Pan PJ. Electromyographic evaluation in children with spina bifida. Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:509–15. Ueda T, Yoshimura N, Yoshida O. Diabetic cystopathy: relationship to autonomic neuropathy detected by sympathetic skin response. J Urol 1997;157:580–4. Valldeoriola F, Valls-Sole J, Tolosa ES, Marti MJ. Striated anal sphincter denervation in patients with progressive supranuclear palsy. Mov Disord 1995;10:550–5. Vodusek DB. Pudendal SEP and bulbocavernosus reflex in women. Electroencephalogr Clin Neurophysiol 1990;77:134–6. Vodusek DB, Zidar J. Perineal motor evoked responses. Neurourol Urodyn 1988;7:236. Vodusek DB, Janko M, Lokar J. Direct and reflex responses in perineal muscles on electrical stimulation. J Neurol Neurosurg Psychiatry 1983;46:67–71. Vodusek DB, Deletis V, Abbott R, Turndorf H. Prevention of iatrogenic micturition disorders through intraoperative monitoring. Neurourol Urodyn 1990;9:444. Vodusek DB, Amarenco G, Batra A, Benson T, Bharucha AE, Podnar S, et al. Clinical neurophysiology. In: Abrams P, Cardozo L, Khoury S, Wein A, editors. Incontinence. Plymouth (UK): Health Publication Ltd; 2005. p. 675–706. Wefer B, Reitz A, Knapp PA, Bannowsky A, Juenemann KP, Schurch B. Conditioning stimulus can influence an external urethral sphincter contraction evoked by a magnetic stimulation. Neurourol Urodyn 2005;24:311–7, discussion 8. Wyndaele JJ, Van Eetvelde B, Callens D. Comparison in young healthy volunteers of 3 different parameters of constant current stimulation used to determine sensory thresholds in the lower urinary tract. J Urol 1996;156:1415–7. Yamamoto T, Sakakibara R, Uchiyama T, Liu Z, Ito T, Awa Y, et al. When is Onuf’s nucleus involved in multiple system atrophy? A sphincter electromyography study. J Neurol Neurosurg Psychiatry 2005;76:1645–8. Yilmaz U, Yang CC, Berger RE. Dartos reflex: a sympathetically mediated scrotal reflex. Muscle Nerve 2006;33:363–8.