EVOKED POTENTIAL TESTING

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EVOKED POTENTIAL TESTING David B. VoduSek, MD, DSc

Neurophysiologic diagnostic methods involving stimulation and recording of responses, together with electromyographic (EMG) methods as applied to the urogenitoanal region and its (sacral) neuromuscular system, constitute a new field-the field of uroneurophysiology. Its mother field is neurourology, as called by urologists, or uroneurology, a term preferred by neurologists. Insofar as the sacral neuromuscular system controls urinary, sexual, and bowel functions (the sacral functions), uroneurophysiology transcends several classic medical specialties, more so than the quite urologically oriented neurourology. This article reviews uroneurophysiologic tests apart from (in the narrow sense) EMG methods. BASIC CONCEPTS

An excitable membrane and transmission of information along this membrane by means of traveling action potentials is characteristic of nerve and muscle cells. This bioelectrical activity is in itself the substrate of function of nervous tissue (i.e., transmission of information) and precedes the function of muscle (i.e., contraction). It is this bioelectrical activity that makes possible the application of electrophysiologic diagnostic methods. To understand how electrophysiologic information is obtained, one must understand two basic procedures: (1)stimulation and (2)

recording (Fig. 1). To obtain information about the bioelectrical activity of muscle, nerve, spinal roots, spinal cord, and brain, recordings (direct or indirect) from these structures are necessary. One can record the ongoing (spontaneous) bioelectrical activity generated in these structures, but often an artificially evoked activity is diagnostically more informative. For this, stimulation is needed. The bioelectrical activity is evoked most often by electrical pulses, but magnetic and mechanical stimulation also can be applied. The targets of mechanical stimuli are receptors, whereas electrical and magnetic stimulation excite sensory and motor nerves, spinal roots, and also parts of the central nervous system. The bioelectrical activity that can be recorded from muscle or nervous tissue as a result of stimulation has been called many different names. Considered generally, all such activity could in principle be called evoked potentials. In the narrower sense only some categories of such responses are called evoked potentials by clinical neurophysiologists. Even if questions of nomenclature are considered tedious, uncertainties about definitions of terms can lead to much perplexity in the naive reader; we therefore try to clarify issues of terminology as much as possible. Evoked potential' is defined as an electric waveform elicited by and temporally related to a stimulus (most commonly an electric stimulus) delivered to a sensory receptor or

From the Department of Neurology, Medical Faculty; and the University Institute of Clinical Neurophysiology, University Medical Centre, Ljubljana, Slovenia

UROLOGIC CLINICS OF NORTH AMERICA

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VODUSEK systems. Within a particular compartment we can distinguish central and peripheral parts. This very simplified anatomic model helps to explain how individual neurophysiologic tests relate to the function of one or several parts in such compartments (Fig. 2). These parts are as follows. The motor system comprises an upper motor neuron (i.e., all neurons participating in supraspinal motor control), a lower motor neuron (alpha motor neurons of the spinal cord), and muscle. The somatosensory system can be divided into a peripheral part (receptors and the sensory input into the spinal cord) and a central part (ascending pathways in the spinal cord and above). Sensory fibers from skin and those accompanying axons from alpha motoneurons are called somatic afferents. If they, however, accompany autonomic (parasympathetic or sympathetic) fibers they are called visceral afferents. With this simplified model of the sacral neuromuscular system as the basis, the clinical neurophysiologic methods can be divided into those evaluating the motor system (motor evoked potentials [MEP]) and those evalu-

Figure 1. Stimulation and recording set up to elicit the sacral reflex on stimulation of the dorsal clitoral (A), and dorsal penile nerve (B). Two surface electrodes (of various designs) are used for stimulation; S(-) is the cathode, S( +) the anode. Different types of either surface or needle (wire) electrodes are used for recording from pelvic floor muscles; R1 and R2 are recording electrodes. With needle or wire electrodes, unilateral recording is possible. The same type of stimulation set up is used for eliciting somatosensory evoked potentials (SEP).

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nerve, or applied directly to a discrete area of the brain, spinal cord, or muscle. It generally is used to refer to studies of waveforms generated in the peripheral and central nervous system, whereas nerve conduction studies refer to studies of waveforms generated in the peripheral nervous system only. Although reflex responses are not strictly ruled out by this definition, neurophysiologists prefer not to call reflex responses evoked potentials.2 Clinical and urodynamic investigations test neural control only indirectly, whereas electrophysiologic methods measure directly the transmission of impulses through the nervous system. To grasp the range of available electrophysiologic methods it is helpful to divide the nervous system conceptually into compartments. Schematically we can distinguish

a motor system and a somatosensory system, as well as somatic and vegetative nervous

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Figure 2. A very simplified model of the nervous system controlling urogenito-anal function. The “Muscle” and “Motor Pathways” represent the somatic motor system (pelvic floor muscles; pudendal nerve and its suprasegmental control). “Receptor” (in the skin or mucosa) and “Sensory Pathways” stand for both “somatic” and “visceral” afferent fibers. It is indicated that part of this neuromuscular system is assessed by which uroneurophysiological test. SEP = somatosensory evoked potential testing; MEP = motor evoked potential testing; Reflex= sacral reflex testing.

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ating the sensory system (sensory evoked potentials). The third group comprises methods assessing reflexes (i.e., evaluating together the respective parts of the sensory system, the central integrative processes, and motor pathways) (see Fig. 2). If such reflexes involve autonomic nerve fibers the methods usually are called autonomic nervous system tests. The only uroneurophysiologic method to test the function of autonomic (i.e., visceral motor) nerves directly is the sympathetic skin response (SSR) in the perineum. There is no evoked potential testing for the sacral parasympathetic. In discussing the individual diagnostic methods we try to clarify issues of terminology, controversies regarding methodology, and clinical relevance. The space does not allow for discussion of detailed aspects of methods or exact comparative tabulating of results from individual authors or groups. It is the overall understanding of uroneurophysiologic testing as applied in research and clinical practice that this article aims to provide. Some illustrative applications of tests are given along with figures. Some general aspects of evoked potential testing, common to all different methods, are as follows. METHODOLOGIC CONSIDERATIONS

Uroneurophysiologic tests rely on complex electronic instruments and various instruments that come into contact with patients. Equipment used is standard neurophysiologic equipment. Some laboratories use specially constructed electrodes, adapted to urogenitoanal anatomy, but in principle all basic tests can be performed with commonly available electrodes. Basic standards for equipment as well as generally for different methodologies generally exist and should be referred There are no generally accepted guidelines, however, for individual uroneurophysiologic tests. All stimulation procedures are safe, but as a precaution electrical and magnetic stimulations are not used in patients with cardiac pacemakers. Both electrical stimulation and recording of bioelectrical activity are achieved through the use of electrodes, which usually are referred to as either surface or needle (special devices are used for magnetic and mechanical stimulation). The important neurophysiologic difference between the two categories of electrodes is their selectivity and the practical

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difference in their invasiveness. The choice of electrodes depends mainly on the degree of selectivity required for a recording. For stimulation, surface electrodes often are used. EMG responses from muscle commonly are recorded with surface electrodes, but use of this method is controversial for recording from sphincters (as, for instance, recording MEPs). Sphincters are very small muscles and lie in proximity to other muscles, which have greater bulk and thus generate large electrical fields. If active simultaneously, they can obscure the activity from the sphincter. In recording bioelectrical activity of nerve tissue (somatosensory evoked potential [SEP] testing), surface electrodes generally are used because needle electrodes are too invasive for use in structures of the nervous system. Also, surface electrodes are used to record shifts in electrical potential from skin (SSR testing). There are some general rules involving stimulation and recording. The electrical stimulus needs to be specified and characterized both in absolute and relative terms (e.g., rectangular pulse, 0.2 millisecond, 15 mA; three times sensory threshold). The simple absolute parameters of the stimulus are not sufficient because of the variable influences of electrode condition, contact, tissue conductivity, and so forth. In stimulation procedures it usually is desirable to use the so-called supramaximal stimuli,' because they produce largest amplitude responses with shortest latencies and are least variable and most easily reproduced. If supramaximal stimuli are not possible (or not desirable) another physiologic (biologic) definition of the stimulus is preferable. It is common practice to define magnetic stimulus strength as percentage of maximum output of the apparatus. The sites of stimulation and recording should be stated. On the scalp they are defined according to the 10 to 20 International Electroencephalogram (EEG) System; elsewhere, anatomic landmarks are used. Because the recorded evoked potentials should be reproducible, at least two consecutive measurements usually are done. Some evoked potentials require averaging because of their low amplitude (to improve the signalto-noise ratio); they otherwise are not recognizable (the SEPs)I2;therefore, many repetitions of stimulation and recording are required (typically 128 or 256). MEP, sacral reflexes, and SSR are recognizable after single stimuli. The recorded potentials are analyzed as related to morphology, latency, and ampli-

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tude of the response.'* With regard to morphology, the presence or absence of a particular. potential needs to be established. This may be true for only some parts of the response (particularly in SEP, but also in sacral reflex testing). The analysis of the shape of potentials is needed because of accurate determination of the latency and amplitude of the response. The latency may be determined by the onset of response (usually revealed in MEP and sacral reflex testing) or to individual peaks of the potentials (usual in SEP assessment). Generally speaking, evoked potentials are recordings that relate to populations of biologic units (neurons, axons, motor units, muscle fibers, and so forth). The latency of such a compound potential informs (if measured to the onset of potential) on the fastest conduction through a particular neural channel. The amplitude of the (compound) potential correlates with the number of activated biologic units. Unfortunately the amplitudes, which are the more relevant physiologic parameter, potentially telling us about the loss of biologic units, depend very much on a variety of biologic and technical factors. They are therefore interindividually quite variable, and, as a consequence, of less diagnostic importance. As a general rule, latency measurements depend less on irrelevant biologic and technical factors and are therefore the more useful parameter in evoked potential studies, although they tell little about the loss of biologic units (axons, and so forth). Having the previously developed simple anatomic model in mind, we can understand that any of the nervous system parts may be involved by a lesion. This leads to either a slowing of conduction or a loss of biologic units. Slowed conduction is caused particularly by diseases affecting the myelin (central or peripheral). Loss of units may be owing to a block of conduction or to degeneration of the biologic unit (e.g., loss of axons). Loss of units may be partial or complete. To reiterate, demyelinative lesions primarily prolong latency or conduction time, whereas axonal lesions lead to a loss of amplitude of evoked potential. Because the latter usually is only qualitatively interpretable because of large variability, the evoked potential tests are weak in revealing partial lesions. The neural control of sacral functions is, of course, much more complex, as can be inferred from the extremely simplified functional anatomic model that we have devel-

oped in this article for better understanding the uroneurophysiologic testing. The measurement of latencies of evoked potentials relates not only to conduction in peripheral and central neural pathways, but also to transmission across synapses. Therefore, conduction may be influenced by factors that are not apparent from a simplified anatomic model, factors that may or may not have something to do with the putative neurogenic condition of the patient. For example, the sacral reflex threshold changes as a consequence of the physiologic state of the bladder; the threshold is much increased during voiding in healthy subjects but not in patients with suprasacral spinal cord lesions.58Applying uroneurophysiologic tests to demonstrate pathophysiologic processes at work is particularly exciting, but we need more experience before we can use them for diagnosis. URONEUROPHYSIOLOGY OF THE MOTOR SYSTEM

In testing of the sacral motor system, EMG techniques have a preeminent role. They record the spontaneous muscle activity as well as muscle activation during voluntary and reflex maneuvers involving pelvic floor musand magnetic stimulation c l e ~ .69~ Electrical ~, has been introduced in order to measure with precision the latency and other parameters of muscle responses, and the resulting evoked potentials have been given various historical names. We can simplify the issues and call all responses that involve both stimulation and recording from the motor system MEPs, but mention other commonly used terms as they apply. Assessment of the Peripheral Motor Pathways

Pudendal Nerve (Motor Branches) For evaluation of limb motor nerves, the measurement of (maximal) motor conduction velocity' is the routine method of functional evaluation; it requires access to stimulation of the nerve at 'two well-separated points, the distance between which can be measured reliably. Efforts to measure pudendal motor conduction velocity'l were not followed by routine use, because stimulation with needle electrodes was required to stimulate the relatively inaccessible nerve at two points. The

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other electrophysiologic parameter available for evaluating a peripheral motor nerve function is the measurement of the (terminal) motor latency’ (of the muscle response), which requires stimulation at only one point of the nerve. The mentioned muscle response is called the compound muscle action potential’ or M-wave,’ or MEP on stimulation of the peripheral nerve. To obtain the terminal motor latency, standard bipolar surface stimulation electrodes placed perianally or perineally

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can be used. The mean latencies of MEPs obtained by this method have been between 4.7 and 5.1 milliseconds as recorded with a concentric needle electrode from the bulbocavernosus and anal and urethral sphincter muscles (Fig. 3)77;this response also has been called the R1 response by the authors. Similar latencies for the same method of stimulation and recording from anal sphincter have been reported by others.5,51 Several investigators have reported recordings of MEP on stimula-

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Figure 3. The “Motor Evoked Potential” on stimulation of the pudendal nerve motor branches in the perineum (with a bipolar surface electrode). Recording is made with a concentric needle electrode from the right half of the anal sphincter. (EMG was consistent with a partially denervated muscle). The patient is a 45-year-old man 2 weeks after surgery for a centrally herniated intervertebral disc L5-S1, and clinical signs of a cauda equina lesion; (with partial sensory loss in the lower sacral segments bilaterally, and urinary retention and obstipation. There were no data on the presence of erection). Concentric needle EMG findings and absent MEP (not shown) were compatible with completely denervated perineal muscles on the left (bulbocavernosus, anal sphincter). (See also Figs. 4A & 4B.)

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tion of the pudendal nerve using a special surface electrode assembly fixed on a gloved index finger. This device was developed at the St. Mark's London Hospital.36It consists of a bipolar stimulating electrode fixed to the tip of the gloved finger with the recording electrode pair placed 3 cm proximally on the base of the finger. The finger is inserted into the rectum and stimulation is performed close to the ischial spine. When this method is used, the terminal motor latency for anal sphincter MEP typically is around 2 milliseconds. If additional recording electrodes are used (e.g., catheter-mounted electrodes), responses from the urethral sphincter also can be obtained. The differences in latencies obtained by the two mentioned methods have not yet been explained. Both methods of eliciting peripheral MEP use standard EMG equipment for nerve conduction studies, rather than the recently developed stimulators used to elicit MEP by activation of spinal roots or motor cortex. Studies of pudendal terminal motor latency (as named by the a u t h o r ~ )have ~ ~ ,been ~ ~ used to investigate urinary and fecal incontinence, particularly in studies that identified pudendal nerve damage as a factor in the cause of stress urinary incontinence and fecal incontinence. The study has shown that childbirth was a significant cause of the denervation injury.6I Even if a test shows differences among populations of subjects, it may still lack sufficient sensitivity or specificity to be useful clinically in individual patients. In the author's experience the measurement of latencies of MEP on distal stimulation is considerably less sensitive than a concentric needle EMG examination to demonstrate partial denervation. This is not surprising, because partial denervation is not necessarily accompanied by significant slowing in the remaining axons. In the author's laboratory, the test is only used in conjunction with a needle EMG examination if a proximal block of conduction in the motor axons is suspected, or when a motor versus sensory lesion of the sacral reflex has

to be differentiated in a patient who has no sacral reflex response (Figs. 3 and 4). Anterior Sacral Roots (Cauda Equina) Transcutaneous stimulation of deeply situated nervous tissue became possible with the development of special e l e ~ t r i c a land ~ ~ magnetic4 stimulators. The electrical stimulators deliver very strong and rapidly decaying stimuli. The magnetic stimulators deliver, through special coils of different shapes, strong magnetic fields, which depolarize underlying nervous tissue by inducing electrical fields. Electrical and magnetic stimulation over the spine is known to stimulate mainly the roots at the exit from the vertebral MEP from urethral and anal sphincters following spinal electrical stimulation at the level of L1 and L4 vertebrae was reported to distinguish between a cauda equina injury and peripheral nerve damage in patients with a partially denervated pelvic floor.62The author stimulates particularly at L1 and S3, and then also perianally and perineally (see previously), to determine motor latencies from different levels of the cauda equina and peripheral nerve (Fig. 5).69 As noted previously, needle rather than surface electrodes should be used to record sphincter motor potentials produced by electric or magnetic stimulation (either cortical or spinal); both depolarize underlying neural structures in a nonselective fashion (and thus lead to activation of several muscles innervated by lumbosacral segments). Therefore, responses from gluteal muscles may contaminate the recordings and lead to erroneous conclusions (Fig. 6).82In this context an important, controversial, but not much mentioned issue relates to latencies of MEP. On stimulation in the back (at the level of upper lumbar vertebrae) authors using surface recording electrodes reported latencies of MEP in perineal muscles of approximately 4 milli45, whereas others using concensecond~,"~, tric needle recordings reported on latencies

Figure 4. A, On electrical stimulation of the dorsal penile nerve there was no sacral reflex response in the right half of the anal sphincter as recorded with a concentric needle electrode (same patient as in Fig. 3). Maximum strength of available stimulation applied (pulse duration 1 ms). The recorded potentials are sporadically firing motor units, typical for anal sphincter. 6, In the patient described in Figures 3 and 4A, the sacral reflex response was not really absent as demonstrated on stimulation of the dorsal penile nerve with double electrical pulse stimulation (pulse duration: 0.2 ms; interpulse interval: 3 ms; observe the stimulus artifact). The recording is from a different EMG apparatus; the first part of examination (Figs. 3 & 4A) of the patient was performed with another EMG machine, that does not have the option of double pulse stimulation.

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Figure 5. Motor evoked potentials (MEPs) recorded with a concentric needle electrode from the anal sphincter on conventional electrical stimulation in the perianal region (upper trace), and on electrical stimulation using Digitimer 180 at the level of S3 (second trace), L4 (third trace), L1 (fourth trace), and the scalp (lowermost trace). The patient was a 58-year-old woman with back pain and urinary incontinence. The MEP latency on perianal stimulation was considered normal, but all other latencies appeared uniformly prolonged. Concentric needle EMG revealed suspicious pathologic spontaneous activity in anal sphincter. Sacral reflex latency and P40 cerebral SEP latency on clitoral stimulation were borderline. A pelvic growth invading the sacral plexus was diagnosed. (Modified from Vodusek DB: Electrophysiology. In Schussler B, Laycock J, Norton P, Stanton S (eds): Pelvic Floor Re-Education, Principles and Practice. London, Springer-Verlag, 1994,pp 83-97;with permission.)

of about 7 to 13 millisecond^.^^,^^ Authors who used surface electrodes believe that the longer latency obtained on needle recordings is related to error in interpretation (stimulus artifacts, and so forth). It should be pointed out, however, that similar longer latencies with needle anal sphincter EMG recording have been obtained by selective intraoperative stimulation of exposed sacral roots”; also, the latencies of EMG responses from the bulbocavernosus muscle on stimulation of conus by epidural electrodes have been found to range between 11 and 14 milliseconds.21From such investigations using better defined points of depolarization it can be concluded safely that the reported longer latencies of MEP48, are valid; the shorter latencies obtained by other authors may well be latencies of complex muscle potentials, including not only sphincter responses but also far field responses from nearby as shown in Figure 6. This controversy really raises serious doubts about the identity of some published sphincter MEP responses and all the reasoning based on such findings. Experience in more than 40 patients with different types of cauda equina and periph-

eral nerve lesions has shown that even though MEP on electrical stimulation in the back easily can be obtained on electrical stimulation in subjects without major sacral nervous system involvement, in patients with partially denervated pelvic floor muscles the absence of MEPs does not always correlate with findings on concentric needle EMG, which the author considers as the gold standard. Recording of MEP on magnetic stimulation has been unsuccessful more often than recording with electrical stimulation, at least 48 sometimes because of with standard c0ils,4~, large stimulus artefacts. Therefore, the author considers that demonstrating the presence of an MEP occasionally may be helpful, but its absence has to be evaluated with restraint. Stimulation in the back may be used to obtain a peripheral conduction time so that a central conduction time (i.e., conduction in central motor pathways from the motor cortex) can be Assessment of Central Motor Pathways

Transcranial depolarization of motor cortex became possible with the construction of spe-

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Figure 6. Motor evoked potentials (MEPs) in anal sphincter (traces 1 and 3) and great gluteal muscle (trace 2 and 4) in a healthy 37-year-old man. Electrical stimulation in the back at L1 (cathode; anode 5 cm paravertebrally). The upper two recordings are made with concenfric needle electrodes, the lower two recordings are made with concentric needle electrodes, the lower two recordings are made with surface electrodes. As can be seen, the latency of the needle recording from the gluteus corresponds to surface recordingfrom the same muscle, but also from the anal sphincter. The needle recording of MEP from the anal sphincter has a longer latency.

cia1 e l e ~ t r i c astimulators. l~~ The brief, rapidly interest, the latencies of MEPs shortened sigdecaying electrical pulses of very high voltnificantly (for up to 8 milliseconds). By applying stimulation both over the scalp age are delivered through surface electrodes and in the back (at level Ll), and subtracting on the scalp (anode at Cz, cathode at Fz of the 10 to 20 International EEG System). The the latency of the respective MEPs, a central method is somewhat painful. Magnetic stimuconduction time can be obtained also by maglation4is delivered through a coil that is held netic stimulation. Central conduction times of centrally over the motor cortex. Magnetic approximately 22 milliseconds without and stimulation is less unpleasant, and electrical 15 milliseconds with the facilitatory maneustimulation now has been almost abandoned ver (i.e., slight voluntary contraction) have for stimulating the motor cortex in patients been reported.& Others have measured simiwho are awake. lar but also different central conduction times, By electrical stimulation over the motor which is not surprising considering the precortex of healthy subjects, MEPs in &1al,6~,82 viously mentioned controversy regarding reurethraP5 sphincter, and bulbocavernosusE2 cording of MEP. Substantially longer central muscles could be obtained. The mean latencconduction time in patients with multiple ies were between 30 and 35 milliseconds if no sclerosis and spinal cord lesions than in facilitatory maneuver was used. If, however, healthy controls has been found,19 but bestimulation is performed during a period of cause all those patients had clinically recogslight voluntary contraction of the muscle of nizable cord disease, the diagnostic contri-

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bution of the method remains somewhat uncertain. Assessment of corticospinal tract conduction in the spinal cord itself by stimulating at levels C6 and L1 has also been reported.60 In the author's hands, the lack of good normative data and the great variability of both total conduction times and central conduction times because of the significant influence of voluntary contraction (and the difficulty of quantitating this or obtaining it at all in patients) makes the method insensitive if not impractical. It may be helpful to prove the presence of a well-formed sphincter MEP with a normal latency in a rare patient with a functional disorder, or in a medicolegal case. Confirmation of the absence of MEP in perineal muscles is of limited value in clarifying diagnostic issues, because with magnetic stimulation this knowledge cannot be reliably obtained in all normal subjects.

URONEUROPHYSIOLOGY OF THE SACRAL SENSORY SYSTEM

Measurement of SEP by stimulation of peripheral nerves or dermatomes is a well-established neurophysiologic technique. Stimulating receptors or sensory nerves leads to a volley of bioelectrical activity ascending in the peripheral nerve, the posterior sacral roots, the spinal cord tracts, and to the somatosensory cortex. In principle, everywhere along this way the bioelectrical activity may be recorded by applying the averaging technique.I2

Assessment of Peripheral Sensory Pathways

The mucocutaneous perineal sensation is carried by the pudendal nerve, whereas sensation from the proximal two-thirds of urethra, the bladder, and the rectum is subserved by sensory fibers traveling with respective motor innervation (also parasympathetic and sympathetic). None of these nerves in the female is reasonably accessible for recording, although they can be stimulated (as well as in the male) by appropriately placed electrodes. In the male the dorsal penile nerve also is accessible for recording.

Electroneurography of the Dorsal Penile Nerve

Placing a pair of stimulating electrodes across the glans and a pair of recording electrodes across the base of penis makes it possible to record a compound nerve action potential' (with an amplitude of approximately 10 pV). The sensory conduction velocity' of the dorsal penile nerve has been reported as 27 m/s; when the penis was stretched by a weight of 1 lb, the calculated velocity increased to approximately 33 m/s.'O The method is claimed to be helpful in diagnosing neurogenic erectile dysfunction as a consequence of sensory penile neuropathy.'O Recording of dorsal penile nerve sensory conduction is not practical in the occasional subject with a short penis; the calculated velocities also are greatly dependent on the lengthening of the penis during the test. The introduction of a standard weight is awkward. Theoretically, the method is valuable in differentiating peripheral from central somatosensory system involvement, but its clinical role is as yet unclear. Electroneurography of Dorsal Sacral Roots

Compound sensory root action potentials on stimulation of dorsal penile and clitoral nerve may be recorded intraoperatively when the sacral roots are exposed.73This has been found to be helpful in preserving roots relevant for perineal sensation in spastic children undergoing dorsal rhizotomy; also, it has decreased the incidence of postoperative voiding dy~function.'~ It is expected to prevent later development of a sexual dysfunction. At the level of lower thoracic and upper lumbar vertebrae the so-called spinal SEPs can be recorded with surface electrodes; it is a very small (below 1 pV), usually monophasic negative potential with a mean peak latency of approximately 12.5 milliseconds,26,31, 72 although some have found much longer latencies of 16 milliseconds (Fig. 7).48 Assessment of the Central Somatosensory System

The term somatosensory is used to distinguish that system from other sensory systems (such as visual, and so forth). In the context of distinguishing somatic and visceral sensory fibers in the urogenitoanal region, the term

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10 ms Figure 7. Somatosensory evoked potentials (SEPs) on stimulation of the dorsal penile nerve as recorded over the scalp (Cz - 2 cm: Fz; upper trace) and in the back (Ll: S1;middle trace). In the lower trace the sacral reflex response is recorded in the perineum. The P40 of the cerebral SEP, the peak of the spinal SEP, and the onset of sacral reflex are indicated. Stimulation and recording with surface electrodes; two consecutive averages of 256 responses are superimposed. Such recording has shown a normal function of the somatosensory afferent system from the penis in this 24-year-old man, who had a nonphysiologically demarcated sensory loss in the lower abdomen, including the genitalia, suspected to be hysterical in nature.

SEP is applicable to tests involving either type of fibers.

surface recording.31,7z Spinal SEPs on stimulation of visceral afferents are too small to be recordable practically.

Spinal SEP

Stimulating the dorsal penile or clitoral nerve and recording with surface electrodes at the level of the Th12 to L2 vertebrae (and the S1, Th6, or iliac spine as reference) reveals the postsynaptic segmental spinal cord activity (the spinal SEP).z6,31, 48, 7z Unfortunately, this spinal SEP may be difficult to record even in healthy obese male subjects,31,48,7z and particularly in female subjects. For this reason such recordings are not in routine use. Even with epidural electrodes sacral root potentials on stimulation of the dorsal penile nerve could be recorded in only 13 subjects, and cord potentials in 9 of 22 subjects.z1Latencies of these spinal SEPs were 11.9 f 1.8 millisecondszl substantiating the results obtained by

Cerebral SEP

The cerebral SEPs are recordable easily on electrical stimulation of the dorsal penile nerve as well as dorsal clitoral nerve, which often is called the pudenda2 SEP.30,31, 48, 63, 71, 72 As a rule, these SEPs are of highest amplitudes (between 0.5 and 12 pV)” at the central recording site (Cz -2 cm: Fz of the Intemational 10 to 20 EEG Systemz8)and are easily reproducible. The first positive peak at 41 f 2.3 milliseconds7z(called P1 or P40) always is defined clearly in healthy subjects, allowing for reliable latency reading if a strong enough stimulus is applied (Figs. 7 and 8). This stimulus is defined biologically as two to four times sensory threshold current strength, or sacral

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Figure 8. SEPs (traces on the left) and sacral reflexes (traces on the right) in a healthy woman. Cerebral SEPs are recorded from Cz - 2 cm: Fz; sacral reflexes from the anal sphincter. The dorsal clitoral nerve is being stimulated (see Fig. 1). Stimulation and recording is performed with surface type electrodes. The cerebral SEP and sacral reflex are recorded simultaneously. In the upper row the stimulation is just above sensory threshold, in the middle row the stimulation is 1.5, and in the lower row at 2-times sensory threshold (pulse duration 0.2 ms; two consecutive averages of 128 responses are superimposed).

reflex suprathreshold current strength, the latter in the case that the sacral reflex is recorded simultaneously (see Figs. 7 and 8).71,72 Later, negative (at c. 55 milliseconds) and positive waves are interindividually quite variable in amplitude. Pudendal SEPs have been used widely in patients with neurogenic erectile dysfunction, with spinal cord lesions,2",63 with multiple scler0sis,3~ and with diabetess1Such measurements have also been advocated for patients with neurogenic bladder dysfunction (e.g., in multiple sclerosis)." It was found, however, that even in patients with multiple sclerosis and bladder symptoms, the tibial cerebral SEE' was abnormal more often than the pudendal SEP.54Cerebral SEP on penile or clitoral stimulation was reported as a possibly valuable intraoperative monitoring method in patients with cauda equina or conus at risk 74 of a surgical pr~cedure.'~, A critical reading of the reports suggests that the sensitivity of the test is quite low in assessment of axonal lesions. The author agrees with the comments that the presence of an abnormal pudendal cerebral SEP in an individual patient is, as a rule, accompanied by other neurologic deficits and that the necessity to measure pudendal SEP, therefore, may be q u e s t i ~ n e d But . ~ ~ in other fields it is also true that the ability to demonstrate and document a dysfunction of the nervous system has led to increased pressure from clinicians to use the available methods to validate clinical findings. There are occasional patients

with multiple sclerosis in whom a combination of an abnormal pudendal SEP and a normal tibial SEP points to an isolated conus 64 inv~lvement.~~, Cerebral SEP also can be obtained on stimulation of bladder m u c o ~ aWhen .~ such measurements are made, it is of utmost importance to use bipolar stimulation in the bladder or proximal urethra; otherwise, fast conduct65 ing somatic afferents can be depolari~ed,5~, an event that may occur even with bipolar tim mu la ti on.^^ The cerebral SEPs have been shown to have a maximum amplitude over ~ potential the midline (Cz -2 cm: F z ) . ~The has, however, low amplitude (1 p,V and less) and a variable configuration, making it difficult to identify even in all normal subjects.2h The typical latency of the most prominent negative potential (Nl) is approximately 100 milliseconds.26,32 The responses are claimed to be more relevant to neurogenic bladder dysfunction as pudendal SEP, because the A delta sensory afferents from bladder and proximal urethra accompany the autonomic fibers relevant for bladder function. The sensory fibers assessed by this test travel primarily in pelvic nerves.32The usefulness of the test is limited, however, by the fact that it is not robust even in normal subjects,32but the demonstration of a normal response in an occasional medicolegal case may be helpful. Nevertheless, it should be remembered that the bladder neck is not too far away from other structures with somatic afferents; theoretically, in a patient with denervated visceral

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afferents from the bladder neck, the stimulus intensity could be increased by the investigator enough to depolarize distant somatic afferents. In fact, two types of cerebral SEP on bladder neck stimulation have been obtained, one being quite similar to the cerebral SEP obtained on pudendal nerve stimulati~n.~~ Another stimulation site in the perineal region is the anal canal; cerebral SEPs with a slightly longer latency than those obtained on the penis or clitoris have been These authors have not been able to record responses from all normal subjects. The rectum and sigmoid colon also have been stimulated, and cerebral SEP of two types recorded. One was similar in shape and latency to pudendal SEP and the other to SEP recorded on stimulation of bladder and posterior urethra.43 Visceral sacral cerebral SEPs do not yet have an established place in routine diagnostics. URONEUROPHYSIOLOGY OF SACRAL REFLEXES

Sacral reflexes are electrophysiologically recordable responses of perineal or pelvic floor muscles to electrical stimulation in the urogenitoanal region. There are two reflexes: (1) the anal and (2) the bulbocavernosus. These commonly are elicited clinically in the lower sacral segments; both have the afferent and efferent limb of their reflex arc in the pudendal nerve and are centrally integrated at the S2 to S4 cord levels. The bulbocavernosus reflex is elicited by squeezing the glans (penis or clitoris), and the response (the contraction of the bulbocavernosus muscle or the anal sphincter) is palpated. The anal reflex is evoked by pricking or scratching the perianal skin and observing the contraction of the anal sphincter. It should be pointed out that the modification of the bulbocavernosus reflex, when the bladder neck is stimulated by pulling on a Foley catheter, is not identical to the previously described bulbocavernosus reflex. It has a different afferent limb. In this case it is the sensory fibers traveling with the pelvic nerves (and not pudendal nerves). Therefore, the two modifications of the clinically elicited bulbocavernosus reflex assess different afferent pathways. Electrophysiologic correlates of all mentioned reflexes have been described, and

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apart from the established clinically used terms, a plethora of new names have been introduced. The confusion is made even greater because the same name may be used for different reflexes and different names may be used for the same reflex. The best way to avoid misunderstanding is for each author to use the term sacral refex and then state the modality and site of stimulation (e.g., electrical; dorsal penile nerve) as well as the type and site of recording (e.g., concentric needle; bulbocavernosus muscle). Terms not including reflex, such as sacral evoked potential^:^ should be particularly discouraged because they lead to confusion with nonreflex electrophysiologic responses. It seems well established that supramaxima1 stimulation at any of the different urogenitoanal sites elicits reflex muscle responses in all pelvic floor muscles: the bulbocavernosus, the urethral and anal sphincter, and the levator ani.” Of course, it is always relevant to be aware of the particular anatomic elements assessed by a particular modification of sacral reflex testing, but the type of the reflex response is determined by the type and site of stimulation and not by the muscle from which it is recorded. It is possible to use electrical (Figs. 4B and 9),2O*22, 39, 56, 66, 77 mechanical (Fig. or magnetic43 stimulation. Whereas the latter two modalities have been applied only to the penis and clitoris, electrical stimulation can be applied at various sites: 39, 56, 66, 77 to the the dorsal penile dorsal clitoral nerve: 67, 71, 77 perianally,5O, 74 and at bladder neck and proximal urethra 57 using a catheter-mounted ring ele~trode.~, Bradley, one of the pioneers of uroneurophysiology, gave this method the name electromyelography? which, however, did not survive. These reflexes are often referred to as vesicourethral and vesic~anal,~~ depending on the muscle from which the reflex responses are recorded. The pudendal nerve itself may be stimulated by applying needle electrodes transperineally70 or by using the already described stimulating ”St. Mark’s” electrode on the gloved finger.15 The authors coined the name deep pudendal reflex.I5 The reportss, 22, 39, 56, 66-68, 71, 77 on sacral reflexes obtained on electrical stimulation of the dorsal penile or clitoral nerve are consistent in giving mean latencies between 31 and 38.5 milliseconds. The latency of responses on mechanical stimulation was reported as similar70 and on magnetic stimulation slightly 10nger.4~Consistent with the shorter afferent

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1

2 0 m s 1OOpV

Figure 9. Concentric needle recording from the bulbocavernosus muscle on stimulation of dorsal penile nerve (with surface electrodes) in a 67-year-old healthy man. Upper beam shows the sacral reflex on just suprathreshold stimulation, the middle beam on stimulation increased by 30 percent, and lower beam on maximal tolerable stimulation (in this case 60 percent suprathreshold). Observe the early component of the sacral reflex being joined by the second component at stronger stimulation; the division in two components is blurred at very strong stimulation. Observe also the slight shortening of latency of the first component at stronger stimulation in comparison with just suprathreshold stimulation.

limb, the sacral reflex obtained on electrical pudendal nerve stimulation in the perineum has a somewhat shorter 1aten~y.l~ On the other hand, sacral reflexes obtained on perianal or bladder neck and proximal urethra stimulation have mean latencies between approximately 50 and 65 milliseconds.y,50, 77 It is obvious that the sacral reflexes obtained on bladder neck and proximal urethral stimula-

40ms

tion have a different afferent limb (the visceral afferent fibers accompanying pelvic nerves, which are thinner myelinated and have a slower conduction velocity than the thicker pudendal afferents). The longer latency anal reflex (sacral reflex on stimulation in the perianal region) also may have thinner myelinated fibers in its afferent limb, because it is produced by nociceptive skin stimulation. On stimulation perianally a short latency MEP can also be recorded, as a result of depolarization of motor branches to the anal sphincter5,77; this MEP was at first mistaken for a reflex response.34 The sacral reflex evoked on dorsal penile or clitoral nerve stimulation (the bulbocavernosus reflex) was proposed to be a flexor reflex35and was shown to be a complex response, often forming two components (see 77**' The first component with typical Fig. 9).3y, latency of about 33 milliseconds is the response that has most often been called the bulbocavernosus reflex. It is more stable, does not habituate, and is proposed to be an oligosynaptic reflex response, because the variability of single motor neuron discharges within this reflex is similar to that of the first component of the blink reflex.76The second component has a latency similar to that of the sacral reflexes evoked by stimulation perianally or from the proximal urethra. The variability of single motor neuron reflex responses within this component is much larger, as is typical for a polysynaptic reflex.76The second component is not always demonstrable as a discrete response (see Fig. 9).70The two components of the reflex may behave somewhat differently in normal subjects and in patients; whereas in normal subjects it is usually the first component that has a lower threshold

IIOOpV

Figure 10. Sacral reflex responses as recorded with a concentric needle electrode from the bulbocavernosus muscle.of a 62-year-old diabetic patient with a cardiac pacemaker and erectile dysfunction. Concentric needle EMG of bulbocavernosus and anal sphincter muscle was normal. As electrical stimulation was contraindicated, mechanical stimulation with a reflex hammer (with a built-in electronic switch) was performed, and the presence of a sacral reflex was demonstrated by tapping the glans penis. Five consecutive reflexes are superimposed. Clinically, the referring urologist could not elicit a bulbocavernosus reflex.

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(although the shortest latency responses can be obtained only on stronger stimulation [see Fig. 9]), in patients with partially denervated pelvic floor muscles often the first reflex component cannot be obtained with single stimuli, but on strong stimulation the later reflex component does 0ccur.3~This may cause much confusion, because very delayed reflex responses may be recorded ir. patients, not recognizing the possibility that it is not a delayed first component but an isolated second component of the reflex. The situation can be clarified by using double stimuli, which facilitate the reflex response70and may reveal in such a patient the first component, which was not obvious on stimulation with single stimuli.53 Double pulse stimulation may in fact reveal a sacral reflex when there is no definite response even on maximal available pulse stimulation (see Fig. 4). One could propose that the findings are pathologic anyway, but that in the latter case the pathology is mirrored in the high threshold. But the absence of a reflex in context of a peripheral lesion carries some weight in neurology; therefore, one should not declare a sacral reflex as absent unless one has applied a double-pulse stimulation (see Fig. 4). Sacral reflex responses recorded with needle or wire electrodes can be analyzed separately for each side of the anal sphincter or each bulbocavernosus muscle.39 This is important because unilateral or asymmetrical lesions are common. It has also been reported that unilateral stimulation of the penis is fea~ible,3~ but the author has found this unreliable in patients in whom sensory loss may lead to application of stronger stimuli; with strong stimuli, bilateral spread of the electrical field from the stimulating electrodes is probable. It has been suggested that sacral reflex responses on stimulation of the dorsal penile and clitoral nerve are valuable in patients with cauda equina and lower motor neuron lesions,22although a reflex with a normal latency does not exclude the possibility of an axonal lesion in its reflex arc. Most commonly, sacral reflex responses on stimulation of the penis have been proposed for evalua63, 66 tion of neurogenic erectile dysfunction.22, It has been shown, however, that many patients with probable neurogenic impotence have reflex latencies within the normal range.18faThat the latency of the sacral reflex per se is not correlated with erectile or lower urinary tract dysfunction was shown in a

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study of patients with hereditary motor and sensory neuropathy who had normal sacral functions and much delayed sacral reflex res p o n s e ~Poor . ~ ~ specificity of the abnormal sacral reflex has been reported by others,41,67 who have shown normal nocturnal erections in patients with prolonged sacral reflex latencies. It was also shown that in diabetics with suspected neurogenic impotence the conduction velocity parameters in limbs were more sensitive in revealing neuropathy than sacral reflex latencies (and cerebral SEPs to dorsal penile nerve stimu1ation);l and others have proposed that testing for autonomic function is more sensitive than all somatic parametersM The sacral reflex response on stimulation of the proximal urethra may be more sensitive to reveal neuropathy in diabetics than the sacral reflex on stimulation of the dorsal penile nerve.7 Most reports deal with abnormally prolonged sacral reflex latencies; it was shown, however, that a very short reflex latency raises the possibility of tethered cord the short latency being attributed particularly to the low location of conus. Shorter latencies of sacral reflexes in patients with suprasacral cord lesions also were This work can be criticized in that supramaximal stimuli in control subjects perhaps were not reached; the thresholds of reflex responses in chronic spinal cord injury patients are lower as a rule, and it is easier to obtain the shortest possible latency with moderate stimuli (but not shorter latencies than the shortest possible). Also, repetitive bursts of EMG activity (following the already mentioned two components of the reflex) are common in patients with upper motor neuron i n ~ o l v e m e n t . ~ ~ Continuous intraoperative recording of sacral reflex responses on penis and clitoris stimulation is feasible if double or a train of stimuli are used. Measuring of sacral reflexes seems to be well established and is the most time-honored uroneurophysiologic diagnostic procedure apart from sphincter EMG. It certainly can be said that the expectations of some authors, that sacral reflex testing offers a single tool to distinguish neurogenic from nonneurogenic sacral dysfunction, have not been fulfilled. On the other hand, testing reflex responses is a valid and very useful method to assess integrity of reflex arcs, and electrophysiologic assessment of sacral reflexes is a more quantitative, sensitive, and reproducible way of assessing the S2 to S4 reflex arcs than any of

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the clinical modifications. It should not be said, therefore, that testing sacral reflexes is not useful, but that uncritical interpretation of results should be discouraged. In the author’s laboratory, sacral reflex testing is a part of the diagnostic battery of which concentric needle EMG exploration of the pelvic floor muscles is the most important part (if the clinical problem is a putative peripheral nervous system lesion) (see Fig. 10). If the clinical problem is central nervous system lesion, sacral reflex testing may be used as a biologic indicator of the adequacy of the stimulus applied for evoking cerebral SEP (see Fig. 5). Sacral reflex and SEP alone (without EMG), with all stimulation and recording performed with surface-type electrodes, may be used in patients with putative neurogenic sacral dysfunctions in whom needle EMG is considered too invasive (i.e., children). SSR The sympathetic nervous system mediates sweat gland activity in the skin. Changes in sweat gland activity lead to changes in skin resistance. On stressful stimulation a potential shift can be recorded with surface electrodes from the skin of palms and soles, and has been reported to be a useful parameter in assessment of neuropathy involving unmyelinated nerve fibers.5yThe response also can be recorded from perineal skin and the penis.16,49 The SSR is, in fact, a reflex; if stressful stimulation is applied to the skin, the reflex arc consists of myelinated sensory fibers, a complex central integrative mechanism, and a sympathetic efferent limb (with postganglionic nonmyelinated C fibers). The stimulus used in clinical practice usually is an electric pulse delivered to the upper or lower limb (to mixed nerves), but the genital organs also can be ~ t i m u l a t e d The . ~ ~ latencies of SSR on the penis (on upper limb stimulation) have been reported between 1.549and 2.3 sI6 and can be obtained in all normal subjects. But the latency variability is quite substantial. The responses are easily habituated and depend on a number of endogenic and exogenic factors, particularly skin temperature, which needs to be at least above 28°C. As a rule, only an absent SSR is taken as an abnormality. SSR recording in limbs was claimed to be more informative than somatic sacral reflex and SEP testing in patients with organic erectile dysfunction,4Oand recording SSR, also on

the penis, was reported to be even more informative,I6 because it assesses (if the afferent limb is normal) the thoracolumbar sympathetic system involved in regulating urogenital function. There is not yet much experience with this test in patients. CONCLUSIONS REGARDING RESEARCH APPLICATIONS

Uroneurophysiologic evoked potentials have until now been applied most often in research. They were used to substantiate hypotheses that a proportion of patients with sacral dysfunctions have involvement of the nervous system, as, for instance, patients with erectile dysfunctionz2,75 and patients with stress urinary and idiopathic fecal incontinence,36,61 and that uroneurophysiologic tests are more sensitive to disclose a neurogenic lesion than some other testing procedures.6 Applying this method, it has been shown that vaginal deliveries lead to abnormalities of pudendal conduction.h’They have been used to establish the function of the sacral nervous system in patients with suprasacral spinal cord injury,”sto reveal consequences of particular surgeries42and to try to elucidate innervation patterns of pelvic floor muscles.52,79 These methods recently have been introduced also to intraoperative monitoring, where evoked potential studies have long been established to help prevent lesions of the neural structures at risk from the surgical procedure.27,74, 75 Further research application of uroneurophysiologic methods is expected, because the neurologic aspects of urologic, gynecologic, and proctologic problems have not yet been much studied. CONCLUSIONS REGARDING CLINICAL APPLICATIONS

The rationale to apply evoked potentials in patients with putative neurogenic sacral dysfunction is to demonstrate a lesion in the neural control as mirrored by an abnormal test result. If statistically significant differences can be shown between control subjects and groups of subjects with a particular neurogenic sacral dysfunction by the application of a particular test, it does not necessarily follow that this test has appropriate sensitivity and specificity to be useful in everyday laboratory diagnosis of individual patients. Expectations that a single ”evoked potential

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test” might sort out all neurogenic patients have been abandoned, particularly because it has become more widely recognized that the majority of neurogenic lesions are of the axonal type, which are not revealed reliably by measuring latencies of evoked potentials. Amplitudes of evoked potentials and sacral reflexes are not analyzed routinely, but the absence of responses is, as a rule, considered abnormal. This is a valid practice, under strict control of technique, in testing sacral reflexes and cerebral SEP on penile stimulation. In the author’s laboratory, cerebral SEP on clitoral stimulation also has been observed to be a robust parameter, and so have sacral reflexes on clitoral stimulation, if needle EMG electrodes are used for recording and, if necessary, double electrical pulses for stimulation. The muscle response (MEP) on stimulation of pudendal nerve is a robust parameter, and so seems to be the SSR recorded on penile and perineal skin on median nerve stimulation, but there is still (in the author’s opinion) too little consensus on their usefulness (sensitivity and specificity). Other potentials have a variable configuration or small amplitudes, or the test is awkward or invasive; they do not as yet seem to be practical for routine application. It seems logical to propose a battery of tests assessing the motor; sensory (both peripheral and central); and the reflex pathways in order to detect and localize (at least roughly) the neurogenic lesion.”, 48 In this context it seems not to be appreciated by all workers in the field that a needle EMG examination of the pelvic floor muscles is still the best single uroneurophysiologic test to diagnose a lower motor neuron lesion in the sacral segments.256y, 78 This has not really been much explored experimentally, one of the reasons being perhaps the invasiveness of the method. In neurophysiologic laboratories it is common practice to establish at least a small in-house data base of control values that is, for obvious reasons, difficult in uroneurophysiology. Regarding uroneurophysiologic evoked potential testing in general, a broad experience and normal values exist only for (somatic) sacral reflex testing and (somatic) cerebral SEP. This might be seen as a very conservative attitude by many eager authors who have been reporting new methods for years. Let them be reminded that the National Institutes of Health Consensus statement on Impotence14 mentions, but does not recommend as routine diagnostic procedures, the uroneurophysio-

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logic tests. The fact that uroneurophysiologic methods assess primarily the thicker myelinated fibers” and the somatic nervous system, whereas it is the parasympathetic nervous system that is most relevant for sacral functions, is always referred Bearing all this in mind, let us consider that the deranged neural control in patients with neurogenic sacral dysfunction does need to be explored, and the information gained by clinical examination and urodynamic testing can and should, at least in selected cases, be upgraded by uroneurophysiologic measurements. In the routine setting a needle EMG exploration of pelvic floor muscles and testing (on stimulation of the penis or clitoris) the sacral reflex as well as the cerebral SEP provides a robust basic battery of tests to which other tests can be added according to the special interest of the individual laboratory. It should be understood that consideration of uroneurophysiologic testing should really be performed within a framework of neurophysiologic tests in general, as required by the clinical problem in an individual patient. SUMMARY

Electrophysiologic tests of the sacral neuromuscular system and its suprasegmental control may be divided into EMG and methods involving stimulation (i.e., evoked potential and sacral reflex testing). The latter group of methods tests the function of defined parts of the motor or sensory nervous system, or reflex arcs. There already is ample experience with testing the somatic sensory pathways (pudendal SEP) and the (somatic) sacral reflex arc, whereas other methods (testing the motor system and tests involving visceral afferents and sympathetic efferents) need further study to establish their proper place in everyday clinical diagnostics. The application of these methods in research has led to important advances in our understanding of nervous system involvement in different pathologic conditions leading to neurogenic sacral dysfunctions. If applied in individual patients, these methods should, however, be used and interpreted with restraint; they should be considered in patients with probable or proved nervous system lesions, those in whom additional clarification regarding proof of, localization of, and the nature (i.e., axonal versus demyelinative) of the lesion is relevant for

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diagnosis and prognosis. If applied in patients with central nervous system involvement, evoked potential studies may be used on their own; but, in the author’s opinion, in patients with putative peripheral nervous system involvement these tests should be considered, as a rule, only as an extension of a needle EMG exploration. It is expected that further experience will clarify the sensitivity and specificity of the available methods. The already available methods certainly will gain a place in the operating room helping the surgeon in selected procedures involving the pelvis and particularly conus and cauda equina better to identify neuromuscular structures and to monitor their function throughout the operation in order to prevent subsequent development of lesions.

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Address reprirzt requests to David B. Vodusek, MD, DSC Institute of Clinical Neurophysiology University Medical Centre Zaroska 7 1105 Ljubljana Slovenia