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Medicine » Diagnostics » "Computational Intelligence in Electromyography Analysis - A Perspective on Current Applications and Future Challenges", book edited by Ganesh R. Naik, ISBN 978-953-51-0805-4, Published: October 17, 2012 under CC BY 3.0 license. © The Author(s).

Chapter 12

Sphincter EMG for Diagnosing Multiple System Atrophy and Related Disorders

By Ryuji Sakakibara, Tomoyuki Uchiyama, Tatsuya Yamamoto, Fuyuki Tateno, Tomonori Yamanishi, Masahiko Kishi and Yohei Tsuyusaki
DOI: 10.5772/45880

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Sphincter EMG for Diagnosing Multiple System Atrophy and Related Disorders

Ryuji Sakakibara1, Fuyuki Tateno1, Masahiko Kishi 1, Yohei Tsuyusaki1, Tomoyuki Uchiyama 2, Tatsuya Yamamoto2 and Tomonori Yamanishi3

1. Introduction

One of the hallmarks in the pathology of multiple system atrophy (MSA) is neuronal loss in the sacral Onuf’s nucleus [11], [33], [37]. Onuf’s nucleus plays a key role in urinary and fecal continence [12]. Neurons in this nucleus receive not only cortical inputs, but also noradrenergic and serotonergic facilitatory inputs via interneurons from various brainstem structures, including the pontine urine-storage center [57], [68]. External anal sphincter (EAS)-electromyography (EMG) is an established method to detect neurogenic change in motor unit potentials (MUP), which mostly reflects denervation and reinnervation of the sphincter muscle [30]. The significance of the EAS-EMG in MSA has been well known [30], [69], [74]. Physiologically, external urethral sphincter (EUS) and EAS share sacral pudendal innervation from Onuf’s nucleus [20]. In this article, we review the normal physiology and pathophysiology of the lower urinary tract and the lower gastrointestinal tract briefly, the current methods and interpretations of EAS or EUS-EMG, and sphincter EMGin autonomic disorders.

2. Physiology and pathophysiology of the lower urinary tract

The lower urinary tract consists of two major components, the bladder and urethra. The bladder is abundant with muscarinic M2,3 receptors (contraction) and adrenergic beta 3 receptors (relaxation) [12]. The urethra is abundant with adrenergic alpha 1A/D receptors (contraction) and nicotinic receptors (contraction)(Fig. 1). The storage and emptying functionsneed an intact neuraxis that involves almost all parts of the nervous system [48]. This is in contrast to postural hypotension, which arises due to lesions below the medullary circulation center [56].


The lower urinary tract consists of two major components, the bladder and the urethra. The bladder is mainly innervated by the parasympathetic pelvic nerve. The urethra is innervated by the sympathetic hypogastric nerve and somatic pudendal nerve, respectively. Urinary storage is dependent on the reflex arc of the sacral spinal cord. The storage reflex is thought to be tonically facilitated by the brain, particularly the pontine storage center. The storage function is thought to be further facilitated by the hypothalamus, cerebellum, basal ganglia, and frontal cortex. Central cholinergic fibers from the nucleus basalis Meynert (NBM, also called the Ch4 cell group) seem to facilitate urinary storage. Micturition is dependent on the reflex arc of the brainstem and spinal cord, which involves the midbrain periaqueductal gray (PAG) and the pontine micturition center (located in or adjacent to the locus coeruleus [LC]). The voiding function is thought to be initiated by the hypothalamus and prefrontal cortex, which overlap the storage-facilitating area.

PVN: paraventricular nucleus, MPOA: medial preoptic area, A: adrenergic/noradrenergic, ZI: zona incerta, VTA: ventral tegmental area, SNC: substantia nigra pars compacta, DLTN: dorsolateral tegmental nucleus, PBN: parabrachial nucleus, IML: IML cell column, GABA: γ-aminobutyric acid, T: thoracic, L: lumbar, S: sacral

(cited from ref. 41)

Figure 1.

Neural circuitry relevant to micturition.

Urinary storage is dependent on the autonomic reflex arc of the sacral cord [12]. This reflex is tonically facilitated by the brain, particularly the pontine storage center, [7], [57] hypothalamus, cerebellum, basal ganglia, and frontal cortex [25].In contrast, micturition is dependent on the autonomic reflex arc of the brainstem and spinal cord [12]. This reflex involves the periaqueductal gray [12], [32], [78] and the pontine micturition center (PMC) [6], [7], [12], [54], [63]. The PMC facilitates the sacral bladder preganglionic nucleus by glutamate [35], while inhibiting the sacral Onuf's nucleus by γ-amino-butyric acid (GABA) and glycine [8]. Thisreflex is regulated by the hypothalamus and prefrontal cortex [16], [25].

Bladder (detrusor) overactivity is the major cause of urinary urgency/frequency and urgency incontinence [66]. In lesions above the brainstem, detrusor overactivity is considered an exaggerated micturition reflex [66]. This is in line with the fact that detrusor overactivity appearing after experimental stroke requires mRNA synthesis in the PMC [83]. The exaggeration of the micturition reflex might be brought about not only by decreased inhibition of the brain (by central cholinergic and D1 dopaminergic mechanisms); that is, it might be further facilitated by glutamatergic and D2 dopaminergic mechanisms [82]. Underactive detrusor (or bladder weakness) is the major cause of voiding difficulty in autonomic disorders. Underactive detrusor results from lesions in either upper or lower neurons innervating the bladder muscles, but typically occurs from lower neuron lesions. [1], [48]

Urinary urgency incontinence and voiding difficulty in MSA result mostly from detrusor overactivity and underactive detrusor, respectively. [1], [48] Patients with MSA often have a combination of detrusor overactivity in the filling phase and underactive detrusor in the voiding phase; this is called detrusor hyperactivity with impaired contractile function (DHIC). DHIC presumably reflects multiple lesions in both the storage-facilitating areas (the basal ganglia, pontine storage center) and the voiding-facilitating areas (the PMC, sacral preganglionic neurons in the intermediolateral [IML] cell columns) of this disorder. [23], [79]In MSA, incomplete emptying is thought to be secondary to IML involvement.

Sphincter dysfunction contributes to voiding difficulty and urinary incontinence in autonomic disorders, although less commonly than over- or underactive detrusor does. When the urethral sphincter does not relax properly during voiding bladder contraction, it is called detrusor-sphincter dyssynergia. [1] Since a coordinated micturition reflex (bladder contraction with sphincter relaxation) needs an intact brainstem–sacral cord axis, [12] disruption of the axis (such as lesions affecting the cervical/thoracic spinal cord) may lead to detrusor–sphincter dyssynergia. Sphincter weakness is a cause of urinary incontinence. Sphincter weakness occurs from lesions in the sacral motoneurons (Onuf’s nucleus), and typically appears in women with MSA as severe stress incontinence [49] or continuous urinary incontinence [34].

3. Physiology and pathophysiology of the lower gastrointestinal tract

The enteric nervous system plays the most important role in regulating the peristalticreflex of the lower gastrointestinal tract [20]. Two types of myoelectrical activity or pressure changes in the colon are documented. Slow phasic pressure waves are the most common manometric phenomenon [26], and in humans are measured as spontaneous phasic rectal contraction [9], [22]. The peristaltic reflex can be evoked by surface stroking or by circumferential stretching. [20] The reflex consists of two components: ascending contraction (mediated by cholinergic fibers) oral to the stimulus site, and descending relaxation (mediated by non-adrenergic, non-cholinergic fibers) caudal to the stimulus site [2].


The function of the lower gastrointestinal tract is thought to depend on the brain and spinal cord, although less significantly than the lower urinary tract (LUT) does. Whereas the small intestine and ascending colon are innervated by the vagus nerves originating in the medulla, the descending colon, sigmoid colon, and rectum primarily share sacral innervation of the LUT(Figure 1). Both the sacral cord and the vagus nuclei receive projecting fibers from Barrington’s nucleus (the pontine micturition/defecation center). Bowel function seems to be modulated by the higher brain structures, including the frontal lobe, the hypothalamus, and the basal ganglia; the main action of the latter on the bowel seems to be inhibitory

NBM: nucleus basalis Meynert, Ch: cholinergic, PVN: paraventricular nucleus, MPOA: medial preoptic area, ZI: zona incerta, A: adrenergic/noradrenergic, VTA: ventral tegmental area, SNC: substantia nigra pars compacta, LC: locus ceruleus, DLTN: dorsolateral tegmental nucleus, PBN: parabrachial nucleus, PAG: periaqueductal gray, IML: IML cell column, GABA: γ-aminobutyric acid, T: thoracic, L: lumbar, S: sacral

(cited from ref. 41)

Figure 2.

Neural circuitry relevant to defecation.

Other types of pressure changes in the colon include giant motor complexes [20]. A giant motor complex is a cyclic contractile activity with a periodicity of 20 to 30 min, and is perhaps analogous to the migrating motor complex of the small intestine [26]. A combination of slow waves and giant motor complexes is thought to promote bowel transport, which in humans is measured by colonic transit time [4].The strength of cholinergic transmission in the enteric nervous system is thought to be regulated by opposing receptors; serotonin 5-HT4 receptor-mediating excitation [31], [73]and dopamine D2 receptor-mediating inhibition [76].

Whereas the rostral lower gastrointestinal tract is innervated by the vagus nerves originating in the medulla, extra-enteric innervation of the caudal lower gastrointestinal tract primarily shares the innervation of the lower urinary tract (Fig. 2) [12], [22]. The lower urinary tract and lower gastrointestinal tracts perform similar functions of storage and emptying. However, they differ profoundly with regard to anatomy (closed bag versus open-ended tube, respectively), luminal contents (liquid versus half-solid), and physiology (dysfunctional transport, rare ureter versus common bowel; smooth muscle contraction, bladder contraction only on emptying versus persistent spontaneous phasic rectal contraction; abdominal strain, minimal on urination versus strong on defecation) [22].In addition, while the lower urinary tract requires an intactneuraxis for storage and emptying [12], it has not been entirely clear to what extent the lower gastrointestinal tract needs the extra-enteric nervous system.

Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain. [58] Some patients also have paradoxical sphincter contraction on defecation (PSCD). [58] The sites responsible for this dysfunction seem to be both the central and peripheral nervous systems, which regulate the lower gastrointestinal tract. Slow colonic transit and decreased phasic rectal contraction most probably reflect peripheral enteric nervous system lesions, whereas weak abdominal strain and PSCD may reflect central lesions. [61] In contrast, fecal incontinence results mostly from a weak anal sphincter due to denervation. [58]

4. Physiology and pathophysiology of the genital organ

The genital organprimarily shares lumbosacral innervation with the lower urinary tract. Erection is a vascular event [3]; occurring secondarily after dilatation of the cavernous helical artery and compression of the cavernous vein to the tunica albuginea [3]. Helical artery dilatation is brought about by activation of cholinergic and nitrergic nerves; this activation facilitates nitric oxide secretion from the vascular endothelium. Ejaculation is brought about by contraction of the vas deferens and the bladder neck, in order to prevent retrograde ejaculation, by activation of adrenergic nerves (Fig. 3). Sacral Onuf’s nucleus innervates the bulbocavernosus muscle; and is thought to participate in erection and ejaculation. Sexual intercourse in healthy men can be divided into 3 phases [65]: a) desire (libido), b) excitement and erection, and c) orgasm, seminal emission from the vas deferens, and ejaculation from the penis. Erection can be further classified into 3 types by the relevant stimulation: 1) psychogenic erection (by audiovisual stimulation), 2) reflexive erection (by somatosensory stimulation), and 3) nocturnal penile tumescence (NPT) (associated with rapid eye movement [REM]-sleep). ‘Morning erection’ is considered the last NPT in the nighttime.


PAG, periaqueductal gray; LC, locus coeruleus; NBM,nucleus basalis Meynert; PVN, paraventricular nucleus; MPOA, medial preoptic area; A,adrenergic/noradrenergic;ZI, zona incerta; VTA, ventral tegmental area; SNC, substantia nigra pars compacta; DLTN, dorsolateral tegmental nucleus; PBN, parabrachial nucleus; IML, intermediolateral nucleus; GABA,γ-aminobutyric acid; T, thoracic; L, lumbar; S, sacral; NA, noradrenaline; Ach, acetylcholine; NO, nitric oxide. See text.

Figure 3.

Neural circuitry relevant to erection.

Among the 3 types of erection, reflexive erectionrequires an intact sacral cord, particularly the intermediolateral (IML) cell columns. Pathology studies have shown that involvement of the IML nucleus is common in MSA, whereas it is uncommon in Parkinson’s disease. Therefore, reflexive erection can be affected in patients with MSA. In patients with a supra-sacral spinal cord lesion, reflexive erection might be preserved, whereas psychogenic erection is severely disturbed because of a lesion in the spinal pathways to the sacral cord. Libido and erection are thought to be regulated by the hypothalamus; particularly themedial preoptic area (MPOA) and the paraventricular nucleus (PVN). [13], [72] Recent neuroimaging studies have shown that penile stimulation or watching pornography activated these areas in humans [70]. NPT [15] seems to be regulated by the hypothalamic lateral preoptic area, [21] raphe nucleus, and locus ceruleus. Oxytocinergic neurons in the hypothalamic PVN are thought to facilitate erection by projecting directly to the sacral cord, and by projecting to the midbrain periaqueductal gray and the Barrington’s nucleus (identical to the PMC).

In experimental animals, dopamine is known to facilitate erection and mating behaviors [13]. The MPOA/PVN receives projections from the nigral dopaminergic neurons. Prolactinergic neurons are thought to be inhibitory in sexual function. Prolactin-producing pituitary tumors often cause gynecomastia and erectile dysfunction in male patients. Hyperprolactinemia occurs after the use of sulpiride, metoclopramide, and chlorpromazine (all dopamine receptor antagonists). Therefore, dopaminergic neurons seem to facilitate oxytocinergic neurons whereas they inhibit prolactinergic neurons.

5. Methods and interpretations of sphincter EMG

In humans, the EUS and EAS share sacral pudendal innervation from Onuf’s nucleus. [12], [20] The EAS lies around the anal canal and forms an 8-shaped sphincter system on the pelvic floor (Fig. 4). Although injury to the peripheral nerves may lead to the dysfunction of the EUS alone, lesions of the sacral Onuf’s nucleus affect both the EAS and EUS. For this reason, we use EAS-EMG to assess urinary incontinence, as it is easier to perform and less painful than EUS-EMG. For the same reason, few studies have utilized EUS-EMG. [14], [17] In women, the EUS muscle can be examined using a perineal approach. Examination of this muscle is more difficult in men; we can approach it with the fingers by feeling for the prostate within the rectum. However, EUS should be chosen in cases exhibitinga decelerating burst (‘whale noise’) with complex repetitive discharge in Fowler’s syndrome. [24]

The EAS can be divided into a deep part (thick; around the rectal neck to the anal canal) and a subcutaneous part (thin; around the anus). The deep EAS is a major constituent in the generation of anal pressure to hold feces in when the rectum is full. The normal range of static anal pressure is more than 40 cmH2O, and that of anal squeeze pressure is more than 50 cmH2O. [22] The former is thought to reflect hypogastric adrenergic innervation, whereas the latter reflects somatic Onuf’s nucleus innervation. [22] The subcutaneous EAS is easy to examine. It is reached by inserting a needle about 1 cm from the anal orifice, to a depth of3–6 mm. [43]

Although the EAS is a skeletal muscle, it usually fires continuously during both waking and sleeping states. To assess EAS, an EMG computer with quantitative, template-operated MUP analysis softwareis recommended. The commonly used amplifier filter setting is 5–10 kHz. The tip of aconcentric needle usually monitors an area approximately 500 micrometers in diameter, which includes approximately 20 MUPs. To assess acute denervation, insertion andspontaneous activities are checked as with the evaluation of otherskeletal muscles. When the muscle is completely denervated, the EMG becomes silent. After an interval of 10–20 days, the insertion potentials become prolonged and abnormal spontaneous muscle activities, e.g., fibrillation potentials and positive sharp waves, appear. However, in the EAS, due to the continuous firing activities, it is not easy to see denervation potentials. In such cases, examination of the bulbocavernosusmuscle has been recommended [44].


This figure illustrates where to insert concentric needles to measure external sphincter EMG.

Figure 4.

The externalanal sphincter and the external urethral sphincter.

A normal MUP usually has a 50–500 microVamplitude, a 3–8 msec duration, and 2–4 phases. In order to assess reinnervation, usually 10–20 single MUPs are recorded, which are automatically provided by an EMG computer. To ascertain single MUP, we still check each wave manually and adjust the onset and offset of each wave. It is particularly important to include late components (satellite potentials) to measure the duration of each unit. [42] When the muscle is chronically denervated, an intact nerve tends to innervate the adjacent denervated muscle fibers. As a result, MUPs become of high amplitude, of long duration, and polyphasic. Among various EMG parameters, the use of duration,MUP area, and number of turns is recommended for optimal diagnostic power (sensitivity andspecificity) in the EAS muscle. [45]In addition, the results are dependent on the methods used; e.g., including or excluding late components. Palace et al. proposed that either of two criteria is sufficient to diagnose neurogenic changes in the EAS-EMG: (a) more than 20% of MUPs have a duration > 10 msec, or (b) the average duration of MUPs > 10 msec, particularly including the late components. [38]When satellite potentials were excluded, the duration of MUPs did not differ significantly between Parkinson’s disease and MSA. [48] When lower motor neuron-type abnormalities are not apparent, it is reported that abnormal MUP recruitment pattern suggests pyramidal tract involvement. [18] In addition to MUP analysis in the external sphincter muscles, other neurophysiologic tests, e.g., pudendal nerve conduction, sacral reflexes, somatosensory evoked potentials and cranial magnetic stimulation, and urodynamic studies, can be of particular value in the study of autonomic patients. [29], [40], [41]

6. Sphincter EMGin autonomic disorders

6.1. MSA

Cardiovascular autonomic failure in MSA is thought to derive from neuron loss in the thoracolumbar intermediolateral (IML)cell columns of the spinal cord and the medullary circulation center. In contrast, lower urinary tract disorder in MSA is thought to reflect multiple lesions in the basal ganglia andthe pontine storage center (storage-facilitating areas), as well as in the pontine micturition center in or adjacent to the locus ceruleus and the sacral IML cell columns (voiding-facilitating areas). [11] In addition, a distinguishing pathology in MSA is neuronal cell loss in the sacral Onuf nucleus. [33], [37]

The first reports on neurogenic changes of EAS-EMG in MSA are attributed to Sakuta et al. (1978). [62] Since then, EAS-EMG results for over 500 MSA patients have been reported, with abnormality rates of more than 70% in many studies [5], [30], [36], [38], [47], [53], [62], [64], [71].EAS-EMG is better tolerated and yields identical results to those from EUS investigation [5]. Abnormalities have also been recorded in the bulbocavernosus muscles in MSA. [67]In a larger study, Beck et al. (1994) reported that all (100%) 62 MSA patientswith urological symptoms had abnormalities in both EAS and EUS-EMG. [5] Palace et al. (1997) reported abnormal EAS-EMG in 103 (82%) of 126 patients with MSA [38]. Chandiramani et al. (1997) found abnormal EAS-EMG in 49 (94%) of 52 patients with MSA [10]. Kirchhof et al. (1999) found abnormal EAS-EMG in 89 (91%)of 98 patients with MSA [28]. Sakakibara et al. (2000) found an abnormal EAS-EMG in 53 (74%) of 71 MSA patients [52]. These abnormalities correspond to selective loss of ventral horn cellsand astrogliosis; the loss is particularly severe in the second and third sacral segments (Onuf’s nucleus)in MSA [11]. Sphincter EMG has been proposed as a means of distinguishing between MSA and idiopathic Parkinson’s disease(as described below), since the anterior horn cells of Onuf’s nucleus are not affectedin idiopathic Parkinson’s disease. [10] In contrast, there have been debates about whether or not sphincter EMG can be used to distinguish MSA from idiopathic Parkinson’s disease. In a study of 13 patients with idiopathic Parkinson’s disease and 10 patients with MSA, Giladi et al. (2000) found significant overlap in allEMG parameters (presence of fibrillation potentials, MUP duration, presence of satellite potentials, percentage of polyphasic potentials) [19]. However, the durations of MUPs in both the MSA and Parkinson’s disease groups were longer than in other studies.

It is reported that EAS-MUP abnormalities can distinguish MSA from idiopathic Parkinson’s disease in the first 5 years after disease onset. [30], [69], [74] However, the prevalence of such abnormalities in the early stages of MSA has not been well known. In our recent study of 84 probable MSA cases, 62% exhibited neurogenic change. [80]The prevalence was relatively low presumably because up to 25% of our patients had a disease duration of 1 year or less. In such early cases, the diagnosis of MSA should be made with extreme caution. In addition to the clinical diagnostic criteria, we usually add an imaging study and we perform gene analysis to the extent possible. The prevalence of neurogenic change was 52% in the first year after disease onset, which increased to 83% by the fifth year (p<0.05)(Fig. 5). Among the patients who underwent repeated studies, many had normal to mild abnormality at the initial examination, which turned into marked abnormality during the course of illness(Fig. 6). Therefore, as expected, it is apparent that the involvement of Onuf’s nucleus in MSA is time-dependent. In the early stages of illness, the prevalence of neurogenic change in MSA does not seem to be high. In 2 patients who underwent repeated studies, the EAS-EMG findings tended to remain normal. We do not know whether some MSA patients never develop neurogenic change during the course of their illness. However, Wenning et al. (1994) reported 3 patients with normal EAS-EMG and a postmortem confirmation of MSA. [77] Therefore, a negative result cannot exclude a diagnosis of MSA. More recently, Paviour et al. (2005) reported that among30 setsof clinical data and postmortem confirmation in MSA cases with a duration of more than 5 years, 24 (80%) had abnormal EAS-EMG, 5 (17%) had a borderlineresult, and only 1 had a normal EMG. [39]


The prevalence of neurogenic sphincter EMG increased during the course of illness.

MUP: motor unit potential

(cited from ref. 74)

Figure 5.

Neurogenic sphincter EMG and duration of illness.


Percentage of MUPs with duration > 10 msec: one of two categories for neurogenic sphincter EMG.

straight figures: the number of patients

oblique figures: the number of patients who underwent the study repeatedly

MUP: motor unit potential

(cited from ref. 74)

Figure 6.

Percentage of MUPs with duration > 10 msec and duration of illness.

The prevalence of neurogenic change also increased with the severity of gait disturbance (p<0.05) in our study. However, neurogenic change was not related to postural hypotension (reflecting adrenergic nerve dysfunction); erectile dysfunction in men (presumably reflecting cholinergic and nitrate oxidergic nerve dysfunction); detrusor overactivity (reflecting the central type of detrusor dysfunction); constipation (presumably reflecting both peripheral and central types of autonomic and somatic dysfunction); or gender(Table 1). The neurogenic change in EAS-MUP was slightly more common in those with detrusor-sphincter dyssynergia (reflecting the central type of sphincter dysfunction). It has been reported that neurogenic change does not correlate directly with a clinically obvious functional deficit. [74] Patients with marked abnormalities in EAS-MUP may have no faecal incontinence, [77] although, in such patients, anal sphincter weakness is not uncommon. [58] In our study, the prevalence of neurogenic change slightly increased with the severity of storage disorder (incontinence). The most common type of urinary incontinence in MSA is urgency incontinence, which results mostly from detrusor (bladder) overactivity. However, we noted urinary incontinence in 17 patients without detrusor overactivity or low-compliance detrusor; in those cases, the urinary incontinence may have had a sphincter etiology. Urinary incontinence was more severe in the patients with neurogenic change than in those without it (p<0.05).

We recently retrospectively analysed 445 case records of EMG cystometry with pressure flow studies, single motor unit potential (MUP) analysis in patients with parkinsonian syndrome, e.g., MSA: n=267, Parkinson's disease (PD): n=129, Dementia with Lewy bodies (DLB): n=25, and progressive supranuclear palsy (PSP): n=24. We carried out receiver operating characteristics (ROC) analysis, revealing that an area under the ROC curve (AUC) in differentiating MSA from other parkinsonian syndrome was 0.70 in duration, 0.62 in phase and 0.51 in amplitude, respectively, with statistically significance. Therefore, duration of MUPs is most sensitive for the differentiation of MSA among MUPs parameters.


Table 1.

Neurogenic sphincter EMG and clinical variables other than duration of illness.

6.2. Lewy body diseases

6.2.1. Idiopathic Parkinson’s disease (IPD)

Several reports of “supposed IPD” have shown severe bladder dysfunctions, e.g., large post-void residuals or neurogenic change in the EAS-EMG. However, some of these reports were published before a definition of MSA was established. Recent studies have reported almost normal EAS-EMG in patients with typical IPD [38], [47], [53], [67]. Stocchi’s study(1997) is important, since EMG in patients with IPD and MSA was performed by researchers blinded to the diagnosis. [67]Pathological studies of IPD have shown a degenerative lesion in the spinal parasympathetic PGN [75], although the lesions are much less developed than those in MSA. No Lewy bodies were found in Onuf’s nucleus innervating the anal sphincter in IPD. [75] In contrast, Libelius and Johansson (2000) described neurogenic change in EAS-EMGin PD after a disease duration of more than 5 years. [30]This remains a matter of controversy; on the other hand, some patients with DLB may show abnormal EAS-EMG, as described below.

6.2.2. Dementia with Lewy bodies (DLB)

DLB is characterized as dementia with fluctuating cognition and visual hallucination, with (sometimes atypical) parkinsonism. Cardiovascular and urinary autonomic failure is another feature. We performed urodynamic studies in 7 patients with DLB, and performed EAS-EMG in 3. Two of those 3 patients exhibitedneurogenic changes in MUPs. [55]

6.2.3. Autonomic failure with Parkinson’s disease(AFPD)

AFPD is an intermediate entity that describes a combination of autonomic failure and IPD, but without dementia. We performed urodynamic studies in 7 patients with AFPD and performed EAS-EMG in 4. Three of those 4 patients exhibitedneurogenic changes in MUPs [55].

6.2.4. Pure autonomic failure (PAF)

Earlier studies reported normal EAS-EMG in small groups of patients with PAF. However, Ravits et al. (1996) [46] found abnormal EAS-EMG in 2 of 7 patients with PAF, although both of them were multiparous women. Sakakibara et al. performed urodynamic studies in 6 patients with PAF and EAS-EMG in 4. Three of those 4 patients exhibited neurogenic changes in MUPs. [51]In PAF, parkinsonism may appear after a 10-year interval. [81]Therefore PAF can be listed in the differential diagnosis of degenerative parkinsonism. To sum up, in all three Lewy body diseases (DLB, AFPD, PAF), the frequency of neurogenic changes seemed higher in EAS-EMG than in IPD but lower than in MSA. This suggests the involvement of the sacral Onuf’s nucleus or its fibers in the external sphincter in these diseases. The prevalence of neurogenic changes in EAS-EMG seems to be: MSA >> DLB = AFPD = PAF >> PD (Table 2). However, these assumptions require confirmation with a larger study. The results seem to be in accordance with the fact that 29% of the DLB patients undergoing EMG-cystometry had a low-compliance detrusor, indicating a pre-ganglionic lesion of the pelvic nerves. The bethanechol test showed that both of these patients had denervation supersensitivity of the detrusor, indicating a post-ganglionic lesion of the pelvic nerves. The results of physiological studies and metaiodobenzylguanidine (MIBG) cardiac scintigraphy suggested post-ganglionic abnormalities in DLB.


Table 2.

Comparison of lower urinary tract function in DLB, AFPD, PAF, PD and MSA. See text.

6.3. Other parkinsonian disorders

6.3.1. Progressive supranuclear palsy (PSP)

We performed urodynamic studies in 9 patients with PSP and performed EAS-EMG in 4. Two of these 4 patients exhibitedneurogenic changes in MUPs. [50]Abnormal sphincter EMG was also reported in 5 of 12 patients by Valldeoriola et al. (1995) [71], and in 2 of 8 patients by Palace et al. (1997) [38]. Libelius and Johansson (2000) also described anal sphincter EMG abnormalities in 2 of 3 patients with PSP. [30]

6.3.2. Corticobasal degeneration (CBD)

We performed urodynamic studies in 6 patients with CBD and EAS-EMG in 5 of them. However, none of the 5 patients showedneurogenic changes in the MUPs. [60] There is a considerable overlap in the clinical presentation of the parkinsonian form of MSA (MSA-P) and that of PSP. Therefore, we should be cautious in interpreting sphincter EMG in these disorders.

6.4. Cerebellar ataxia

6.4.1. Spinocerebellar ataxia 3 (SCA3)/Machado-Joseph disease

We performed urodynamic studies in 11 patients with spinocerebellar ataxia 3 (SCA3) and performed EAS-EMG in 9. Six of the 9 patients showedneurogenic changes in MUPs. [59]

6.4.2. Late cortical cerebellar atrophy (LCCA)

We performed urodynamic studies in 7 patients with LCCA, which is a pure cerebellar ataxia without heredity, and EAS-EMG in 3 of them. However, none of the 3 patients exhibitedneurogenic changes in the MUPs.

6.4.3. Spinocerebellar ataxia 6 (SCA6)

We performed urodynamic studies in 9 patients with spinocerebellar ataxia 6 (SCA6) and performed EAS-EMG in 8. Five of the8 patients showedneurogenic changes in MUPs.

6.5. Other diseases

Sakuta et al. performed EAS-EMG in 30 patients with amyotrophic lateral sclerosis (ALS). [62] None of them exhibitedneurogenic changes in the MUPs, which contrasted with common neurogenic changes in the limb muscles in this disorder. These EMG findings correspond to the postmortem selective sparing of sacral Onuf’s nucleus, which contrasts with severe loss of anterior horn cells innervating the limbs, tongue, and bulbar muscles [2]. Neurons in Onuf’s nucleus demonstrate some morphological differences from the anterior horn cells innervating limb muscle [33]. However, more recent studies have shown abnormalities in the Onuf’s nucleus in most advanced cases with ALS [27], particularly in patients under mechanical ventilation.

7. Conclusions

We have reviewed the normal physiology and pathophysiology of the lower urinary tract and the lower gastrointestinal tract, the current methods and interpretations of sphincter EMG, and the application of this technique to various autonomic disorders.Sphincter EMG makes it easier todistinguish MSA fromidiopathic Parkinson’s disease in the first 5 years after disease onset, reflecting the significant involvement of the sacral spinal cord in MSA. However, abnormal sphincter EMG is also seen in some, though not many, patients with DLB or PSP. It is noteworthy that sphincter denervation leads to severe urinary and fecal incontinence in some female patients with MSA, which severely affects their quality of life. Sphincter EMG and relevant sacral autonomic tests aregood diagnostic tools in autonomic disorders.


1 - P. Abrams, L. Cardozo, M. Fall, D. Griffiths, P. Rosier, U. Ulmsten, P. van Kerrebrock, A. Victor, A. Wein, 2002The standardization of terminology of lower urinary tract function: report from the standardization sub-committee of the international continence society. Neurourol Urodynam 21167178
2 - P. Amborova, P. Hubkal, I. Ulkova, I. Hulin, 2003The pacemaker activity of interstitial cells of cajal and gastric electrical activity. Physiol Res 52275284
3 - A. Argiolas, M. R. Melis, 2005Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol 76121
4 - G. Bassotti, D. Maggio, E. Battaglia, O. Giulietti, F. Spinozzi, G. Reboldi, A. M. Serra, G. Emanuelli, G. Chiarioni, 2000Manometric investigation of anorectal function in early and late stage Parkinson’s disease. J Neurol Neurosurg Psychiatry 68; 768770
5 - Beck RO, Betts CD, Fowler CJ1994Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 15113361341
6 - C. D. Betts, R. Kapoor, C. J. Fowler, 1992Pontine pathology and voiding dysfunction. Br J Urol. 70100102
7 - B. F. Blok, G. Holstege, 1999The central control of micturition and continence: implications for urology. Br J Urol Int 83 Suppl 216
8 - B. F. Blok, H. de Weerd, G. Holstege, 1997The pontine micturition center projects to sacral cord GABA immunoreactive neurons in the cat. Neurosci Lett 233109112
9 - P. Broens, D. Vanbeckevoort, E. Bellon, F. Penninckx, 2002Combined radiographic and manometric study of rectal filling sensation. Dis Colon Rectum 4510161022
10 - V. A. Chandiramani, J. Palace, C. J. Fowler, 1997How to recognize patients with parkinsonism who should not have urological surgery. Br J Urol80100104
11 - Daniel SE1992The neuropathology and neurochemistry of multiple system atrophy. In Autonomic Failure, 3rd ed., R Bannister and CJ Mathias, eds. Oxford Medical Publications, Oxford, UK, 564585
12 - de Groat WC2006Integrative control of the lower urinary tract: preclinical perspective. BJP 147: S25S40
13 - Dominguez JM, Hull EM2005Dopamine, the medial preoptic area, and male sexual behavior. Physiol Behavior 86356368
14 - I. Eardley, N. P. Quinn, C. J. Fowler, R. S. Kirby, H. F. Parkhouse, C. D. Marsden, R. Bannister, 1989The value of urethral sphincter electromyography in the differential diagnosis of parkinsonism. Br J Urol 64360362
15 - C. Fisher, J. Gross, A. J. Zuch, 1965Cycle of penile erection synchronous with dreaming (REM) sleep. Arch Gen Psychiatry; 122945
16 - Fowler CJ2006Integrated control of lower urinary tract: clinical perspective. BJP 147: S14S24
17 - C. J. Fowler, R. S. Kirby, MJ Milroy. E. J. Harrison, R. Turner-Warwick, 1984Individual motor unit analysis in the diagnosis of disorders of urethral sphincter innervation. J Neurol Neurosurg Psychiatry 47637641
18 - R. Gilad, N. Giladi, A. D. Korczyn, T. Gurevich, M. Sadeh, 2001Quantitative anal sphincter EMG in multisystem atrophy and 100 controls. J Neurol Neurosurg Psychiatry.71596599
19 - N. Giladi, E. S. Simon, A. D. Korczyn, G. B. Groozman, Y. Orlov, H. Shabtai, V. E. Drory, 2000Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson’s disease. Muscle Nerve 23731734
20 - Hansen MB2003Neurohumoral control of GI motility. Physiol Res 52130
21 - M. Hirschkowitz, M. H. Schmidt, 2005Sleep-related erections: clinical perspectives and neural mechanisms. Sleep Med Rev 9311329
22 - T. Ito, R. Sakakibara, T. Uchiyama, Z. Liu, T. Yamamoto, T. Hattori, 2006bVideomanometry of the pelvic organs; a comparison of the normal lower urinary and GI tracts. Int J Urol 132935
23 - T. Ito, R. Sakakibara, K. Yasuda, T. Yamamoto, T. Uchiyama, Z. Liu, T. Yamanishi, Y. Awa, K. Yamamoto, T. Hattori, 2006Incomplete emptying and urinary retention in multiple system atrophy:when does it occur and how do we manage it? Mov Disord 21816823
24 - R. B. Kavia, S. N. Datta, R. Dasgupta, S. Elneil, C. J. Fowler, 2006Urinary retention in women: its causes and management. BJU Int 97281287
25 - R. B. C. Kavia, R. Dasgupta, C. J. Fowler, 2005Functional imaging and the central control of the bladder. J Comp Neurol 4932732
26 - J. E. Kellow, M. Delvaux, F. Azpiroz, M. Camilleri, E. M. M. Quigley, D. G. Thompson, 1999Principles of applied neurogastroenterology: physiology/motility-sensation. Gut 45; 1724
27 - T. Kihira, S. Yoshida, F. Yoshimasu, I. Wakayama, Y. Yase, 1997Involvement of Onuf’s nucleus in amyotrophic lateral sclerosis. J Neurol Sci 1478188
28 - K. Kirchhof, C. J. Mathias, C. J. Fowler, 1999The relationship of uro-genital dysfunction to other features of autonomic failure in MSA. Clin Auton Res 9128
29 - Lefaucheur JP2006Neurophysiological testing in anorectal disorders. Muscle Nerve. 33324333
30 - R. Libelius, F. Johansson, 2000Quantitative electromyography of the external anal sphincter in Parkinson’s disease and multiple system atrophy. Muscle Nerve 2312501256
31 - M. T. Liu, S. Rayport, L. Jiang, D. L. Murphy, MD Gershon, 2002Expression and function of 5HT3 receptors in the enteric neurons of mice lacking the serotonin transporter. Am J Physiol Gastrointest Liver Physiol 283: G1398-G1411
32 - Z. Liu, R. Sakakibara, K. Nakazawa, T. Uchiyama, T. Yamamoto, T. Ito, T. Hattori, 2004Micturition-related neuronal firing in the periaqueductal gray area in cats. Neuroscience 12610751082
33 - T. Mannen, M. Iwata, Y. Toyokura, K. Nagashima, 1982The Onuf’s nucleus and the external anal sphincter muscles in amyotrophic lateral sclerosis and Shy-Drager syndrome. Acta Neuropathol 58255260
34 - T. Mashidori, T. Yamanishi, K. Yoshida, R. Sakakibara, K. Sakurai, K. Hirata, Continuous urinary incontinence presenting as the initial symptoms demonstrating acontractile detrusor and intrinsic sphincter deficiency in multiple system atrophy. Int J Urol. 14: 10; 9729742007
35 - G. Matsumoto, T. Hisamitsu, W. C. De Groat, 1995Role of glutamate and NMDA receptors in the descending limb of the spinobulbospinal micturition reflex pathway of the rat. Neurosci Lett 1835861
36 - F. Nahm, R. Freeman, 2003Sphincter electromyography and multiple system atrophy. Muscle Nerve 281826
37 - B. Onufrowicz, 1899Notes on the arrangement and function of the cell groups in the sacral region of the spinal cord. J Nerv Ment Dis 26498504
38 - J. Palace, V. A. Chandiramani, C. J. Fowler, 1997Value of sphincter electromyography in the diagnosis of multiple system atrophy. Muscle Nerve 2013961403
39 - Paviour DC, Williams DC, Fowler CJ, Quinn NP, Lees AJ2005Is sphincter electromyography a helpful investigation in the diagnosis of multiple system atrophy? A retrospective study with pathological diagnosis. Mov Disord 2014251430
40 - A. Pellegrinetti, G. Moscato, G. Siciliano, U. Bonuccelli, G. Orlandi, P. Maritato, F. Sartucci, 2003Electrophysiological evaluation of genito-sphincteric dysfunction in multiple system atrophy. Int J Neurosci. 11313531369
41 - S. Podnar, 2007Neurophysiology of the neurogenic lower urinary tract disorders. Clin Neurophysiol.11814231437
42 - S. Podnar, C. J. Fowler, 2004Sphincter electromyography in diagnosis of multiple system atrophy: technical issues. Muscle Nerve 29151156
43 - S. Podnar, Z. Rodi, A. Lukanovic, B. Trsinar, D. B. Vodusek, 1999Standardization of anal sphincter EMG: technique of needle examination. Muscle Nerve 22400403
44 - S. Podnar, D. B. Vodusek, 2001Protocol for clinical neurophysiologic examination of the pelvic floor. Neurourol Urodyn20669682
45 - S. Podnar, 2007Neurophysiology of the neurogenic lower urinary tract disorders. Clin Neurophysiol. 11814231437
46 - J. Ravits, M. Hallett, J. Nilsson, R. Polinsky, J. Dambrosia, 1996Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes. Muscle Nerve. 19758763
47 - Z. Rodi, M. Denislic, D. Vodusek, 1996External anal sphincter electromyography in the differential diagnosis of parkinsonism. J Neurol Neurosurg Psychiatry 60460461
48 - R. Sakakibara, C. J. Fowler, 2001Brain disease (Chapter 9). In: Seminars in Clinical Neurology (by World Federation of Neurology). Neurologic bladder, bowel, and sexual function. Edited by Fowler CJ, Elsevier, Boston, 229243
49 - Sakakibara R, Hattori T, Kita K, Arai K, Yamanishi T, Yasuda K : Stress-induced urinary incontinence in patients with spinocerebellar degeneration J Neurol Neurosurg Psychiatry 64: 3; 389-391 1998
50 - R. Sakakibara, T. Hattori, M. Tojo, T. Yamanishi, K. Yasuda, K. Hirayama, 1993Micturitional disturbance in progressive supranuclear palsy. J Auton Nerv Syst.45101106
51 - R. Sakakibara, T. Hattori, T. Uchiyama, M. Asahina, T. Yamanishi, 2000Micturitional disturbance in pure autonomic failure. Neurology.54499501
52 - R. Sakakibara, T. Hattori, T. Uchiyama, K. Kita, M. Asahina, A. Suzuki, T. Yamanishi, 2000Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation? Neurol Neurosurg Psychiatry 686569
53 - R. Sakakibara, T. Hattori, T. Uchiyama, T. Yamanishi, 2001Videourodynamic and sphincter motor unit potential analyses in Parkinson’s disease and multiple system atrophy. J Neurol Neurosurg Psychiatry71600606
54 - R. Sakakibara, T. Hattori, K. Yasuda, T. Yamanishi, 1996Micturitional disturbance and pontine tegmental lesion; urodynamic and MRI analyses of the vascular cases. J Neurol Sci 141105110
55 - R. Sakakibara, T. Ito, T. Uchiyama, M. Asahina, Z. Liu, T. Yamamoto, Y. Yamanaka, T. Hattori, 2005Lower urinary tract function in dementia of Lewy body type (DLB). J Neurol Neurosurg Psychiatry 76729732
56 - R. Sakakibara, M. Mori, T. Fukutake, K. Kita, (199, 1997Orthostatic hypotension in a case with multiple sclerosis. Clin Auton Res 7163165
57 - R. Sakakibara, K. Nakazawa, K. Shiba, Y. Nakajima, T. Uchiyama, M. Yoshiyama, T. Yamanishi, T. Hattori, 2002Firing patterns of micturition-related neurons in the pontine storage centre in cats. Auton Neurosci Basic Clin 992430
58 - R. Sakakibara, T. Odaka, T. Uchiyama, M. Asahina, K. Yamaguchi, T. Yamaguchi, T. Yamanishi, T. Hattori, 2004Colonic transit time, sphincter EMG and rectoanal videomanometry in multiple system atrophy. Mov Disord 19924929
59 - R. Sakakibara, T. Uchiyama, K. Arai, T. Yamanishi, T. Hattori, 2004Lower urinary tract dysfunction in Machado-Joseph disease: a study of 11 clinical-urodynamic observations. J Neurol Sci.2186772
60 - R. Sakakibara, T. Uchiyama, T. Yamanishi, T. Hattori, 2004Urinary function in patients with corticobasal degeneration; comparison with normal subjects. Neurourol Urodyn. 23154158
61 - R. Sakakibara, T. Uchiyama, T. Yamanishi, K. Shirai, T. Hattori, 2008Bladder and bowel dysfunction in Parkinson’s disease. J Neural Transm 115443460
62 - M. Sakuta, T. Nakanishi, Y. Toyokura, 1978Anal muscle electromyograms differ in amyotrophic lateral sclerosis and Shy-Drager syndrome. Neurology 2812891293
63 - M. Sasaki, 2005Role of Barrington’s nucleus in micturition. J Comp Neurol 4932126
64 - J. Schwarz, M. Kornhuber, C. Bischoff, A. Straube, 1997Electromyography of the external anal sphincter in patients with Parkinson’s disease and multiple system atrophy: frequency of abnormal spontaneous activity and polyphasic motor unit potentials. Muscle Nerve2011671172
65 - C. Singer, W. J. Weiner, J. R. Sanchez-Ramos, M. Ackerman, 1989Sexual dysfunction in men with Parkinson’s disease. J Neurol Rehab 3199204
66 - Steers WD2002Pathophysiology of overactiveand urge urinaryincontinence. Rev Urol 4 Suppl 4: S7S18
67 - F. Stocchi, A. Carbone, M. Inghilteri, A. Monge, S. Ruggieri, A. Berardelli, M. Manfredi, 1997Urodynamic and neurophysiological evaluation in Parkinson’s disease and multiple system atrophy. J Neurol Neurosurg Psychiatry 62507511
68 - Thor KB2003Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: implications for treating stress urinary incontinence. Urology 6239
69 - F. Tison, P. Arne, C. Sourgen, V. Chrysostome, F. Yeklef, 2000The value of external anal sphincter electromyography for the diagnosis of multiple system atrophy. Mov Disord 1511481157
70 - A. Tsujimura, Y. Miyagawa, K. Fujita, Y. Matsuoka, T. Takahashi, T. Takao, K. Matsumiya, Y. Osaki, M. Takasawa, N. Oku, J. Hatazawa, Kaneko. S. Shigeo, A. Okuyama, 2006Brain processing of audiovisual sexual stimuli inducing penile erection: a positron emission tomography study. J Urol176679683
71 - F. Valldeoriola, J. Valls-Sole, E. Tolosa, M. Marti, 1995Striated anal sphincter denervation in patients with progressive supranuclear palsy. Mov Disord 10550555
72 - W. R. van Furth, G. Wolterink, J. M. van Ree, 1995Regulation of masculine sexual behavior; involvement of brain opioids and dopamine. Brain Research Reviews 21162184
73 - . , C. J. Vaughan, A. M. Aherne, E. Lane, O. Power, R. M. Carey, D. P. O’Connell, 2000Identification and regional distribution of the dopamine D1A receptor in the GI tract. Am J Physiol Regulatory Integrative Comp Physiol 279: R599R609
74 - Vodusek DB2001Sphincter EMG and differential diagnosis of multiple system atrophy. Mov Disord 16600607
75 - K. Wakabayashi, H. Takahashi, 1997Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol. 38 Suppl 227
76 - Walker JK, Gainetdinov RR, Mangel AW, Caron MG, Shetzline MA2000Mice lacking the dopamine transporter display altered regulation of distal colonic motility. Am J Physiol Gastrointest Liver Physiol. 279: G311318
77 - G. K. Wenning, Y. Ben-Schlomo, M. Magalhaes, S. Daniel, N. Quinn, (199, 1994Clinical features and natural history of multiple system atrophy. Brain 117835845
78 - H. Yaguchi, H. Soma, Y. Miyazaki, J. Tashiro, I. Yabe, S. Kikuchi, H. Sasaki, H. Kakizaki, F. Moriwaka, K. Tashiro, 2004A case of acute urinary retention caused by periaqueductal grey lesion. J Neurol Neurosurg Psychiatry 75; 12021203
79 - T. Yamamoto, R. Sakakibara, T. Uchiyama, Z. Liu, T. Ito, Y. Awa, T. Yamanishi, T. Hattori, 2006Neurological diseases that cause detrusor hyperactivity with impaired contractile function. Neurourol Urodynam 25356360
80 - T. Yamamoto, R. Sakakibara, T. Uchiyama, Z. Liu, T. Ito, Y. Awa, T. Yamanishi, T. Hattori, 2005When is Onuf’s nucleus involved in multiple system atrophy?A sphincter electromyography study. J Neurol Neurosurg Psychiatry7616451648
81 - Y. Yamanaka, M. Asahina, A. Hiraga, R. Sakakibara, H. Oka, T. Hattori, 2007Over 10 years of isolated autonomic failure preceding dementia and Parkinsonism in 2 patients with Lewy body disease. Mov Disord 22595597
82 - O. Yokoyama, M. Yoshiyama, M. Namiki, W. C. de Groat, 2002Changes in dopaminergic and glutamatergic excitatory mechanisms of micturition reflex after middle cerebral artery occlusion in conscious rats. Exp Neurol 173129135
83 - O. Yokoyama, S. Yotsuyanagi, H. Akino, H. Moriyama, Y. Matsuta, M. Namiki, 2003RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat. J Urol. 16918781884