Sphincter EMG as a diagnostic tool in autonomic disorders
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- Sakakibara, R., Uchiyama, T., Yamanishi, T. et al. Clin Auton Res (2009) 19: 20. doi:10.1007/s10286-008-0489-5
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Multiple system atrophy (MSA) is a neurodegenerative disease presenting with a combination of parkinsonian, cerebellar, and autonomic (including cardiovascular, urinary, and anorectal) dysfunction. It is pathologically defined, but at present lacks a definitive clinical diagnostic test. The majority of patients with probable MSA have an abnormal sphincter EMG. Patients with idiopathic Parkinson’s disease do not show marked sphincter EMG abnormalities. Therefore, these abnormalities can be used to distinguish MSA from idiopathic Parkinson’s disease in the first 5 years after disease onset. In contrast, similar sphincter EMG abnormalities are found in some, though not many, patients with dementia with Lewy bodies, pure autonomic failure, progressive supranuclear palsy, and spinocerebellar ataxia type 3. Thus, the limitations of the sphincter EMG test should also be kept in mind. Sphincter EMG and relevant sacral autonomic tests are diagnostic tools for autonomic disorders, reflecting the common and significant involvement of the sacral cord in MSA.
Keywordsmultiple system atrophyidiopathic Parkinson’s diseaseexternal sphincter electromyographyautonomic nervous systemOnuf’s nucleus
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 . 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 [56, 67]. 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 . The significance of the EAS-EMG in MSA is well known [30, 68, 73]. Physiologically, external urethral sphincter (EUS) and EAS share sacral pudendal innervation from Onuf’s nucleus . 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 EMG in autonomic disorders.
Physiology and pathophysiology of the lower urinary tract
Urinary storage is dependent on the autonomic reflex arc of the sacral cord . This reflex is tonically facilitated by the brain, particularly the pontine storage center [7, 56], hypothalamus, cerebellum, basal ganglia, and frontal cortex . In contrast, micturition is dependent on the autonomic reflex arc of the brainstem and spinal cord . This reflex involves the periaqueductal gray [12, 32, 77] and the pontine micturition center (PMC) [6, 7, 12, 53, 62]. The PMC facilitates the sacral bladder preganglionic nucleus by glutamate , while inhibiting the sacral Onuf’s nucleus by γ-amino-butyric acid (GABA) and glycine . This reflex is regulated by the hypothalamus and prefrontal cortex [16, 25].
Bladder (detrusor) overactivity is the major cause of urinary urgency/frequency and urgency incontinence . In lesions above the brainstem, detrusor overactivity is considered an exaggerated micturition reflex . This is in line with the fact that detrusor overactivity appearing after experimental stroke requires mRNA synthesis in the PMC . 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 . 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, 47].
Urinary urgency incontinence and voiding difficulty in MSA result mostly from detrusor overactivity and underactive detrusor, respectively [1, 47]. 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, 78]. 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 . Since a coordinated micturition reflex (bladder contraction with sphincter relaxation) needs an intact brainstem–sacral cord axis , 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  or continuous urinary incontinence .
Physiology and pathophysiology of the lower gastrointestinal tract
The enteric nervous system plays the most important role in regulating the peristaltic reflex of the lower gastrointestinal tract . Two types of myoelectrical activity or pressure changes in the colon are documented. Slow phasic pressure waves are the most common manometric phenomenon , 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 . 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 .
Other types of pressure changes in the colon include giant motor complexes . A giant motor complex is a cyclic contractile activity with a periodicity of 20–30 minutes, and is perhaps analogous to the migrating motor complex of the small intestine . A combination of slow waves and giant motor complexes is thought to promote bowel transport, which in humans is measured by colonic transit time . 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, 72] and dopamine D2 receptor-mediating inhibition .
Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain . Some patients also have paradoxical sphincter contraction on defecation (PSCD) . 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 . In contrast, fecal incontinence results mostly from a weak anal sphincter due to denervation .
Physiology and pathophysiology of the genital organ
Among the three types of erection, reflexive erection requires 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 the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) [13, 71]. Recent neuroimaging studies have shown that penile stimulation or watching pornography activated these areas in humans . NPT  seems to be regulated by the hypothalamic lateral preoptic area , 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 . 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.
Methods and interpretations of sphincter EMG
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 . The former is thought to reflect hypogastric adrenergic innervation, whereas the latter reflects somatic Onuf’s nucleus innervation . The subcutaneous EAS is easy to examine. It is reached by inserting a needle about 1 cm from the anal orifice, to a depth of 3–6 mm .
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 software is recommended. The commonly used amplifier filter setting is 5–10 kHz. The tip of a concentric needle usually monitors an area approximately 500 mm in diameter, which includes approximately 20 MUPs. To assess acute denervation, insertion and spontaneous activities are checked as with the evaluation of other skeletal 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 bulbocavernosus muscle has been recommended .
A normal MUP usually has a 50–500 µV amplitude, a 3–8 ms 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 . 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 and specificity) in the EAS muscle . 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 ms, or (b) the average duration of MUPs >10 ms, particularly including the late components . When satellite potentials were excluded, the duration of MUPs did not differ significantly between Parkinson’s disease and MSA . When lower motor neuron-type abnormalities are not apparent, it is reported that abnormal MUP recruitment pattern suggests pyramidal tract involvement . 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].
Sphincter EMG in autonomic disorders
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 and the 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) . 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. . 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, 46, 52, 61, 63, 70]. EAS-EMG is better tolerated and yields identical results to those from EUS investigation . Abnormalities have also been recorded in the bulbocavernosus muscles in MSA . In a larger study,  reported that all (100%) 62 MSA patients with urological symptoms had abnormalities in both EAS and EUS-EMG. Palace et al.  reported abnormal EAS-EMG in 103 (82%) of 126 patients with MSA. Chandiramani et al.  found abnormal EAS-EMG in 49 (94%) of 52 patients with MSA. Kirchhof et al.  found abnormal EAS-EMG in 89 (91%) of 98 patients with MSA. Sakakibara et al.  found an abnormal EAS-EMG in 53 (74%) of 71 MSA patients. These abnormalities correspond to selective loss of ventral horn cells and astrogliosis; the loss is particularly severe in the second and third sacral segments (Onuf’s nucleus) in MSA . 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 affected in idiopathic Parkinson’s disease . 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.  found significant overlap in all EMG parameters (presence of fibrillation potentials, MUP duration, presence of satellite potentials, percentage of polyphasic potentials). However, the durations of MUPs in both the MSA and Parkinson’s disease groups were longer than in other studies.
Neurogenic sphincter EMG and clinical variables other than duration of illness
Patients with neurogenitic sphincter EMG
Patients with neurogenitic sphincter EMG
Age <60 years
Age <60 years
Independent walking (1–3a)
Wheelchair bound (6–7a)
P < 0.05
Postural hypotension (−)
Postural hypotension (+)
Erectile dysfunction (−)
Erectile dysfunction (+)
RU <200 ml
RU >200 ml
Detrusor overadivity (−)
Detrusor overadivity (+)
Lewy body diseases
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, 46, 52, 66]. Stocchi’s study (1997) is important, since EMG in patients with IPD and MSA was performed by researchers blinded to the diagnosis . Pathological studies of IPD have shown a degenerative lesion in the spinal parasympathetic PGN , 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 . In contrast, Libelius and Johansson  described neurogenic change in EAS-EMG in PD after a disease duration of more than 5 years. This remains a matter of controversy; on the other hand, some patients with DLB may show abnormal EAS-EMG, as described below.
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 seven patients with DLB, and performed EAS-EMG in three. Two of those three patients exhibited neurogenic changes in MUPs .
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 seven patients with AFPD and performed EAS-EMG in four. Three of those four patients exhibited neurogenic changes in MUPs .
Pure autonomic failure (PAF)
Comparison of lower urinary tract function in DLB, AFPD, PAF, PD and MSA
LUT symptoms (%)
Uniary incontinence (storage dys function) (%)
PVR > 100 ml (voiding dys function) (%)
No. of patients
Detrus or overativity (central type) (%)
Low compliance (pre GGL type) (%)
Bathaneschal super sensitivity (denervation) (postGGL type)
Neurogenic change of sphincter MUPs (denervation (Onuf’s nudaus)
No. of patients
Other parkinsonian disorders
Progressive supranuclear palsy (PSP)
We performed urodynamic studies in nine patients with PSP and performed EAS-EMG in four. Two of these four patients exhibited neurogenic changes in MUPs . Abnormal sphincter EMG was also reported in 5 of 12 patients by Valldeoriola et al. , and in 2 of 8 patients by Palace et al. . Libelius and Johansson  also described anal sphincter EMG abnormalities in 2 of 3 patients with PSP.
Corticobasal degeneration (CBD)
We performed urodynamic studies in six patients with CBD and EAS-EMG in five of them. However, none of the five patients showed neurogenic changes in the MUPs . 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.
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 nine patients showed neurogenic changes in MUPs .
Late cortical cerebellar atrophy (LCCA)
We performed urodynamic studies in seven patients with LCCA, which is a pure cerebellar ataxia without heredity, and EAS-EMG in three of them. However, none of the three patients exhibited neurogenic changes in the MUPs.
Sakuta et al.  performed EAS-EMG in 30 patients with amyotrophic lateral sclerosis (ALS). None of them exhibited neurogenic 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 . Neurons in Onuf’s nucleus demonstrate some morphological differences from the anterior horn cells innervating limb muscle . However, more recent studies have shown abnormalities in the Onuf’s nucleus in most advanced cases with ALS , particularly in patients under mechanical ventilation.
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 to distinguish MSA from idiopathic 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 are good diagnostic tools in autonomic disorders.