|Year : 2006 | Volume
| Issue : 3 | Page : 225-230
Corpus cavernosum electromyography, a usable clinical diagnostic method for erectile dysfunction?
Gorm Wagner1, Xiaogang Jiang2
1 Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
2 Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
Institute of Preventive Medicine, Copenhagen University Hospital, Øster Søgade 18-1, DK-1357 Copenhagen K
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Corpus cavernosum electromyography (CC-EMG) has been intensively studied as a potential clinical tool for evaluating the function of the cavernous smooth muscle and its autonomic innervations since 1989. Both basic and clinical studies have shown promising results. However, its application as a diagnostic tool with clinical relevance was hindered by insufficient knowledge of cavernous smooth muscle electrophysiology and a series of technical and practical difficulties. Recently, major progress has been made to overcome these difficulties. Multichannel monopolar recording method has been proved to be superior to traditional one or two-channel bipolar recording. Correlation techniques have been applied as a comprehensive, objective and easy-to-use method to analyze CC-EMG recordings. Using these newly developed techniques, CC-EMG has been demonstrated to be discriminative in erectile dysfunction patients with conditions that are associated with cavernous smooth muscle degeneration and/or autonomic neuropathy from men with normal erectile function. However, before CC-EMG can be used as a robust method for erectile dysfunction-diagnostics, some basic and clinical issues are still to be solved. This review presents an overview of the latest advances in CC-EMG studies, mainly focusing on the clinical application of this method as a diagnostic tool. Furthermore, the background knowledge of cavernous electrophysiology, the problems to be overcome and future perspectives are also discussed.
Keywords: CC-EMG, corpus cavernosum, erectile dysfunction
|How to cite this article:|
Wagner G, Jiang X. Corpus cavernosum electromyography, a usable clinical diagnostic method for erectile dysfunction?. Indian J Urol 2006;22:225-30
| Introduction|| |
Penile erection is a complicated neurovascular process, requiring the integrity of penile vasculature, the cavernous smooth muscle (CSM) and the autonomic innervation. As a result of basic science and clinical advances, the diagnosis of erectile dysfunction (ED) has undergone revolutionary improvement over the past two decades. Thanks to the inventions of pharmacotesting and penile-pharmaco duplex ultrasonography, the penile vasculature can be evaluated reliably in a minimally invasive way. However, a noninvasive method to directly investigate the CSM and its autonomic innervation is still lacking. Penile biopsy and a series of neurological tests have been introduced to serve this purpose. However, nowadays these methods are rarely applied by urologists, due to either their invasiveness or limited and unreliable information obtained.,
This major deficit in the diagnosis of ED was first addressed by Wagner et al in 1989 by proposing the registration of electrical activity originating from the corpus cavernosum (CC). Since then this method attracted much attention and was intensively investigated by several investigators.,,, A formal denomination, corpus cavernosum electromyography (CC-EMG), was coined in 1993 at the first standardization workshop. Studies in different institutions indicated that CC-EMG is able to diagnose myo- and neuropathy in patients with specific clinical conditions such as diabetes mellitus, radical prostatectomy and spinal cord lesions.,,,,,, Notwithstanding these promising findings, its application as a diagnostic tool has never reached the level of routine clinical practice due to a series of technical and practical difficulties, which were intensively discussed in a review article published in 2004. Since then some new achievements have been made to overcome these difficulties and to forward the progress of the development of CC-EMG as a useful diagnostic tool for ED.
This review presents an overview of the latest advances in CC-EMG studies, mainly focusing on the clinical application of this method as a diagnostic tool. Furthermore, the background knowledge of cavernous electrophysiology, the problems to be overcome and future perspectives are also discussed.
| Physiology of erection|| |
Penile flaccidity and erection are dependent on contraction and relaxation of the CSM, respectively, which are mainly controlled by the autonomic innervations. The intracellular concentration of free Ca 2+sub ([Ca 2+]i) and the sensitivity of contractile protein to Ca 2+sub are the keys to regulate the CSM tone. Release of norepinephrine from the sympathetic nerve terminals leads to contraction of the CSM resulting from both Ca 2+sub release from intracellular stores and Ca 2+sub influx through L-type voltage-gated Ca 2+sub channels (VGCCs). In addition, spontaneous contractions may contribute to the overall tone of the CSM. Relaxation of the CSM is principally mediated by nitric oxide which is released from both parasympathetic nerves and endothelial cells.
| Materials and methods of CC-EMG|| |
1. Needle and surface CC-EMG
Needle electrodes were firstly used to record CC-EMG signals., Stief et al described that the signals measured by surface electrodes are comparable with needle electrodes. Surface CC-EMG has an obvious advantage that it is completely noninvasive, making this examination highly acceptable to patients as well as investigators. Furthermore, by using surface electrodes, the disturbing signals caused by higher adrenergic tone secondary to insertion of needle electrodes, can be diminished. The main disadvantage of surface electrodes is that they may record sympathetic skin response (SSR)., However, usually SSR is provoked by a different stimulus. Evidence showed that at least under resting conditions without stimulus, the signals recorded with surface electrodes placed on the penile skin only pick up signals that originate from the CC.,
2. Bipolar and monopolar recordings
CC-EMG can be measured bipolarly or monopolarly. The former method measures the potential difference between two monopolar electrodes (or between the two poles of a bipolar electrode) on/in the cavernous bodies. The latter method uses one active electrode on/in the cavernous body and one reference electrode which is not located on the penis. In the literature most investigators performed bipolar recording.,,,,,, Since a bipolar signal is a deduction of potentials between two monopolar electrodes, a substantial part of information may be lost. Furthermore, the signals recorded bipolarly are dependent on the exact location of the electrodes and the interelectrode distance. Because the dimensions of the penis vary widely depending on penile tumescence, it is difficult to fix the interelectrode distance exactly. These problems do not exist in monopolar recording. Although bipolar recording has the advantage that it may reduce unwanted signal components, all the information contained in bipolar recording is present in monopolar recording, since a posthoc bipolar montage scheme can be derived from monopolar raw data, but not vice versa. Moreover, multichannel monopolar recording allows the evaluation of the relation of signals simultaneously recorded at different sites of the penis.
3. Spontaneous and evoked activity
Spontaneous CC-potentials can be recorded during flaccidity in the majority of patients. However, in a number of patients as well as volunteers, none or few CC-potentials can be recorded at rest, most likely due an over-relaxed state of the subject,, although the possibility that in some patients it is caused by structural or functional changes of the sympathetic innervation and/or the CSM cannot be ruled out. Being a complementary measure, in those patients electrical activity evoked by a variety of stimuli can be measured. However, whether the mechanisms underlying spontaneous and evoked activity and their characteristics are the same has to be clarified.
Wagner et al evaluated the global pattern of a whole recording, mainly focusing on appearance and disappearance of CC activity. In addition to the evaluation of the global pattern of the whole recording, Truss and coworkers introduced a method called "SPACE" to analyze individual CC-potentials and define the values of parameters such as amplitude, duration, polyphasity, etc. This method was accepted by several other researchers., However, the values of parameters are measured manually and therefore this method is time-consuming, imprecise and not objective. Later, the same group introduced fast Fourier analysis and computerized classification of CC-potential components by fuzzy logic and neural networks. However, these methods have not been applied by other centers probably because the required basic knowledge of linear systems analysis is generally beyond the expertise of clinical physicians. Jiang et al applied correlation techniques, including autocorrelation and cross-correlaiton, in the analysis of CC-potentials. In neurophysiology, correlation analysis is a well-established methodology to quantify the properties of striated muscle EMG and other bioelectrical signals. By analyzing the original signals and their autocorrelation function, individual CC-potentials can be characterized. The cross - correlation function allows quantifying the similarity of CC-potentials simultaneously recorded at different sites of the CC and estimating their mutual time delay. This method has been demonstrated to be easy-to-use, objective and comprehensive.
| The origin of CC-potential|| |
Since the introduction of CC-EMG, doubts about the origin of the recorded signals have persisted., Whether the signals originate from the penis or other organs, whether the signals reflect electrical activity of the CC or the skin activity and what kind of activity the CC signals stand for need to be clarified.
With electrodes placed on the penis and the other parts of the body, CC-potentials were only recorded from the penis but not from the other parts of the body at rest., Furthermore, by placing several electrodes on the penis and the pubic region close to the penis, clear spatial voltage gradients related to CC-potentials were observed on the pubic region. These evidences strongly indicate that the penis is the origin of the recorded signals. Moreover, CC-potentials recorded at different sites of the penile shaft were not synchronized, but with a clear time delay., This fact provides important evidence that CC-potentials are generated from the penis, since it is common knowledge that signals from a distant source would be synchronous. Finally, the observations that CC-potentials were only recorded from the penis but not from other parts of the body at rest indicate that they are unlikely to be SSR, because SSR is a widespread and not a local phenomenon.
After proving that CC-potentials originate from the penis, the next question to be answered is what activity within the penis the signals reflect. Based on the existent knowledge, it has been supposed that CC-potentials reflect sympathetically medicated activity of the CSM. This theory was supported by the following evidence: by performing CC-EMG during morning naps, Jiang et al observed a consistent disappearance of CC-potentials during tumescence and a reappearance of continuous CC-potential oscillations during detumescence; during flaccidity, CC-potentials appeared together with penile shrinkage. More specifically, CC-potentials were supposed to reflect the summation of membrane currents caused by Ca 2+sub influx through L-type VGCCs of a group of CSM cells, which was evidenced by the finding that a blockage of L-type VGCCs can abolish the electrical activity of rabbit CC strips. However, the contributions of the cross-membrane transportation of other ions cannot be ruled out.
| Results of clinical studies|| |
Studies in healthy volunteers
In the literature there is much debate on what constitutes a normal CC-EMG recording. The recorded signals from different centers only showed some rough similarity but were not sufficient to perform a quantitative comparison. This is at least partly due to the lack of standardization of the measurement and interpretation. Despite these deficits, some characteristics of CC-EMG in normal subjects can be defined. In the beginning of a CC-EMG recording irregular signals are commonly observed and gradually the recordings became stable and regular. The baseline was flat or showed slow wave-like activity, interrupted by the typical spindle-like polyphasic CC-potentials. CC-potentials emerged nonperiodically and the quality of the recordings and the frequency of CC-potentials seemed to be stress-dependent: the more relaxed the subject is, the better quality of the recordings and the fewer CC-potentials. The maximum peak to peak amplitude varies around a mean of 350 mV. The duration of CC-potential varies around a mean of 12 seconds. In multichannel measurements CC-potentials from different parts of the penis appeared within a short timeframe and their waveforms were similar. [Figure - 1] shows a recording in a healthy young man. It is noteworthy that some normal subjects showed "abnormal" recordings: either almost no potential or irregular signals were observed. 0 Most likely an over-relaxed state of the subject is the reason that few CC-potentials, while irregular signals are supposed to be caused by an elevated sympathetic tone due to stress, movement artifacts or a faulty connection of the electrodes.,,,
Dramatic changes of potentials are observed during tumescence and erection induced by audiovisual sexual stimulation; with increasing tumescence and rigidity, an increase of frequency of the potentials with a simultaneous decrease of amplitude and polyphasity is seen. During full erection, potentials with low amplitude but high frequency can still be recorded., In contrast, no potential ("electrical silence") is recorded during spontaneous erection in sleep. Presumably, during audiovisually induced erection the sympathetically mediated activity of the CSM has not completely switched off due to nervousness, embarrassment and distraction. Nonetheless, as long as parasympathetic input is strong enough to overwhelm sympathetic activity, erection still occurs.
Patient with ED
Knowing that the CSM is the source of the electrical activity recorded as CC-potentials and that this activity is mainly controlled by the autonomic input one would expect that specific clinical conditions associated with CSM loss and/or neuropathy go along with specific CC-EMG changes. Available results of clinical study in the literature have fitted in with this hypothesis.
- Patients with conditions associated with CSM degeneration Since CC-potentials are supposed to reflect the summation of membrane current of a group of CSM cells, a decrease in CSM content may lead to a decrease in CC-potential amplitude. A correlation between CSM content and amplitude of CC-potentials has been demonstrated before by Sattar et al . Jiang et al reported that 13 out of the 14 patients with severe penile fibrosis caused by priapism or an implant and removal of penile prosthesis did not show any distinguishable CC-potentials. This was in line with the finding of Merckx et al that a postpriapsm ED patient did not show any CC-potentials. It should be noted that the absence of detectable CC-potentials does not necessarily represent a total "electrical silence", but that the CC-potentials are too weak to be distinguished from baseline fluctuations. In the literature penile (ultra)structure analyses have demonstrated that patients with cavernous arterial insufficiency (CAI) showed signs of CSM degeneration (penile fibrosis). Interestingly, patients with proven CAI had a significantly decreased CC-potential amplitude [Figure - 2].
- Patients with conditions associated with peripheral autonomic nerve damage Truss et al observed that patients following radical prostatectomy showed CC-potentials of low amplitude, high frequency, irregular periodicity and asynchronism. Some patients showed abnormal as well as normal potentials, especially patients after nerve-sparing radical prostatectomy, suggestive of partially disrupted peripheral autonomic supply. Sasso et al demonstrated that following radical cystoprostatectomy, the impotent patients showed a typical pattern of low-amplitude/low-frequency potentials, whereas after nerve-sparing cystoprostatectomy, all of the impotent patients showed mean amplitude similar to controls. Consistent to the previous study, Jiang et al found that patients following radical prostatectomy had a lower CC-potential amplitude and decreased coordination of CC-potentials recorded from different parts of the penis [Figure - 3]. The disruption of the autonomic input as well as CSM degeneration with loss of gap junctions secondary to nerve damage may be responsible for such changes.
- Patients with conditions associated with spinal cord lesions Compared to the patients with peripheral autonomic neuropathy, patients with spinal cord lesions showed more variable patterns of CC-EMG recordings. Truss et al reported that abnormal potentials and "whips" as well as rather normal looking potentials were observed in patients with spinal cord injury. Jiang et al did not detect any significant change in any parameters in the patients with spinal cord lesions. This may be caused by the fact that the location and extent of neurogenic damage of the patients were variable. Since the sympathetic pathway originates from the eleventh thoracic to the second lumber spinal segments, while the parasympathetic pathway arises from the second, third and fourth sacral spinal cord segments, theoretically it is possible that patients with spinal cord lesions have normal sympathetically mediated activity, but impaired parasympathetically mediated activity or vice versa.
| Problems and future perspectives|| |
After addressing methodological and practical issues hindering the clinical application of CC-EMG, still a number of basic questions as well as some clinical issues need to be clarified before CC-EMG can be used as a robust clinical tool.
First, although in vitro studies indicate that membrane currents caused by Ca 2+sub influx through L-type VGCCs of CSM cells represent a source of CC-potentials, convincing evidence from in vivo study is still lacking. Furthermore, the contribution of other ion currents to CC-potentials remains unclear. With regard to the concept of coordination and propagation of electrical activity, the autonomic innervation and gap junctions are believed to play an important role. However, our understanding about the detailed mechanisms of signal initiation, propagation and coordination within the CC is still incomplete, making precise interpretation of CC-EMG recordings difficult. For example, how the changes in the function of sympathetic nerves and gap junctions affect the coordination of electrical activity at different sites of the CC and whether or not a linear relation between CSM content and CC-potential amplitude exists needs to be clarified. We believe that animal models are necessary to study these fundamental questions. Animal studies have the advantage that a variety of interventions can be employed, which are impossible in human studies.
Second, as a major shortcoming of CC-EMG study, the fact that a "gold standard" to precisely determine the etiology of ED is unavailable makes the validation of CC-EMG difficult. Penile-pharmaco duplex ultrasonography is one of few objective methods widely accepted for diagnosing vasculogenic factors, although its sensitivity and specificity are not 100%. Penile structural analysis would be the best method to validate CC-EMG,, however, nowadays penile biopsy is not feasible due to its invasiveness. Therefore, the physician's judgment based on the clinical findings plays an important role in classifying the ED patients.
Third, to define normative data and cut-off values of the parameters a larger number of patients and potent men is required. Patients should be further catalogued according to the type, duration and adjustment of co-morbidity or conditions that are associated with ED; unilateral, bilateral or non"nerve sparing" techniques during the RRP; and the location and extent of neuropathy, allowing more precisely determining CC-EMG patterns in different clinical conditions.
And finally, to our knowledge presently there is only minimal research activity on CC-EMG going on and studies at different centers are poorly coordinated. The presence of aforementioned difficulties hindering the clinical application of CC-EMG is a major reason that only a few groups are still active in this field. Furthermore, in the oral medication era many patients with ED can be treated without knowing the exact etiology and, therefore, the need of specific examinations such as CC-EMG has decreased. We believe that by solving those difficulties and making CC-EMG objective and easy to use, this method will be widely accepted and play a unique role in the management of ED. To reach this goal, obviously a better coordination among different centers is warranted.
| Conclusion|| |
Considering the fact that a valid and noninvasive method to evaluate the CSM and its autonomic innervations is still lacking, CC-EMG still seems to be of major interest to be developed further. The recent advances in this field bring CC-EMG closer to be a useful clinical tool than ever before. However, before CC-EMG can be used as a robust method for ED-diagnostics, some basic and clinical issues still remain to be resolved.
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[Figure - 1], [Figure - 2], [Figure - 3]