Francois Giuliano MD, PhD and David L. Rowland, PhD
ONLINE: April 11, 2013 – The Journal of Sexual Medicine
DOI: 10.1111/jsm.12164
Neurophysiological Assessment of Erectile Dysfunction (ED)
To assess erectile dysfunction, standard operating procedure should include:
• Investigation of the neural control of the tone of smooth muscle cells of the erectile tissue and the penile arterial supply
• Assessment of penile sensory innervation
Bulbocarvernosus Reflex (BCR) Latency Time
Rationale and Method
The dorsal penile nerve and pudendal nerve are important for conveying most penile sensory information. This method assesses the integrity of the afferent-somatic efferent- penile reflex arc.
BCR is measured by placing needle electrodes into the bulbocarvernosus muscles. A ring electrode is placed on the distal penile shaft. Stimuli are applied every 40-60 seconds and 10 consecutive responses are recorded. Missing reflexes or latency above 45 milliseconds indicate pathology.
Pudendal Somatosensory Evoked Potentials (P-SSEPs)
Rationale and Method
P-SSEPs assess the degree of involvement of the spinal dorsal funiculi so that the integrity/lesion of the afferent sensory spinal pathways may be analyzed. They are measured through electrical stimulation using ring electrodes on the penis. Latency times are recorded using two scalp electrodes. Then, two sets of 500 responses are averaged and superimposed.
Results for BCR and P-SSEP
In past studies:
• 50% of 130 men with ED had pathologic BCR patterns.
• 31% of 116 men with ED had pathologic P-SSEP results.
• 66% of 130 patients had neurophysiologic abnormalities.
• 47% of 123 patients had pathologic results on various neurophysiologic tests.
Sympathetic Skin Response (SSR)
Rationale and Method
SSR is a multisynaptic somatic sympathetic reflex with long latency. Central control is found in the brain. It is recorded to assess the efferent outflow of the spinal sympathetic tract. The test uses a somatic afferent/sympathetic reflex that activates sweat gland secretion.
To record SSR, surface electrodes are attached to the right hand, right foot, perineum, and suprapubic area. Electrical stimulation is then applied. Normal SSR can be reliably reproduced three consecutive times with the typical latencies of 1.4-1.7 seconds at the palms and 2.2-2.7 seconds at the feet.
Results
Past research has shown that SSR was considerably lower on the penis than on the hand or on the sole. There was a good correlation with the validated International Index of Erectile Function-5 score, but no correlation with neuropathy. This suggests that ED may be a “sentinel symptom” in patients with autonomic abnormalities.
Corpus Cavernosum Electromyography (CC-EMG)
Rationale and Method
Scientists have tried using corpus CC-EMG to assess penile autonomic innervation and the cavernous smooth muscle. This had been difficult, however, since recording techniques had not been standardized and there had been no objective criteria to analyze recorded signals. Revised recording and interpretation methods have simplified this process.
Results
The revised method of performing corpus CC-EMG appears to be able to discriminate ED patients with conditions that are associated with cavernous smooth muscle degeneration and/or autonomic neuropathy from men with reported normal erectile function. The test can detect abnormalities, but such abnormalities may be caused by damage to autonomic penile innervation and degenerative processes of the cavernous smooth muscle.
Neurophysiological Assessment of ED: General Comment and Conclusion
BCR, P-SSEP, and SSR are not recommended for assessing ED patients because there are no agreed-upon standard criteria and no standardized methodology. None of these procedures can assess the integrity of the efferent parasympathetic penile innervation.
CC-EMG is still an experimental – and not routine – procedure for evaluating ED etiology, as there are still no general accepted standard criteria for distinguishing among normal, pathologic, and etiologic ED forms.
Neurophysiological Assessment of Premature Ejaculation (PE)
PE may be assessed by a number of procedures that examine the ejaculatory reflex, which is almost always triggered by direct penile stimulation, involving both somatic (qualitative and quantitative awareness of the stimulation) and autonomic (erotogenic nature of the stimulation) responses.
Penile Sensitivity
Rationale and Method
Clinical observations and the physiology of the somatic nervous system have led to the assumption that men with PE have greater penile sensitivity. Men with PE sometimes say their penis is hypersensitive and there is an assumption that they might have a lower sensory threshold that causes them to ejaculate more quickly. Topical anesthetics are (incorrectly) believed to counter this hypersensitivity.
Standard psychophysical scaling can help determine penile thresholds. Stimuli may be presented in order of magnitude or in random order. Biased-free procedures (such as forced choice methodology) are superior, but few studies have used them.
To determine a threshold, the mean of several crossings should be calculated. Vibrotactile stimulation must vary in intensity and be either perpendicular or lateral to the surface of the skin. Frequency of vibration of stimuli should also vary. To date, there are no standards for setting the parameters of vibrotactile stimulation.
There is also no agreement on where vibrotactile stimulation should be applied. Most studies have used the glans penis but others have used non-glans areas.
Results
Past studies have investigated vibrotactile stimulation in different penile locations in different populations of men. Penile sensitivity appears to be substantially decreased in aging men, diabetic men, and men with ED.
Studies comparing men with PE to men without PE have had ambiguous results. In one study, there was no difference in vibrotactile thresholds and a subgroup of men who had both PE and ED had a higher threshold. They had low sensitivity, but rapid ejaculation.
In contrast, another study found lower thresholds in a PE group. But subsequent studies have not shown that men with PE typically have penile sensitivity. One found no difference in threshold when comparing men with PE and men without PE. Another found either hyposensitivity or similar sensitivity when comparing the two groups.
Comment and Conclusion
Men with PE may believe they have penile hypersensitivity, but research has not confirmed this. Therefore, penile sensitivity cannot be used to diagnose PE.
The authors were not surprised by these findings, as penile surface receptors are not necessarily involved with the ejaculatory reflex. However, using topical anesthetics to treat PE may make sense because this can still increase latency time to ejaculation.
Other Components of the Penile Sensory Pathways
Rationale and Method
Even though penile sensitivity does not appear to be much involved with PE, other components of the afferent sensory pathways, such as EPs, could be. SSEPs, which come from touch sensation, measure how quickly and completely the neural signal reaches the brain. Usually electrical stimulation of peripheral nerves yields the most effective responses. Experimental manipulation, neuropathy, and aging may affect SSEP parameters. This procedure can assess latency and amplitude of the wave as well as interwave latency and latency asymmetry.
For PE, researchers speculate that a more sensitive pathway between the penis and brain might have decreased latency or increased amplitude of the cortical SSEP wave.
Results
Two studies have investigated SSEPs in response to stimulation of the pudendal nerve (or its dorsal nerve branch). One showed both decreased latency and increased amplitude in cortical SSEPs in men with PE compared to controls. The other showed only increased amplitude.
A study examining event-related potentials (ERPs) to auditory stimulation found longer latencies in men with PE, but the meaning of this is unclear. A suggested explanation that “men with PE take longer time to evaluate and categorize stimuli” is tenuous.
A 2002 study found no differences in either latency or amplitude of SSEPs in men with PE compared to controls.
Comment and Conclusion
Because research is sparse and results are inconsistent, SSEP analysis is not an appropriate method for assessing PE. Also, this invasive procedure is not cost-effective because of the labor and technology involved. However, it is still a worthwhile procedure for research.
Research on SSEP analysis has uncovered two interesting findings. First, topical anesthetic creams have increased the latency of the SSEP wave in men with PE, so they appear to directly affect the penile sensory pathways. Second, clomipramine does not affect SSEP latency or amplitude, suggesting that serotonin reuptake inhibitors influence central mechanisms instead of afferent spinal ones.
Reflex Motor Pathways
Rationale and Method
Some studies have measured EPs related to BCR to examine the motor component of the ejaculatory response. This reflex is related to seminal expulsion. Men with PE might have greater motor responsiveness (hyperexcitability) with ejaculation than men without PE.
Results
Studies on this procedure have found:
• Differences in the amplitude of EPs related to BCR
• Differences in sensory thresholds required to evoke BCR, but not in the latencies of the response
• No differences in motor EPs or BCR
Comment and Conclusion
Findings on EPs related to BCR are insufficient and inconsistent. Therefore, this procedure is not appropriate for diagnosing PE.
Disturbance of Central Serotonergic Neurotransmission
Rationale
Some studies report that selective serotonin reuptake inhibitors (SSRIs) delay ejaculation and suggest that men with PE have a problem with the central serotonergic system.
This idea is skewed for several reasons:
• Other neurotransmitter systems play a role in ejaculatory response and the problem could be with any of those systems.
• SSRIs delay ejaculation in all men, not just those with PE. Therefore, SSRIs are probably interfering with the ejaculatory process, not “correcting” a problem in the ejaculatory reflex.
• The ejaculatory threshold is influenced by the level of sexual arousal. So, it is difficult to know whether men with PE have a lower threshold or are more likely to exceed the threshold because they are more aroused.
Several studies have found that SSRIs both decrease arousal and inhibit ejaculation. However, the serotonergic explanation remains prominent because competing hypotheses have not been developed.
There are currently no neurophysiological assessments that detect anomalies in serotonergic synthesis, release, or reuptake. There are also no assessments (in living organisms) that look for irregularities in presynaptic or postsynaptic receptor numbers or sensitivity that could distinguish men with PE from those without PE.
Neurophysiological Assessment of PE: General Comment and Conclusion
To date, no neurophysiological assessments give us additional information that can consistently help diagnose PE. The most relevant diagnostic data can come from a man’s ejaculatory latency, his ability to delay or control ejaculation, and his level of distress.
Overall Conclusion
Specific neurophysiological assessments are helpful for research and may effectively distinguish groups of men. However, they are not helpful for diagnosis because of the time, cost, and effort involved, along with their lack of reliability. They are not recommended as part of the standard operating procedure to diagnose either ED or PE.