International Journal of Impotence Research (2009) 21, 301–305 & 2009 Nature Publishing Group All rights reserved 0955-9930/09 $32.00 www.nature.com/ijir ORIGINAL ARTICLE Evoked cavernous activity: neuroanatomic implications U Yilmaz1, B Vicars1 and CC Yang1,2 1Department of Urology, University of Washington, Seattle, WA, USA and 2VA Puget Sound Healthcare System, Seattle, WA, USA We investigated the autonomic innervation of the penis by using evoked cavernous activity (ECA). We recruited seven men with thoracic spinal cord injury (SCI) and sexual dysfunction, and six men who were scheduled to have pelvic surgery (PS), specifically non-nerve-sparing radical cystoprostatectomy. In the PS patients, ECA was performed both pre- and postoperatively. The left median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. In the SCI group, all but one patient had reproducible hand SSRs. None of these patients had ECA or foot SSRs. All the PS patients had reproducible ECA and SSRs, both preoperatively and postoperatively. There was no difference in the latency and amplitude measurements of ECA and SSRs in the postoperative compared with that of the pre-operative period (P40.05). In conclusion, ECA is absent in men with SCI above the sympathetic outflow to the genitalia. In men, after radical pelvic surgery, ECA is preserved, indicating the preservation of sympathetic fibers. International Journal of Impotence Research (2009) 21, 301–305; doi:10.1038/ijir.2009.34; published online 16 July 2009 Keywords: ECA; autonomic nerve; electrodiagnostic test; erectile dysfunction; penis Introduction more, there are no direct measures of parasym- pathetic function for the penis. Intact autonomic neural pathways are prerequisites In earlier studies, we showed the absence of for the vascular changes during erection and ECA in men with dysautonomias2 and in most men detumescence, with signals traveling through the after non-nerve-sparing radical pelvic surgery.4 The spinal cord tracts, the pelvic and hypogastric absence of ECA was interpreted as the disruption plexuses, and the cavernous nerves. Only a few of sympathetic innervation to the corpora, which tests exist to assess the autonomic components of was presumed to affect the erectile function. We genital innervation. One autonomic testing tech- conducted this study to further investigate the nique called evoked cavernous activity (ECA) autonomic innervation of the penis and the associa- measures intrapenile electrical activity after a brief tion to erectile function by using ECA to evaluate noxious stimulus. An applied noxious stimulus two groups of men with erectile dysfunction (ED): results in a generalized, sympathetic nervous system one cohort with ED from central nervous system discharge that manifests throughout the body, disruption due to spinal cord injury (SCI), and one including the corpus cavernosum.1,2 In healthy, group with peripheral (cavernous) nerve disruption potent men of varying ages, ECA is seen with due to pelvic surgery (PS). Our hypothesis was that consistent latency measurements.3 Although the either peripheral or central injury to the autonomic sympathetic discharge mediates corporal vaso- innervation to the penis would result in loss of constriction, and thus is anti-erectile, it is still a ECA. This result would be the basis from reflection of overall autonomic innervation. Further- which ECA could be used as a diagnostic test for neurogenic ED. Correspondence: Dr CC Yang, Department of Urology, University of Washington, Box 356510, Seattle, WA 98195- Methods 6510, USA. E-mail [email protected] After the study protocol approval by the Human Received 22 April 2009; revised 15 June 2009; accepted 15 Subjects Review Committee of our hospital, we June 2009; published online 16 July 2009 recruited seven men with complete thoracic SCI and ECA: neuroanatomic considerations U Yilmaz et al 302 Figure 1 (a) Diagram of evoked cavernous activity (ECA) reflex. Afferent signals travel through the median nerve to the CNS. The resultant sympathetic discharge is manifested throughout the body, including the erectile tissue. (b) Waveforms of ECA and sympathetic skin responses (SSRs) of a pelvic surgery patient in the pre-operative period. The stimulus is delivered at time 0 and the latency is measured between 0 and L, whereas the amplitudes are measured from the peak of the first deflection to the peak of the after (opposite) deflection. The time-base is 1 s per division, and the entire trace measures 10 s. sexual dysfunction, and six men who were scheduled If ECA was present after the first six stimuli, then for PS, specifically non-nerve-sparing radical cysto- no further stimuli were given. If ECA was not readily prostatectomy. All men in the PS group were sexually identifiable after all of the first six stimuli, then active preoperatively. Exclusion criteria for all groups more stimuli were delivered, up to a total of 12. included moderate to severe cardiovascular disease, The latency was measured at the first deflection diabetes mellitus, untreated hypertension, current from baseline after the stimulus delivery, and drug or alcohol abuse, major psychiatric disorder, amplitude measurements were made peak to peak. and unwillingness or inability to complete the Three responses were averaged for final latency questionnaire. Except for spinal cord injury, there and amplitude values. Sympathetic skin responses was no evidence of other neurological disease. (SSRs) were measured simultaneously from the Each participant underwent a history and hand and foot contralateral to the median nerve physical examination, with a detailed urological stimulus. SSRs are slow wave recordings that are and neurological examination of extremities and temporally related to ECA and share similar wave- genitalia. forms (Figure 1). These responses were recorded as a All participants completed the International In- control for the presence of a generalized sympa- dex of Erectile Function (IIEF) questionnaire5 before thetic discharge. Latency and amplitude measure- ECA testing. In the PS group, ECA was performed ments of the SSRs from the hand and foot were preoperatively and at the third post-operative month measured in a standard manner.6 visit. Statistical analyses ECA testing The groups were compared using the Kruskal– The electrodiagnostic technique for ECA was pre- Wallis and Mann–Whitney U-tests. In the PS group, viously described.2–4 Briefly, a noxious stimulus the parameters were also compared between the was delivered to the median nerve on the left wrist pre-operative and post-operative periods using the from a Viking IV electrophysiology machine (Viasys Wilcoxon test. Healthcare, Madison, WI, USA) with the participant in the supine position. The stimulus amplitude was 5–7 mA, duration 0.5 ms, and delivered at irregular Results intervals of at least 60 s in to avoid habituation. ECA was recorded from both corpora cavernosa through All participants tolerated the procedure well. concentric 28-gauge gold-plated needle electrodes Average age of the SCI group was younger than the ± ± (20-mm long, 0.4-mm diameter, Nicolet Biomedical PS group (34.7 7.6 years vs 59.1 5.6 years, Inc., WI, USA) placed into the corpora at the lateral Po0.001). aspects at the base of the penis, with the tip of the electrodes positioned in the center of each corporal body. The band-pass filters were set to 0.5–100 Hz. A IIEF ground plate was affixed to the skin overlying the The results of the erectile domain of the IIEF were right anterior/superior iliac crest. tabulated (Table 1). The post-operative PS IIEF and International Journal of Impotence Research ECA: neuroanatomic considerations U Yilmaz et al 303 Table 1 Mean ECA amplitude and latency measurements PS group (n ¼ 6) SCI group (n ¼ 7) Preoperative Postoperative Mean (s.d.) Mean (s.d.) Mean (s.d.) Latency (ms) Right ECA 1841 (405) 2212.2 (1100) No response Left ECA 1842 (437) 1725 (185) No response Hand SSR 1692 (184) 1675 (360) 1716 (170) Foot SSR 2071 (98) 2577 (1383) No response Amplitude (mV) Right ECA 295 (140) 493 (592) No response Left ECA 288 (238) 451 (577) No response Hand SSR 2670 (2366) 1763 (854) 2793 (2187) Foot SSR 1658 (1136) 1870 (1298) No response IIEF, erectile domain (total possible score ¼ 30) 16.3 (5.6) 5.6 (6.5) 10.7 (10.3) Abbreviations: ECA, evoked cavernous activity; IIEF, International Index of Erectile Function; PS, pelvic surgery group; SCI, spinal cord injury; SSR, sympathetic skin response. Figure 2 Evoked cavernous activity (ECA) in patient with spinal cord injury. (a) Diagram of disrupted ECA reflex and (b) ECA waveforms. Note the absence of activity in both corpora cavernosa and foot sympathetic skin response (SSR). Deflections off the baseline before 1 s in the right ECA and foot SSR trace are artefact. Stimulus is delivered at time 0. The time-base is 1 s per division, and the entire trace measures 10 s. Amplitude sensitivities are set higher than those in Figure 1. SCI IIEF scores were not statistically different from dry skin, and thus ECA was not recordable. None each other (P ¼ 0.268). of the individuals with SCI had foot SSRs or ECA (Figure 2). ECA All the PS patients had reproducible ECA and SSRs, Discussion both preoperatively and postoperatively (Figure 1). There was no difference in the latency and ampli- Evoked cavernous activity is a measure of sympa- tude measurements of ECA and SSRs in the post- thetic (autonomic) discharge in the erectile tissue of operative compared with that of the pre-operative the penis. In this study, we examined the measure- period (Table 1, P40.05). Both pre-operative and ments in men with ED due to central nervous system post-operative values were within the normal disruption from spinal cord injury, and men with ED limits.3 Despite the reported loss of erectile function due to peripheral (cavernous) nerve disruption after in the post-surgery group, there was not a corres- radical pelvic surgery.