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The application of intraoperative neurophysiological monitoring in selective dorsal neurotomy for primary premature ejaculation: a prospective single-center study

1 Department of Andrology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing 210008, China
2 Department of Urology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China
3 Department of Pathology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China
4 Department of Pathology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing 210008, China

Date of Submission02-Sep-2021
Date of Acceptance24-Feb-2022
Date of Web Publication22-Apr-2022

Correspondence Address:
Yu-Tian Dai,
Department of Andrology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing 210008

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aja202211


Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.

Keywords: intraoperative neurophysiological monitoring; primary premature ejaculation; selective dorsal neurotomy

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How to cite this URL:
Tang QL, Song T, Han YF, Yang BB, Chen JH, Xu ZP, Xu CL, Xu Y, Yu W, Qiu W, Shi J, Zhang ES, Dai YT. The application of intraoperative neurophysiological monitoring in selective dorsal neurotomy for primary premature ejaculation: a prospective single-center study. Asian J Androl [Epub ahead of print] [cited 2022 May 21]. Available from: https://www.ajandrology.com/preprintarticle.asp?id=343768

Qing-Lai Tang, Tao Song
These authors contributed equally to this work.

  Introduction Top

As the most common male sexual dysfunction, premature ejaculation (PE) seriously affects approximately 20%–30% men's sexual life worldwide.[1] PE is traditionally divided into primary or life-long PE (PPE/LPE) and secondary or acquired PE (SPE/APE). In patients with PPE, ejaculation occurs within about 1 min after vaginal insertion, even before sexual intercourse.[2] PE patients are empirically treated with psychological/behavioral therapy, selective serotonin reuptake inhibitors (SSRIs), phosphodiesterase 5 inhibitors (PDE5is), and local anesthetics.[2],[3],[4] However, if empirical therapies did not show good efficacy, some patients with PPE would choose to undergo surgery.

In recent years, selective dorsal neurotomy (SDN) has become more common in several Asian countries as a treatment for PE. According to the report from Alyaev and Akhvlediani,[5] SDN could effectively prolong the intravaginal ejaculation latency time (IELT) and improve the satisfaction of 88% patients with PPE. Another survey by the Korean Society for Sexual Medicine and Andrology (KSSMA) showed that 96.6% of patients were satisfied with SND.[6] However, few clinical studies have reported the long-term efficacy of the surgery. One study found that 11.8% of the patients who underwent SDN had complications including glans penis pain and discomfort (4.9%), penile edema (4.2%), surgical incision rupture (2.1%), and delayed ejaculation (0.6%).[7] Therefore, it is essential to control the degree of resection in SDN and balance long-term efficacy with safety.

In recent years, penile neurophysiological tests for PE, usually involving measurement of the penile sensory-evoked potential (PSEP) represented by the glans penis sensory-evoked potential (GPSEP), dorsal nerve sensory-evoked potential (DNSEP), and penile sympathetic skin response (PSSR), have attracted interest in the diagnosis and evaluation of PE. In our previous study, we proposed a new classification system for PE based on the results of penile neurophysiological testing in PE patients.[8] According to this classification system, PE can be divided into the following four types: penile sensory hyperexcitability (with abnormal PSEP and normal PSSR), penile sympathetic hyperexcitability (with abnormal PSSR and normal PSEP), mixed type (with abnormal PSEP and PSSR), and other type (with normal PSEP and PSSR).[9] The specialist consensus of treating PE included the value of penile neurophysiological tests in the preoperative diagnosis and evaluation, as well as indications for SDN, for PE patients.

In recent years, multimodal intraoperative neurophysiological monitoring (IONM) can be used to identify intraoperative neurological insults to minimize irreversible damage to the neural tissue and prevent postoperative neurologic deficits. It has been applied to effectively avoid permanent neurologic damage from surgery in orthopedics and neurosurgery.[10],[11],[12],[13] Thus, we wonder if IONM could be applied during SDN to guide the surgery. In this study, we introduced IONM into SDN and selected the DNSEP, which can be monitored during surgery, as the main outcome measurement.

  Patients and Methods Top


All patients were consecutively enrolled from the Department of Andrology in Nanjing Drum Tower Hospital (Nanjing, China) from October 2017 to December 2020. One hundred and twenty patients with penile sensory hyperexcitability type of PPE were enrolled. They were previously provided local anesthetics or condoms according to the classification by our previous study[9] and showed good effect of prolonging IELT (≥300 s), but these patients did not want to continue to use or could not use them consistently, and they had a strong desire to undergo SDN. The 120 PE patients were randomly divided into the IONM group and the non-IONM group. One hundred and twenty patients without PE who would undergo high ligation of spermatic vein were enrolled as the normal group for the control of parameters. DNSEP detection was performed before surgery and when each nerve branch was removed until the end of the surgery, while DNSEP detection was only performed twice for non-IONM group and the normal group before and after general anesthesia (GA). Flow chart of this study design is shown in [Supplementary Figure 1]. The study complied with the Declaration of Helsinki and was approved by the ethics committee of Nanjing Drum Tower Hospital (No. 2015-053-01). All patients signed written informed consent.

The inclusion criteria for all patients were as follows: (1) a stable, heterosexual relationship lasting >6 months and frequency of sexual activity >6 times per month in the past three months; (2) normal secondary sexual signs and sexual organs; and (3) International Index of Erectile Function-5 (IIEF-5) questionnaire score >21. Additional inclusion criteria for the normal group were as follows: (1) premature ejaculation diagnostic tool (PEDT) score <8 and IELT >180 s (the average of three ejaculations, recorded with stopwatch by the sexual partner); and (2) normal results of penile neurophysiological tests. Additional inclusion criteria for the PE group were as follows: (1) age more than 19 years; (2) PEDT score >11 and IELT <60 s; (3) abnormal PSEP (GPSEP latency <40.83 ms and/or DNSEP latency <39.03 ms) and normal PSSR (latency ≥1184.6 ms);[9] (4) significant effective (IELT ≥300 s) when using topical anesthetics or condoms, but not intending to continue to use or unable to use them consistently; and (5) strong willingness to undergo SDN.

The exclusion criteria for all participants were as follows: (1) systemic diseases such as mental illness, serious cardiovascular and cerebrovascular diseases, liver and kidney dysfunction, malignant tumors, endocrinopathies (e.g., diabetes mellitus, hypo- or hyperthyroidism, hyperprolactinemia, etc.), or sleep disorders; (2) spinal cord injury, genitourinary tract injury, inflammation, or genital malformations; (3) alcohol abuse, recreational drug use, or “male performance” supplements; (4) other sexual dysfunction; (5) wash-out period of drug >2 weeks; or (6) any contraindications for SDN.

Neurophysiological tests

As shown in [Figure 1], the equipment for neurophysiological tests was as follows: (1) Nicolet™ EDX electromyography/evoked potential system (Natus Medical Incorporated, Middleton, WI, USA); (2) surface electrodes (SEAg-J-22*32, Xi'an Friendship Medical Electronics Co., Ltd., Xi'an, China); (3) ring electrodes, alligator-clip wires (Natus, Galway, Ireland); and (4) grounding wires (VIASYS Healthcare, Houten, The Netherlands). Methods for measuring the PSSR and PSEP were previously described in Yang et al.'s[9] study (PSSR and PSEP waveforms are shown in [Figure 2]).
Figure 1: Electromyography/evoked potential system and materials. (a) Electromyography/evoked potential system; (b) disk-shaped electrodes; (c) grounding electrodes; (d) surface electrode wires; (e) surface electrode slices; (f) ring electrodes; and (g) stimulating electrodes.

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Figure 2: Penile skin sympathetic response and penile somatosensory-evoked potential waveforms and parameters. (a) PSSR and (b) GPSEP+DNSEP. PSSR: penile sympathetic skin response; GPSEP: glans penis sensory-evoked potential; DNSEP: dorsal nerve sensory-evoked potential; SEP: sensory-evoked potential; N-R: normal-repeat; Lat: latency; Amp: amplitude; ARM-R: arm-right.

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SDN procedures and IONM-DNSEP monitoring

Carl-Zeiss VARIO S88 surgical microscope (Carl Zeiss AG, Oberkochen, Germany) was used in SDN. For the non-IONM group, SDN procedures were conducted. First, the skin was circumferentially incised 0.8–1.5 cm below the coronal sulcus of the penis. After separating the fascia layer by layer, the microscope was moved into the field of vision. Branches of the dorsal nerve of the penis (DNP; slightly yellow, elastic, and rich in blood vessels on the surface, with a transverse diameter of approximately 0.2–1.5 mm; [Figure 3]) were exposed on the surface of the tunica albuginea. The exposed branches were parted from the midline (the 12 o'clock position) to either side using fine-tipped tweezers and micro-mosquito separation forceps until they reached the corpus cavernosum and the urethra at the ventral side of the penis. Each branch to be removed was marked by a silk thread. At least one branch (diameter greater than 1.5 mm) of the DNP was preserved on each side of the deep dorsal artery. Other branches were removed at least 2 cm towards the distal end.
Figure 3: Intraoperative neurophysiological monitoring. (a) Neurophysiological monitoring in SDN under microscope; (b) dissociating the branches of dorsal penile nerve under microscope; and (c) intraoperative anesthesia depth monitoring. SDN: selective dorsal neurotomy.

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For the IONM group, the same operative procedures were conducted. After the complete separation of the DNP branches during the surgery, DNSEP monitoring was performed for each nerve branch to be removed. The latency of DNSEP was horizontally compared with that of the same-height patient in the normal group under GA in real time and was also longitudinally compared with the same patient's latency under GA before the surgical procedure. Since the range of bilateral medical reference values for normal distribution is the mean ± 1.96 times the standard deviation (s.d.), the value “1.96 times the standard deviation of the DNSEP latency in healthy men” from our previous study was taken as one of the diagnostic criteria for peripheral premature ejaculation,[12] and the deviation value was approximately 10% of the measured value. Therefore, the longitudinal comparison criterion was set at “over 10% of the measured value under GA”. When the latency of DNSEP was in the range of the longitudinal or horizontal comparison, the resection was suspended. In real-time monitoring, if the value did not reach the standard, the nerve branches were removed one by one until either of the criteria was met. However, regardless of whether the latency met the above two criteria, at least one branch of DNP on either side was retained before the end of surgery to ensure safety in SDN [Figure 3].

Clinical evaluation

IELT (recorded with stopwatch by the sexual partner), PEDT score, premature ejaculation profile (PEP) score and IIEF-5 score were collected from all patients and compared before and 3 months after the surgery. IELT was evaluated 3 months after SDN, and the average value of three IELT measurements was taken. An IELT ≥300 s was considered as significantly effective, IELT ≥120 s and <300 s as effective, and IELT <120 s as ineffective. The operative duration, intraoperative blood loss, and postoperative complications (mainly penile head paraesthesia and decreased erectile function) were recorded, and the Freiburg Index of Patient Satisfaction (FIPS) was surveyed with a score of 1–6 (excellent to very poor)[14] for intergroup comparison and analysis.

Statistical analyses

SPSS 22.0 software (SPSS, Chicago, IL, USA) was used for data analysis. First, the Shapiro-Wilk test was used to test the normality of the initial data. Continuous data following normal distribution were expressed as mean ± s.d., and Student's t-test was used for comparison between two groups. Data not following a normal distribution were expressed as median (interquartile range [IQR]), and the Mann-Whitney U test was used for comparison. Chi-square test and Wilcoxon rank sum test were used for counting data. Z-test was used for testing two proportions with the unpooled variance and power was computed using the normal approximation method by PASS 15.0.5 (NCSS, Kaysville, UT, USA).

  Results Top

Comparison of PSEP between groups under natural and GA states

PSEP waveforms were stable in all 240 patients (both the normal group and PE group) under natural and GA states. A comparison of general data and electrophysiological values between the normal group and PE group is shown in [Table 1]. There were significant differences in the DNSEP and GPSEP latency values between the PE group and normal group, as well as between the GA and natural states (P < 0.001).
Table 1: Comparison of general data and electrophysiological values between normal group and PE group

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Differences of PSEP between PE groups with and without IONM

The preoperative general data of the IONM group and non-IONM group showed no significant differences in age, body mass index (BMI), etc. SDN using microscope was successfully performed in all PPE patients under GA. In the IONM group, 91.7% (55/60) of the patients showed stable DNSEP waveforms and gradually prolonged DNSEP latency, including 4 patients who were still unable to reach the longitudinal reference standard even when only 2 branches of the DNP were remained. During one-by-one nerve branch resection, 5 patients showed unstable waveforms or irregular changes of DNSEP latency. The duration of surgery in the IONM group was significantly longer than that in the non-IONM group (P < 0.001), but there was no significant difference in intraoperative bleeding (P = 0.330). The removed tissue was confirmed as nerve tissue by hematoxylin and eosin (H&E) staining. The results of the three-month follow-up after SDN of 5 patients in the IONM group and 7 patients in the non-IONM group were lost. The FIPS scores of the IONM group were better than those of the non-IONM group (P = 0.002). Comparison and statistical analysis of general data and research parameters such as the IELT, the IIEF-5, PEDT, and PEP scores and the DNSEP latency between the IONM and non-IONM groups are shown in [Table 2].
Table 2: Comparison of general data and research parameters between IONM group and non-IONM group

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Differences of effectiveness and complications between PE groups with and without IONM

Three-month follow-up showed that no incision infections occurred in either group, and no severe edema or haematoma occurred in any patient after the surgery. In the IONM group (n = 55), the SDN was significantly effective, effective and ineffective for 35 (63.6%), 17 (30.9%) and 3 (5.5%) patients, respectively; in the non-IONM group (n = 53), it was significantly effective, effective and ineffective for 18 (34.0%), 31 (58.5%) and 4 (7.5%) patients, respectively. The clinical efficacy of SDN was significantly better in the IONM than non-IONM group (P = 0.004), and the power was 0.899 at a significance level of 0.05. Fifteen patients had complications (penile paraesthesia, including decreased sensation or varying degrees of numbness or pain and decreased erectile function), including 12 patients with penile sensory abnormalities (4 patients in the IONM group and 8 patients in the non-IONM group) and 3 patients with mild erectile dysfunction (all in the non-IONM group) according to the follow-up survey. The difference in complications between the two groups was significant (P = 0.043; [Table 3]). SSRIs were effective in the 7 patients who did not respond to SDN, and their electrophysiological examination results after SDN were normal.
Table 3: Comparisons of therapeutic effects and complications between IONM group and non-IONM group

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  Discussion Top

In this study, we conducted SDN for PPE patients and compared the efficacy of the surgery between groups with or without IONM during surgery. The results showed that more patients in IONM groups achieved better sexual performance. Only PPE patients of penile sensor hyperexcitability type were chosen for this study. Our previous studies reported a novel PE classification system based on the results of neurophysiological tests, which could be useful for making accurate diagnoses and evaluations and choosing effective treatments.[9] The IELT was more significantly improved in PPE patients with abnormal PSEP results after treatment with condoms or topical local anesthetics than other types of patients.[10],[12] For those patients with abnormal PSSR, sertraline treatment showed better efficacy in reducing the sympathetic nervous system activity.[15]

A study reported that PPE patients have more branches of the DNP than non-PE patients, and the sensitivity of the glans penis and penile skin can be decreased by removing some DNP branches during SDN.[16] Recently, with the development of neurophysiological tests and microsurgery, more clinical studies on SDN under microscopy have been performed in Asian countries. However, some experts, especially those in Europe and the USA, are still skeptical about the necessity of surgical treatment for PE, as seen in the European Association of Urology (EAU) and American Urological Association (AUA) guidelines.[17],[18] This might be due to the lack of unified indications and standardization for the procedure, such as how to determine the number, location and lengths of DNP branches to be removed, as well as concerns about postoperative complications.

PSSR, which directly reflects the penile skin's sympathetic nerve function in the awake state, cannot be used as an IONM item because it cannot be detected under GA state, while the PSEP reflects the brain's bioelectric activity after stimulation of the penis and can be detected in both natural and GA states. Our recent study showed that stable PSEP waveforms can be obtained under GA in beagle dogs and that the latency of PSEP changed significantly during dorsal penile nerve resection in dogs.[19] The depth of anesthesia is critical to the detection of PSEP. If GA was too light, it was hard to meet the requirements of anesthesia management, and it would be too difficult to trigger PSEP waveforms if GA was too deep. Therefore, in this study, the bispectral index (BIS) was used as a monitoring indicator of anesthesia depth to reflect the excitation or depression of the cerebral cortex through electroencephalography (EEG) frequency, amplitude and phase determination and analysis,[20] and it can guide the anesthesia process and help in obtaining satisfactory PSEP waveforms when its value is 40–60. DNSEP was an electroencephalographic response from sending stimuli to the somatic sensory area of the penile dorsal nerve and that the GPSEP was a modification of the DNSEP that sent stimuli to the glans penis.[21] Thus, in the IONM study, only the DNSEP was selected as the indicator for monitoring, as it was more manageable and practical than the GPSEP for SDN.

Based on latency, the sensory evoked potential (SEP) can be divided into short, medium, and long. The DNSEP reflects the pathway from the DNP through the spinal cord and finally to the cerebral cortex and is a short latency SEP (SSEP) affected by relatively few factors with stable waveforms. SSEPs can be repeatedly recorded and used for intraoperative monitoring.[22],[23] The DNP is an unmyelinated peripheral nerve, and its excitatory conduction is mainly affected by the diameter of the nerve fiber in addition to temperature (the greater the diameter, the faster the conduction). In our study, as the operating room temperature was constant, the one-by-one removal of DNP branches reduced the total diameter of the nerve fibers; and as a result, nerve conduction slowed and latency increased. The gradual prolongation of the DNSEP latency during the surgery could thus be explained by the above electrophysiological characteristics of peripheral nerves, serving as an important theoretical basis for the IONM study.

The results of this study showed that GA had a negative effect on PSEP monitoring in the normal group and PE group, most of whom showed prolonged latency and decreased amplitude of the DNSEP and GPSEP. Intraoperative, real-time monitoring of the DNSEP can be used to observe changes in latency during DNP branch removal. In most patients, the latency was gradually prolonged as DNP branches were removed one by one, which provided an important reference for guiding the SDN surgery. Once the PSEP latency was significantly prolonged and reached the reference standard, the surgery was stopped, which ensured effectiveness and prevented complications caused by excessive removal. However, if the PSEP latency was not prolonged to the reference standard when the marked DNP branches were all removed until only one branch was left on either side, the surgery was also terminated to ensure a safe SDN procedure, which is also the “bottom line” required by clinical research.[10]

In this study, IIEF-5, PEP, and PEDT scores, the IELT, and neurophysiological examinations were used as indicators for preoperative assessment and therapeutic effectiveness.[24],[25] In clinical trials, the FIPS has been widely used to evaluate postoperative patient satisfaction,[26] and it was used to compare the short-term satisfaction of patients in the IONM group and the non-IONM group in this study. The outcomes of the above evaluation indicators suggested that there is certain clinical application value in neurophysiological monitoring for improving the short-term apparent efficiency rate and satisfaction, as well as reducing complications of SDN in patients with peripheral-type PPE.

However, IONM is a time-consuming procedure, and it is still in the exploratory stage. We found that a small number of IONM group patients did not show progressive monitoring changes, which indicated that the guidance value of IONM might be limited in some PPE patients. SSRIs were effective in patients for whom SDN was ineffective, but their neurophysiological examination results were normal, suggesting that the neurophysiological examination itself was complicated and that patients might react differently to treatment. Moreover, the number of patients in this study was small, and intraoperative reference standards need to be further discussed.

  Conclusions Top

In conclusion, our findings suggest that IONM in SDN could be used to observe changes in PSEP parameters, which might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN, especially for PPE patients of penile sensor hyperexcitability type (abnormal PSEP and normal PSSR). However, the successful application of IONM during SDN needs to be supported by more data from further multicenter, long-term, large-sample and prospective controlled studies.

  Author Contributions Top

QLT, TS, and YTD contributed to the design of the study. TS, ZPX, CLX, YX, and WY contributed to case collection and operation. YFH and ESZ contributed to intraoperative monitoring. WQ and JS contributed to pathological examination of nerve tissue. QLT, TS, BBY, and JHC performed the analyses and wrote the paper. All authors contributed to the interpretation of analyses and read and approved the final manuscript.

  Competing Interests Top

All authors declare no competing interest.

  Acknowledgments Top

This work was supported by Jiangsu provincial key R & D plan special fund (Social Development) project in China (No. BE2019606).

Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.

  References Top

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  [Table 1], [Table 2], [Table 3]


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