Nerve Grafting: Selected Indications

Number: 0416


Aetna considers nerve grafts (e.g., sural nerve graft, cavernous nerve graft, genito-femoral nerve graft, or collagen tube nerve graft) during radical retropubic prostatectomy experimental and investigational because there is insufficient scientific evidence demonstrating their value in the management of individuals with erectile dysfunction following radical retropubic prostatectomy.

Aetna considers the Avance Nerve Graft, Axogen 2 Nerve Wrap, Integra Neural Wrap, the NeuraGen Nerve Guide, the NeuraWrap Nerve Protector, Neuromatrix collagen nerve cuff, and NeuroMend collagen nerve wrap experimental and investigational for all indications because of insufficient evidence in the peer-reviewed literature.


The incidence of erectile dysfunction (ED) in men treated for prostate cancer has been reported to be between 20 and 88 %.  Despite the use of nerve sparing techniques, ED is still a common adverse effect in patients, especially older men, after radical retropubic prostatectomy.  The successful use of autologous nerve grafts in reconstructive surgery has led to the advent of bilateral nerve graft (sural nerve) during radical retropubic prostatectomy to replace the resected cavernous nerves.

However, there is insufficient scientific evidence to demonstrate the value of sural nerve graft in the management of patients with ED following radical prostatectomy.  In particular, there are no comparative studies between this approach and standard medical therapy.  Early institution of medical therapy, specifically intracorporal injections, after 2 months post-operatively has resulted in a higher incidence of spontaneous return of erections at 1 year.  Furthermore, intracorporal injection has been reported to be the most effective approach for treating ED after radical retropubic prostatectomy.  Other methods include the use of vacuum erection devices, sildenafil (Viagra), and implantation of a penile prosthesis.  Penile prostheses are expensive and require invasive surgery, but satisfaction rates among patients and partners who have used them have been in the range of 85 %, the highest satisfaction rate among all of the treatments of ED.

Further investigation, using prospective, randomized, controlled studies, is needed to ascertain the role of sural nerve graft during radical retropubic prostatectomy in the management of patients who undergo radical prostatectomy for the treatment of localized prostate cancer.  In a study that described their preliminary experience with cavernous nerve graft reconstruction using sural nerve grafts with radical prostatectomy or radical cystectomy, Anastasiadis et al (2003) concluded that sural nerve grafts are feasible and safe after radical prostatectomy and cystectomy.  However, candidates usually present with high stage disease, high-risk for recurrence and frequent requirement for adjuvant therapy that further compromises erectile function.  Randomized studies with more patients and long follow-up periods are necessary in order to define the ideal candidate for nerve graft procedures.

In recent years, researchers have experimented with absorbable collagen matrix tubes (known as Neuragen Nerve Guide) instead of autologous nerve graft materials when performing nerve grafting to reduce the morbidity of ankle numbness as a consequence of harvesting of the sural nerve.  It is thought that by securing the proximal and distal cut ends of the neurovascular bundle into the collage matrix tube, complete capture of regrowing axons is more likely to occur than with an autologous sural nerve graft; thus improving the chances of success.  The clinical value of this approach needs to be validated by well-designed controlled studies.

Saito et al (2007) examined the effect of an interposition nerve graft on sexual function after radical prostatectomy.  This study included 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation.  Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle.  Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively.  As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted.  Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the 3 groups.  In the age-matched analysis, the post-operative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months post-operatively.  The difference in the SXF score between the UNG and UNS groups began to appear after 6 months post-operatively and increased steadily with time.  However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of co-morbidities were different between the UNG and UNS groups.  The authors concluded that the difference of the SXF score between the UNG and UNS groups increased with time after 6 months post-operatively.  However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.

Secin et al (2007) stated that cavernous nerve graft is an option for men requiring bilateral cavernous nerve resection for cancer control during radical prostatectomy.  These investigators determined the success rate and identified determinants of success of bilateral cavernous nerve grafting following resection of the 2 nerves during radical prostatectomy in patients who were potent pre-operatively.  These researchers retrospectively reviewed the records of 44 consecutive patients who underwent bilateral nerve grafting from 1999 to 2004.  Post-operative erectile function was defined as the achievement of erections satisfactory for intercourse with or without oral medication.  They calculated cumulative erectile function recovery rates using Kaplan-Meier curves.  The log rank test was used to compare variables affecting erectile function recovery with p < 0.0083 considered significant after adjusting for the number of variables evaluated using the Bonferroni correction.  The overall 5-year cumulative recovery of erectile function permitting penetration was 34 % and the rate of consistent penetration was 11 %.  None of the analyzed variables was significantly associated with recovery of post-operative erectile function, including patient age (p = 0.3), incomplete bilateral cavernous nerve resection (p = 0.045), sural nerve grafts compared to genito-femoral or ilio-inguinal nerves as donor sites (p = 0.067), post-radiation salvage radical prostatectomy (p = 0.15), neoadjuvant hormone therapy (p = 0.7) and co-morbidities (p = 0.15) or medications (p = 0.4) affecting erectile function.  The authors concluded that bilateral cavernous nerve grafts might be beneficial in select patients.  A definitive answer awaits the performance of a multi-institutional, randomized, controlled trial.

Fujioka et al (2007) presented their experience of cavernous nerve graft reconstruction to restore potency following radical prostatectomy (RP).  A total of 8 patients with prostate cancer who required radical resection involving 1 cavernous nerve had sural nerve grafting, with 2 or 3 sutures using the autologous vein-guide technique, were included in this study.  Seven of the 8 patients had spontaneous erectile activity after grafting and 6 of these patients were able to have intercourse.  The findings of this study need to be validated by studies with larger sample size and long-term follow-up.

Joffe and Klotz (2007) evaluated the success of erectile function preservation and recovery in a select group of patients with extensive disease unilaterally on biopsy who were candidates for unilateral nerve sparing and contralateral genito-femoral interposition nerve-grafting RP.  Because of its low donor site morbidity, the genito-femoral nerve is an appealing donor source for cavernous nerve grafting during RP.  Nerve-sparing RP was performed according to the technique of Walsh on 22 patients with prostate cancer.  At follow-up, the patients completed an 11-item self-report questionnaire that included the erectile function (EF) domain of the International Index of Erectile Function.  The mean patient age was 62 years (range of 48 to 76).  The mean follow-up time was 23 months (range of 9 to 37).  Of the 22 patients, 3 reported no ED (EF score of 26 to 30), 3 reported mild ED (EF score of 22 to 25), 1 reported moderate ED (EF score of 11 to 16), and 15 reported severe ED (EF score of less than 11).  Eight men continued to experience mild chronic thigh or scrotal numbness after the genito-femoral nerve graft procedure.  The authors concluded that the benefits of unilateral nerve grafting with the genito-femoral nerve remain uncertain.  They stated that a prospective randomized trial is needed before the widespread adoption of unilateral nerve grafting.

Namiki et al (2007) performed a 3-year longitudinal study assessing the impact of unilateral sural nerve graft on recovery of potency and continence following RP.  A total of 113 patients undergoing radical retropubic prostatectomy were classified into 3 groups according to the degree of nerve sparing, that is unilateral nerve preservation with contralateral sural nerve graft interposition, bilateral nerve sparing and unilateral nerve sparing.  Urinary continence and potency were estimated by the UCLA Prostate Cancer Index questionnaire.  Patients in the nerve sparing plus sural nerve graft group were younger than those in the bilateral nerve sparing or unilateral nerve sparing groups.  At baseline the unilateral nerve sparing plus sural nerve graft group and the bilateral nerve sparing group reported better sexual function than the unilateral nerve sparing group (62.1 and 61.5 versus 49.9, p < 0.05).  The bilateral nerve sparing group showed more rapid recovery than the unilateral nerve sparing plus sural nerve graft group after radical retropubic prostatectomy (p < 0.01).  After 24 months there were no significant differences observed between the bilateral nerve sparing and the unilateral nerve sparing plus sural nerve graft group (28.7 versus 32.9).  The bilateral nerve sparing group reported a better sexual function score than the unilateral nerve sparing group throughout the postoperative period (p < 0.05).  The bilateral nerve sparing group maintained significantly better urinary function at 1 month after radical retropubic prostatectomy than the unilateral nerve sparing plus sural nerve graft group (p < 0.05).  After 3 months these groups were almost continent.  The unilateral nerve sparing group reported lower urinary function scores during the first year compared to the other groups.  The authors concluded that the nerve graft procedure may contribute to the recovery of urinary function as well as sexual function after radical retropubic prostatectomy.  They noted that this finding needs to be validated in a randomized trial.

Mikhail et al (2007) reported their experience with sural nerve grafting during robot-assisted laparoscopic radical prostatectomy (RLRP).  Patients with pre-operative potency and a minimum of 6 months follow-up were included in this prospective review.  A total of 333 patients met these criteria including 22 of the 25 patients who underwent sural nerve grafting.  Patients were divided into 5 groups to compare unilateral and bilateral sural nerve cohorts with non-nerve-sparing and unilateral and bilateral nerve-sparing groups.  Patients were followed prospectively using health-related quality-of-life questionnaires.  Twenty-two patients underwent sural nerve grafting that included 3 bilateral grafts.  Mean follow-up was 14 months.  There was no statistical difference in patients' ages, body mass index, pre-operative prostate-specific antigen level, blood loss, complications, and positive margin rate.  Operative time was statistically longer for both sural graft cohorts when compared with unilateral (without graft) and bilateral nerve sparing cohorts.  No significant differences in subjective or objective sexual function, sexual bother, or urinary function were seen with 6 and 12 months follow-up, possibly related to smaller sural cohorts.  Graft-related complications include leg pain in 1 patient.  The authors concluded that sural nerve grafting during RLRP is technically feasible and safe and offers improved dexterity and visualization deep within the pelvis.  However, they stated that a larger randomized cohort of patients will be needed to validate any improved benefits afforded by the robot system.

Zorn and colleagues (2008) assessed the functional, pathological, and oncological outcomes of men who underwent robot-assisted sural-nerve graft (SNG) interposition.  Between February 2003 and May 2007, 1,175 consecutive men underwent robot-assisted laparoscopic radical prostatectomy (RLRP).  Database analysis identified 27 men who had SNG: 4 bilateral (BL) and 23 unilateral (UL).  Sexual function (SF) was prospectively evaluated pre-operatively and at 1, 3, 6, 12, and 24 months post-operatively using validated questionnaires.  Positive surgical margins (PSMs), biochemical recurrence (BCR), and potency were evaluated.  Compared with RLRP patients without SNG, patients with SNG were younger (57.2 versus 61.8 yrs, p = 0.02), had a higher Gleason score (p = 0.02), and had a higher clinical and pathological stage (p < 0.001 for both).  Mean surgical time was significantly longer (349 versus 195 mins, p < 0.001) in patients with SNG.  With a mean follow-up of 26.1 months, 11 (47.8 %) patients with UL-SNG and zero men with BL-SNG regained potency.  No significant difference in SF was observed between UL nerve sparing and no SNG (56 %) compared with UL nerve sparing with UL-SNG (p = 0.44). Rates of return-to-baseline SF (RTB-SF) at 6, 12, and 24 months were 11 %, 36 % and 45 % for UL-SNG, respectively, which were also comparable to UL nerve sparing only (p > 0.05).  No patient (0 %) in the BL-SNG group ever achieved RTB-SF status at any time point.  Positive surgical margins were observed in 37 % (10/27) of all patients.  Biochemical recurrence occurred in 9 patients (33.3 %), 7 of whom had PSM (78 %); treatment failure occurred within 6 months of surgery, necessitating androgen deprivation therapy.  The authors concluded that despite optimism regarding SNG, long-term functional outcomes have been disappointing, particularly for BL nerve interposition.  Unilateral sural-nerve graft does not appear to improve outcomes when compared with men with UL nerve preservation.  With the greater risk of PSM and BCR in patients who are considered candidates for SNG, newer treatment modalities are needed to cure their disease while preserving SF.

In a phase II clinical trial, Davis et al (2009) examined if UNS RP plus SNG results in a 50 % relative increase in potency at 2 yrs compared to UNS RP alone.  Participants were men with localized prostate cancer recommended for UNS RP, less than 66 yrs old, normal baseline erectile function, and willing to participate in early erectile dysfunction (ED) therapy.  Patients were followed-up to 2 yrs; they underwent UNS RP and ED therapy starting at 6 wks: oral prostaglandin type-5 (PDE5) inhibitor, vacuum erection device (VED), and intra-cavernosal injection therapy.  In the SNG group, a plastic surgeon performed the procedure at the time of RP.  Main outcome measure was the ability to have an erection suitable for intercourse with or without a PDE5 inhibitor at 2 yrs.  The hypothesis was that SNG would result in a 60 % potency rate compared to 40 % for controls (80 % power, 5 % 2-way significance).  The trial planned to enroll 200 patients, but an interim analysis at 107 patients met criteria for futility and the trial was closed.  For patients completing the protocol to 2 yrs, potency was recovered in 32 of 45 (71 %) of SNG and 14 of 21 (67 %) of controls (p = 0.777).  By intent-to-treat analysis, potency recovered in 32 of 66 (48.5 %) of SNG and 14 of 41 (34 %) of controls (p = 0.271).  No differences were seen in time to potency or quality of life scores for ED and urinary function.  Limitations included slower-than-expected accrual and poor compliance with ED therapy: less than 65 % for VED and less than 40 % for injections.  The authors concluded that the addition of SNG to a UNS RP did not improve potency at 2 yrs following surgery.

In a systematic review on “Advances of peripheral nerve repair techniques to improve hand function”, Mafi and colleagues (2012) stated that concepts of neuronal damage and repair date back to ancient times.  The research in this topic has been growing ever since and numerous nerve repair techniques have evolved throughout the years.  In this review, these researchers examined advances of peripheral nerve repair techniques to improve hand function.  They noted that there are no reviews bringing together and summarizing the latest research evidence concerning the most up-to-date techniques used to improve hand function.  Thus, by identifying and evaluating all the published literature in this field, these investigators have summarized all the available information about the advances in peripheral nerve techniques used to improve hand function.  The most important ones are the use of resorbable poly[(R)-3-hydroxybutyrate] (PHB), epineural end-to-end suturing, graft repair, nerve transfer, side-to-side neurorrhaphy and end-to-side neurorrhaphy between median, radial and ulnar nerves, nerve transplant, nerve repair, external neurolysis and epineural sutures, adjacent neurotization without nerve suturing, Agee endoscopic operation, tourniquet induced anesthesia, toe transfer and meticulous intrinsic repair, free auto nerve grafting, use of distal based neurocutaneous flaps and tubulization.  At the same time the authors found that the patient's age, tension of repair, time of repair, level of injury and scar formation following surgery affect the prognosis.  They stated that despite the thorough findings of this systematic review, further research in this field is needed.

Siddiqui et al (2014) examined the long-term outcome of SNG during radical retropubic prostatectomy (RRP) performed by a single surgeon.  A total of 66 patients with clinically localized prostate cancer and pre-operative International Index of Erectile Function (IIEF) score greater than 20 who underwent RRP were included in this study.  Neuro-vascular bundles (NVB) excision was performed if the risk of side-specific extra-capsular extension (ECE) was greater than 25 % on Ohori' nomogram.  Sural nerve graft was harvested by a plastic surgeon, contemporaneously as the urologic surgeon was performing RRP; IIEF questionnaire was used pre- and post-operatively and at follow-up.  Main outcome measure was post-operative IIEF score at 3 years of men undergoing RRP with SNG.  Recovery of potency was defined as post-operative IIEF-EF domain score greater than 22.  There were 43 (65 %) unilateral SNG and 23 (35 %) bilateral SNG.  Mean surgical time was 164 minutes (71 to 221).  The mean pre-operative IIEF score was 23.4 +/- 1.6.  With a mean follow-up of 35 months, 19 (28.8 %) patients had IIEF score greater than 22.  The IIEF-EF scores for those who had unilateral SNG and bilateral SNG were 12.9 +/- 4.9 and 14.8 +/- 5.3 respectively.  History of diabetes (p = 0.001) and age (p = 0.007) negatively correlated with recovery of EF; 60 % patients used PDE5i and showed a significantly higher EF recovery (43 % versus 17 %, p = 0.009).  The authors concluded that SNG can potentially improve EF recovery for potent men with higher stage prostate cancer undergoing RP.  These findings need to be validated by well-designed studies..

Patel et al (2015) presented a propensity-matched analysis of patients undergoing placement of dehydrated human amnion/chorion membrane (dHACM) around the NVB during NS robot-assisted laparoscopic prostatectomy (RARP).  From March 2013 to July 2014, a total of 58 patients who were pre-operatively potent (Sexual Health Inventory for Men [SHIM] score greater than 19) and continent (no pads) underwent full NS RARP.  Post-operative outcomes were analyzed between propensity-matched graft and no-graft groups, including time to return to continence, potency, and biochemical recurrence.  Use of dHACM was not associated with increased operative time or blood loss or negative oncologic outcomes (p > 0.500).  Continence at 8 weeks returned in 81.0 % of the dHACM group and 74.1 % of the no-dHACM group (p = 0.373). Mean time to continence was enhanced in group 1 patients (1.21 months) versus (1.83 months; p = 0.033).  Potency at 8 weeks returned in 65.5 % of the dHACM patients and 51.7 % of the no-dHACM group (p = 0.132).  Mean time to potency was enhanced in group 1, (1.34 months), compared to group 2 (3.39 months; p = 0.007).  Graft placement enhanced mean time to continence and potency.  The authors concluded that post-operative SHIM scores were higher in the dHACM group at maximal follow-up (mean score 16.2 versus 9.1).  They stated that dHACM allograft use appears to hasten the early return of continence and potency in patients following RARP.  The major drawbacks of this study were its modest sample size and short-term follow-up; these preliminary findings need to be validated by well-designed studies.

NeuroMatrixTM  Collagen Nerve Cuff and NeuroMendTM Collagen Nerve Wrap

Peripheral nerves possess the capacity of self-regeneration after traumatic injury.  Transected peripheral nerves can be bridged by direct surgical coaptation of the 2 nerve stumps or by interposing autografts or biological (veins) or synthetic nerve conduits.  Nerve conduits are tubular structures that guide the regenerating axons to the distal nerve stump.  Early synthetic nerve conduits were primarily made of silicone because of the relative flexibility and biocompatibility.  Nerve conduits are now made of biodegradable materials such as collagen, aliphatic polyesters, or polyurethanes (Pfister et al, 2007).  Studies are in progress to assess the long-term biocompatibility of these implants and their effectiveness in nerve reconstruction.

According to the Collagen Matrix, Inc. (Franklin Lakes, NJ) website, NeuroMatrix is a resorbable, semi-permeable collagen-based tubular matrix that provides a protective environment for peripheral nerve repair after injury and creates a conduit for axonal growth across a nerve gap.  The device slowly resorbs in vivo.  The device is engineered from highly purified type I collagen fibers and are composed of dense fibers for mechanical strength.  Collagen Nerve Cuff was cleared by the FDA via the 510(k) process in September 2001.  It is intended for use in repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity; however, there is insufficient scientific evidence regarding its effectiveness for peripheral nerve repair or for any other indication.

NeuroMend Nerve Wrap is a resorbable, semi-permeable, type 1 collagen nerve wrap used in peripheral nerve repair.

NeuroMend (Collagen Matrix, Inc., Franklin Lakes, NJ) is a resorbable, collagen-based rolled membrane matrix intended for use in the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue.  It has the same technological characteristics as NeuroMatrix.  Collagen Nerve Wrap was cleared by the FDA via the 510(k) process on July 14, 2006; however, there is insufficient scientific evidence regarding its effectiveness for peripheral nerve repair or for any other indication.

Avance Nerve Graft

Avance Nerve Graft is a processed, decedecellularized nerve allograft, used as an alternative to nerve conduits for nerve repair procedures.

In a case report and review of the literature, Gunn et al (2010) presented a rare case of facial nerve paraganglioma and novel use of a processed allograft for facial nerve reconstruction. A 34-year old female presented with progressive onset right sided facial palsy for 5 months; CT and MRI demonstrated an irregular mass in the right facial nerve canal from the intra-tympanic segment to the stylo-mastoid foramen.  Following trans-mastoid resection, the defect was repaired using processed allograft.  Pathologic analysis was consistent with a paraganglioma.  Facial nerve paraganglioma is a rare entity that has been reported only 10 times in the literature.  The authors concluded that traditional methods of facial nerve reconstruction, including autologous and cadaveric grafting, can lead to significant patient morbidity.  Autologous nerve grafts are the "gold standard" for superior regenerative capability, but are limited by the length and potential neuroma formation at the donor site.  Allogenic grafts from donors or cadavers have shown some effectiveness, but can require immunosuppression.  The Avance nerve graft (Avance Nerve Graft, AxoGen, Inc.) is a cadaveric graft, processed and decellularized to maintain an extracellular matrix with laminin and intact endoneural tubes, thus providing support for the growing axon without generating an immune response.  The authors concluded that initial studies of the Avance graft in animals and humans have examined repair of peripheral nerves, but this was the first reported case of human facial nerve reconstruction.

Brooks et al (2012) reported on the outcomes from a multi-center study on processed nerve allografts (Avance Nerve Graft). A total of 12 sites with 25 surgeons contributed data from 132 individual nerve injuries.  Data was analyzed to determine the safety and effectiveness of the nerve allograft.  Sufficient data for effectiveness analysis were reported in 76 injuries (49 sensory, 18 mixed, and 9 motor nerves).  The mean age was 41 ± 17 (18 to 86) years.  The mean graft length was 22 ± 11 (5 to 50) mm.  Subgroup analysis was performed to determine the relationship to factors known to influence outcomes of nerve repair such as nerve type, gap length, patient age, time to repair, age of injury, and mechanism of injury.  Meaningful recovery was reported in 87 % of the repairs reporting quantitative data.  Subgroup analysis demonstrated consistency, showing no significant differences with regard to recovery outcomes between the groups (p > 0.05 Fisher's Exact Test).  No graft related adverse experiences were reported and a 5 % revision rate was observed.  The authors concluded that processed nerve allografts performed well and were found to be safe and effective in sensory, mixed and motor nerve defects between 5 and 50 mm.  They stated that the outcomes for safety and meaningful recovery observed in this study compared favorably to those reported in the literature for nerve autograft and were higher than those reported for nerve conduits.  The main drawbacks of this study were its retrospective design and the lack of a comparison group.

In a case-series study, Zuniga (2015) described the results of using a processed nerve allograft, Avance Nerve Graft, as an extracellular matrix scaffold for the reconstruction of lingual nerve (LN) and inferior alveolar nerve (IAN) discontinuities. A retrospective analysis of the neurosensory outcomes for 26 subjects with 28 LN and IAN discontinuities reconstructed with a processed nerve allograft was conducted to determine the treatment safety and effectiveness.  Sensory assessments were conducted pre-operatively and 3, 6, and 12 months after surgical reconstruction.  The outcomes population, those with at least 6 months of post-operative follow-up, included 21 subjects with 23 nerve defects.  The neurosensory assessments included brush stroke directional sensation, static 2-point discrimination, contact detection, pressure pain threshold, and pressure pain tolerance.  Using the clinical neurosensory testing scale, sensory impairment scores were assigned pre-operatively and at each follow-up appointment. Improvement was defined as a score of normal, mild, or moderate.  The neurosensory outcomes from LNs and IANs that had been micro-surgically repaired with a processed nerve allograft were promising.  Of those with nerve discontinuities treated, 87 % had improved neurosensory scores with no reported adverse experiences.  Similar levels of improvement, 87 % for the LNs and 88 % for the IANs, were achieved for both nerve types.  Furthermore, 100 % sensory improvement was achieved in injuries repaired within 90 days of the injury compared with 77 % sensory improvement in injuries repaired after 90 days.  The authors concluded that these results suggested that processed nerve allografts are an acceptable treatment option for reconstructing trigeminal nerve discontinuities; additional studies will focus on reviewing the outcomes of additional cases.

Nerve Grafting after Radical Prostatectomy

Souza and colleagues (2017) examined a novel penile re-innervation technique using 4 sural nerve grafts and end-to-side neurorraphies connecting bilaterally the femoral nerve and the cavernous corpus and the femoral nerve and the dorsal penile nerves.  A total of 10 patients (mean [± SD; range] age 60.3 [± 4.8; 54 to 68] years), who had undergone RP at least 2 years previously, underwent penile re-innervation in the present study; 4 patients had undergone radiotherapy after RP.  All patients reported satisfactory sexual activity prior to RP.  The surgery involved bridging of the femoral nerve to the dorsal nerve of the penis and the inner part of the corpus cavernosum with sural nerve grafts and end-to-side neurorraphies.  Patients were evaluated using the IIEF questionnaire and pharmaco-penile Doppler ultrasonography (PPDU) pre-operatively and at 6, 12 and 18 months post-operatively, and using a Clinical Evolution of Erectile Function (CEEF) questionnaire, administered after 36 months.  The IIEF scores showed improvements with regard to ED, satisfaction with intercourse and general satisfaction.  Evaluation of PPDU velocities did not reveal any difference between the right and left sides or among the different time-points.  The introduction of nerve grafts neither caused fibrosis of the corpus cavernosum, nor reduced penile vascular flow; CEEF results showed that sexual intercourse began after a mean of 13.7 months with frequency of sexual intercourse varying from once-daily to once-monthly.  Acute complications were minimal.  The authors concluded that a total of 60 % of patients were able to achieve full penetration, on average, 13 months after re-innervation surgery.  Patients previously submitted to radiotherapy had slower return of erectile function. They stated that penile re-innervation surgery is a viable technique, with effective results, and could offer a new therapeutic option for ED after RP.  Moreover, they stated that this study was limited by the small number of cases (n = 10).

Nerve Grafting for Neonatal Brachial Plexus Palsy

Chang and colleagues (2018) stated that the use of nerve transfers versus nerve grafting for neonatal brachial plexus palsy (NBPP) remains controversial.  In adult brachial plexus injury, transfer of an ulnar fascicle to the biceps branch of the musculocutaneous nerve (Oberlin transfer) is reportedly superior to nerve grafting for restoration of elbow flexion.  In pediatric patients with NBPP, recovery of elbow flexion and forearm supination is an indicator of resolved NBPP.  Currently, limited evidence exists of outcomes for flexion and supination when comparing nerve transfer and nerve grafting for NBPP.  In a retrospective cohort study, these researchers compared 1-year post-operative outcomes for infants with NBPP who underwent Oberlin transfer versus nerve grafting.  This trial included patients with NBPP who underwent Oberlin transfer (n = 19) and nerve grafting (n = 31) at a single institution between 2005 and 2015.  A single surgeon conducted intra-operative exploration of the brachial plexus and determined the surgical nerve reconstruction strategy undertaken.  Active range of motion (ROM) was evaluated pre-operatively and post-operatively at 1 year.  No significant difference between treatment groups was observed with respect to the mean change (pre- to post-operatively) in elbow flexion in adduction and abduction and biceps strength.  The Oberlin transfer group gained significantly more supination (100 degrees versus 19 degrees; p < 0.0001).  Forearm pronation was maintained at 90 degrees in the Oberlin transfer group whereas it was slightly improved in the grafting group (0 degree versus 32 degrees; p = 0.02).  Shoulder, wrist, and hand functions were comparable between treatment groups.  The authors concluded that these preliminary data demonstrated that the Oberlin transfer conferred an advantageous early recovery of forearm supination over grafting, with equivalent elbow flexion recovery.  Moreover, they stated that further studies that monitor real-world arm usage are needed to provide more insight into the most appropriate surgical strategy for NBPP.


van Neerven and colleagues (2017) noted that progress in material development has enabled the production of nerve guides that increasingly resemble the characteristics of an autologous nerve graft.  In the present study, 20 mm adult rat sciatic nerve defects were bridged with the collagen-based, 2-component nerve guide “Neuromaix”, the commercially available NeuraGen nerve tube or an autologous nerve graft.  Neuromaix was able to support structural as well as functional regeneration across this gap.  The majority of the axons grew across the scaffold into the distal nerve segment and retrograde tracing confirmed that these axons were of somatosensory and motor origin.  Histomorphology revealed that axons regenerating through Neuromaix exhibited reduced myelin sheath thickness, whereas axon diameter and axon density were comparable to those of the autograft.  Neuromaix implantation resulted in re-innervation of the gastrocnemius muscle to a level that was not significantly different from that supported by the autograft, as shown by electrophysiology.  The authors concluded that these findings showed that the use of the Neuromaix scaffold not only allowed axonal regeneration across large nerve gaps, but that the regenerating axons were also able to functionally re-innervate the muscles.  They noted that these data provided a promising perspective for the first in human application of the materials.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

There is no specific code for sural nerve, cavernous, or genitofemoral grafts:

CPT codes not covered for indications listed in the CPB:

64911     with autogenous vein graft (includes harvest of vein graft), each nerve
64912 Nerve repair; with nerve allograft, each nerve, first strand (cable)
64913 Nerve repair; with nerve allograft, each additional strand (List separately in addition to code for primary procedure)

Other CPT codes related to the CPB:

55840 Prostatectomy, retropubic radical, with or without nerve sparing
55842     with lymph node biopsy(s) (limited pelvic lymphadenectomy)
55845     with bilateral pelvic lymphadenectomy, including external iliac, hypogastric, and obturator nodes
55866 Laparoscopy, surgical prostatectomy, retropubic radical, including nerve sparing, includes robotic assistance when performed

HCPCS codes not covered for indications listed in the CPB:

C9352 Microporous collagen implantable tube (Neuragen Nerve Guide), per centimeter length
C9353 Microporous collagen implantable slit tube (Neurawrap Nerve Protector), per centimeter length
C9355 Collagen nerve cuff (neuromatrix), per 0.5 centimeter length
C9361 Collagen matrix nerve wrap (neuromend collagen nerve wrap), per 0.5 centimeter length

ICD-10 codes not covered for indications listed in the CPB:

G51.0 Bell's Palsy
N52.01 - N52.9 Male erectile dysfunction [status post radical retropubic prostatectomy]

The above policy is based on the following references:

  1. Kim ED, Seo JT. Minimally invasive technique for sural nerve harvesting: Technical description and follow-up. Urology. 2001;57(5):921-924.
  2. Kim ED, Nath R, Kadmon D, et al. Bilateral nerve graft during radical retropubic prostatectomy: 1-year follow-up. J Urol. 2001;165(6 Pt 1):1950-1956.
  3. Baniel J, Israilov S, Segenreich E, et al. Comparative evaluation of treatments for erectile dysfunction in patients with prostate cancer after radical retropubic prostatectomy. BJU Int. 2001;88(1):58-62.
  4. Kim HL, Stoffel DS, Mhoon DA, Brendler CB. A positive caver map response poorly predicts recovery of potency after radical prostatectomy. Urology. 2000;56(4):561-564.
  5. Mulcahy JJ. Erectile function after radical prostatectomy. Semin Urol Oncol. 2000;18(1):71-75.
  6. Kim ED, Scardino PT, Hampel O, et al. Interposition of sural nerve restores function of cavernous nerves resected during radical prostatectomy. J Urol. 1999;161(1):188-192.
  7. Kim ED, Nath R, Slawin KM, et al. Bilateral nerve grafting during radical retropubic prostatectomy: Extended follow-up. Urology. 2001;58(6):983-987.
  8. Canto EI, Nath RK, Slawin KM. Cavermap-assisted sural nerve interposition graft during radical prostatectomy. Urol Clin North Am. 2001;28(4):839-847.
  9. Scardino PT, Kim ED. Rationale for and results of nerve grafting during radical prostatectomy. Urology. 2001;57(6):1016-1019.
  10. Walsh PC. Nerve grafts are rarely necessary and are unlikely to improve sexual function in men undergoing anatomic radical prostatectomy. Urology. 2001;57 (6):1020-1024.
  11. Kaouk JH, Desai MM, Abreu SC, et al. Robotic assisted laparoscopic sural nerve grafting during radical prostatectomy: Initial experience. J Urol. 2003;170:909-912.
  12. Anastasiadis AG, Benson MC, Rosenwasser MP, et al. Cavernous nerve graft reconstruction during radical prostatectomy or radical cystectomy: Safe and technically feasible. Prostate Cancer Prostatic Dis. 2003;6(1):56-60.
  13. Singh H, Karakiewicz P, Shariat SF, et al. Impact of unilateral interposition sural nerve grafting on recovery of urinary function after radical prostatectomy. Urology. 2004;63(6):1122-1127.
  14. Montorsi F, Briganti A, Salonia A, et al. Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. Eur Urol. 2004;45(2):123-133.
  15. Kendirci M, Hellstrom WJ. Current concepts in the management of erectile dysfunction in men with prostate cancer. Clin Prostate Cancer. 2004;3(2):87-92.
  16. Nelson BA, Chang SS, Cookson MS, Smith JA Jr. Morbidity and efficacy of genitofemoral nerve grafts with radical retropubic prostatectomy. Urology. 2006;67(4):789-792.
  17. Saito S, Namiki S, Numahata K, et al. Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study. Int J Urol. 2007;14(2):133-139.
  18. Secin FP, Koppie TM, Scardino PT, et al. Bilateral cavernous nerve interposition grafting during radical retropubic prostatectomy: Memorial Sloan-Kettering Cancer Center experience. J Urol. 2007;177(2):664-668.
  19. Fujioka M, Tasaki I, Kitamura R, et al. Cavernous nerve graft reconstruction using an autologous nerve guide to restore potency. BJU Int. 2007;100(5):1107-1109.
  20. Joffe R, Klotz LH. Results of unilateral genitofemoral nerve grafts with contralateral nerve sparing during radical prostatectomy. Urology. 2007;69(6):1161-1164.
  21. Namiki S, Saito S, Nakagawa H, et al. Impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy: 3-year longitudinal study. J Urol. 2007;178(1):212-216; discussion 216.
  22. Mikhail AA, Song DH, Zorn KC, et al. Sural nerve grafting in robotic laparoscopic radical prostatectomy: Interim report. J Endourol. 2007;21(12):1547-1551.
  23. Zorn KC, Bernstein AJ, Gofrit ON, et al. Long-term functional and oncological outcomes of patients undergoing sural nerve interposition grafting during robot-assisted laparoscopic radical prostatectomy. J Endourol. 2008;22(5):1005-1012.
  24. Davis JW, Chang DW, Chevray P, et al. Randomized phase II trial evaluation of erectile function after attempted unilateral cavernous nerve-sparing retropubic radical prostatectomy with versus without unilateral sural nerve grafting for clinically localized prostate cancer. Eur Urol. 2009;55(5):1135-1143.
  25. Siemionow M, Bozkurt M, Zor F. Regeneration and repair of peripheral nerves with different biomaterials: Review. Microsurgery. 2010;30(7):574-588.
  26. Mafi P, Hindocha S, Dhital M, Saleh M. Advances of peripheral nerve repair techniques to improve hand function: A systematic review of literature. Open Orthop J. 2012;6:60-68.
  27. Siddiqui KM, Billia M, Mazzola CR, et al. Three-year outcomes of recovery of erectile function after open radical prostatectomy with sural nerve grafting. J Sex Med. 2014;11(8):2119-2124.
  28. Patel VR, Samavedi S, Bates AS, et al. Dehydrated human amnion/chorion membrane allograft nerve wrap around the prostatic neurovascular bundle accelerates early return to continence and potency following robot-assisted radical prostatectomy: Propensity score-matched analysis. Eur Urol. 2015;67(6):977-980.
  29. Gunn S, Cosetti M, Roland JT Jr. Processed allograft: Novel use in facial nerve repair after resection of a rare racial nerve paraganglioma. Laryngoscope. 2010;120 Suppl 4:S206.
  30. Brooks DN, Weber RV, Chao JD, et al. Processed nerve allografts for peripheral nerve reconstruction: A multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery. 2012;32(1):1-14.
  31. Zuniga JR. Sensory outcomes after reconstruction of lingual and inferior alveolar nerve discontinuities using processed nerve allograft -- a case series. J Oral Maxillofac Surg. 2015;73(4):734-744.
  32. Jiang CQ, Hu J, Xiang JP, et al. Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: Similar outcomes to autologous nerve grafts. Neural Regen Res. 2016;11(11):1845-1850.
  33. Capkın S, Akhisaroglu M, Ergur BU, Bacakoglu AA. A biological tube technique for the repair of peripheral nerve defects using 'stuffed nerves'. Ulus Travma Acil Cerrahi Derg. 2017;23(1):7-14.
  34. Souza Trindade JC, Viterbo F, Petean Trindade A, et al. Long-term follow-up of treatment of erectile dysfunction after radical prostatectomy using nerve grafts and end-to-side somatic-autonomic neurorraphy: A new technique. BJU Int. 2017;119(6):948-954.
  35. van Neerven SGA, Haastert-Talini K, Boecker A, et al. Two-component collagen nerve guides support axonal regeneration in the rat peripheral nerve injury model. J Tissue Eng Regen Med. 2017;11(12):3349-3361.
  36. Chang KWC, Wilson TJ, Popadich M, et al. Oberlin transfer compared with nerve grafting for improving early supination in neonatal brachial plexus palsy. J Neurosurg Pediatr. 2018;21(2):178-184.