Combat Injury of the Sciatic Nerve – An Institutional Experience

Combat Injury of the Sciatic Nerve – An Institutional Experience Abstract Introduction Combat injury of the sciatic nerve tends to be severe with variable but often profound consequences, is often associated with widespread soft tissue and bone injuries, significant neurologic impairment, severe neuropathic pain, and a prolonged recovery time. There is little contemporary data that describes the treatment and outcome of this significant military acquired peripheral nerve injury. We describe our institution’s experience treating patients with combat-acquired sciatic nerve injury in the recent Iraq and Afghanistan wars. Materials and Methods IRB approval was obtained, and a retrospective review was performed of the records of 5,137 combat-related extremity injuries between June 2007 and June 2015 to identify patients with combat-acquired sciatic nerve injury without traumatic amputation of the injured leg. The most common mechanisms of injury were gunshot wound to the upper thigh or pelvis, followed by blast injury. Thirteen patients were identified that underwent sciatic nerve exploration and repair. Nine patients had nerve repair using long-length acellular cadaveric allografts. Five patients underwent nerve surgery within 30 d of injury and eight had surgery on a delayed basis. The postoperative follow-up period was at least 2 yr. Results Reduction of neuropathic pain was significant, 7/10 points on the 11-point pain intensity numerical rating scale. Eight patients displayed electrodiagnostic evidence of reinnervation distal to the injury zone; however, functional recovery was poor, as only 3 of 10 patients had detectable motor units distal to the knee, and recovery was only in tibial nerve innervated muscles. There were no serious surgical complications, in particular, wound infection or graft rejection associated with long-length cadaver allograft placement. Conclusion Early surgery to repair sciatic nerve injury possibly promotes significant pain reduction, reduces narcotic usage and facilitates a long rehabilitation process. Allograft nerve placement is not associated with serious complications. A follow-up period longer than 3 yr would be required and is ongoing to assess the efficacy of our treatment of patients with combat-acquired sciatic nerve injury. INTRODUCTION Combat-related peripheral nerve injuries (PNI) present exceedingly complex challenges for surgeons. The nerve injuries result from penetrating mechanisms such as gunshot wounds, blast fragments, or bone fractures associated with high-energy skeletal insult that cause nerve transection, stretch or shear (Fig. 1A–D). These nerve injuries are typically associated with local and systemic vascular compromise, bone and soft tissue damage.14,15 Several studies have demonstrated a relatively high prevalence of sciatic nerve injury, with very poor outcomes following surgical repair.16,18,19 Electrodiagnostic testing, magnetic resonance imaging, and ultrasound enhance the clinical evaluation with physiological and anatomic information that determine extent and localization of the nerve injury (Fig. 1, 1–6).21 These tests may facilitate decisions regarding the timing of surgical intervention post-trauma, as well as the specific approaches; however, whether they assist in long-term outcome is not completely known. This overall experience underscores the need for a continued effort to investigate the management of sciatic nerve injury. FIGURE 1. View largeDownload slide High-energy fractures such as (A) and (C) subtrochanteric and (B) and (D) diaphyseal femur fractures are commonly associated with traumatic sciatic nerve injury (A and B are pre-reduction/fixation, C and D are postoperative). Magnetic resonance imaging may be used to evaluate the 1 and 2 normal architecture of the sciatic nerve as well as 3 and 4 fascicular disruption and 5 and 6 distal stump neuroma (all are T1 weighted axial sequence images). Normal fascicles are hyper-attenuating “dots” within the iso- to slightly hypo-attenuating sciatic nerve that is indicated by the white arrows. At the point of fascicle disruption the hyper-attenuating dots can no longer be appreciated, and at the point of neuroma formation the overall diameter of the sciatic nerve is increased, with the neuroma itself appearing as a large and mixed attenuation area that does not appear to preserve the organized architecture of the nerve. FIGURE 1. View largeDownload slide High-energy fractures such as (A) and (C) subtrochanteric and (B) and (D) diaphyseal femur fractures are commonly associated with traumatic sciatic nerve injury (A and B are pre-reduction/fixation, C and D are postoperative). Magnetic resonance imaging may be used to evaluate the 1 and 2 normal architecture of the sciatic nerve as well as 3 and 4 fascicular disruption and 5 and 6 distal stump neuroma (all are T1 weighted axial sequence images). Normal fascicles are hyper-attenuating “dots” within the iso- to slightly hypo-attenuating sciatic nerve that is indicated by the white arrows. At the point of fascicle disruption the hyper-attenuating dots can no longer be appreciated, and at the point of neuroma formation the overall diameter of the sciatic nerve is increased, with the neuroma itself appearing as a large and mixed attenuation area that does not appear to preserve the organized architecture of the nerve. The best functional outcomes following surgery for PNI are in cases of partially injured nerves that undergo external neurolysis for decompression, or after direct end-to-end suture of a clean cut severed nerve. This is rarely the case in combat-related PNI, as large nerve gaps are often present and repair often requires nerve grafting or tubulization.3,20 A nerve graft is recommended over tubulization when the nerve gap is longer than 3 cm.20 Sural nerve autograft has been the gold standard for peripheral nerve reconstruction,3 but harvesting sufficient sural nerve autograft to span and connect a wide caliber nerve such as the sciatic nerve has been challenging and relatively ineffective.11 Alternatively, processed decellularized freeze-dried cadaveric allografts can be used. These allografts have good nerve regeneration potential, are not in limited supply, and are readily available for surgical implantation.4,7 The high incidence of associated multiple extremity injuries and amputations unique to military patients renders many donor sites unacceptable, providing further support for using allograft material as a practical graft alternative. Allograft use also diminishes potential donor site morbidity such as loss of sensation, wound infection, dehiscence, and postoperative painful donor site neuroma. Following PNI, up to 6 mo of observation prior to nerve repair may be accepted to allow for spontaneous proximal axonal sprouting and reinnervation. Seimienow et al20 question this approach. Cautious watchful waiting will not be beneficial in instances of nerve discontinuity. Furthermore, the supporting Schwann cells required for axonal regeneration and the motor endplates necessary for muscle reinnervation can be expected to degenerate by 18–24 mo. In rat models, delay in repair beyond 3 mo of PNI is associated with a decline in the number of viable Schwann cells and subsequent regenerated axons at the injury site.3,6,8,10,22 The purpose this retrospective study is to provide early outcome data following surgical repair of the sciatic nerve in patients injured during Operation Iraqi Freedom and Operation Enduring Freedom, hopefully to assist in the management of these patients and to possibly inspire further development in this area of military medicine. METHODS Our research protocol was submitted, reviewed, and approved after administrative, scientific, and ethical review by the Department of Research Programs and the Walter Reed National Military Medical Center Institutional Review Board (Research Project IRBNET # 402914-1). Patient Selection The inpatient and outpatient medical records, operative reports, radiologic and clinical photographs of all patients treated for sciatic nerve injuries between June 2007 and June 2017 treated at the Walter Reed Army Medical Center in Silver Spring, Maryland or the National Naval Medical Center in Bethesda, Maryland or the now merged Walter Reed National Military Medical Center in Bethesda, Maryland were retrospectively reviewed. We identified 13 patients who sustained sciatic nerve injury as a result of combat wounds that did not have a traumatic amputation of the injured leg. Data on patient age, sex, mechanism of injury, time from injury to nerve surgery, self-reported pain, narcotic and neuropathic pharmaceutical usage, and size of the nerve defect at time of surgery were recorded. All patients had documentation of preoperative clinical and electrophysiological assessments. Time from Injury to Surgery The date of injury was retrieved from the hospital medical records or the “in theater” (war zone) medical records. The date of the nerve surgery was defined as the date when definitive treatment of the nerve injury was performed. The time between the date of injury and date of nerve surgery was calculated and reported in days. Calculation of Narcotic Use All narcotic use was converted to oxycodone (the most common narcotic used in our patient population) use in milligrams per day using a narcotic conversion calculator (Simplicity GmbH, Therwil, Switzerland).17 Direct comparisons of oxycodone requirements were then made for study patients, and the percentage change over time per patient was calculated. We documented changes in narcotic use 6 mo after surgery to allow time for equilibration of pain regimens. A multidisciplinary Pain Team managed multi-trauma patients with complex pain medication requirements. Surgical Nerve Grafting Techniques Surgery was performed with the patient in prone position with the knees and hips flexed to approximately 15 degrees (Fig. 2A). Intraoperative electro-physiologic monitoring was performed to record compound muscle action potentials and nerve action potential (NAP) across regions of injured nerve. If after the initial external neurolysis a NAP could be recorded, then no further intervention was taken. If no NAP was recorded, then further external and internal neurolysis was performed, and fascicular stimulation with NAP recording was repeated. If NAPs were present in a fascicle then no further action was taken. If no fascicular NAPs were present, then serial axial cuts of the fascicle were made until normal fascicular architecture was appreciated at both the proximal and distal ends of the injured section. If the nerve was transected, then serial axial cuts of the proximal and distal stump neuromas were made until the normal fascicular architecture was appreciated. The remaining nerve gap was then measured and if the remaining nerve ends could be approximated with no tension then an end-to-end repair was performed. If direct approximation of the nerve ends was not possible without tension, then the nerve was grafted with ipsilateral sural nerve autograft, or processed decellularized freeze-dried cadaver allograft (Avance Nerve Graft, AxoGen Co., Alachua, FL, USA). Grafts were secured using 8-0 nylon and coaptation sites were wrapped with AxoGuard Nerve Protector (Cook Biotech Inc, West Lafayette, IN, USA). FIGURE 2. View largeDownload slide (A) An extensive infra-gluteal incision is used to gain exposure deep to the gluteal sling in high sciatic nerve injuries. (B) In this patient, a proximal sciatic nerve transection was found with stump neuromas at of both the common sciatic and tibial and peroneal components, represented by the white S, T, and P, respectively. The (C) proximal and (D) distal stump neuromas are resected to healthy appearing fascicular architecture. FIGURE 2. View largeDownload slide (A) An extensive infra-gluteal incision is used to gain exposure deep to the gluteal sling in high sciatic nerve injuries. (B) In this patient, a proximal sciatic nerve transection was found with stump neuromas at of both the common sciatic and tibial and peroneal components, represented by the white S, T, and P, respectively. The (C) proximal and (D) distal stump neuromas are resected to healthy appearing fascicular architecture. Evaluation of Pain We evaluated pain generated by the nerve injury with an emphasis on neuropathic pain, as this was the most disabling component. Neuropathic pain was defined as burning paresthesias (dysesthesias), electric shocks, hyperalgesia, and allodynia. Self-reported patient pain scores were recorded using the 11-point pain intensity numeric rating scale (PI-NRS)5 during preoperative encounters and postoperative assessments for each patient, and reported as a preoperative pain score and 6-wk postoperative pain score. Determination of Graft Rejection The patients who received cadaver allografts were monitored for potential graft rejection. The presence of fever, skin rash and/or erythema, onset of increasing local pain, or wound drainage were all noted during postoperative clinical exams as indicators of potential graft rejection. Outcome Assessments Each patient had multiple neurological assessments of motor and sensory deficits and at least one repeat electrodiagnostic electromyography/nerve conduction (EMG/NCS) study 6 mo after surgery. Patients were followed-up for a 3-yr minimum postoperative period. RESULTS Selected Patients Thirteen patients underwent surgical exploration of a combat-acquired sciatic nerve injury. The mean patient age was 28 yr with a range of 19–48 yr. All patients were men. The predominant mechanisms of injury were gunshot wound (9 of 13, 69%) followed by improvised explosive device (IED) blast (2 of 13, 12%), and rocket propelled grenade (RPG) or missile blast (2 of 13, 12%). Nearly all patients had additional injuries. Sixty percent had ipsilateral femoral bone shaft or neck fractures, seven (54%) of those injured by gunshot wound received multiple gunshot wounds to other parts of their body, two patients (12%) had contralateral lower extremity amputation, and two patients (12%) had major arterial injuries (Table I). Table I. Injury Characteristics Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Table I. Injury Characteristics Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Time from Injury to Nerve Surgery A bimodal distribution was noted whereby six patients underwent nerve exploration and repair less than 30 d from injury (range 12–30 d), and seven patients had nerve surgery at a significantly later time (mean 373 d, range 159–1142 d). These two groups were thenceforth referred to as the early treatment and late treatment group, respectively (Table I). Findings at the Time of Surgery Four patients had a neuroma-in-continuity with no recordable NAP distal to the lesion. In three, following external and internal neurolysis, NAPs were recorded and no further action was taken. The fourth had a neuroma-in-continuity in a portion of the peroneal division, and no NAP was recordable following internal and external neurolysis. These non-conducting fascicles were resected and an interfascicular graft with processed decellularized allograft nerve was placed. The other nine patients had transected sciatic nerves exhibiting stump neuromas of either or both the peroneal or tibial components (Fig. 2B). In these nerves, the stump neuromas were resected until normal appearing fascicles were exposed (Fig. 2C and D). An end-to-end nerve repair was possible in one patient. The remainder had nerve gap repair with multiple interfascicular nerve grafts using either decellularized allograft nerve or sural nerve autograft (Fig. 3A and B). The mean length of the nerve gap after debridement of the retracted, scarred nerve was 6.2 cm, with a maximum of 7 cm. FIGURE 3. View largeDownload slide The segmental nerve defect is addressed with (A) an interfascicular repair of the (s) sciatic nerve proper and (t) tibial and (p) peroneal divisions using processed, decellularized allograft nerve (thin white arrow) and (B) the coaptation sites are reinforced with collagen nerve wraps (white block arrows). FIGURE 3. View largeDownload slide The segmental nerve defect is addressed with (A) an interfascicular repair of the (s) sciatic nerve proper and (t) tibial and (p) peroneal divisions using processed, decellularized allograft nerve (thin white arrow) and (B) the coaptation sites are reinforced with collagen nerve wraps (white block arrows). Pain Twelve patients had severe neuropathic pain necessitating combinations of oral analgesic medications, topical analgesics, and non-pharmacological interventions (desensitization and cognitive). The average postoperative pain reduction on the PI-NRS scale was seven points (a reduction of two points or a reduction of approximately 30% in the PI-NRS is a clinically important difference). Two patients reported no change in pain and one reported an increase. Among patients with gunshot wounds, the early nerve surgery group had a mean 5-point pain reduction (range 3–8), while the late group had a mean reduction of 2.8 points (range 2–8) (Table II). Two patients had spinal cord stimulators placed prior to surgery. Following nerve surgery, the stimulator was removed in one patient, and turned off in the other. Table II. Pain Scores Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Pain outcome. aFour patients were not taking narcotics preoperatively, one of these patients was taking narcotics at 6 mo after surgery. Table II. Pain Scores Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Pain outcome. aFour patients were not taking narcotics preoperatively, one of these patients was taking narcotics at 6 mo after surgery. Narcotic Usage The mean oxycodone (or equivalent) narcotic usage decreased from 127 mg (range 0-960 mg) preoperatively to 21.5 mg (range 0-188 mg) daily 6 mo postoperatively. Six patients were not taking any narcotics 6 mo postoperatively. Of those with gunshot wounds, the early nerve surgery patients had a 90% reduction in narcotic use compared with 82% for the late nerve surgery group (Table II). Graft Rejection and Complications No patients with cadaveric allografts developed deep wound infection, graft infection, or need for further surgery. The reoperation rate was 0%. Three patients had minor complications. One reported increased pain after surgery with an increase of two points on the PI-NRS scale 6 wk postoperatively. At the 6-mo postoperative evaluation, the pain was reduced to a minimal level and he was no longer taking narcotic pain medications. Another patient had an initial unexplained increase in narcotic use that subsequently resolved. One patient developed a superficial cellulitis that resolved after a short course of oral antimicrobial. Electrodiagnostics Ten of 13 patients obtained EMG/NCS studies at least 6 mo after surgery. Eight of 10 patients demonstrated electromyographic evidence of tibial and peroneal nerve reinnervation distal to the injury site; only three had detectable motor unit potentials distal to the knee, all in tibial nerve innervated muscles. No patients demonstrated reinnervation of the tibialis anterior muscle (peroneal nerve innervation). Functional Recovery No patient had regained full strength or meaningful functional recovery distal to the knee joint in the 2 or more yr follow-up period. Dorsiflexion strength remained 0/5 (MRC scale) in all. One patient had an elective trans-tibial amputation 3 yr later to facilitate ambulation. DISCUSSION In a recent study of 100 British military patients that described 261 total peripheral nerve injuries, Birch et al1 observed that two of the three most commonly injured peripheral nerves were the tibial and peroneal divisions of the sciatic nerve. Eighteen of the 261 peripheral nerve injuries were deemed to have poor outcomes defined as persistent and severe pain, failure of regeneration, and atrophy of innervated muscle groups at a mean follow up of 28.4 mo. Eleven of the 18 poor outcomes occurred in patients with injuries to one or both divisions of the sciatic nerve, with the peroneal nerve demonstrating the worst recovery. Three other large recent studies also demonstrated a poor prognosis for peroneal nerve injury.16,18,19 These findings are akin to our observations. In our study, 8 of 10 patients displayed electrophysiological evidence of new motor unit action potentials in muscles that were undetectable prior to neurolysis or grafting. This highly supports the utility of surgical techniques in assisting axonal sprouting and muscle reinnervation. Unfortunately, the degree of reinnervation was significantly less than what was necessary for improved neurological function. Notably, no patient ever demonstrated clinical dorsiflexion after surgical intervention with persistent 0/5 strength. Furthermore, there was never any sub-clinical, electrophysiological evidence of reinnervation of the tibialis anterior muscle. This was true even with reinnervation of the gastrocnemius muscle after a graft reconstruction in patients with complete transection of the tibial nerve portion of the sciatic nerve. Therefore, the distance required for axonal regrowth insufficiently explains why the tibialis anterior muscle is particularly resistant to reinnervation. Some patients subsequently underwent tendon transfers, and one elected to undergo a trans-tibial amputation due to persistent neurological deficits, precluding further axonal growth and longer term observations. In 1998, Kline et al13 noted significant recovery in the peroneal division of 36% of patients needing suture or graft repairs for sciatic nerve injuries. In a 2004 follow-up study by the same group, surgical outcome data following sciatic nerve injuries were reported for thigh level versus buttock level localizations.12 In the patients with gunshot wounds who required either direct epineural suture repair or sural nerve graft, good recovery in the tibial and peroneal components was 60% and 20%, respectively with buttock level lesions, and 86% and 50% with thigh-level lesions. Though modest, these results are significantly better compared with ours. The mechanisms of injury were likely more severe in our population, to include the gunshot wounds and explosions by powerful military-grade weaponry, and several other sites of bodily injury. All of our patients had preoperative electrodiagnostic EMG/NCS studies demonstrating complete absence of motor unit potentials in the tibialis anterior muscle. The other reports noted the use of electrodiagnostics, but did not report the data, and therefore it is possible that some of those patients may have had some preservation of peroneal nerve fibers preoperatively. Our cohort included only those with complete axonotmesis or neurotmesis. The differences in surgical techniques, to include the use of allograft as opposed to sural nerve autograph, cannot be discounted. Our findings demonstrate that surgery on the sciatic nerve to resect painful neuromas and repair the injured nerve with long length processed decellularized allograft is a safe and an efficacious means of reducing pain. Eleven of 12 patients with severe preoperative pain experienced significant reduction on the PI-NRS scale (the 0 to 10 scale that is routinely used in most clinical settings in the United States, with 0 being no pain and 10 being the worst pain that the patient has ever experienced or could imagine), with reduction of narcotic usage irrespective of whether they underwent early or late surgery. This is consistent with a previously completed study of combat-acquired nerve injuries that demonstrated great pain relief after neurolysis or nerve grafting in 83% of patients.1 A paper describing combat-associated sciatic nerve repairs in Iran noted neuropathic pain in less than 10% of patients, a marked difference from our experience.9 We wish to promote the viewpoint that early surgery to repair an injured sciatic nerve for the goal of achieving significant pain reduction should be an important, independent variable when considering the timing of surgery, as pain reduction promotes rehabilitation and patient well-being. It should be noted that this interpretation is somewhat limited given that or study is observational and we do not have a non-surgical control group, as well as the complexity of pain management in these patients who all had numerous other injuries and were often taking other agents that may affect pain (e.g., gabapentin). While the correlation is clear in our series of patients, this principle should cautiously be applied to the larger population of patients with combat-related peripheral nerve injuries. In our study, the possibility of surgical placebo bias in controlling pain cannot be discounted. However, the overall long-term reduction of pain months after surgery, in addition to the near-term benefits supports a genuine effect of surgery. There is also the potential that pain may have subsided independent of surgical intervention with passage of time from injury. Though possible, we observed that the late surgical group of gunshot wound patients in addition to the early group, still had persistent pain up until the surgical intervention, and both also had marked postoperative reductions in pain and decreased narcotic use. Neuropathic pain in severe PNI can be disabling, interfere with rehabilitation, and be irresponsive to pharmacological and other pain management techniques. Thus surgical intervention for the indication of pain control alone may be appropriate. In this series of sciatic nerve injury, 71% of the injuries occurred from gunshot wounds, in contrast to previous combat-related studies, where a blast mechanism was causative in 63% of all nerve injuries.1 In a series of 353 sciatic nerve injuries sustained over a greater than 30-yr period in a civilian population, approximately 22% (79/353) were attributed to gunshot wounds.12 The wide disparity in injury rate and functional effect of penetrating trauma between military and civilian patients underscores the need to report the management and challenges of sciatic nerve injury. The primary method to bridge a long nerve gap in our patients was to use commercially available processed decellularized freeze-dried human cadaver allografts. This practice mitigated the possibility of donor nerve graft site morbidity, and decreased surgical operative time as no additional time was taken to harvest autograft. While the use of sural nerve autograft is still considered the “gold standard” in the treatment of segmental nerve defects and was offered to our patients, it was not always possible or desirable in our patient population, as some patients sustained multiple traumatic injuries to all four extremities, and in some patients one or more amputations rendered autograft donor sites inappropriate for use. In addition, some patients elected to have the processed decellularized allograft used over autograft in anticipation of no further neurological deficit or complications. Recent studies demonstrated equivalence of processed decellularized allograft versus autograft to bridge short segment nerve injury,2,4 which further supported using longer length (greater than 5 cm) decellularized autograft. The supply of varied 1–5 mm diameter decellularized processed allograft nerve allowed us to provide an equivalent caliber match to the repaired nerve fascicles, this match potentially increases the number of axons able to cross the segmental defect. The decellularized processed allograft nerve also maintains many of the ultrastructural components of the native nerve, mitigating the Wallerian degeneration process and deleterious consequences of scar tissue in the defect area (Fig. 3C and D). Processed decellularized allograft nerve is deemed to be an acceptable alternative toward repairing segmental defects of large caliber nerves. There are several limitations of our study. It was comprised of a relatively small patient population, the form was a retrospective review, and there were no controls. The follow-up period was relatively short, namely 2 yr minimum; and it may require several more years to adequately assess long-term outcome. The most notable outcomes from this study were noted within 2 yr, in that nerve repair with long length processed decellularized freeze-dried cadaver allograft is safe, and markedly diminishes pain and improves management. These findings may facilitate decisions in civilian practice, where gunshot wounds are more likely to be of lower intensity, have less soft tissue destruction, and are more amenable to early surgical repair. CONCLUSIONS Traditionally, observation periods up to 6 mo following PNI are suggested prior to nerve repair to account for potential spontaneous reinnervation. However, during this observational period patients may suffer from severe neuropathic pain. We have demonstrated that the repair of combat-acquired sciatic nerve injury performed early after injury is likely a safe and efficacious means of reducing pain, despite no definitive improvement in motor strength. The high likelihood for significant pain reduction represents an important variable in the formulation of surgical decision, and may negate the traditional role of waiting 6 mo. Long length processed decellularized allograft use is safe, without serious complications, reduces donor site morbidity, and is practical in patients with multiple limb injuries. Presentations Portions of this work were presented in abstract and poster forum at the annual meeting of the Congress of Neurological Surgeons, Section of Disorders of the Spine and Peripheral Nerves, New Orleans, LA, USA, September 2015; American Society for Peripheral Nerve Annual Meeting, Paradise Island, Bahamas, January 2015; Society of Military Orthopedic Surgeons 56th Annual Meeting, Scottsdale, AZ, USA, December 2014. Acknowledgments We thank the support staff of the Walter Reed National Military Medical Center, Bethesda, MD, USA and the Peripheral Nerve Clinic staff for their assistance in performing this study. 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Google Scholar CrossRef Search ADS PubMed 21 Smith JK , Miller ME , Carroll CG , Faillace WJ , Nesti LJ , Cawley C , Landau ME : High resolution ultrasound in combat-related peripheral nerve injuries . Muscle and Nerve 2016 ; 54 : 1139 – 44 . Google Scholar CrossRef Search ADS PubMed 22 You S , Petrov T , Chung PH , Gordon T : The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells . Glia 1997 ; 20 : 87 – 100 . Google Scholar CrossRef Search ADS PubMed Author notes The views expressed in this presentation are those of the authors and do not reflect the official policy of the Department of the Army/Navy/Air Force, Department of Defense, U.S. Government, Walter Reed National Military Medical Center, or the Uniformed Services University of the Health Sciences. The identification of specific products does not constitute endorsement or implied endorsement on the part of the authors, Department of Defense, or any component agency. © Association of Military Surgeons of the United States 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Military Medicine Oxford University Press

Combat Injury of the Sciatic Nerve – An Institutional Experience

Military Medicine , Volume 183 (9) – Sep 1, 2018

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Abstract

Abstract Introduction Combat injury of the sciatic nerve tends to be severe with variable but often profound consequences, is often associated with widespread soft tissue and bone injuries, significant neurologic impairment, severe neuropathic pain, and a prolonged recovery time. There is little contemporary data that describes the treatment and outcome of this significant military acquired peripheral nerve injury. We describe our institution’s experience treating patients with combat-acquired sciatic nerve injury in the recent Iraq and Afghanistan wars. Materials and Methods IRB approval was obtained, and a retrospective review was performed of the records of 5,137 combat-related extremity injuries between June 2007 and June 2015 to identify patients with combat-acquired sciatic nerve injury without traumatic amputation of the injured leg. The most common mechanisms of injury were gunshot wound to the upper thigh or pelvis, followed by blast injury. Thirteen patients were identified that underwent sciatic nerve exploration and repair. Nine patients had nerve repair using long-length acellular cadaveric allografts. Five patients underwent nerve surgery within 30 d of injury and eight had surgery on a delayed basis. The postoperative follow-up period was at least 2 yr. Results Reduction of neuropathic pain was significant, 7/10 points on the 11-point pain intensity numerical rating scale. Eight patients displayed electrodiagnostic evidence of reinnervation distal to the injury zone; however, functional recovery was poor, as only 3 of 10 patients had detectable motor units distal to the knee, and recovery was only in tibial nerve innervated muscles. There were no serious surgical complications, in particular, wound infection or graft rejection associated with long-length cadaver allograft placement. Conclusion Early surgery to repair sciatic nerve injury possibly promotes significant pain reduction, reduces narcotic usage and facilitates a long rehabilitation process. Allograft nerve placement is not associated with serious complications. A follow-up period longer than 3 yr would be required and is ongoing to assess the efficacy of our treatment of patients with combat-acquired sciatic nerve injury. INTRODUCTION Combat-related peripheral nerve injuries (PNI) present exceedingly complex challenges for surgeons. The nerve injuries result from penetrating mechanisms such as gunshot wounds, blast fragments, or bone fractures associated with high-energy skeletal insult that cause nerve transection, stretch or shear (Fig. 1A–D). These nerve injuries are typically associated with local and systemic vascular compromise, bone and soft tissue damage.14,15 Several studies have demonstrated a relatively high prevalence of sciatic nerve injury, with very poor outcomes following surgical repair.16,18,19 Electrodiagnostic testing, magnetic resonance imaging, and ultrasound enhance the clinical evaluation with physiological and anatomic information that determine extent and localization of the nerve injury (Fig. 1, 1–6).21 These tests may facilitate decisions regarding the timing of surgical intervention post-trauma, as well as the specific approaches; however, whether they assist in long-term outcome is not completely known. This overall experience underscores the need for a continued effort to investigate the management of sciatic nerve injury. FIGURE 1. View largeDownload slide High-energy fractures such as (A) and (C) subtrochanteric and (B) and (D) diaphyseal femur fractures are commonly associated with traumatic sciatic nerve injury (A and B are pre-reduction/fixation, C and D are postoperative). Magnetic resonance imaging may be used to evaluate the 1 and 2 normal architecture of the sciatic nerve as well as 3 and 4 fascicular disruption and 5 and 6 distal stump neuroma (all are T1 weighted axial sequence images). Normal fascicles are hyper-attenuating “dots” within the iso- to slightly hypo-attenuating sciatic nerve that is indicated by the white arrows. At the point of fascicle disruption the hyper-attenuating dots can no longer be appreciated, and at the point of neuroma formation the overall diameter of the sciatic nerve is increased, with the neuroma itself appearing as a large and mixed attenuation area that does not appear to preserve the organized architecture of the nerve. FIGURE 1. View largeDownload slide High-energy fractures such as (A) and (C) subtrochanteric and (B) and (D) diaphyseal femur fractures are commonly associated with traumatic sciatic nerve injury (A and B are pre-reduction/fixation, C and D are postoperative). Magnetic resonance imaging may be used to evaluate the 1 and 2 normal architecture of the sciatic nerve as well as 3 and 4 fascicular disruption and 5 and 6 distal stump neuroma (all are T1 weighted axial sequence images). Normal fascicles are hyper-attenuating “dots” within the iso- to slightly hypo-attenuating sciatic nerve that is indicated by the white arrows. At the point of fascicle disruption the hyper-attenuating dots can no longer be appreciated, and at the point of neuroma formation the overall diameter of the sciatic nerve is increased, with the neuroma itself appearing as a large and mixed attenuation area that does not appear to preserve the organized architecture of the nerve. The best functional outcomes following surgery for PNI are in cases of partially injured nerves that undergo external neurolysis for decompression, or after direct end-to-end suture of a clean cut severed nerve. This is rarely the case in combat-related PNI, as large nerve gaps are often present and repair often requires nerve grafting or tubulization.3,20 A nerve graft is recommended over tubulization when the nerve gap is longer than 3 cm.20 Sural nerve autograft has been the gold standard for peripheral nerve reconstruction,3 but harvesting sufficient sural nerve autograft to span and connect a wide caliber nerve such as the sciatic nerve has been challenging and relatively ineffective.11 Alternatively, processed decellularized freeze-dried cadaveric allografts can be used. These allografts have good nerve regeneration potential, are not in limited supply, and are readily available for surgical implantation.4,7 The high incidence of associated multiple extremity injuries and amputations unique to military patients renders many donor sites unacceptable, providing further support for using allograft material as a practical graft alternative. Allograft use also diminishes potential donor site morbidity such as loss of sensation, wound infection, dehiscence, and postoperative painful donor site neuroma. Following PNI, up to 6 mo of observation prior to nerve repair may be accepted to allow for spontaneous proximal axonal sprouting and reinnervation. Seimienow et al20 question this approach. Cautious watchful waiting will not be beneficial in instances of nerve discontinuity. Furthermore, the supporting Schwann cells required for axonal regeneration and the motor endplates necessary for muscle reinnervation can be expected to degenerate by 18–24 mo. In rat models, delay in repair beyond 3 mo of PNI is associated with a decline in the number of viable Schwann cells and subsequent regenerated axons at the injury site.3,6,8,10,22 The purpose this retrospective study is to provide early outcome data following surgical repair of the sciatic nerve in patients injured during Operation Iraqi Freedom and Operation Enduring Freedom, hopefully to assist in the management of these patients and to possibly inspire further development in this area of military medicine. METHODS Our research protocol was submitted, reviewed, and approved after administrative, scientific, and ethical review by the Department of Research Programs and the Walter Reed National Military Medical Center Institutional Review Board (Research Project IRBNET # 402914-1). Patient Selection The inpatient and outpatient medical records, operative reports, radiologic and clinical photographs of all patients treated for sciatic nerve injuries between June 2007 and June 2017 treated at the Walter Reed Army Medical Center in Silver Spring, Maryland or the National Naval Medical Center in Bethesda, Maryland or the now merged Walter Reed National Military Medical Center in Bethesda, Maryland were retrospectively reviewed. We identified 13 patients who sustained sciatic nerve injury as a result of combat wounds that did not have a traumatic amputation of the injured leg. Data on patient age, sex, mechanism of injury, time from injury to nerve surgery, self-reported pain, narcotic and neuropathic pharmaceutical usage, and size of the nerve defect at time of surgery were recorded. All patients had documentation of preoperative clinical and electrophysiological assessments. Time from Injury to Surgery The date of injury was retrieved from the hospital medical records or the “in theater” (war zone) medical records. The date of the nerve surgery was defined as the date when definitive treatment of the nerve injury was performed. The time between the date of injury and date of nerve surgery was calculated and reported in days. Calculation of Narcotic Use All narcotic use was converted to oxycodone (the most common narcotic used in our patient population) use in milligrams per day using a narcotic conversion calculator (Simplicity GmbH, Therwil, Switzerland).17 Direct comparisons of oxycodone requirements were then made for study patients, and the percentage change over time per patient was calculated. We documented changes in narcotic use 6 mo after surgery to allow time for equilibration of pain regimens. A multidisciplinary Pain Team managed multi-trauma patients with complex pain medication requirements. Surgical Nerve Grafting Techniques Surgery was performed with the patient in prone position with the knees and hips flexed to approximately 15 degrees (Fig. 2A). Intraoperative electro-physiologic monitoring was performed to record compound muscle action potentials and nerve action potential (NAP) across regions of injured nerve. If after the initial external neurolysis a NAP could be recorded, then no further intervention was taken. If no NAP was recorded, then further external and internal neurolysis was performed, and fascicular stimulation with NAP recording was repeated. If NAPs were present in a fascicle then no further action was taken. If no fascicular NAPs were present, then serial axial cuts of the fascicle were made until normal fascicular architecture was appreciated at both the proximal and distal ends of the injured section. If the nerve was transected, then serial axial cuts of the proximal and distal stump neuromas were made until the normal fascicular architecture was appreciated. The remaining nerve gap was then measured and if the remaining nerve ends could be approximated with no tension then an end-to-end repair was performed. If direct approximation of the nerve ends was not possible without tension, then the nerve was grafted with ipsilateral sural nerve autograft, or processed decellularized freeze-dried cadaver allograft (Avance Nerve Graft, AxoGen Co., Alachua, FL, USA). Grafts were secured using 8-0 nylon and coaptation sites were wrapped with AxoGuard Nerve Protector (Cook Biotech Inc, West Lafayette, IN, USA). FIGURE 2. View largeDownload slide (A) An extensive infra-gluteal incision is used to gain exposure deep to the gluteal sling in high sciatic nerve injuries. (B) In this patient, a proximal sciatic nerve transection was found with stump neuromas at of both the common sciatic and tibial and peroneal components, represented by the white S, T, and P, respectively. The (C) proximal and (D) distal stump neuromas are resected to healthy appearing fascicular architecture. FIGURE 2. View largeDownload slide (A) An extensive infra-gluteal incision is used to gain exposure deep to the gluteal sling in high sciatic nerve injuries. (B) In this patient, a proximal sciatic nerve transection was found with stump neuromas at of both the common sciatic and tibial and peroneal components, represented by the white S, T, and P, respectively. The (C) proximal and (D) distal stump neuromas are resected to healthy appearing fascicular architecture. Evaluation of Pain We evaluated pain generated by the nerve injury with an emphasis on neuropathic pain, as this was the most disabling component. Neuropathic pain was defined as burning paresthesias (dysesthesias), electric shocks, hyperalgesia, and allodynia. Self-reported patient pain scores were recorded using the 11-point pain intensity numeric rating scale (PI-NRS)5 during preoperative encounters and postoperative assessments for each patient, and reported as a preoperative pain score and 6-wk postoperative pain score. Determination of Graft Rejection The patients who received cadaver allografts were monitored for potential graft rejection. The presence of fever, skin rash and/or erythema, onset of increasing local pain, or wound drainage were all noted during postoperative clinical exams as indicators of potential graft rejection. Outcome Assessments Each patient had multiple neurological assessments of motor and sensory deficits and at least one repeat electrodiagnostic electromyography/nerve conduction (EMG/NCS) study 6 mo after surgery. Patients were followed-up for a 3-yr minimum postoperative period. RESULTS Selected Patients Thirteen patients underwent surgical exploration of a combat-acquired sciatic nerve injury. The mean patient age was 28 yr with a range of 19–48 yr. All patients were men. The predominant mechanisms of injury were gunshot wound (9 of 13, 69%) followed by improvised explosive device (IED) blast (2 of 13, 12%), and rocket propelled grenade (RPG) or missile blast (2 of 13, 12%). Nearly all patients had additional injuries. Sixty percent had ipsilateral femoral bone shaft or neck fractures, seven (54%) of those injured by gunshot wound received multiple gunshot wounds to other parts of their body, two patients (12%) had contralateral lower extremity amputation, and two patients (12%) had major arterial injuries (Table I). Table I. Injury Characteristics Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Table I. Injury Characteristics Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Patient Number Mechanism of Injury Time from Injury to Surgery (D) Nerve Defect After Debridement 1 Missile blast 17 5 cm 2 IED blast 1,142 No defect 3 RPG blast 16 5 cm 4 GSW 245 6 cm 5 GSW 446 7 cm 6 IED blast 384 No defect 7 GSW 241 7 cm 8 GSW 332 No defect 9 GSW 251 6 cm 10 GSW 159 6 cm 11 GSW 30 7 cm 12 GSW 20 7 cm 13 GSW 28 6 cm Time from Injury to Nerve Surgery A bimodal distribution was noted whereby six patients underwent nerve exploration and repair less than 30 d from injury (range 12–30 d), and seven patients had nerve surgery at a significantly later time (mean 373 d, range 159–1142 d). These two groups were thenceforth referred to as the early treatment and late treatment group, respectively (Table I). Findings at the Time of Surgery Four patients had a neuroma-in-continuity with no recordable NAP distal to the lesion. In three, following external and internal neurolysis, NAPs were recorded and no further action was taken. The fourth had a neuroma-in-continuity in a portion of the peroneal division, and no NAP was recordable following internal and external neurolysis. These non-conducting fascicles were resected and an interfascicular graft with processed decellularized allograft nerve was placed. The other nine patients had transected sciatic nerves exhibiting stump neuromas of either or both the peroneal or tibial components (Fig. 2B). In these nerves, the stump neuromas were resected until normal appearing fascicles were exposed (Fig. 2C and D). An end-to-end nerve repair was possible in one patient. The remainder had nerve gap repair with multiple interfascicular nerve grafts using either decellularized allograft nerve or sural nerve autograft (Fig. 3A and B). The mean length of the nerve gap after debridement of the retracted, scarred nerve was 6.2 cm, with a maximum of 7 cm. FIGURE 3. View largeDownload slide The segmental nerve defect is addressed with (A) an interfascicular repair of the (s) sciatic nerve proper and (t) tibial and (p) peroneal divisions using processed, decellularized allograft nerve (thin white arrow) and (B) the coaptation sites are reinforced with collagen nerve wraps (white block arrows). FIGURE 3. View largeDownload slide The segmental nerve defect is addressed with (A) an interfascicular repair of the (s) sciatic nerve proper and (t) tibial and (p) peroneal divisions using processed, decellularized allograft nerve (thin white arrow) and (B) the coaptation sites are reinforced with collagen nerve wraps (white block arrows). Pain Twelve patients had severe neuropathic pain necessitating combinations of oral analgesic medications, topical analgesics, and non-pharmacological interventions (desensitization and cognitive). The average postoperative pain reduction on the PI-NRS scale was seven points (a reduction of two points or a reduction of approximately 30% in the PI-NRS is a clinically important difference). Two patients reported no change in pain and one reported an increase. Among patients with gunshot wounds, the early nerve surgery group had a mean 5-point pain reduction (range 3–8), while the late group had a mean reduction of 2.8 points (range 2–8) (Table II). Two patients had spinal cord stimulators placed prior to surgery. Following nerve surgery, the stimulator was removed in one patient, and turned off in the other. Table II. Pain Scores Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Pain outcome. aFour patients were not taking narcotics preoperatively, one of these patients was taking narcotics at 6 mo after surgery. Table II. Pain Scores Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Days from Injury to Surgery Preoperative NRS-11 Score Postoperative (6 wks) NRS-11 Score Narcotic Usage at 6 mo Early less than 31 d (N = 5) 8 range 10–6 2.2 range 4–0 90% reduction Standard greater than 150 d (N = 8) 5.9 range 9–1 4.3 range 7–1 50% reductiona GSW patients only  Early less than 31 d (N = 3) 8.3 3.3 90% reduction  Standard greater than 150 d (N = 6) 4 3 82.5% reduction Pain outcome. aFour patients were not taking narcotics preoperatively, one of these patients was taking narcotics at 6 mo after surgery. Narcotic Usage The mean oxycodone (or equivalent) narcotic usage decreased from 127 mg (range 0-960 mg) preoperatively to 21.5 mg (range 0-188 mg) daily 6 mo postoperatively. Six patients were not taking any narcotics 6 mo postoperatively. Of those with gunshot wounds, the early nerve surgery patients had a 90% reduction in narcotic use compared with 82% for the late nerve surgery group (Table II). Graft Rejection and Complications No patients with cadaveric allografts developed deep wound infection, graft infection, or need for further surgery. The reoperation rate was 0%. Three patients had minor complications. One reported increased pain after surgery with an increase of two points on the PI-NRS scale 6 wk postoperatively. At the 6-mo postoperative evaluation, the pain was reduced to a minimal level and he was no longer taking narcotic pain medications. Another patient had an initial unexplained increase in narcotic use that subsequently resolved. One patient developed a superficial cellulitis that resolved after a short course of oral antimicrobial. Electrodiagnostics Ten of 13 patients obtained EMG/NCS studies at least 6 mo after surgery. Eight of 10 patients demonstrated electromyographic evidence of tibial and peroneal nerve reinnervation distal to the injury site; only three had detectable motor unit potentials distal to the knee, all in tibial nerve innervated muscles. No patients demonstrated reinnervation of the tibialis anterior muscle (peroneal nerve innervation). Functional Recovery No patient had regained full strength or meaningful functional recovery distal to the knee joint in the 2 or more yr follow-up period. Dorsiflexion strength remained 0/5 (MRC scale) in all. One patient had an elective trans-tibial amputation 3 yr later to facilitate ambulation. DISCUSSION In a recent study of 100 British military patients that described 261 total peripheral nerve injuries, Birch et al1 observed that two of the three most commonly injured peripheral nerves were the tibial and peroneal divisions of the sciatic nerve. Eighteen of the 261 peripheral nerve injuries were deemed to have poor outcomes defined as persistent and severe pain, failure of regeneration, and atrophy of innervated muscle groups at a mean follow up of 28.4 mo. Eleven of the 18 poor outcomes occurred in patients with injuries to one or both divisions of the sciatic nerve, with the peroneal nerve demonstrating the worst recovery. Three other large recent studies also demonstrated a poor prognosis for peroneal nerve injury.16,18,19 These findings are akin to our observations. In our study, 8 of 10 patients displayed electrophysiological evidence of new motor unit action potentials in muscles that were undetectable prior to neurolysis or grafting. This highly supports the utility of surgical techniques in assisting axonal sprouting and muscle reinnervation. Unfortunately, the degree of reinnervation was significantly less than what was necessary for improved neurological function. Notably, no patient ever demonstrated clinical dorsiflexion after surgical intervention with persistent 0/5 strength. Furthermore, there was never any sub-clinical, electrophysiological evidence of reinnervation of the tibialis anterior muscle. This was true even with reinnervation of the gastrocnemius muscle after a graft reconstruction in patients with complete transection of the tibial nerve portion of the sciatic nerve. Therefore, the distance required for axonal regrowth insufficiently explains why the tibialis anterior muscle is particularly resistant to reinnervation. Some patients subsequently underwent tendon transfers, and one elected to undergo a trans-tibial amputation due to persistent neurological deficits, precluding further axonal growth and longer term observations. In 1998, Kline et al13 noted significant recovery in the peroneal division of 36% of patients needing suture or graft repairs for sciatic nerve injuries. In a 2004 follow-up study by the same group, surgical outcome data following sciatic nerve injuries were reported for thigh level versus buttock level localizations.12 In the patients with gunshot wounds who required either direct epineural suture repair or sural nerve graft, good recovery in the tibial and peroneal components was 60% and 20%, respectively with buttock level lesions, and 86% and 50% with thigh-level lesions. Though modest, these results are significantly better compared with ours. The mechanisms of injury were likely more severe in our population, to include the gunshot wounds and explosions by powerful military-grade weaponry, and several other sites of bodily injury. All of our patients had preoperative electrodiagnostic EMG/NCS studies demonstrating complete absence of motor unit potentials in the tibialis anterior muscle. The other reports noted the use of electrodiagnostics, but did not report the data, and therefore it is possible that some of those patients may have had some preservation of peroneal nerve fibers preoperatively. Our cohort included only those with complete axonotmesis or neurotmesis. The differences in surgical techniques, to include the use of allograft as opposed to sural nerve autograph, cannot be discounted. Our findings demonstrate that surgery on the sciatic nerve to resect painful neuromas and repair the injured nerve with long length processed decellularized allograft is a safe and an efficacious means of reducing pain. Eleven of 12 patients with severe preoperative pain experienced significant reduction on the PI-NRS scale (the 0 to 10 scale that is routinely used in most clinical settings in the United States, with 0 being no pain and 10 being the worst pain that the patient has ever experienced or could imagine), with reduction of narcotic usage irrespective of whether they underwent early or late surgery. This is consistent with a previously completed study of combat-acquired nerve injuries that demonstrated great pain relief after neurolysis or nerve grafting in 83% of patients.1 A paper describing combat-associated sciatic nerve repairs in Iran noted neuropathic pain in less than 10% of patients, a marked difference from our experience.9 We wish to promote the viewpoint that early surgery to repair an injured sciatic nerve for the goal of achieving significant pain reduction should be an important, independent variable when considering the timing of surgery, as pain reduction promotes rehabilitation and patient well-being. It should be noted that this interpretation is somewhat limited given that or study is observational and we do not have a non-surgical control group, as well as the complexity of pain management in these patients who all had numerous other injuries and were often taking other agents that may affect pain (e.g., gabapentin). While the correlation is clear in our series of patients, this principle should cautiously be applied to the larger population of patients with combat-related peripheral nerve injuries. In our study, the possibility of surgical placebo bias in controlling pain cannot be discounted. However, the overall long-term reduction of pain months after surgery, in addition to the near-term benefits supports a genuine effect of surgery. There is also the potential that pain may have subsided independent of surgical intervention with passage of time from injury. Though possible, we observed that the late surgical group of gunshot wound patients in addition to the early group, still had persistent pain up until the surgical intervention, and both also had marked postoperative reductions in pain and decreased narcotic use. Neuropathic pain in severe PNI can be disabling, interfere with rehabilitation, and be irresponsive to pharmacological and other pain management techniques. Thus surgical intervention for the indication of pain control alone may be appropriate. In this series of sciatic nerve injury, 71% of the injuries occurred from gunshot wounds, in contrast to previous combat-related studies, where a blast mechanism was causative in 63% of all nerve injuries.1 In a series of 353 sciatic nerve injuries sustained over a greater than 30-yr period in a civilian population, approximately 22% (79/353) were attributed to gunshot wounds.12 The wide disparity in injury rate and functional effect of penetrating trauma between military and civilian patients underscores the need to report the management and challenges of sciatic nerve injury. The primary method to bridge a long nerve gap in our patients was to use commercially available processed decellularized freeze-dried human cadaver allografts. This practice mitigated the possibility of donor nerve graft site morbidity, and decreased surgical operative time as no additional time was taken to harvest autograft. While the use of sural nerve autograft is still considered the “gold standard” in the treatment of segmental nerve defects and was offered to our patients, it was not always possible or desirable in our patient population, as some patients sustained multiple traumatic injuries to all four extremities, and in some patients one or more amputations rendered autograft donor sites inappropriate for use. In addition, some patients elected to have the processed decellularized allograft used over autograft in anticipation of no further neurological deficit or complications. Recent studies demonstrated equivalence of processed decellularized allograft versus autograft to bridge short segment nerve injury,2,4 which further supported using longer length (greater than 5 cm) decellularized autograft. The supply of varied 1–5 mm diameter decellularized processed allograft nerve allowed us to provide an equivalent caliber match to the repaired nerve fascicles, this match potentially increases the number of axons able to cross the segmental defect. The decellularized processed allograft nerve also maintains many of the ultrastructural components of the native nerve, mitigating the Wallerian degeneration process and deleterious consequences of scar tissue in the defect area (Fig. 3C and D). Processed decellularized allograft nerve is deemed to be an acceptable alternative toward repairing segmental defects of large caliber nerves. There are several limitations of our study. It was comprised of a relatively small patient population, the form was a retrospective review, and there were no controls. The follow-up period was relatively short, namely 2 yr minimum; and it may require several more years to adequately assess long-term outcome. The most notable outcomes from this study were noted within 2 yr, in that nerve repair with long length processed decellularized freeze-dried cadaver allograft is safe, and markedly diminishes pain and improves management. These findings may facilitate decisions in civilian practice, where gunshot wounds are more likely to be of lower intensity, have less soft tissue destruction, and are more amenable to early surgical repair. CONCLUSIONS Traditionally, observation periods up to 6 mo following PNI are suggested prior to nerve repair to account for potential spontaneous reinnervation. However, during this observational period patients may suffer from severe neuropathic pain. We have demonstrated that the repair of combat-acquired sciatic nerve injury performed early after injury is likely a safe and efficacious means of reducing pain, despite no definitive improvement in motor strength. The high likelihood for significant pain reduction represents an important variable in the formulation of surgical decision, and may negate the traditional role of waiting 6 mo. Long length processed decellularized allograft use is safe, without serious complications, reduces donor site morbidity, and is practical in patients with multiple limb injuries. Presentations Portions of this work were presented in abstract and poster forum at the annual meeting of the Congress of Neurological Surgeons, Section of Disorders of the Spine and Peripheral Nerves, New Orleans, LA, USA, September 2015; American Society for Peripheral Nerve Annual Meeting, Paradise Island, Bahamas, January 2015; Society of Military Orthopedic Surgeons 56th Annual Meeting, Scottsdale, AZ, USA, December 2014. Acknowledgments We thank the support staff of the Walter Reed National Military Medical Center, Bethesda, MD, USA and the Peripheral Nerve Clinic staff for their assistance in performing this study. 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The identification of specific products does not constitute endorsement or implied endorsement on the part of the authors, Department of Defense, or any component agency. © Association of Military Surgeons of the United States 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

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Military MedicineOxford University Press

Published: Sep 1, 2018

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