SURGICAL ONCOLOGY AND RECONSTRUCTION
Sensory Outcomes After Reconstruction of Lingual and Inferior Alveolar Nerve Discontinuities Using Processed Nerve Allograft—A Case Series John R. Zuniga, DMD, MS, PhD* Purpose:
The present study describes 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.
Patients and Methods:
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 effectiveness and safety. Sensory assessments were conducted preoperatively and 3, 6, and 12 months after surgical reconstruction. The outcomes population, those with at least 6 months of postoperative 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 preoperatively and at each follow-up appointment. Improvement was defined as a score of normal, mild, or moderate.
Results:
The neurosensory outcomes from LNs and IANs that had been microsurgically 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. Also, 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.
Conclusions: These results suggest 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. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 73:734-744, 2015
Trigeminal nerve injuries have a profound effect on the patients experiencing them. Patients have reported functional issues such as drooling while eating or drinking, unintentional chewing of the tongue and lip, pain, heat and cold sensitivity, and difficulty speaking.1 The branches of the trigeminal nerve
most often subject to injury, primarily owing to their location and variable anatomic positioning, are the lingual nerves (LNs) and inferior alveolar nerves (IANs). Even with imaging, many of these injuries cannot be avoided. In addition, certain dentoalveolar procedures, such as surgical excision of cysts and
*Professor and Robert V. Walker DDS Chair, Division of Oral and
versity of Texas Southwestern Medical Center at Dallas, 5323
Maxillofacial Surgery, Department of Surgery, University of Texas
Harry Hines Blvd, Dallas, TX 75390-9109; e-mail: John.Zuniga@
Southwestern Medical Center at Dallas, Dallas, TX.
utsouthwestern.edu
Dr Zuniga is a paid consultant for AxoGen Inc. (Alachua, FL). No financial support was provided by AxoGen to perform or report the
Received March 21 2014 Accepted October 31 2014
present study.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
Conflict of Interest Disclosures: None of the authors reported any
0278-2391/14/01631-0
disclosures.
http://dx.doi.org/10.1016/j.joms.2014.10.030
Address correspondence and reprint requests to Dr Zuniga: Division of Oral and Maxillofacial Surgery, Department of Surgery, Uni-
734
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JOHN R. ZUNIGA
tumors, often necessitate removal of segments of the patient’s nerve tissue. Historically, the surgical options for reconstruction of trigeminal nerves have been limited, with severe and permanent neurosensory impairment. These types of injuries necessitate surgical intervention to recover functionality. One of the earliest and most commonly used techniques to reconstruct a peripheral nerve was direct neurorrhaphy. Direct neurorrhaphy is indicated when the transected nerve can be coapted without tension. Nerve regeneration can be negatively affected by tension, which will constrict the cross-sectional area of the fascicles of the nerve. This constriction increases the internal pressure, compromising the intrafascicular nutritive blood flow.2,3 Preclinical studies have shown ischemia with as little as 5% elongation and impaired axonal regeneration with 7.4% nerve elongation.2,4 In an attempt to alleviate tension, techniques were developed for tension-free repairs. One of the more common tension-free repair options is to reconstruct the nerve defect with an autologous nerve graft or autograft. Typically, the donor nerves for trigeminal nerve injuries have been the sural and greater auricular nerves. The use of autografts for the surgical reconstruction of trigeminal nerve injuries has been well-documented, with positive outcomes in recent published studies ranging from 87.3 to 100%.5-7 However, this reconstructive technique necessitates a secondary surgical procedure to remove healthy donor nerve tissue. Several comorbidities have been associated with harvesting of an autologous nerve graft. Because a healthy nerve is sacrificed, donor site morbidity can occur.8,9 Also, the operating time and risk of infection are increased. A review of the long-term effects of sural nerve harvesting found sural nerve donor site morbidity after 34 years of follow-up. Of the 29 subjects in the study, 76% had sensory loss, 34% had cold sensitivity, 24% had scar discomfort, 17% reported pain, and 17% had functional impairment.10 Hollow tube conduits, also referred to as nerve cuffs, were developed as an off-the-shelf option to alleviate tension, reduce misalignment of the severed nerve endings, and isolate the reconstructed nerve during the healing process from the surrounding tissues.11-13 Regeneration through conduits is achieved predominately through a fibrin cable formed between the proximal and distal nerve stumps. Because axonal regeneration using a conduit predominately relies on the gross guidance provided by the fibrin clot, the clinical outcomes become more variable at gap lengths greater than 5 mm.14 However, wrapping a peripheral nerve after neurolysis or nerve reconstruction with a conduit or nerve wrap isolates the injured nerve from the surrounding tissue, minimizes scar formation and the potential for nerve entrapment, and allows for the nerve to glide.15 A 9-
patient series using a collagen hollow tube conduit to wrap around severed LNs (n = 6) and IANs (n = 3) reanastomosed by direct neurorrhaphy showed favorable results, with 8 of 9 nerve reconstructions showing sensory improvement.16 Processed nerve allografts were developed as an offthe-shelf option for tension-free repairs. Processed nerve allografts are derived from nerve tissue from human donors. Once recovered from the donor, the nerve allograft is cleaned to remove cells and cellular debris, treated with enzymes to suppress naturally occurring inhibitors to axonal regeneration, and sterilized with gamma irradiation. After processing, sizing, and trimming, the allografts are stored frozen, at less than 40 C, for up to 3 years. Before implantation, the processed nerve allografts are completely thawed in either sterile saline or lactated Ringer’s solution for 5 to 10 minutes. The thawed allografts are implanted using the same microsurgical technique used for implanting an autograft nerve. Processed nerve allografts have been shown to be clinically effective and safe for peripheral nerve discontinuities from 5 to 50 mm.17 In the largest multicenter registry for peripheral nerve reconstruction, peripheral nerves reconstructed with processed nerve allograft had an overall 87.3% meaningful recovery using the Medical Research Council Classification of nerve injuries.18 A published single case report on an inferior alveolar nerve reconstructed with a processed nerve allograft showed meaningful recovery of S3+ sensation in 1 patient.19 Previous clinical studies of processed nerve allografts focused on reconstructions within the upper extremity. These reconstructions were predominately performed by orthopedic and plastic surgeons. With only limited clinical data on the outcomes after trigeminal nerve reconstruction using processed nerve allografts and considering that most of the surgeons who perform microsurgery on trigeminal nerves have been oral-maxillofacial surgeons, it is important to monitor and report on the outcomes of patients who undergo trigeminal nerve reconstruction with an allograft. The present case series describes the results of using processed nerve allografts (Avance Nerve Graft, AxoGen, Inc, Alachua, FL) to microsurgically reconstruct LN and IAN defects.
Patients and Methods The total population for processed nerve allografts included 26 subjects with 28 nerve injuries. The present retrospective study was approved by the institutional review board at the University of Texas Southwestern Medical Center at Dallas (protocol 062010-166). All nerve injuries were deemed to have a Sunderland IV or V degree of injury before reconstruction. All nerve reconstructions were
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performed from 2007 to 2013. Two subjects underwent bilateral nerve reconstruction. Six nerve defects resulted from surgical excision of benign tumors. Preoperatively, the nerves had been evaluated as normal. With complete transection of the nerve, no neurosensory function was present (ie, they met the requirements for a Sunderland class V degree of injury). Of the 26 patients in the study, 14 were male and 12 were female, with 17 LN and 11 IAN injuries. The etiology of the nerve injuries was third molar odontectomy (17 injuries, 61%), dental implant surgery (3 injuries, 11%), oncologic surgery (6 injuries, 21%), and bilateral sagittal split osteotomy (2 injuries, 7%). The subjects ranged in age from 9 to 82 years (mean age 36.5 18.3). The interval until reconstructive microsurgery ranged from 0 to 518 days (average 152 160). The mean nerve gap was 32.4 24.1 mm (range 8 to 70; Table 1). Sensory assessments of the trigeminal nerve injuries were conducted preoperatively and 3, 6, and 12 months after surgical reconstruction with
Table 1. DEMOGRAPHICS OF TOTAL AND OUTCOMES POPULATIONS
Variable Gender Male Female Age (yr) Mean SD Range Interval to repair (days) Mean SD Range Repair within 90 days Repair after 90 days Etiology Third molar Implant Oncologic BSSO Nerve location Lingual Inferior alveolar Gap length (mm) Mean SD Range
Total Population
Outcomes Population
14 (54) 12 (46)
11 (52) 10 (48)
36.5 18.3 9-82
33.3 17.0 9-67
152 160 0-518 12 (43) 16 (57)
148 160 0-518 10 (43) 13 (57)
17 (61) 3 (11) 6 (21) 2 (7)
13 (57) 2 (8.5) 6 (26) 2 (8.5)
17 (61) 11 (39)
15 (65) 8 (35)
32.4 24.1 8-70
34.2 25.5 8-70
a processed nerve allograft. The neurosensory assessment included brush stroke directional sensation, static 2-point discrimination, contact detection, pressure pain threshold, and pressure pain tolerance. From the neurosensory assessment, the neurosensory test (NST), sensory impairment was assessed as normal, mild, moderate, severe, or complete20 (Table 2). The NST assessments in the present study are reported for the latest follow-up appointment. Subjects with at least 6 months of follow-up neurosensory assessments were included in the outcomes analysis. A repair was considered to have resulted in improvement if it scored as normal, mild, or moderate using the NST scale. Additional analysis of the data set was conducted to search for trends in outcomes by nerve gap size, interval to surgery, nerve location, gender, and comorbidities known to have an effect on nerve recovery. Neuropathic pain was assessed pre- and postoperatively as stimulus-induced or spontaneous pain associated with allodynia (painful response to normally nonpainful stimulus at level A testing), hyperpathia (painful response to repetitive nonpainful stimulus with after sensation, overshoot, summation, or delayed onset at level B testing), hyperalgesia (lowered pain threshold to painful stimulus at level C testing), or anesthesia dolorosa or sympathetically mediated (anesthetic or autonomic blocks at level D testing). In addition to the neurosensory assessment, the subjects were monitored postoperatively for adverse experiences, such as infection, graft rejection, and wound dehiscence.
Table 2. NEUROSENSORY TESTING ASSESSMENT SCALE USED TO EVALUATE SENSORY NERVE RECOVERY
Reported Sensory Level Levels A, B, and C within normative limits Level A abnormal, but level B and C within normative limits Levels A and B abnormal, but level C within normative limits Levels A and B abnormal, but level C has elevated measures Levels A and B abnormal and level C has absent measures
NST Normal Mild Moderate Severe Complete
Data presented as n (%), unless otherwise noted. Abbreviations: BSSO, bilateral sagittal split osteotomy; SD, standard deviation.
Level A test, spatiotemporal sensory perception with brushstroke, directional sensitivity, and static 2-point discrimination; level B test, contact detection with Semmes-Weinstein monofilaments; level C test, pain threshold and tolerance using an algometer, thermode, or sharp instrument. Abbreviation: NST, neurosensory testing. Data from Zuniga et al.20
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
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JOHN R. ZUNIGA SURGICAL TECHNIQUE
The LNs were exposed using an intraoral supraperiosteal approach, and the IANs were exposed using transoral lateral corticotomy for those without a tumor etiology.21 An extraoral approach for the subjects with benign tumors was used to expose the IAN. On exposure of the LN or IAN, an operating microscope with 25 magnification was brought into the operative field and positioned. External neurolysis was performed, and, if indicated, neuromas, scar tissue, or benign tumors were excised. The severed nerve endings were examined and trimmed to normal fascicular anatomy. After determining that a tension-free repair could not be performed using direct neurorrhaphy, an allograft nerve graft was selected according to the length and diameter of the proximal nerve stump. Processed nerve allografts are available in several diameters (range 1 to 5 mm) and lengths (range 15 to 70 mm; Table 3). LN defects were reconstructed using either 3- to 4-mm (female subjects) or 4- to 5-mm (male subjects) processed nerve allografts. IAN defects were reconstructed with 2- to 3-mm (male and female subjects) processed nerve allografts. The allograft length was selected according to the length of the nerve defect. LN defects ranged from 8 to 30 mm and IAN defects from 15 to 70 mm. The selected processed nerve allograft was opened, thawed for up to 10 minutes in room temperature saline, and, if necessary, trimmed to size. Each of the severed nerve endings was coapted to the processed nerve allograft using 9-0 monofilament nylon sutures on a cutting edge needle. Initially, 3 sutures were placed at the 4-, 8-, and 12-o’clock positions at each coaptation site (Fig 1). If any gaps were observed between the nerve stumps and the processed nerve allograft, up to 3 additional sutures were placed at the 2-, 6-, and 10-o’clock positions. Table 3. PROCESSED NERVE ALLOGRAFT (AVANCE NERVE GRAFT, AXOGEN, INC) SIZES AND PRODUCT CODES
Length (mm) Diameter (mm) 1-2 2-3* 3-4y 4-5z
15
30
50
70
111,215 211,215 311,215 411,215
111,230 211,230 311230 411,230
111,250 211,250 311,250 411,250
111,270 211,270 311,270 411,270
* All inferior alveolar nerves were reconstructed with processed nerve allografts 2-3 mm in diameter. y All lingual nerves in the females were reconstructed with processed nerve allografts 3-4 mm in diameter. z All lingual nerves in the males were reconstructed with processed nerve allografts 4-5 mm in diameter. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Next, the repaired nerve was examined and any excess suture trimmed. Also, all but 3 nerve reconstructions used a commercially available nerve wrap in conjunction with the repair (AxoGuard, AxoGen, Inc, Alachua, FL). These nerve wraps served to isolate the nerve repair from the traumatized wound bed, minimized the risk of entrapment, and contained regenerating axons during the healing process. Once the reconstruction was complete, the microscope was moved out of the operative field, and the surgical sites were closed according to standard of care procedures.
Results A total of 21 subjects with 23 nerve injuries had sufficient postoperative follow-up data available. Improvement in sensory function was reported for 87% of the reconstructions (Table 4). The neurosensory test results ranged from normal to severe across the outcomes population. The NST impairment scores reported at the last follow-up visit were normal for 12 (52%), mild for 2 (9%), moderate for 6 (26%), and severe for 3 (13%; Fig 2). The subjects were grouped by treated gap length into 2 categories, 8 to 20 mm and 30 to 70 mm. Of the 14 injuries with a gap length of 8 to 20 mm, 86% showed neurosensory improvement compared with 89% neurosensory improvement for injuries with a gap length of 30 to 70 mm. Neurosensory improvement occurred across all gap lengths, including long defects at 70 mm, for which 6 (5 normal, 1 moderate) of the 7 nerves had improvement in their neurosensory impairment scores (Table 5). The interval to repair did not seem to be a determining factor on neurosensory recovery. The reconstruction with the longest interval between injury and surgical reconstruction, 518 days, had normal neurosensory impairment (Table 6). Of the 10 reconstructions occurring within the first 90 days, 100% had improvement in the neurosensory impairment scores. In contrast, of the 13 injuries repaired more than 90 days after the original injury, 77% had improvement (Figs 3, 4). The nerve location did not appear to have an impact on neurosensory recovery. The LN injuries had improved sensory recovery in 87% of the nerves reconstructed. Similarly, 88% of IANs were assessed as having neurosensory improvement (Figs 5 to 7). The subject’s gender did not appear to have an impact on neurosensory recovery. Females reported sensory improvement in 10 of 12 nerves reconstructed with a processed nerve allograft, and males reported sensory improvement in 10 of 11 nerves reconstructed (Fig 8).
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FIGURE 1. Microsuture sequence of neurorrhaphy. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
When evaluating outcomes by age group (pediatric, adult, and older adult), sensory improvement was reported in 3 of 4 injuries in the pediatric cohort (sub-
jects aged 9 to 18 years), 10 of 11 in the adult cohort (subjects aged 19 to 49 years), and 5 of 6 injuries in the older adult cohort (subjects aged 50 to 67 years).
Table 4. NEUROSENSORY IMPAIRMENT OUTCOME AFTER NERVE RECONSTRUCTION WITH PROCESSED NERVE ALLOGRAFT
Pt. No. Z01 Z02 Z03 Z04 Z06 Z07 Z08 Z09 Z10 Z11 Z11L Z12 Z13 Z14 Z15 Z15L Z16 Z17 Z18 Z20 Z21 Z22 Z26
Age (yr)
Gender
Injury Type (Class)
67 26 17 50 35 22 27 9 34 57 Repeat 21 57 16 31 Repeat 34 37 19 11 22 50 58
Male Female Male Male Male Female Male Male Male Female Repeat Female Female Female Female Repeat Male Male Female Male Female Female Male
IAN V LN V LN IV LN IV IAN V LN V LN V IAN IV LN V IAN IV IAN IV LN IV LN IV-V LN IV LN V LN V LN V IAN V LN V IAN V LN IV IAN V LN V
Etiology
Gap Length (mm)
Interval to Repair (days)
Wrap Used
Oncologic Third molar Third molar Third molar Oncologic BSSO Third molar Oncologic BSSO Implant Implant Third molar Third molar Third molar Third molar Third molar Third molar Oncologic Third molar Oncologic Third molar Oncologic Third molar
50 20 20 18 70 15 15 70 15 70 70 15 15 15 15 15 15 70 30 70 15 70 8
0 80 112 90 0 147 153 0 42 228 228 146 484 518 116 116 57 0 493 0 118 0 286
Yes No Yes No Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Abbreviations: NST, neurosensory testing; Pt. No., patient number. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Postoperative NST Outcome Normal Moderate Severe Moderate Normal Normal Normal Normal Moderate Severe Moderate Moderate Mild Normal Moderate Severe Normal Normal Normal Normal Normal Normal Mild
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FIGURE 2. Neurosensory impairment scores for nerves reconstructed with processed nerve allografts. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Table 5. NEUROSENSORY IMPAIRMENT SCORES AND GAP LENGTH (NERVE DEFICIT)
NST Impairment Score Normal Mild Moderate Severe Complete
Gap Length (mm) 15, 15, 15, 15, 15, 30, 50, 70, 70, 70, 70, 70 8, 15 15, 15, 15, 18, 20, 70 15, 20, 70 —
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
FIGURE 3. Neurosensory impairment scores stratified by the interval to repair within 90 days of injury. NST, neurosensory testing. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Table 6. NEUROSENSORY IMPAIRMENT SCORES AND INTERVAL TO REPAIR
NST Impairment Score Normal Mild Moderate Severe Complete
Interval to Repair (days) 0, 0, 0, 0, 0, 0, 57, 118, 147, 153, 493, 518 286, 484 42, 80, 90, 116, 146, 228 112, 116, 228 —
Abbreviation: NST, neurosensory testing.
FIGURE 4. Neurosensory impairment scores stratified by an interval to repair longer than 90 days of injury. NST, neurosensory testing.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
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SENSORY OUTCOMES AFTER LN AND IAN RECONSTRUCTION
FIGURE 5. Neurosensory impairment scores stratified by nerve location (lingual nerve and inferior alveolar nerve) did not show a difference in neurosensory recovery. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
In the outcomes population, all 4 subjects with conditions known to impede nerve regeneration (smoking, diabetes, hypertension) had sensory improvement, with 2 of these 4 subjects reporting normal NST impairment scores (Table 7). Two subjects reported preoperative neuropathic pain. These 2 subjects had no change in their neuropathic pain scores after surgery. The subjects without neuropathic pain preoperatively did not develop neuropathic pain postoperatively. None of the subjects reported adverse events, such as infection, graft rejection, or wound dehiscence.
Discussion LN and IAN injuries have been reported as a result of dentoalveolar surgery. Some of the major causes of these types of injuries are third molar odontectomy, dental implant surgery, orthognathic surgery, and oncologic surgery for cysts and benign and malignant tumors. Published studies have reported incidence
rates for permanent neurosensory dysfunction from dentoalveolar surgery ranging from 0 to 100% for these procedures22 (Table 8). Microsurgical techniques for trigeminal nerve defects have been developed for the reconstruction of these defects. If a nerve defect can be directly coapted without tension, primary neurorrhaphy is typically performed. However, when the segmental defect is sufficient to necessitate using a ‘‘bridging’’ material to coapt the severed nerve endings, tension-free techniques are indicated. Historically, the patient’s own tissue has been used in tension-free repairs of trigeminal nerve injuries with some limited usage of hollow tube conduits. Autografts are beneficial, because they have inherent structural and neurochemical guides that support axonal regeneration. However, the autograft technique can only be performed by surgically removing a healthy uninvolved nerve deemed less important than the nerve targeted for reconstruction. The comorbidities associated with a secondary surgical site, the additional operative time for harvesting the autograft,
FIGURE 6. Neurosensory impairment scores for lingual nerve repairs. NST, neurosensory testing.
FIGURE 7. Neurosensory impairment scores for inferior alveolar nerve (IAN) repairs. NST, neurosensory testing.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
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FIGURE 8. Neurosensory impairment scores stratified by gender did not vary. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
and the variability and possible limitation in size (diameter and length) led to the development of off-the-shelf alternatives, such as the hollow tube conduit and processed nerve allograft. The nerve conduit acts as a containment device for regenerating axons. Regeneration occurs primarily through a fibrin cable formed between the proximal and distal nerve stumps. Because no structural guides or cues are present, the regeneration tends to be disorganized. Also, as the length between the nerves stumps increases, the fibrin cable becomes thinner and more hourglass-shaped or does not form at all. Studies have shown a correlation between gap length and negative clinical outcomes with the use of hollow tube conduits14,16; therefore, typically, their use for gap lengths greater than 5 mm cannot be recommended. The processed nerve allograft, Avance Nerve Graft (AxoGen, Inc), is nerve tissue cleansed, enzymatically treated, and sterilized from human donors. Commercially available since 2007, processed nerve allografts provide an organized microstructure and extracellular matrix inherent to nerve tissue and is implanted using the same microsurgical technique as for an autograft nerve. As an off-the-shelf option, it is readily available and affords the ability to match diameters up to
5 mm and lengths up to 70 mm, eliminating the need for an additional surgical site or the sacrifice of a healthy nerve. Early preclinical studies of the processed nerve allograft showed outcomes favorable to those with the isograft23 and superior to those with hollow tube conduits.24-26 Previous studies using processed nerve allografts have shown rates of meaningful recovery of 86 to 100%.17–19,27–29 Porcine-derived small intestinal submucosa (SIS), AxoGuard (AxoGen), is a minimally processed extracellular matrix. Porcine-derived SIS is designed to protect and isolate the peripheral nerve tissue during the healing process. The processing of this material preserves the native architecture of the tissue and the components that support optimal nerve repair.30,31 Preclinical studies that wrapped the sciatic nerves of rabbits with porcine-derived extracellular matrix showed healthy, myelinated, and well-vascularized nerves. Explants of the material were well-vascularized and had been incorporated.32 In the present case series, the outcomes of nerve reconstruction with processed nerve allografts showed an 87% improvement in neurosensory function in trigeminal sensory nerve defects 8 to 70 mm in length. All but 3 of these repairs had included a
Table 7. NEUROSENSORY IMPAIRMENT SCORES FOR SUBJECTS WITH COMORBIDITIES (SMOKING, DIABETES, HYPERTENSION)
Pt. No. Age (yr) Gender Comorbidity Z01 Z06 Z12 Z13
67 35 21 57
Male Male Female Female
HTN Smoker Smoker Smoker
Etiology
Gap Length (mm) Interval to Repair (days)
Tumor Tumor Third molar Third molar
50 70 15 15
Abbreviations: NST, neurosensory testing; Pt. No., patient number. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
0 0 146 484
Postoperative NST Score Normal Normal Moderate Mild
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length into 2 categories, 8 to 20 mm (15.4 2.8 mm, n = 14) and 30 to 70 mm (63.3 14.1 mm, n = 9). For injuries with a gap length of 8 to 20 mm, 86% had improved neurosensory results. However, 89% of the injuries with a gap length of 30 to 70 mm also had improved neurosensory function. Previous studies have shown that peripheral nerve injuries reconstructed within 3 months of the injury have better outcomes than delayed repairs.17,18 One study of LN injuries found a decrease in positive outcomes of 5.8% for every month after injury.6 In the national registry study using processed nerve allograft, meaningful recovery was achieved in 89% of repairs within 3 months and 83% of repairs 3 months after injury.18 The present study showed a trend as expected, with 100% sensory improvement achieved in injuries repaired within 90 days of injury and 77% sensory improvement in injuries repaired after 90 days. The published data have suggested that LN injuries would be expected to have greater neurosensory improvement than inferior alveolar nerves injuries. Bagheri et al6,7 reported 90.5% sensory improvement in LNs (222 injuries) and 81.7% sensory improvement in IANs (186 injuries). Our data set, however, had similar levels of recovery, with 87% sensory improvement in LNs and 88% sensory improvement in IANs treated with a processed nerve allograft. Although these early findings are promising, a larger sample size is needed to determine the significance. Those subjects with preoperative neuropathic pain continued to have the pain after nerve reconstruction. Those subjects without preoperative neuropathic pain did not develop it after nerve reconstruction. These findings concur with those from a study showing that trigeminal nerve microsurgery of the IAN and LN was not a risk factor for postoperative trigeminal
Table 8. INCIDENCE RATE FOR PERMANENT NERVE INJURY AFTER DENTOALVEOLAR SURGERY OR TRAUMA
Procedure
Permanent NSD (%)
Local anesthetic injection Third molar odontectomy Genioplasty Mandibular sagittal split osteotomy Sagittal split ramus osteotomy plus genioplasty Mandibular intraoral vertical ramus osteotomy Mandibular distraction osteogenesis Mandible fracture Zygomaticomaxillary complex fracture Mandibular vestibuloplasty Dental implant
0.54 0.001-0.040 3.33-10 12.8-39 66.6 0.01
Sensory Outcomes After Reconstruction of Lingual and Inferior Alveolar Nerve Discontinuities Using Processed Nerve Allograft—A Case Series John R. Zuniga, DMD, MS, PhD* Purpose:
The present study describes 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.
Patients and Methods:
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 effectiveness and safety. Sensory assessments were conducted preoperatively and 3, 6, and 12 months after surgical reconstruction. The outcomes population, those with at least 6 months of postoperative 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 preoperatively and at each follow-up appointment. Improvement was defined as a score of normal, mild, or moderate.
Results:
The neurosensory outcomes from LNs and IANs that had been microsurgically 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. Also, 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.
Conclusions: These results suggest 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. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 73:734-744, 2015
Trigeminal nerve injuries have a profound effect on the patients experiencing them. Patients have reported functional issues such as drooling while eating or drinking, unintentional chewing of the tongue and lip, pain, heat and cold sensitivity, and difficulty speaking.1 The branches of the trigeminal nerve
most often subject to injury, primarily owing to their location and variable anatomic positioning, are the lingual nerves (LNs) and inferior alveolar nerves (IANs). Even with imaging, many of these injuries cannot be avoided. In addition, certain dentoalveolar procedures, such as surgical excision of cysts and
*Professor and Robert V. Walker DDS Chair, Division of Oral and
versity of Texas Southwestern Medical Center at Dallas, 5323
Maxillofacial Surgery, Department of Surgery, University of Texas
Harry Hines Blvd, Dallas, TX 75390-9109; e-mail: John.Zuniga@
Southwestern Medical Center at Dallas, Dallas, TX.
utsouthwestern.edu
Dr Zuniga is a paid consultant for AxoGen Inc. (Alachua, FL). No financial support was provided by AxoGen to perform or report the
Received March 21 2014 Accepted October 31 2014
present study.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
Conflict of Interest Disclosures: None of the authors reported any
0278-2391/14/01631-0
disclosures.
http://dx.doi.org/10.1016/j.joms.2014.10.030
Address correspondence and reprint requests to Dr Zuniga: Division of Oral and Maxillofacial Surgery, Department of Surgery, Uni-
734
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tumors, often necessitate removal of segments of the patient’s nerve tissue. Historically, the surgical options for reconstruction of trigeminal nerves have been limited, with severe and permanent neurosensory impairment. These types of injuries necessitate surgical intervention to recover functionality. One of the earliest and most commonly used techniques to reconstruct a peripheral nerve was direct neurorrhaphy. Direct neurorrhaphy is indicated when the transected nerve can be coapted without tension. Nerve regeneration can be negatively affected by tension, which will constrict the cross-sectional area of the fascicles of the nerve. This constriction increases the internal pressure, compromising the intrafascicular nutritive blood flow.2,3 Preclinical studies have shown ischemia with as little as 5% elongation and impaired axonal regeneration with 7.4% nerve elongation.2,4 In an attempt to alleviate tension, techniques were developed for tension-free repairs. One of the more common tension-free repair options is to reconstruct the nerve defect with an autologous nerve graft or autograft. Typically, the donor nerves for trigeminal nerve injuries have been the sural and greater auricular nerves. The use of autografts for the surgical reconstruction of trigeminal nerve injuries has been well-documented, with positive outcomes in recent published studies ranging from 87.3 to 100%.5-7 However, this reconstructive technique necessitates a secondary surgical procedure to remove healthy donor nerve tissue. Several comorbidities have been associated with harvesting of an autologous nerve graft. Because a healthy nerve is sacrificed, donor site morbidity can occur.8,9 Also, the operating time and risk of infection are increased. A review of the long-term effects of sural nerve harvesting found sural nerve donor site morbidity after 34 years of follow-up. Of the 29 subjects in the study, 76% had sensory loss, 34% had cold sensitivity, 24% had scar discomfort, 17% reported pain, and 17% had functional impairment.10 Hollow tube conduits, also referred to as nerve cuffs, were developed as an off-the-shelf option to alleviate tension, reduce misalignment of the severed nerve endings, and isolate the reconstructed nerve during the healing process from the surrounding tissues.11-13 Regeneration through conduits is achieved predominately through a fibrin cable formed between the proximal and distal nerve stumps. Because axonal regeneration using a conduit predominately relies on the gross guidance provided by the fibrin clot, the clinical outcomes become more variable at gap lengths greater than 5 mm.14 However, wrapping a peripheral nerve after neurolysis or nerve reconstruction with a conduit or nerve wrap isolates the injured nerve from the surrounding tissue, minimizes scar formation and the potential for nerve entrapment, and allows for the nerve to glide.15 A 9-
patient series using a collagen hollow tube conduit to wrap around severed LNs (n = 6) and IANs (n = 3) reanastomosed by direct neurorrhaphy showed favorable results, with 8 of 9 nerve reconstructions showing sensory improvement.16 Processed nerve allografts were developed as an offthe-shelf option for tension-free repairs. Processed nerve allografts are derived from nerve tissue from human donors. Once recovered from the donor, the nerve allograft is cleaned to remove cells and cellular debris, treated with enzymes to suppress naturally occurring inhibitors to axonal regeneration, and sterilized with gamma irradiation. After processing, sizing, and trimming, the allografts are stored frozen, at less than 40 C, for up to 3 years. Before implantation, the processed nerve allografts are completely thawed in either sterile saline or lactated Ringer’s solution for 5 to 10 minutes. The thawed allografts are implanted using the same microsurgical technique used for implanting an autograft nerve. Processed nerve allografts have been shown to be clinically effective and safe for peripheral nerve discontinuities from 5 to 50 mm.17 In the largest multicenter registry for peripheral nerve reconstruction, peripheral nerves reconstructed with processed nerve allograft had an overall 87.3% meaningful recovery using the Medical Research Council Classification of nerve injuries.18 A published single case report on an inferior alveolar nerve reconstructed with a processed nerve allograft showed meaningful recovery of S3+ sensation in 1 patient.19 Previous clinical studies of processed nerve allografts focused on reconstructions within the upper extremity. These reconstructions were predominately performed by orthopedic and plastic surgeons. With only limited clinical data on the outcomes after trigeminal nerve reconstruction using processed nerve allografts and considering that most of the surgeons who perform microsurgery on trigeminal nerves have been oral-maxillofacial surgeons, it is important to monitor and report on the outcomes of patients who undergo trigeminal nerve reconstruction with an allograft. The present case series describes the results of using processed nerve allografts (Avance Nerve Graft, AxoGen, Inc, Alachua, FL) to microsurgically reconstruct LN and IAN defects.
Patients and Methods The total population for processed nerve allografts included 26 subjects with 28 nerve injuries. The present retrospective study was approved by the institutional review board at the University of Texas Southwestern Medical Center at Dallas (protocol 062010-166). All nerve injuries were deemed to have a Sunderland IV or V degree of injury before reconstruction. All nerve reconstructions were
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performed from 2007 to 2013. Two subjects underwent bilateral nerve reconstruction. Six nerve defects resulted from surgical excision of benign tumors. Preoperatively, the nerves had been evaluated as normal. With complete transection of the nerve, no neurosensory function was present (ie, they met the requirements for a Sunderland class V degree of injury). Of the 26 patients in the study, 14 were male and 12 were female, with 17 LN and 11 IAN injuries. The etiology of the nerve injuries was third molar odontectomy (17 injuries, 61%), dental implant surgery (3 injuries, 11%), oncologic surgery (6 injuries, 21%), and bilateral sagittal split osteotomy (2 injuries, 7%). The subjects ranged in age from 9 to 82 years (mean age 36.5 18.3). The interval until reconstructive microsurgery ranged from 0 to 518 days (average 152 160). The mean nerve gap was 32.4 24.1 mm (range 8 to 70; Table 1). Sensory assessments of the trigeminal nerve injuries were conducted preoperatively and 3, 6, and 12 months after surgical reconstruction with
Table 1. DEMOGRAPHICS OF TOTAL AND OUTCOMES POPULATIONS
Variable Gender Male Female Age (yr) Mean SD Range Interval to repair (days) Mean SD Range Repair within 90 days Repair after 90 days Etiology Third molar Implant Oncologic BSSO Nerve location Lingual Inferior alveolar Gap length (mm) Mean SD Range
Total Population
Outcomes Population
14 (54) 12 (46)
11 (52) 10 (48)
36.5 18.3 9-82
33.3 17.0 9-67
152 160 0-518 12 (43) 16 (57)
148 160 0-518 10 (43) 13 (57)
17 (61) 3 (11) 6 (21) 2 (7)
13 (57) 2 (8.5) 6 (26) 2 (8.5)
17 (61) 11 (39)
15 (65) 8 (35)
32.4 24.1 8-70
34.2 25.5 8-70
a processed nerve allograft. The neurosensory assessment included brush stroke directional sensation, static 2-point discrimination, contact detection, pressure pain threshold, and pressure pain tolerance. From the neurosensory assessment, the neurosensory test (NST), sensory impairment was assessed as normal, mild, moderate, severe, or complete20 (Table 2). The NST assessments in the present study are reported for the latest follow-up appointment. Subjects with at least 6 months of follow-up neurosensory assessments were included in the outcomes analysis. A repair was considered to have resulted in improvement if it scored as normal, mild, or moderate using the NST scale. Additional analysis of the data set was conducted to search for trends in outcomes by nerve gap size, interval to surgery, nerve location, gender, and comorbidities known to have an effect on nerve recovery. Neuropathic pain was assessed pre- and postoperatively as stimulus-induced or spontaneous pain associated with allodynia (painful response to normally nonpainful stimulus at level A testing), hyperpathia (painful response to repetitive nonpainful stimulus with after sensation, overshoot, summation, or delayed onset at level B testing), hyperalgesia (lowered pain threshold to painful stimulus at level C testing), or anesthesia dolorosa or sympathetically mediated (anesthetic or autonomic blocks at level D testing). In addition to the neurosensory assessment, the subjects were monitored postoperatively for adverse experiences, such as infection, graft rejection, and wound dehiscence.
Table 2. NEUROSENSORY TESTING ASSESSMENT SCALE USED TO EVALUATE SENSORY NERVE RECOVERY
Reported Sensory Level Levels A, B, and C within normative limits Level A abnormal, but level B and C within normative limits Levels A and B abnormal, but level C within normative limits Levels A and B abnormal, but level C has elevated measures Levels A and B abnormal and level C has absent measures
NST Normal Mild Moderate Severe Complete
Data presented as n (%), unless otherwise noted. Abbreviations: BSSO, bilateral sagittal split osteotomy; SD, standard deviation.
Level A test, spatiotemporal sensory perception with brushstroke, directional sensitivity, and static 2-point discrimination; level B test, contact detection with Semmes-Weinstein monofilaments; level C test, pain threshold and tolerance using an algometer, thermode, or sharp instrument. Abbreviation: NST, neurosensory testing. Data from Zuniga et al.20
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
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JOHN R. ZUNIGA SURGICAL TECHNIQUE
The LNs were exposed using an intraoral supraperiosteal approach, and the IANs were exposed using transoral lateral corticotomy for those without a tumor etiology.21 An extraoral approach for the subjects with benign tumors was used to expose the IAN. On exposure of the LN or IAN, an operating microscope with 25 magnification was brought into the operative field and positioned. External neurolysis was performed, and, if indicated, neuromas, scar tissue, or benign tumors were excised. The severed nerve endings were examined and trimmed to normal fascicular anatomy. After determining that a tension-free repair could not be performed using direct neurorrhaphy, an allograft nerve graft was selected according to the length and diameter of the proximal nerve stump. Processed nerve allografts are available in several diameters (range 1 to 5 mm) and lengths (range 15 to 70 mm; Table 3). LN defects were reconstructed using either 3- to 4-mm (female subjects) or 4- to 5-mm (male subjects) processed nerve allografts. IAN defects were reconstructed with 2- to 3-mm (male and female subjects) processed nerve allografts. The allograft length was selected according to the length of the nerve defect. LN defects ranged from 8 to 30 mm and IAN defects from 15 to 70 mm. The selected processed nerve allograft was opened, thawed for up to 10 minutes in room temperature saline, and, if necessary, trimmed to size. Each of the severed nerve endings was coapted to the processed nerve allograft using 9-0 monofilament nylon sutures on a cutting edge needle. Initially, 3 sutures were placed at the 4-, 8-, and 12-o’clock positions at each coaptation site (Fig 1). If any gaps were observed between the nerve stumps and the processed nerve allograft, up to 3 additional sutures were placed at the 2-, 6-, and 10-o’clock positions. Table 3. PROCESSED NERVE ALLOGRAFT (AVANCE NERVE GRAFT, AXOGEN, INC) SIZES AND PRODUCT CODES
Length (mm) Diameter (mm) 1-2 2-3* 3-4y 4-5z
15
30
50
70
111,215 211,215 311,215 411,215
111,230 211,230 311230 411,230
111,250 211,250 311,250 411,250
111,270 211,270 311,270 411,270
* All inferior alveolar nerves were reconstructed with processed nerve allografts 2-3 mm in diameter. y All lingual nerves in the females were reconstructed with processed nerve allografts 3-4 mm in diameter. z All lingual nerves in the males were reconstructed with processed nerve allografts 4-5 mm in diameter. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Next, the repaired nerve was examined and any excess suture trimmed. Also, all but 3 nerve reconstructions used a commercially available nerve wrap in conjunction with the repair (AxoGuard, AxoGen, Inc, Alachua, FL). These nerve wraps served to isolate the nerve repair from the traumatized wound bed, minimized the risk of entrapment, and contained regenerating axons during the healing process. Once the reconstruction was complete, the microscope was moved out of the operative field, and the surgical sites were closed according to standard of care procedures.
Results A total of 21 subjects with 23 nerve injuries had sufficient postoperative follow-up data available. Improvement in sensory function was reported for 87% of the reconstructions (Table 4). The neurosensory test results ranged from normal to severe across the outcomes population. The NST impairment scores reported at the last follow-up visit were normal for 12 (52%), mild for 2 (9%), moderate for 6 (26%), and severe for 3 (13%; Fig 2). The subjects were grouped by treated gap length into 2 categories, 8 to 20 mm and 30 to 70 mm. Of the 14 injuries with a gap length of 8 to 20 mm, 86% showed neurosensory improvement compared with 89% neurosensory improvement for injuries with a gap length of 30 to 70 mm. Neurosensory improvement occurred across all gap lengths, including long defects at 70 mm, for which 6 (5 normal, 1 moderate) of the 7 nerves had improvement in their neurosensory impairment scores (Table 5). The interval to repair did not seem to be a determining factor on neurosensory recovery. The reconstruction with the longest interval between injury and surgical reconstruction, 518 days, had normal neurosensory impairment (Table 6). Of the 10 reconstructions occurring within the first 90 days, 100% had improvement in the neurosensory impairment scores. In contrast, of the 13 injuries repaired more than 90 days after the original injury, 77% had improvement (Figs 3, 4). The nerve location did not appear to have an impact on neurosensory recovery. The LN injuries had improved sensory recovery in 87% of the nerves reconstructed. Similarly, 88% of IANs were assessed as having neurosensory improvement (Figs 5 to 7). The subject’s gender did not appear to have an impact on neurosensory recovery. Females reported sensory improvement in 10 of 12 nerves reconstructed with a processed nerve allograft, and males reported sensory improvement in 10 of 11 nerves reconstructed (Fig 8).
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FIGURE 1. Microsuture sequence of neurorrhaphy. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
When evaluating outcomes by age group (pediatric, adult, and older adult), sensory improvement was reported in 3 of 4 injuries in the pediatric cohort (sub-
jects aged 9 to 18 years), 10 of 11 in the adult cohort (subjects aged 19 to 49 years), and 5 of 6 injuries in the older adult cohort (subjects aged 50 to 67 years).
Table 4. NEUROSENSORY IMPAIRMENT OUTCOME AFTER NERVE RECONSTRUCTION WITH PROCESSED NERVE ALLOGRAFT
Pt. No. Z01 Z02 Z03 Z04 Z06 Z07 Z08 Z09 Z10 Z11 Z11L Z12 Z13 Z14 Z15 Z15L Z16 Z17 Z18 Z20 Z21 Z22 Z26
Age (yr)
Gender
Injury Type (Class)
67 26 17 50 35 22 27 9 34 57 Repeat 21 57 16 31 Repeat 34 37 19 11 22 50 58
Male Female Male Male Male Female Male Male Male Female Repeat Female Female Female Female Repeat Male Male Female Male Female Female Male
IAN V LN V LN IV LN IV IAN V LN V LN V IAN IV LN V IAN IV IAN IV LN IV LN IV-V LN IV LN V LN V LN V IAN V LN V IAN V LN IV IAN V LN V
Etiology
Gap Length (mm)
Interval to Repair (days)
Wrap Used
Oncologic Third molar Third molar Third molar Oncologic BSSO Third molar Oncologic BSSO Implant Implant Third molar Third molar Third molar Third molar Third molar Third molar Oncologic Third molar Oncologic Third molar Oncologic Third molar
50 20 20 18 70 15 15 70 15 70 70 15 15 15 15 15 15 70 30 70 15 70 8
0 80 112 90 0 147 153 0 42 228 228 146 484 518 116 116 57 0 493 0 118 0 286
Yes No Yes No Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Abbreviations: NST, neurosensory testing; Pt. No., patient number. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Postoperative NST Outcome Normal Moderate Severe Moderate Normal Normal Normal Normal Moderate Severe Moderate Moderate Mild Normal Moderate Severe Normal Normal Normal Normal Normal Normal Mild
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FIGURE 2. Neurosensory impairment scores for nerves reconstructed with processed nerve allografts. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Table 5. NEUROSENSORY IMPAIRMENT SCORES AND GAP LENGTH (NERVE DEFICIT)
NST Impairment Score Normal Mild Moderate Severe Complete
Gap Length (mm) 15, 15, 15, 15, 15, 30, 50, 70, 70, 70, 70, 70 8, 15 15, 15, 15, 18, 20, 70 15, 20, 70 —
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
FIGURE 3. Neurosensory impairment scores stratified by the interval to repair within 90 days of injury. NST, neurosensory testing. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
Table 6. NEUROSENSORY IMPAIRMENT SCORES AND INTERVAL TO REPAIR
NST Impairment Score Normal Mild Moderate Severe Complete
Interval to Repair (days) 0, 0, 0, 0, 0, 0, 57, 118, 147, 153, 493, 518 286, 484 42, 80, 90, 116, 146, 228 112, 116, 228 —
Abbreviation: NST, neurosensory testing.
FIGURE 4. Neurosensory impairment scores stratified by an interval to repair longer than 90 days of injury. NST, neurosensory testing.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
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SENSORY OUTCOMES AFTER LN AND IAN RECONSTRUCTION
FIGURE 5. Neurosensory impairment scores stratified by nerve location (lingual nerve and inferior alveolar nerve) did not show a difference in neurosensory recovery. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
In the outcomes population, all 4 subjects with conditions known to impede nerve regeneration (smoking, diabetes, hypertension) had sensory improvement, with 2 of these 4 subjects reporting normal NST impairment scores (Table 7). Two subjects reported preoperative neuropathic pain. These 2 subjects had no change in their neuropathic pain scores after surgery. The subjects without neuropathic pain preoperatively did not develop neuropathic pain postoperatively. None of the subjects reported adverse events, such as infection, graft rejection, or wound dehiscence.
Discussion LN and IAN injuries have been reported as a result of dentoalveolar surgery. Some of the major causes of these types of injuries are third molar odontectomy, dental implant surgery, orthognathic surgery, and oncologic surgery for cysts and benign and malignant tumors. Published studies have reported incidence
rates for permanent neurosensory dysfunction from dentoalveolar surgery ranging from 0 to 100% for these procedures22 (Table 8). Microsurgical techniques for trigeminal nerve defects have been developed for the reconstruction of these defects. If a nerve defect can be directly coapted without tension, primary neurorrhaphy is typically performed. However, when the segmental defect is sufficient to necessitate using a ‘‘bridging’’ material to coapt the severed nerve endings, tension-free techniques are indicated. Historically, the patient’s own tissue has been used in tension-free repairs of trigeminal nerve injuries with some limited usage of hollow tube conduits. Autografts are beneficial, because they have inherent structural and neurochemical guides that support axonal regeneration. However, the autograft technique can only be performed by surgically removing a healthy uninvolved nerve deemed less important than the nerve targeted for reconstruction. The comorbidities associated with a secondary surgical site, the additional operative time for harvesting the autograft,
FIGURE 6. Neurosensory impairment scores for lingual nerve repairs. NST, neurosensory testing.
FIGURE 7. Neurosensory impairment scores for inferior alveolar nerve (IAN) repairs. NST, neurosensory testing.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
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FIGURE 8. Neurosensory impairment scores stratified by gender did not vary. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
and the variability and possible limitation in size (diameter and length) led to the development of off-the-shelf alternatives, such as the hollow tube conduit and processed nerve allograft. The nerve conduit acts as a containment device for regenerating axons. Regeneration occurs primarily through a fibrin cable formed between the proximal and distal nerve stumps. Because no structural guides or cues are present, the regeneration tends to be disorganized. Also, as the length between the nerves stumps increases, the fibrin cable becomes thinner and more hourglass-shaped or does not form at all. Studies have shown a correlation between gap length and negative clinical outcomes with the use of hollow tube conduits14,16; therefore, typically, their use for gap lengths greater than 5 mm cannot be recommended. The processed nerve allograft, Avance Nerve Graft (AxoGen, Inc), is nerve tissue cleansed, enzymatically treated, and sterilized from human donors. Commercially available since 2007, processed nerve allografts provide an organized microstructure and extracellular matrix inherent to nerve tissue and is implanted using the same microsurgical technique as for an autograft nerve. As an off-the-shelf option, it is readily available and affords the ability to match diameters up to
5 mm and lengths up to 70 mm, eliminating the need for an additional surgical site or the sacrifice of a healthy nerve. Early preclinical studies of the processed nerve allograft showed outcomes favorable to those with the isograft23 and superior to those with hollow tube conduits.24-26 Previous studies using processed nerve allografts have shown rates of meaningful recovery of 86 to 100%.17–19,27–29 Porcine-derived small intestinal submucosa (SIS), AxoGuard (AxoGen), is a minimally processed extracellular matrix. Porcine-derived SIS is designed to protect and isolate the peripheral nerve tissue during the healing process. The processing of this material preserves the native architecture of the tissue and the components that support optimal nerve repair.30,31 Preclinical studies that wrapped the sciatic nerves of rabbits with porcine-derived extracellular matrix showed healthy, myelinated, and well-vascularized nerves. Explants of the material were well-vascularized and had been incorporated.32 In the present case series, the outcomes of nerve reconstruction with processed nerve allografts showed an 87% improvement in neurosensory function in trigeminal sensory nerve defects 8 to 70 mm in length. All but 3 of these repairs had included a
Table 7. NEUROSENSORY IMPAIRMENT SCORES FOR SUBJECTS WITH COMORBIDITIES (SMOKING, DIABETES, HYPERTENSION)
Pt. No. Age (yr) Gender Comorbidity Z01 Z06 Z12 Z13
67 35 21 57
Male Male Female Female
HTN Smoker Smoker Smoker
Etiology
Gap Length (mm) Interval to Repair (days)
Tumor Tumor Third molar Third molar
50 70 15 15
Abbreviations: NST, neurosensory testing; Pt. No., patient number. John R. Zuniga. Sensory Outcomes After LN and IAN Reconstruction. J Oral Maxillofac Surg 2015.
0 0 146 484
Postoperative NST Score Normal Normal Moderate Mild
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length into 2 categories, 8 to 20 mm (15.4 2.8 mm, n = 14) and 30 to 70 mm (63.3 14.1 mm, n = 9). For injuries with a gap length of 8 to 20 mm, 86% had improved neurosensory results. However, 89% of the injuries with a gap length of 30 to 70 mm also had improved neurosensory function. Previous studies have shown that peripheral nerve injuries reconstructed within 3 months of the injury have better outcomes than delayed repairs.17,18 One study of LN injuries found a decrease in positive outcomes of 5.8% for every month after injury.6 In the national registry study using processed nerve allograft, meaningful recovery was achieved in 89% of repairs within 3 months and 83% of repairs 3 months after injury.18 The present study showed a trend as expected, with 100% sensory improvement achieved in injuries repaired within 90 days of injury and 77% sensory improvement in injuries repaired after 90 days. The published data have suggested that LN injuries would be expected to have greater neurosensory improvement than inferior alveolar nerves injuries. Bagheri et al6,7 reported 90.5% sensory improvement in LNs (222 injuries) and 81.7% sensory improvement in IANs (186 injuries). Our data set, however, had similar levels of recovery, with 87% sensory improvement in LNs and 88% sensory improvement in IANs treated with a processed nerve allograft. Although these early findings are promising, a larger sample size is needed to determine the significance. Those subjects with preoperative neuropathic pain continued to have the pain after nerve reconstruction. Those subjects without preoperative neuropathic pain did not develop it after nerve reconstruction. These findings concur with those from a study showing that trigeminal nerve microsurgery of the IAN and LN was not a risk factor for postoperative trigeminal
Table 8. INCIDENCE RATE FOR PERMANENT NERVE INJURY AFTER DENTOALVEOLAR SURGERY OR TRAUMA
Procedure
Permanent NSD (%)
Local anesthetic injection Third molar odontectomy Genioplasty Mandibular sagittal split osteotomy Sagittal split ramus osteotomy plus genioplasty Mandibular intraoral vertical ramus osteotomy Mandibular distraction osteogenesis Mandible fracture Zygomaticomaxillary complex fracture Mandibular vestibuloplasty Dental implant
0.54 0.001-0.040 3.33-10 12.8-39 66.6 0.01
