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Lingual Nerve Repair: To Graft or Not to Graft? Michael Miloro, DMD, MD,* Phil Ruckman III, DDS,y and Antonia Kolokythas, DDS, MScz
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Purpose:
Because no studies have compared direct and graft repair of the lingual nerve, we examined the subjective and objective outcomes of lingual nerve repair by direct epineurial repair and indirect graft repair, assessed the effect of other confounding variables, and compared the outcomes of autograft and allograft repairs.
Patients and Methods:
All patients who had undergone microneurosurgical repair of the lingual nerve from 2000 to 2012 by 1 surgeon (M.M.) were asked to complete an online questionnaire regarding their current neurosensory status at least 2 years after nerve repair. A direct comparison was made between patients who had undergone direct epineurial repair and those who had undergone interpositional nerve graft repair. Student’s t test and c2 test was used to determine whether a significant difference existed in the success between the 2 techniques and whether age, gender, race, delay from injury to repair, or degree of initial nerve deficit influenced the success of nerve repair.
Results:
Of the 72 patients identified, 43, who had undergone 47 nerve repairs (18 direct, 29 indirect graft repairs [4 bilateral]; 28 female and 19 male patients; mean age 28.3 years), were interviewed. The objective results of functional sensory recovery, defined by a Medical Research Council Scale grade of S3, S3+, or S4, was 89% for the graft repairs and 85% for the direct repairs (P = .01). The subjective patient satisfaction score (0 to 10 scale) was 8.9 for the graft repairs and 8.1 for the direct repairs (P = .02). The autograft and allograft repairs performed comparably, and the other variables (ie, age, gender, race, delay from injury to nerve repair, gap length, and initial Sunderland grade injury) were not found to be significant (P > .05).
Conclusion:
Graft repair of the lingual nerve provides superior long-term (>2 years) objective and subjective outcomes compared with direct repair. This might be because of the lack of tension at the repair site, more freedom with nerve stump preparation, and the addition of neurotropic and neurotrophic factors from the donor nerve graft at the site of injury to augment neurosensory recovery. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1-7, 2015
Third molar extractions are the most common cause of injury to the inferior alveolar (IAN) and lingual (LN) nerves owing to the proximity of the nerves in the area.1 However, treatment of pathologic lesions, orthognathic surgery, maxillofacial trauma, local anesthetic injection, endodontic therapy, and dental implant placement have also been implicated as etiologic factors in trigeminal nerve injuries.2-5 After a nerve injury, proper documentation with clinical
neurosensory testing is imperative to determine whether and when microneurosurgical intervention is warranted.6 Ideally, nerve repair, when indicated, should be performed within 1 to 3 months after the initial injury for the LN and 3 to 6 months for the IAN. Diagnostic imaging of the trigeminal nerve remains in the developmental stages, with magnetic resonance neurography showing the most promise in the ability to distinguish a neuroma from normal nerve tissue in
Received from Department of Oral and Maxillofacial Surgery,
at Chicago College of Dentistry, 801 S Paulina St, Chicago, IL
University of Illinois at Chicago College of Dentistry, Chicago, IL. *Professor and Head.
60612; e-mail: [email protected] Received February 11 2015
yChief Resident.
Accepted March 5 2015
zAssociate Professor and Program Director.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
Dr Miloro is a consultant with AxoGen, Inc.
0278-2391/15/00268-2
Address correspondence and reprint requests to Dr Miloro:
http://dx.doi.org/10.1016/j.joms.2015.03.018
Department of Oral and Maxillofacial Surgery, University of Illinois
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the LN and IAN.7-9 Therefore, the clinical examination (subjective and objective testing) remains the mainstay of diagnosis and treatment planning. The indications for microneurosurgery include complete postoperative anesthesia, observed nerve transection, and minimal residual sensation, which is typically seen with Sunderland grade III, IV, and V injuries.10 Nerve repair can be performed using a direct epineurial repair (Fig 1) or an indirect (graft) neurorrhaphy procedure (Fig 2), using a graft if tension is perceived at the nerve repair site. The 2 options for graft repair include autogenous nerve grafts (autografts) and allogeneic nerve grafts (allografts). The most appropriate autogenous nerve graft for the trigeminal nerve is the sural nerve because of the diameter and fascicular pattern match with the trigeminal nerve anatomy.11 Only 1 allograft is available, the Avance nerve graft (available in a variety of diameters and lengths; AxoGen, Inc, Alachua, FL). In considering the outcomes of direct versus graft repair, conventional thinking has maintained that a direct repair would result in a greater likelihood of recovery than a grafted repair owing to the increased length of nerve regeneration required from the cell body to the target site through the graft and the need for 2 sites of epineurial anastomosis with the potential for 2 separate sites of fascicular misalignment (poor coaptation), 2 sites of potential axonal microsprouting outside the epineurium, and 2 sites of nerve scarring that could impede neural regeneration.12 The overall success rates of microneurosurgery of the trigeminal nerve have varied considerably in the published data from 26 to 92%,13 and subjective success has not always correlated with objective improvement.14 Additionally, standardization in the reported studies of trigeminal nerve repair regarding successful outcomes, as defined by functional (or useful) sensory recovery according to the Medical Research Council Scale (MRCS), is lacking.15 Although many studies have reported individual surgeon experience with trigeminal nerve repair, no study has evaluated the difference in the success of direct versus indirect repair techniques for the trigeminal nerve.
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FIGURE 1. A, Diagram of direct epineurial nerve repair technique. B, Diagram of indirect (graft) nerve repair technique. Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
FIGURE 2. Direct epineurial repair showing poor fascicular cooptation and collateral axonal microsprouting outside the confines of the epineurium. Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
Patients and Methods After approval by the University of Illinois institutional review board (IRB no. 2013-1098), the Common Procedural Terminology codes for trigeminal nerve repair (codes 64716, 64727, 64864, and 64885) were used to search for nerve repair cases completed by 1 surgeon (M.M.) from April 2000 to December 2012, with at least 2 years of follow-up data after the nerve repair procedure. The patient demographic information was taken from a retrospective medical record review and evaluation of the clinical notes. Once the subject was identified, the patient was interviewed by telephone (P.R.) and asked for a valid e-mail address. The subject was e-mailed a link to complete a 20-question online survey (Survey Monkey, Palo Alto, CA) and a consent form to access their individual written or electronic medical record (EMR) for age, gender, race, type of nerve repair, and information regarding the neurologic examination at the initial presentation before the nerve repair and at the follow-up examinations. The results of the questionnaire and the data from the EMRs were analyzed for significance, specifically comparing the direct and indirect nerve repair techniques. Student’s t test and the c2 test were used to determine whether a significant difference existed in the success between the 2 techniques and whether age, gender, race, gap length, degree of initial nerve deficit (Sunderland grade), and type of nerve graft (autograft vs allograft) influenced the outcomes of the nerve repair. Subjective neurosensory recovery was evaluated by individual patient responses to the subjective survey questions, and the objective questions of neurosensory recovery were correlated with the MRCS, with grades S3, S3+, and S4 indicating the presence of functional (or useful) sensory recovery (FSR).16 An FSR score of S3 corresponds to a return of some superficial pain and tactile sensation without over-response and 2-point discrimination of >15 mm (Table 1).17
Results Patient data were available for 43 of the 72 patients (65.3%). Of the 43 patients, 25 were female (58.1%) and 18 were male (41.9%), and the mean age of the
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Table 1. MEDICAL RESEARCH COUNCIL SCALE
Grade* S0 S1 S2 S2+ S3 S3+ S4
Description No sensation Deep cutaneous pain in autonomous zone Some superficial pain and touch Superficial pain and touch plus hyperesthesia Superficial pain and touch without hyperesthesia: static 2-point discrimination >15 mm Same as S3 with good stimulus localization; static 2-point discrimination of 7-15 mm Same as S3; static 2-point discrimination of 2-6 mm
* Grades S3, S3+, and S4 indicate functional (useful) sensory recovery.13 Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
43 patients was 28.3 years (range 17 to 52). These demographic data are consistent with other studies with regard to the risk factors for lingual nerve injury, including advanced age and female gender.18 A total of 47 LN repairs were performed in the 43 patients, including 19 direct epineurial repairs (40.4%) and 28 indirect repairs (4 bilateral graft repairs) (59.6%). Of the 28 graft repairs, 24 were sural nerve autografts (85.7%) and 4 were Avance (AxoGen) allografts (14.3%). Three of the bilateral cases were repaired with a sural nerve graft, and 1 patient was treated with a bilateral Avance nerve graft. The median interval between nerve injury and repair was 3.2 months (range 0.75 to 16.4). The etiology of nerve injury was third molar odontectomy in 34 of 43 patients (79%), followed by pathologic excision in 5 (12.0%), orthognathic surgery in 3 (7.0%), and dental implants in 1 (2.0%). Of the LN injuries, 29 were right sided (61.7%) and 18 were left sided (38.3%). The Sunderland19 grades of initial nerve injury included 1 Sunderland grade II, 5 Sunderland grade III, 18 Sunderland grade IV, and 23 Sunderland grade V injuries using standard clinical neurosensory testing.20 Another 2 cases of LN injury were explored, and the patients underwent external neurolysis without the need for direct or indirect neurorrhaphy, and these patients were excluded from the study group of 47 repairs. These 2 cases might have represented injection-related injuries to the LN.21,22 Of the patients in the present study, all had hypoesthesia or anesthesia, but none had symptoms of neuropathic pain before surgery or after surgical repair.23 In addition, a trend was observed such that the patients who experienced improved outcomes after LN repair also reported on the questionnaire that the sural nerve harvest site was not a significant cause of unpleasant symptoms or concern or significant hypoesthesia or dysesthesia.11 An additional
finding was that the outcomes of the 4 bilateral cases were comparable to those of the unilateral cases (>80% subjective and objective satisfaction), and the injuries and intraoperative findings were consistent within the patients with bilateral injuries. All 4 patients with bilateral injuries presented with bilateral Sunderland grade V injuries due to third molar removal by non–oral and maxillofacial surgeons, and the intraoperative findings were consistent with complete transection in all cases bilaterally. Finally, 3 of the 4 bilateral cases received sural nerve autografts and did not report significant sural deficit or morbidity.11 All surgical procedures were performed by 1 surgeon (M.M.) with the assistance of residents in training in oral and maxillofacial surgery. The surgeries were performed with loupe magnification (3.5 power), and a standard subperiosteal approach to the LN was used to identify the proximal and distal nerve segments and then working toward the site of injury.24 Notation was made of the condition of the injured nerve, and this was correlated with the preoperative clinical neurosensory testing results and Sunderland classification.20 The preoperative clinical neurosensory testing was grouped into 1 of 5 categories (Sunderland I, normal [n = 0]; Sunderland II, mild injury [n = 1]; Sunderland III, moderate injury [n = 5]; Sunderland IV, severe injury [n = 18]; Sunderland V, complete injury, [n = 23]). The intraoperative findings were also categorized into 5 groups (normal/intact in 0, compressed/intact in 2, neuroma-in-continuity in 5, partial transection in 18, and complete transection in 22). A fairly good linear correlation was found between the preoperative neurosensory testing results and the condition of the LN observed at nerve repair, with only 1 degree of difference in 5 cases (Fig 3). Next, the area of injury was addressed by resection of the visible neuroma and sequential resection of 1- to 2-mm segments of both proximal and distal nerve stumps to visualize healthy axoplasm with vascularity to ensure that no neuroma remained in either the proximal or distal nerve stumps. At this point, a subjective clinical determination was made regarding whether the resultant nerve gap length (mean gap length 1.6 mm for direct repairs and 14.3 mm for gap repairs) could be reapproximated with blunt proximal and distal nerve stump dissection and release (into the pterygomandibular space proximally and into the floor of the mouth distally). On occasion, a single epineurial suture was placed to visualize how much tension would be placed on the repair site with direct epineurial repair. If it were determined that the proximal and distal nerve stumps could not lie in direct apposition without a gap between the segments that would result in undue tension on epineurial repair, the decision was made to use a nerve graft for repair (Fig 4).
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FIGURE 3. Scatter plot representing the relationship between the preoperative sensory impairment score and the severity of lingual nerve injury identified at nerve repair (n = 47 nerves). C/I, compressed/intact; CT, complete transection; N/I, normal/intact; NIC, neuroma-in-continuity; PT, partial transection.
protectors, consisting of porcine small intestine submucosa (AxoGuard, Axogen), were used with the allografts at the proximal and distal neurorrhaphy sites to prevent axonal microsprouting and prevent adherence and scarring to the surrounding soft tissues during healing (Fig 5). The objective results of functional sensory recovery, defined by a Medical Research Council System score of S3, S3+, or S4, was 89% for the graft repairs and 85% for the direct repairs. The subjective patient satisfaction score (0 to 10 scale) was 8.9 for the graft repairs and 8.1 for the direct repairs (Fig 6). These differences were statistically significant for both the objective outcomes (P = .01) and subjective outcomes (P = .02). In addition, an evaluation of the other variables, including age, gender, race, interval from injury to repair, gap length, and initial Sunderland grade of injury were not significant in terms of objective and subjective patient outcomes (P > .05).
Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
Discussion Before 2008, all grafts were performed using a sural nerve (medial sural cutaneous nerve from the sacral plexus S1-S2) graft.11 However, since then, most grafts have been performed using an cadaveric nerve allograft (Avance, AxoGen), typically, 2 to 3 mm or 3 to 4 mm in diameter, depending on the recipient nerve, with the length ranging from 10 to 30 mm, depending on the gap length for the LN.25,26 In addition, nerve
Studies on the outcomes of trigeminal nerve repair have focused on the cumulative results of both LN and IAN repair, mostly from individual surgeon experience, and the surgical reports have included a mixture of direct and indirect repair procedures.27-33 To date, no study has evaluated the difference in subjective and objective outcomes between direct and indirect trigeminal nerve repair techniques.
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FIGURE 4. A, Intraoperative view of a direct epineurial left lingual nerve repair. B, Intraoperative view of an indirect epineurial left lingual nerve repair with an autogenous sural nerve graft (note, 2 sites of neurorrhaphy). Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
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FIGURE 5. A, Intraoperative view of an indirect epineurial right lingual nerve repair with an allograft (Avance, AxoGen). B, Nerve protectors (AxoGuard, AxoGen) in place to protect the 2 sites of neurorrhaphy repair. Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
The general assumption is that a direct repair should perform better than a grafted nerve repair for many reasons. First, to qualify for a direct repair without tension, the gap defect must be small. Therefore, the magnitude of injury to the nerve (ie, size of the neuroma) would likely need to be small, with minimal Wallerian degeneration, and, would thus have an improved chance of recovery after surgical repair. Pogrel34 suggested that early repairs might have less neuroma formation and therefore require less resection and a lower chance of requiring a nerve graft and a better prognosis for recovery. Pogrel34 suggested that direct repair has improved outcomes compared with graft repair, although he did not compare the outcomes of direct versus graft repair (most of the ‘‘grafts’’ were vein graft conduits). In contrast, perhaps in an attempt to avoid the additional morbidity of nerve graft harvest or because of a lack of surgeon expertise in graft harvesting, less than adequate resection of neuromatous tissue could be a compromised intraoperative decision, which would certainly result in worse outcomes by leaving neuroma in the nerve stumps (and performing a neuroma-to-neuroma repair) rather than abandoning the neurorrhaphy procedure completely. In addition, in an attempt to avoid a nerve graft, perhaps more tension than ideally desired (ideal tension is no tension)35 could be present at the repair site, resulting in vascular compromise, poor healing, and scar formation at the anastomosis site. Another theoretical reason that direct repairs should perform better than graft repairs is that
there is only 1 site of neurorrhaphy (nerve suture anastomosis) instead of the 2 sites in graft repair. This would result in a lower risk of fascicular adaptation (coaptation) mismatch (at 1 site vs 2 sites) and would also lessen the chance of collateral axonal microsprouting outside the epineurium at the repair site by 50% (Fig 2). Finally, with a smaller amount of neuroma resection and a minimal, or no, nerve gap with a direct repair, anterograde and retrograde axonal transport across the repair site should occur more readily and rapidly from the cell body to the target site in a direct repair versus a graft repair. However, the factors that favor an improved outcome with graft repair compared with direct repair include the ability of the surgeon to resect neuromatous tissue both proximally and distally with impunity, but only to the certain point at which additional nerve resection will not permit neurorrhaphy owing to the inability to access the proximal and/or distal nerve stumps. This ‘‘surgical freedom’’ would permit an improved chance of reaching normal healthy fascicular tissue (well-vascularized mushrooming axoplasm) in both the proximal and the distal nerve stumps. Also, an additional benefit of using a nerve graft is the ability to bring healthy nerve tissue, along with the associated potent neurotropic and neurotrophic factors, to a site of injury to augment recovery after repair.36,37 This is true of both autografts and allografts, although the primary goal of the graft is the transfer of the fascicular conduit architecture that will accept and
FIGURE 6. A, Objective outcomes functional sensory recovery after direct (81%) and graft (89%) repairs (P = .01). B, Subjective outcomes after direct (8.1) and graft (8.9) repairs (P = .02). Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
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guide the proximal regenerating nerve sprouts toward the distal nerve stump and target site. Although many studies have shown a lack of correlation between objective and subjective testing of neurosensory function,38 this present study showed a correlation between the 2 assessments, likely because the patient questionnaire was completed by the patient for both the subjective and the objective questions, with the known limitation of the study being that objective clinical neurosensory testing by an experienced clinician was not possible owing to the various locations of the patients and their inability to travel for a formal follow-up examination. In addition, the lack of significance of the interval from injury to repair conflicts with the results of some previous studies.39 However, this might have resulted from aggressive resection to healthy fascicular tissue, which was a critical consideration in the present study, and the threshold for considering nerve graft repair was very low. Therefore, any additional scar tissue formation or Wallerian degeneration of the nerve stumps as a result of an increased interval from injury to repair was likely not a significant factor in the outcomes of our study, because it was aggressively resected. In conclusion, the present study has documented that indirect graft nerve repair, using an autograft (sural nerve) or allograft (Avance nerve graft) is associated with improved objective and subjective nerve outcomes compared with direct nerve repair. Surgeons who perform microneurosurgical repair of the trigeminal nerve must recognize the importance of resection of all neuromatous tissue and a tensionfree repair on achieving successful outcomes. Also, they must be capable of performing nerve graft repair, with either harvest of an autograft or the use of a stock allograft. To further determine appropriate evidencebased decisions and treatment recommendations for patients who sustain injuries to the terminal branches of the trigeminal nerve, including the LN and IAN, a prospective multicenter, multisurgeon clinical trial is warranted, because the last attempt at such a study more than 2 decades ago, had significant limitations.40
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35. Millesi H: Nerve grafting. Clin Plast Surg 11:105, 1984 36. Hudson TW, Evans GR, Schmidt CE: Engineering strategies for peripheral nerve repair. Clin Plast Surg 26:617, 1999 37. Chimutengwende-Gordon M, Khan W: Recent advances and developments in neural repair and regeneration for hand surgery. Open Orthop J 6:103, 2012 38. Gregg JM: Studies of traumatic neuralgias in the maxillofacial region: Symptom complexes and response to microsurgery. J Oral Maxillofac Surg 48:135, 1990 39. Susarla SM, Kaban LB, Donoff RB, Dodson TB: Does early repair of lingual nerve injuries improve functional sensory recovery? J Oral Maxillofac Surg 65:1070, 2007 40. Labanc JP, Gregg JM: Trigeminal nerve injuries: Basic problems, historical perspectives, early successes, and remaining challenges. Oral Maxillofac Surg Clin North Am 4:277, 1992
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Lingual Nerve Repair: To Graft or Not to Graft? Michael Miloro, DMD, MD,* Phil Ruckman III, DDS,y and Antonia Kolokythas, DDS, MScz
Q3
Purpose:
Because no studies have compared direct and graft repair of the lingual nerve, we examined the subjective and objective outcomes of lingual nerve repair by direct epineurial repair and indirect graft repair, assessed the effect of other confounding variables, and compared the outcomes of autograft and allograft repairs.
Patients and Methods:
All patients who had undergone microneurosurgical repair of the lingual nerve from 2000 to 2012 by 1 surgeon (M.M.) were asked to complete an online questionnaire regarding their current neurosensory status at least 2 years after nerve repair. A direct comparison was made between patients who had undergone direct epineurial repair and those who had undergone interpositional nerve graft repair. Student’s t test and c2 test was used to determine whether a significant difference existed in the success between the 2 techniques and whether age, gender, race, delay from injury to repair, or degree of initial nerve deficit influenced the success of nerve repair.
Results:
Of the 72 patients identified, 43, who had undergone 47 nerve repairs (18 direct, 29 indirect graft repairs [4 bilateral]; 28 female and 19 male patients; mean age 28.3 years), were interviewed. The objective results of functional sensory recovery, defined by a Medical Research Council Scale grade of S3, S3+, or S4, was 89% for the graft repairs and 85% for the direct repairs (P = .01). The subjective patient satisfaction score (0 to 10 scale) was 8.9 for the graft repairs and 8.1 for the direct repairs (P = .02). The autograft and allograft repairs performed comparably, and the other variables (ie, age, gender, race, delay from injury to nerve repair, gap length, and initial Sunderland grade injury) were not found to be significant (P > .05).
Conclusion:
Graft repair of the lingual nerve provides superior long-term (>2 years) objective and subjective outcomes compared with direct repair. This might be because of the lack of tension at the repair site, more freedom with nerve stump preparation, and the addition of neurotropic and neurotrophic factors from the donor nerve graft at the site of injury to augment neurosensory recovery. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1-7, 2015
Third molar extractions are the most common cause of injury to the inferior alveolar (IAN) and lingual (LN) nerves owing to the proximity of the nerves in the area.1 However, treatment of pathologic lesions, orthognathic surgery, maxillofacial trauma, local anesthetic injection, endodontic therapy, and dental implant placement have also been implicated as etiologic factors in trigeminal nerve injuries.2-5 After a nerve injury, proper documentation with clinical
neurosensory testing is imperative to determine whether and when microneurosurgical intervention is warranted.6 Ideally, nerve repair, when indicated, should be performed within 1 to 3 months after the initial injury for the LN and 3 to 6 months for the IAN. Diagnostic imaging of the trigeminal nerve remains in the developmental stages, with magnetic resonance neurography showing the most promise in the ability to distinguish a neuroma from normal nerve tissue in
Received from Department of Oral and Maxillofacial Surgery,
at Chicago College of Dentistry, 801 S Paulina St, Chicago, IL
University of Illinois at Chicago College of Dentistry, Chicago, IL. *Professor and Head.
60612; e-mail: [email protected] Received February 11 2015
yChief Resident.
Accepted March 5 2015
zAssociate Professor and Program Director.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
Dr Miloro is a consultant with AxoGen, Inc.
0278-2391/15/00268-2
Address correspondence and reprint requests to Dr Miloro:
http://dx.doi.org/10.1016/j.joms.2015.03.018
Department of Oral and Maxillofacial Surgery, University of Illinois
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the LN and IAN.7-9 Therefore, the clinical examination (subjective and objective testing) remains the mainstay of diagnosis and treatment planning. The indications for microneurosurgery include complete postoperative anesthesia, observed nerve transection, and minimal residual sensation, which is typically seen with Sunderland grade III, IV, and V injuries.10 Nerve repair can be performed using a direct epineurial repair (Fig 1) or an indirect (graft) neurorrhaphy procedure (Fig 2), using a graft if tension is perceived at the nerve repair site. The 2 options for graft repair include autogenous nerve grafts (autografts) and allogeneic nerve grafts (allografts). The most appropriate autogenous nerve graft for the trigeminal nerve is the sural nerve because of the diameter and fascicular pattern match with the trigeminal nerve anatomy.11 Only 1 allograft is available, the Avance nerve graft (available in a variety of diameters and lengths; AxoGen, Inc, Alachua, FL). In considering the outcomes of direct versus graft repair, conventional thinking has maintained that a direct repair would result in a greater likelihood of recovery than a grafted repair owing to the increased length of nerve regeneration required from the cell body to the target site through the graft and the need for 2 sites of epineurial anastomosis with the potential for 2 separate sites of fascicular misalignment (poor coaptation), 2 sites of potential axonal microsprouting outside the epineurium, and 2 sites of nerve scarring that could impede neural regeneration.12 The overall success rates of microneurosurgery of the trigeminal nerve have varied considerably in the published data from 26 to 92%,13 and subjective success has not always correlated with objective improvement.14 Additionally, standardization in the reported studies of trigeminal nerve repair regarding successful outcomes, as defined by functional (or useful) sensory recovery according to the Medical Research Council Scale (MRCS), is lacking.15 Although many studies have reported individual surgeon experience with trigeminal nerve repair, no study has evaluated the difference in the success of direct versus indirect repair techniques for the trigeminal nerve.
Q2
FIGURE 1. A, Diagram of direct epineurial nerve repair technique. B, Diagram of indirect (graft) nerve repair technique. Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
FIGURE 2. Direct epineurial repair showing poor fascicular cooptation and collateral axonal microsprouting outside the confines of the epineurium. Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
Patients and Methods After approval by the University of Illinois institutional review board (IRB no. 2013-1098), the Common Procedural Terminology codes for trigeminal nerve repair (codes 64716, 64727, 64864, and 64885) were used to search for nerve repair cases completed by 1 surgeon (M.M.) from April 2000 to December 2012, with at least 2 years of follow-up data after the nerve repair procedure. The patient demographic information was taken from a retrospective medical record review and evaluation of the clinical notes. Once the subject was identified, the patient was interviewed by telephone (P.R.) and asked for a valid e-mail address. The subject was e-mailed a link to complete a 20-question online survey (Survey Monkey, Palo Alto, CA) and a consent form to access their individual written or electronic medical record (EMR) for age, gender, race, type of nerve repair, and information regarding the neurologic examination at the initial presentation before the nerve repair and at the follow-up examinations. The results of the questionnaire and the data from the EMRs were analyzed for significance, specifically comparing the direct and indirect nerve repair techniques. Student’s t test and the c2 test were used to determine whether a significant difference existed in the success between the 2 techniques and whether age, gender, race, gap length, degree of initial nerve deficit (Sunderland grade), and type of nerve graft (autograft vs allograft) influenced the outcomes of the nerve repair. Subjective neurosensory recovery was evaluated by individual patient responses to the subjective survey questions, and the objective questions of neurosensory recovery were correlated with the MRCS, with grades S3, S3+, and S4 indicating the presence of functional (or useful) sensory recovery (FSR).16 An FSR score of S3 corresponds to a return of some superficial pain and tactile sensation without over-response and 2-point discrimination of >15 mm (Table 1).17
Results Patient data were available for 43 of the 72 patients (65.3%). Of the 43 patients, 25 were female (58.1%) and 18 were male (41.9%), and the mean age of the
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Table 1. MEDICAL RESEARCH COUNCIL SCALE
Grade* S0 S1 S2 S2+ S3 S3+ S4
Description No sensation Deep cutaneous pain in autonomous zone Some superficial pain and touch Superficial pain and touch plus hyperesthesia Superficial pain and touch without hyperesthesia: static 2-point discrimination >15 mm Same as S3 with good stimulus localization; static 2-point discrimination of 7-15 mm Same as S3; static 2-point discrimination of 2-6 mm
* Grades S3, S3+, and S4 indicate functional (useful) sensory recovery.13 Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
43 patients was 28.3 years (range 17 to 52). These demographic data are consistent with other studies with regard to the risk factors for lingual nerve injury, including advanced age and female gender.18 A total of 47 LN repairs were performed in the 43 patients, including 19 direct epineurial repairs (40.4%) and 28 indirect repairs (4 bilateral graft repairs) (59.6%). Of the 28 graft repairs, 24 were sural nerve autografts (85.7%) and 4 were Avance (AxoGen) allografts (14.3%). Three of the bilateral cases were repaired with a sural nerve graft, and 1 patient was treated with a bilateral Avance nerve graft. The median interval between nerve injury and repair was 3.2 months (range 0.75 to 16.4). The etiology of nerve injury was third molar odontectomy in 34 of 43 patients (79%), followed by pathologic excision in 5 (12.0%), orthognathic surgery in 3 (7.0%), and dental implants in 1 (2.0%). Of the LN injuries, 29 were right sided (61.7%) and 18 were left sided (38.3%). The Sunderland19 grades of initial nerve injury included 1 Sunderland grade II, 5 Sunderland grade III, 18 Sunderland grade IV, and 23 Sunderland grade V injuries using standard clinical neurosensory testing.20 Another 2 cases of LN injury were explored, and the patients underwent external neurolysis without the need for direct or indirect neurorrhaphy, and these patients were excluded from the study group of 47 repairs. These 2 cases might have represented injection-related injuries to the LN.21,22 Of the patients in the present study, all had hypoesthesia or anesthesia, but none had symptoms of neuropathic pain before surgery or after surgical repair.23 In addition, a trend was observed such that the patients who experienced improved outcomes after LN repair also reported on the questionnaire that the sural nerve harvest site was not a significant cause of unpleasant symptoms or concern or significant hypoesthesia or dysesthesia.11 An additional
finding was that the outcomes of the 4 bilateral cases were comparable to those of the unilateral cases (>80% subjective and objective satisfaction), and the injuries and intraoperative findings were consistent within the patients with bilateral injuries. All 4 patients with bilateral injuries presented with bilateral Sunderland grade V injuries due to third molar removal by non–oral and maxillofacial surgeons, and the intraoperative findings were consistent with complete transection in all cases bilaterally. Finally, 3 of the 4 bilateral cases received sural nerve autografts and did not report significant sural deficit or morbidity.11 All surgical procedures were performed by 1 surgeon (M.M.) with the assistance of residents in training in oral and maxillofacial surgery. The surgeries were performed with loupe magnification (3.5 power), and a standard subperiosteal approach to the LN was used to identify the proximal and distal nerve segments and then working toward the site of injury.24 Notation was made of the condition of the injured nerve, and this was correlated with the preoperative clinical neurosensory testing results and Sunderland classification.20 The preoperative clinical neurosensory testing was grouped into 1 of 5 categories (Sunderland I, normal [n = 0]; Sunderland II, mild injury [n = 1]; Sunderland III, moderate injury [n = 5]; Sunderland IV, severe injury [n = 18]; Sunderland V, complete injury, [n = 23]). The intraoperative findings were also categorized into 5 groups (normal/intact in 0, compressed/intact in 2, neuroma-in-continuity in 5, partial transection in 18, and complete transection in 22). A fairly good linear correlation was found between the preoperative neurosensory testing results and the condition of the LN observed at nerve repair, with only 1 degree of difference in 5 cases (Fig 3). Next, the area of injury was addressed by resection of the visible neuroma and sequential resection of 1- to 2-mm segments of both proximal and distal nerve stumps to visualize healthy axoplasm with vascularity to ensure that no neuroma remained in either the proximal or distal nerve stumps. At this point, a subjective clinical determination was made regarding whether the resultant nerve gap length (mean gap length 1.6 mm for direct repairs and 14.3 mm for gap repairs) could be reapproximated with blunt proximal and distal nerve stump dissection and release (into the pterygomandibular space proximally and into the floor of the mouth distally). On occasion, a single epineurial suture was placed to visualize how much tension would be placed on the repair site with direct epineurial repair. If it were determined that the proximal and distal nerve stumps could not lie in direct apposition without a gap between the segments that would result in undue tension on epineurial repair, the decision was made to use a nerve graft for repair (Fig 4).
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FIGURE 3. Scatter plot representing the relationship between the preoperative sensory impairment score and the severity of lingual nerve injury identified at nerve repair (n = 47 nerves). C/I, compressed/intact; CT, complete transection; N/I, normal/intact; NIC, neuroma-in-continuity; PT, partial transection.
protectors, consisting of porcine small intestine submucosa (AxoGuard, Axogen), were used with the allografts at the proximal and distal neurorrhaphy sites to prevent axonal microsprouting and prevent adherence and scarring to the surrounding soft tissues during healing (Fig 5). The objective results of functional sensory recovery, defined by a Medical Research Council System score of S3, S3+, or S4, was 89% for the graft repairs and 85% for the direct repairs. The subjective patient satisfaction score (0 to 10 scale) was 8.9 for the graft repairs and 8.1 for the direct repairs (Fig 6). These differences were statistically significant for both the objective outcomes (P = .01) and subjective outcomes (P = .02). In addition, an evaluation of the other variables, including age, gender, race, interval from injury to repair, gap length, and initial Sunderland grade of injury were not significant in terms of objective and subjective patient outcomes (P > .05).
Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
Discussion Before 2008, all grafts were performed using a sural nerve (medial sural cutaneous nerve from the sacral plexus S1-S2) graft.11 However, since then, most grafts have been performed using an cadaveric nerve allograft (Avance, AxoGen), typically, 2 to 3 mm or 3 to 4 mm in diameter, depending on the recipient nerve, with the length ranging from 10 to 30 mm, depending on the gap length for the LN.25,26 In addition, nerve
Studies on the outcomes of trigeminal nerve repair have focused on the cumulative results of both LN and IAN repair, mostly from individual surgeon experience, and the surgical reports have included a mixture of direct and indirect repair procedures.27-33 To date, no study has evaluated the difference in subjective and objective outcomes between direct and indirect trigeminal nerve repair techniques.
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FIGURE 4. A, Intraoperative view of a direct epineurial left lingual nerve repair. B, Intraoperative view of an indirect epineurial left lingual nerve repair with an autogenous sural nerve graft (note, 2 sites of neurorrhaphy). Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
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FIGURE 5. A, Intraoperative view of an indirect epineurial right lingual nerve repair with an allograft (Avance, AxoGen). B, Nerve protectors (AxoGuard, AxoGen) in place to protect the 2 sites of neurorrhaphy repair. Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
The general assumption is that a direct repair should perform better than a grafted nerve repair for many reasons. First, to qualify for a direct repair without tension, the gap defect must be small. Therefore, the magnitude of injury to the nerve (ie, size of the neuroma) would likely need to be small, with minimal Wallerian degeneration, and, would thus have an improved chance of recovery after surgical repair. Pogrel34 suggested that early repairs might have less neuroma formation and therefore require less resection and a lower chance of requiring a nerve graft and a better prognosis for recovery. Pogrel34 suggested that direct repair has improved outcomes compared with graft repair, although he did not compare the outcomes of direct versus graft repair (most of the ‘‘grafts’’ were vein graft conduits). In contrast, perhaps in an attempt to avoid the additional morbidity of nerve graft harvest or because of a lack of surgeon expertise in graft harvesting, less than adequate resection of neuromatous tissue could be a compromised intraoperative decision, which would certainly result in worse outcomes by leaving neuroma in the nerve stumps (and performing a neuroma-to-neuroma repair) rather than abandoning the neurorrhaphy procedure completely. In addition, in an attempt to avoid a nerve graft, perhaps more tension than ideally desired (ideal tension is no tension)35 could be present at the repair site, resulting in vascular compromise, poor healing, and scar formation at the anastomosis site. Another theoretical reason that direct repairs should perform better than graft repairs is that
there is only 1 site of neurorrhaphy (nerve suture anastomosis) instead of the 2 sites in graft repair. This would result in a lower risk of fascicular adaptation (coaptation) mismatch (at 1 site vs 2 sites) and would also lessen the chance of collateral axonal microsprouting outside the epineurium at the repair site by 50% (Fig 2). Finally, with a smaller amount of neuroma resection and a minimal, or no, nerve gap with a direct repair, anterograde and retrograde axonal transport across the repair site should occur more readily and rapidly from the cell body to the target site in a direct repair versus a graft repair. However, the factors that favor an improved outcome with graft repair compared with direct repair include the ability of the surgeon to resect neuromatous tissue both proximally and distally with impunity, but only to the certain point at which additional nerve resection will not permit neurorrhaphy owing to the inability to access the proximal and/or distal nerve stumps. This ‘‘surgical freedom’’ would permit an improved chance of reaching normal healthy fascicular tissue (well-vascularized mushrooming axoplasm) in both the proximal and the distal nerve stumps. Also, an additional benefit of using a nerve graft is the ability to bring healthy nerve tissue, along with the associated potent neurotropic and neurotrophic factors, to a site of injury to augment recovery after repair.36,37 This is true of both autografts and allografts, although the primary goal of the graft is the transfer of the fascicular conduit architecture that will accept and
FIGURE 6. A, Objective outcomes functional sensory recovery after direct (81%) and graft (89%) repairs (P = .01). B, Subjective outcomes after direct (8.1) and graft (8.9) repairs (P = .02). Miloro, Ruckman, and Kolokythas. Lingual Nerve Repair. J Oral Maxillofac Surg 2015.
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guide the proximal regenerating nerve sprouts toward the distal nerve stump and target site. Although many studies have shown a lack of correlation between objective and subjective testing of neurosensory function,38 this present study showed a correlation between the 2 assessments, likely because the patient questionnaire was completed by the patient for both the subjective and the objective questions, with the known limitation of the study being that objective clinical neurosensory testing by an experienced clinician was not possible owing to the various locations of the patients and their inability to travel for a formal follow-up examination. In addition, the lack of significance of the interval from injury to repair conflicts with the results of some previous studies.39 However, this might have resulted from aggressive resection to healthy fascicular tissue, which was a critical consideration in the present study, and the threshold for considering nerve graft repair was very low. Therefore, any additional scar tissue formation or Wallerian degeneration of the nerve stumps as a result of an increased interval from injury to repair was likely not a significant factor in the outcomes of our study, because it was aggressively resected. In conclusion, the present study has documented that indirect graft nerve repair, using an autograft (sural nerve) or allograft (Avance nerve graft) is associated with improved objective and subjective nerve outcomes compared with direct nerve repair. Surgeons who perform microneurosurgical repair of the trigeminal nerve must recognize the importance of resection of all neuromatous tissue and a tensionfree repair on achieving successful outcomes. Also, they must be capable of performing nerve graft repair, with either harvest of an autograft or the use of a stock allograft. To further determine appropriate evidencebased decisions and treatment recommendations for patients who sustain injuries to the terminal branches of the trigeminal nerve, including the LN and IAN, a prospective multicenter, multisurgeon clinical trial is warranted, because the last attempt at such a study more than 2 decades ago, had significant limitations.40
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