Outcome Following Lingual Nerve Repair With Vein Graft Cuff: A Preliminary Report

SURGICAL ONCOLOGY AND RECONSTRUCTION

Outcome Following Lingual Nerve Repair With Vein Graft Cuff: A Preliminary Report Shigeyuki Fujita, DDS, DMedSc,* Itaru Tojyo, DDS, PhD,y Masai Yamada, DDS,z Yoshihiko Go, DDS,x Takashi Matsumoto, DDS, PhD,k and Norifumi Kiga, DDS, PhD{ Purpose:

The object of this study was to assess the effects of an inside-out vein graft as a cuff after direct suture on human lingual nerve regeneration and recovery after iatrogenic lingual nerve injury.

Patients and Methods:

Ten patients with unilateral lingual nerve anesthesia as a complication of iatrogenic injury after third molar extraction underwent microneurosurgical procedures for the injured lingual nerve under general anesthesia. The patients were randomized into 2 groups. In group A, after removing the neuromas and peripheral scars surrounding the torn nerves, the 2 nerve ends were sutured without tension. In group B, after the same procedure, including the same suturing procedure, an inside-out vein graft was placed as a cuff after the direct suture. Each group was followed at least once every 6 months for 1 year after the procedure. Postoperative outcomes were evaluated using the Pogrel criteria, the Sunderland grade, and the British Medical Research Council Scale (MRCS).

Results:

There were no particular differences between groups A and B at 6 and 12 months after the operation. However, based on the MRCS criteria, there was a clearly better result in group B than in group A at 6 and 12 months after the operation, and the recovery of gustatory sensation tended to be better in group B than in group A 1 year after the operation.

Conclusion:

This inside-out vein graft as a cuff after direct suturing may facilitate faster lingual nerve regeneration than the traditional direct suture approach. The inside-out vein graft as a cuff may provide the advantages of preventing axonal escape at the suture lines, minimizing nerve entrapment, and preventing neuroma formation in the space between the sutured nerves. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:e1-e7, 2014

The lingual nerve plays an important role in multiple functions, including gustatory sensation, contact sensitivity, and thermosensitivity. Repair of the injured lingual nerve is considered more difficult than repair of the inferior alveolar nerve.1,2 After continuous observation and diagnosis of the injury, in cases involving significant disruption of lingual nerve function, microneurosurgical reconstruction of the nerve is performed.3 Thick scars are often found around the torn lingual nerve, complicating correct repositioning of the nerve. Direct anastomosis of the torn nerve ends without tension is the recommended

approach.4,5 However, in cases that present significant gaps between injured nerve ends, nerve grafts or conduits (veins or tubes of various materials) are used.6 Unfortunately, these methods often achieve worse results than direct anastomosis because of continuous postoperative pain from the gap reconstruction or less effective recovery of gustatory sensation. Recently, the importance of nerve regeneration across the space between injured nerve ends has been widely acknowledged.7-13 With a rigid sutured vein cuff, the contact of endothelial cells with the regenerating axon may give rise

Received from the Department of Oral and Maxillofacial Surgery

University, 811-1 Kimiidera, Wakayama City 641-8509, Japan;

Wakayama Medical University, Wakayama City, Japan.

e-mail: [email protected]

*Professor.

Received November 11 2013

yAssociate Professor.

Accepted March 19 2014

zResearch Fellow.

Ó 2014 American Association of Oral and Maxillofacial Surgeons

xResearch Fellow. kResearch Fellow.

0278-2391/14/00331-0$36.00/0 http://dx.doi.org/10.1016/j.joms.2014.03.018

{Assistant Professor. Address correspondence and reprint requests to Dr Fujita: Department of Oral and Maxillofacial Surgery Wakayama Medical

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e2 to a constriction caused by the connective tissue invasion. Moreover, it is said that inside-out vein grafts probably provide a better microenvironment for the regenerating axon, likely because of the balance among collagen, laminin, fibronectin, and other substances in the vein wall, than standard vein grafts.14

Patients and Methods From April 2002 to March 2012, 10 patients (2 men, 8 women; age range, 17 to 55 yr; mean age, 39.2 yr) were referred to the authors’ department with unilateral lingual nerve anesthesia as a complication of iatrogenic injury after third molar extraction. All patients were seen and evaluated by 1 of the authors (S.F.), and the patients did not show any signs of recovery during close follow-up for at least 3 months. The patients’ general medical condition was good. All patients met the following requirements. 1) Rating of the subjective sensation of the affected area was less than half that of the healthy area. 2) Brushstroke directional discrimination showed no directionality. 3) Sharp touch reaction was poor, as assessed by a pinprick test. 4) Two-point discrimination with blunt tips was greater than 20 mm. 5) Cold sensation (ice, 0 C) and heat sensation (hot water, 42 C) were poor. 6) The Semmes-Weinstein monofilament (SWM) test using Touch Test Sensory Evaluators (North Coast Medical, Inc, Gilroy, CA), which is an improved version of the von Frey hairs test, showed considerably lower sensitivity compared with the control side of the tongue. 7) Gustatory sensation, assessed with localized Testing Discs (Sanwa Kagaku Kenkyusho, Nagoya, Japan; salt, sodium chloride 1 mol/L; sweet, sucrose 1 mol/L; sour, acetic acid 0.4 mol/L; bitter, quinine 0.1 mol/L), was absent for all reagents on the injured side of the tongue. Written, informed consent was obtained from all patients before the microneurosurgical operation under general anesthesia. The duration from nerve injury to surgical repair varied from 3 to 7 months. Detailed preoperative data are presented in Table 1. This study followed the Declaration of Helsinki on medical protocol and ethics and the regional ethical review board of Wakayama Medical University (Wakayama City, Japan) approved the study. Patient selection was randomized by the study controller. SURGICAL PROCEDURE

The lingual nerve was exposed through an intraoral mucosal incision and lingual flap reflection. Optical magnifying glasses (250 mm) and an operating microscope (Superlux 301, Zeiss, Jena, Germany) were available during surgery. In all cases, the lingual nerves were completely disrupted and heavily trapped by

LINGUAL NERVE REPAIR WITH VEIN GRAFT CUFF

dense scar tissue. Most cases showed neuromas at the torn nerve ends. The neuromas and peripheral scars surrounding the torn nerves were completely removed; after this procedure, the 2 nerve ends could touch without tension. As much scar tissue as possible was removed from the torn nerve, and the transected lingual nerve stumps were identified, mobilized, and trimmed to the point where the fascicles could be identified in the microsurgical field. In all cases, direct end-to-end epineural nerve sutures without tension were performed at 8 or more sites around the stump, using 8-0 or 9-0 nylon. Nerve grafts were not required in any case (Fig 1). In 5 patients (group B), a fragment of the external jugular vein, approximately 40 mm in length, was tagged for use as a cuff to cover the sutured nerve. The Langer line of the skin was incised at the operation side of the neck, and the external jugular vein was exposed. The autogenous vein graft was split longitudinally and turned inside-out as described by Wang et al.8 The graft encased the sutured site with at least a 15-mm margin and was attached to the epineural membrane with 8-0 or 9-0 nylon at 8 or more sites on each side (Fig 2). As a result, the sutured injured nerve was encased within the vein cuff. In the remaining 5 patients (group A), no cuff was used. All patients were examined after surgery using the aforementioned assessments for 6- and 12-month neurosensory testing by another full-time faculty member who was blinded to the study groups.

Results All patients examined in this study presented with unilateral damage to the lingual nerve after extraction of the lower third molar, which, on close follow-up for at least 3 months, did not show any signs of recovery. In all these patients, preoperative symptoms indicated that 2-point discrimination was greater than 20 mm, brush-stroke directional discrimination was negative, thermal tests indicated allodynia or no reaction, and pinprick nociception was very weak. All patients were followed at 6 months and 1 year after the microsurgical procedure. Compared with preoperative conditions, all patients showed improved sensory reactions. Preoperative and postoperative assessment data are presented in Tables 1, 2, 3, and 4. Postoperative outcomes were classified using the Pogrel criteria,9 the Sunderland grade, and the Medical Research Council Scale (MRCS). Outcomes using the Pogrel criteria were classified as follows. Good improvement was considered present if 2 of the following 3 criteria were achieved: 1) improvement of at least 5 on the von Frey hairs test; 2) improvement of at least 10 mm in 2-point discrimination; and 3) improvement in temperature sensation

FUJITA ET AL

Table 1. PREOPERATIVE CONDITION ANALYZED BY SUNDERLAND GRADE, MRCS, AND GUSTATORY SENSATION

Case

Age (yr)

Gender

Time From Injury to Repair (mo)

1 2 3 4 5 6 7 8 9 10

30 17 48 42 33 53 22 36 26 55

F M M F F F F F F F

3 4 7 6 3 3 5 6 3 4

Brush-Stroke Directional Discrimination no response no response no response no response no response no response no response no response no response no response

2-Point Discrimination (mm)* >20 (5) >20 (5) >20 (5) >20 (5) >20 (5) >20 (5) >20 (5) >20 (5) >20 (5) >20 (5)

SWM Test*y

Thermal Discrimination (Hot/Cold)

Pinprick Test

Sunderland Grade

MRCS

Gustatory Sensationz

10 (2) 16 (1) 8 (2) 13 (1) 19 (2) 12 (2) 11 (1) 9 (2) 12 (2) 16 (1)

allodynia/no response no response/no response allodynia/allodynia no response/no response no response/no response allodynia/no response allodynia/allodynia allodynia/allodynia no response/no response allodynia/no response

no response no response no response no response no response no response no response no response no response no response

IV V IV V V IV IV IV V V

S2 S0 S2 S0 S0 S2 S2 S2 S0 S2

no response no response no response no response no response no response no response no response no response no response

Abbreviations: F, female; M, male; MRCS, Medical Research Council Scale; SWM, Semmes-Weinstein monofilament. * Data for the undamaged side are presented within parentheses. y The Semmes-Weinstein monofilament instrument is composed of 20 different diameter monofilaments. Number 1 was assigned to the smallest-diameter monofilament (1.65 to 0.008 g) and number 20 was assigned to the largest-diameter monofilament (6.65 to 300 g). z Gustatory sensation was assessed with localized Testing Discs (Sanwa Kagaku Kenkyusho, Nagoya, Japan; salt, sodium chloride 1 mol/L; sweet, sucrose 1 mol/L; sour, acetic acid 0.4 mol/L; bitter, quinine 0.1 mol/L) for all reagents on the injured side of the tongue. Fujita et al. Lingual Nerve Repair With Vein Graft Cuff. J Oral Maxillofac Surg 2014.

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LINGUAL NERVE REPAIR WITH VEIN GRAFT CUFF

FIGURE 1. End-to-end suture without tension (group A). Fujita et al. Lingual Nerve Repair With Vein Graft Cuff. J Oral Maxillofac Surg 2014.

from no sensation to the ability to detect hot and cold water or from the ability to detect hot and cold water to the ability to differentiate between Minnesota Thermal Discs that were no more than 3 discs apart. Some improvement was considered present if any 2 of the following were achieved: 1) an improvement of 2 to 5 on the von Frey hairs test; 2) an improvement of 5 to 10 mm in 2-point discrimination; and 3) an improve-

ment in temperature sensation. No improvement was considered present if any 2 of the following were recorded: 1) an improvement or a decrease in Frey hairs testing of up to 2 hairs in either direction; 2) a change in 2-point discrimination less than 5 mm in either direction; and 3) no improvement in temperature sensation. A patient was considered worse after microneurosurgery if at least 1 of the following was

FIGURE 2. Sutured nerve encased with the vein (group B). Fujita et al. Lingual Nerve Repair With Vein Graft Cuff. J Oral Maxillofac Surg 2014.

e5 no response no response no response no response no response no response no response no response no response no response S3 S3 S3+ S3+ S3 S3+ S3 S3+ S3+ S3 III II III II II III III III II II

Fujita et al. Lingual Nerve Repair With Vein Graft Cuff. J Oral Maxillofac Surg 2014.

Abbreviations: F, female; M, male; MRCS, Medical Research Council Scale; SWM, Semmes-Weinstein monofilament.

no improvement no improvement some improvement good improvement some improvement some improvement some improvement some improvement good improvement some improvement response response response response response response response response response response allodynia/response response/response allodynia/allodynia response/response response/response allodynia/no response allodynia/allodynia allodynia/allodynia response/response response/response 10 (2) 10 (1) 6 (2) 6 (1) 9 (2) 10 (2) 8 (1) 7 (2) 5 (2) 7 (1) 15 (5) 18 (5) 8 (5) 10 (5) 20 (5) 8 (5) 14 (5) 8 (5) 8 (5) 13 (5) no response response response response response response response response response response 3 4 7 6 3 3 5 6 3 4 30 17 48 42 33 53 22 36 26 55 1 2 3 4 5 6 7 8 9 10

Gender Case

F M M F F F F F F F

MRCS Sunderland Grade Pogrel Classification Pinprick Test Thermal Discrimination (Hot/Cold) SWM Test 2-Point Discrimination (mm) Brush-Stroke Directional Discrimination Time From Injury to Repair (mo) Age (yr)

Table 2. POSTOPERATIVE DATA BY THE POGREL CLASSIFICATION, SUNDERLAND GRADE, MRCS, AND GUSTATORY SENSATION AT SIX MONTHS

Gustatory Sensation

FUJITA ET AL

recorded: 1) a decrease on the Frey hairs test of more than 2 hairs; 2) an increase in 2-point discrimination of at least 5 mm; and 3) any loss of temperature sensation compared with the preoperative values. At 6 months after the operation, based on the Pogrel criteria, 2 patients in group A showed no improvement, whereas 2 showed some improvement and 1 showed good improvement. In group B, 4 patients showed some improvement and 1 showed good improvement. According to the Sunderland grading, in group A, 2 cases were classified as grade III and the 3 other cases were classified as grade II. In group B, 3 cases were classified as grade III and the 2 other cases were classified as grade II. Based on the MRCS criteria, in group A, 3 of 5 cases showed S3 and 2 of 5 cases showed S3+. In group B, 2 of 5 cases showed S3 and 3 of 5 cases showed S3+. These data are presented in Table 2. At 1 year after the operation, based on the Pogrel criteria, 3 patients in group A showed some improvement, whereas 2 showed good improvement. In group B, 2 patients showed some improvement and 3 showed good improvement. By the Sunderland grade, in group A, 2 cases were classified as grade III and the 3 other cases were classified as grade II. In group B, all cases were classified as grade II. Based on the MRCS criteria, in group A, all cases showed S3+, whereas in group B, 2 of 5 cases showed S3+ and 3 of 5 cases showed S4. These data are presented in Tables 1, 2, 3, and 4. According to the Pogrel criteria and the Sunderland grade, there were no particular differences between groups A and B at 6 and 12 months after the operation. However, based on the MRCS criteria, there was a clearly better result in group B than in group A at 6 and 12 months after the operation, and the recovery of gustatory sensation tended to be better in group B than in group A 1 year after the operation. These data are presented in Table 4. Group B tended to show earlier improvement in sensation than group A. In particular, concerning brush-stroke reaction and hot and cold sensation, group B showed faster recovery than group A. The assessments of recovery to allodynia tended to be better in group B than in group A.

Discussion There is still controversy regarding the timing of lingual nerve microsurgery. Bagheri et al10 reported that microsurgical repair of lingual nerve injury has the best chance of successful restoration of acceptable neurosensory function if performed within 9 to 12 months of the injury.11 Conversely, Smith and Robinson12 found no relation between the results of sensory tests and the delay before microsurgical repair. In the present study, only cases presenting

e6 no no no sweet, sour, salt no no bitter sour, salt, bitter no sweet no response no response no response partial response no response no response partial response partial response no response partial response S3+ S3+ S3+ S3+ S3+ S4 S4 S3+ S4 S3+

Fujita et al. Lingual Nerve Repair With Vein Graft Cuff. J Oral Maxillofac Surg 2014.

Abbreviations: F, female; M, male; MRCS, Medical Research Council Scale; SWM, Semmes-Weinstein monofilament.

III II III II II II II II II II some improvement good improvement some improvement good improvement some improvement good improvement some improvement some improvement good improvement good improvement response response response response response response response response response response allodynia/response response/response response/allodynia response/response response/response response/response response/response response/response response/response response/response 2 (2) 9 (1) 5 (2) 5 (1) 8 (1) 7 (2) 7 (1) 5 (2) 5 (2) 7 (1) 10 (5) 7 (5) 8 (5) 10 (5) 12 (5) 5 (5) 5 (5) 8 (5) 6 (5) 10 (5) response response response response response response response response response response 3 4 7 6 3 3 5 6 3 4 F M M F F F F F F F 30 17 48 42 33 53 22 36 26 55 1 2 3 4 5 6 7 8 9 10

Gustatory Sensation Sunderland Grade MRCS Pogrel Classification Pinprick Test Thermal Discrimination (Hot/Cold) 2-Point Time From Brush-Stroke Directional Discrimination SWM Injury to Age (mm) Test Case (yr) Gender Repair (mo) Discrimination

Table 3. POSTOPERATIVE DATA BY THE POGREL CLASSIFICATION, SUNDERLAND GRADE, MRCS, AND GUSTATORY SENSATION AT 12 MONTHS

Recovered Gustatory Sensation

LINGUAL NERVE REPAIR WITH VEIN GRAFT CUFF

within 7 months of the injury were analyzed. The purpose of the present investigation was to report 1-year outcomes of microsurgical repair of lingual nerve injuries by comparing direct end-to-end suturing with and without a vein cuff. Some clinicians have tried to microsurgically reconstruct the severed nerve by bridging the gap with an autogenous nerve graft or collagen-based conduits. During dissection of the injured lingual nerve, especially the distal portion of the injured stump, the authors found that the severed nerve follows a significantly twisted course into the posterior side of the floor of mouth. By extensively dissecting the scar or connective tissue, the nerve could be significantly mobilized. Then, by taking advantage of the extra length achieved by straightening the twisted nerve, the stumps could be brought into contact without tension, thereby eliminating the necessity for a nerve graft in all the present cases. In cases treated with an autogenous nerve graft or collagen conduit, regeneration time is longer than in cases treated with direct end-to-end suture, and recovery may be accompanied by continuous pain for a longer period. Smith and Robinson12 showed that repair of a short gap in the lingual nerve by stretch repair with endto-end anastomosis, even with some degree of tension, is followed by better recovery than that after nerve grafting. In the present cases, end-to-end direct suture was performed without tension between the nerve ends, and the first 8-0 nylon suture was easily placed without tension, as described by Miyamoto.13 Ferrari et al14 described a method by which the rat saphenous nerve was sectioned and repaired by inside-out vein grafts and standard vein grafts. Inside-out vein grafting to repair a sensory nerve facilitated better nerve regeneration than standard vein grafts. Inside-out vein grafts probably provide a better microenvironment for the regenerating axon, perhaps because of the balance among collagen, laminin, fibronectin, and other substances in the vein wall.14 In the present procedure, the rigid sutured vein cuff around the suture line between the epineurium and the vein fragment prevents stretching between the sutured stumps in the healing period after the microsurgery. The presence of neurotropic and neurotrophic factors on the outside surface of the vessel is controversial. The use of a vein graft seems to have distinct advantages for transected peripheral nerves because it can be used for autogenous transplantation, does not provoke any noticeable foreign-body reaction, and can be harvested through minor surgery. Moreover, collagen materials are more expensive than an autogenous vein fragment graft and sometimes may cause a foreign-body reaction. According to the authors’ observations more than 1 year after surgery, there was

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III II III II II II II II II II

no response no response no response partial response no response no response partial response partial response no response partial response

no no no sweet, sour, salt no no bitter sour, salt, bitter no sweet

no morbidity associated with neck dissection for harvesting the external jugular vein in all cases with a vein graft. In particular, there was no conspicuous scar tissue formation in the donor site of the neck, because of the fine sutures in the subcutaneous tissues and the dressing technique on the wound after the operation. These represent significant potential advantages of this procedure. However, because of the small number of cases analyzed in this study, it is not possible to make any definite conclusions from these preliminary findings. In conclusion, this technique may have a tendency to facilitate faster lingual nerve regeneration than the traditional direct suture approach for repair of the lingual nerve. When the effectiveness of end-to-end anastomosis without a cuff is comparable to that with a cuff, the inside-out vein graft as a cuff may provide the advantages of preventing axonal escape at the suture lines, minimizing nerve entrapment, preventing neuroma formation, and providing neurotrophic promoting factors in the space between sutured nerves.

References

Fujita et al. Lingual Nerve Repair With Vein Graft Cuff. J Oral Maxillofac Surg 2014.

Abbreviations: F, female; M, male; MRCS, Medical Research Council Scale; SWM, Semmes-Weinstein monofilament.

S3+ S3+ S3+ S3+ S3+ S4 S4 S3+ S4 S3+ some improvement good improvement some improvement good improvement some improvement good improvement some improvement some improvement good improvement good improvement III II III II II III III III II II S3 S3 S3+ S3+ S3 S3+ S3 S3+ S3+ S3 no improvement no improvement some improvement good improvement some improvement some improvement some improvement some improvement good improvement some improvement IV V IV V V IV IV IV V V 3 4 7 6 3 3 5 6 3 4 F M M F F F F F F F 30 17 48 42 33 53 22 36 26 55 1 2 3 4 5 6 7 8 9 10

Gustatory Sensation Sunderland MRCS Grade Sunderland MRCS Grade

Pogrel Classification

12 mo Postoperatively 6 mo Postoperatively

Pogrel Classification Time From Preoperative Age Injury to Sunderland Case (yr) Gender Repair (mo) Grade

Table 4. POSTOPERATIVE OUTCOMES BY POGREL CLASSIFICATION, SUNDERLAND GRADE, MRCS, AND RECOVERED GUSTATORY SENSATION

Recovered Gustatory Sensation

FUJITA ET AL

1. Miloro M: Microneurosurgery, in Miloro M, Ghali GE, Larsen PE, et al (eds). Peterson’s Principles of Oral and Maxillofacial Surgery (ed 2). Hamilton, Ontario, Canada, BC Decker, 2004. pp 819–837 2. Ziccardi VB, Rivera L, Gomes J: Comparison of lingual and inferior alveolar nerve microsurgery outcomes. Quintessence Int 40:295, 2009 3. Robinson PP, Loescher AR, Yates JM, et al: Current management of damage to the inferior alveolar and lingual nerves as a result of removal of third molars. Br J Oral Maxillofac Surg 42:285, 2004 4. Smith KG, Robinson PP: An experimental study of lingual nerve repair using epineurial sutures or entubulation. Br J Oral Maxillofac Surg 33:211, 1995 5. Robinson PP, Smith KG: A study on the efficacy of late lingual nerve repair. Br J Oral Maxillofac Surg 34:96, 1996 6. Cornelius CP, Roser M, Ehrenfeld M: [Microneural reconstruction after iatrogenic lesions of the lingual nerve and the inferior alveolar nerve. Critical evaluation]. Mund Kiefer Gesichtschir 1: 213, 1997 (in German) 7. Robinson PP, Loescher AR, Smith KG: A prospective, quantitative study on the clinical outcome of lingual nerve repair. Br J Oral Maxillofac Surg 38:255, 2000 8. Wang KK, Costas PD, Bryan DJ, et al: Inside-out vein graft repair compared with nerve grafting for nerve regeneration in rats. Microsurgery 16:65, 1995 9. Pogrel MA: The results of microneurosurgery of the alveolar and lingual nerve. J Oral Maxillofac Surg 60:485, 2002 10. Bagheri SC, Meyer RA, Khan HA, et al: Retrospective review of microsurgical repair of 222 lingual nerve injuries. J Oral Maxillofac Surg 68:715, 2010 11. Susarla SM, Kaban LB, Donoff RB, et al: Does early repair of lingual nerve injuries improve functional sensory recovery? J Oral Maxillofac Surg 65:1070, 2007 12. Smith KG, Robinson PP: An experimental study of three methods of lingual nerve effect repair. J Oral Maxillofac Surg 53:1052, 1995 13. Miyamoto Y: Experimental study of results of nerve suture under tension vs. nerve grafting. Plast Reconstr Surg 64:540, 1979 14. Ferrari F, De Castro Rodrigues A, Malvezzi CK, et al: Inside-out vs. standard vein graft to repair a sensory nerve in rats. Anat Rec 256:227, 1999