Prognostic Factors for Functional Recovery after Lingual Nerve Reconstruction Using an Artificial Nerve Conduit

Prognostic Factors for Functional Recovery after Lingual Nerve Reconstruction Using an Artificial Nerve Conduit | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic Factors for Functional Recovery after Lingual Nerve Reconstruction Using an Artificial Nerve Conduit Shigeyuki Fujita, Shigeru Suzuki, Osamu Sakaguchi, Itaru Tojyo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7726878/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Jan, 2026 Read the published version in Maxillofacial Plastic and Reconstructive Surgery → Version 1 posted 20 You are reading this latest preprint version Abstract Background Lingual nerve injury following dental procedures, such as lower third molar extractions, can cause significant sensory deficits. For patients with persistent severe symptoms, surgical reconstruction of the lingual nerve using a nerve conduit is often considered. However, the degree of recovery varies, the significance of the nerve gap distance and the optimal timing of intervention remain subjects of ongoing debate. Objectives Using the Medical Research Council Scale (MRCS) as a standardized measure of sensory function, this study aims to clarify the effects of the timing of surgery, nerve gap length, and other potential prognostic factors on nerve functional recovery. Methods This study retrospectively analyzed a cohort of patients who underwent lingual nerve repair surgery. The MRCS score was used as an outcome variable to assess postoperative recovery. Predictors included time to surgery, nerve gap length, age, sex, and the presence or absence of diabetes. Statistical analyses included both ordinal logistic regression and multivariate logistic regression analysis to evaluate the association between each predictor and the postoperative MRCS score. Results Ordinal logistic regression analysis showed no statistically significant correlation between the time to surgery or nerve gap length and postoperative recovery based on the MRCS score. Furthermore, to clarify the clinical significance, multivariate logistic regression analysis was performed. The results indicated a statistically significant association between a shorter time to surgery and a favorable prognosis. Conclusion Early surgical intervention and accurate identification of the injured nerve are considered crucial factors for improving postoperative sensory recovery following lingual nerve injury. Further prospective studies are needed to validate these findings. Background Peripheral nerve injury is a well-known complication of various dental procedures, particularly the extraction of impacted mandibular third molars [ 1 , 2 , 3 ]. Patients afflicted with this condition may experience a range of sensory disturbances, including dysesthesia, paresthesia, and numbness in the distribution of the lingual nerve, which can have a significant impact on their quality of life. For patients with persistent severe symptoms, surgical reconstruction of the lingual nerve using a nerve conduit is often considered. However, the degree of recovery varies, and the optimal timing of intervention and the significance of the nerve gap distance remain subjects of clinical debate. Previous studies have suggested that early surgical intervention may lead to better outcomes, but conclusive evidence is lacking and opinions are divided༻4,5,6༽. Furthermore, the extent of nerve recovery is influenced by multiple factors, such as the patient's sex, general health status, and the extent of nerve damage. The purpose of this study is to elucidate the effects of the timing of surgery, nerve gap length, and other potential prognostic factors on postoperative nerve recovery, using MRCS as a standardized measure of sensory function. To achieve this objective, multivariate analysis was used to identify independent factors associated with improvement in MRCS scores after lingual nerve repair surgery. Materials and Methods This study is a retrospective observational study of cases who underwent microsurgical repair of lingual nerve injury using a nerve conduit (Renerve) by the same oral surgeon from 2017 to 2025. The inclusion criteria were as follows: (1) Patients diagnosed with severe lingual nerve injury preoperatively using the Clinical Neurosensory Testing (CNT) method recommended by the American Association of Oral and Maxillofacial Surgeons, and in whom lingual nerve injury was confirmed intraoperatively [ 7 ]. (2) Patients who underwent microsurgical repair of the lingual nerve using a nerve conduit (Renerve). (3) Patients whose affected sensation was evaluated using the Medical Research Council Scale (MRCS) preoperatively and one year postoperatively. Patients with incomplete records or inadequate follow-up were excluded. Out of 65 cases who underwent surgery in this study, 49 cases (10 male, 39 female) met the selection criteria and were included as valid cases. Evaluation Items The primary outcome measure was postoperative nerve recovery, as assessed by the MRCS sensory score. The MRCS scale classifies sensory recovery into stages S0-S4, and logistic regression analysis was performed. Predictors The explanatory variables were as follows: • Time to surgery (months) • Distance from the injury site to the nerve severance site (mm) • Patient's age (at the time of surgery) • Sex (male = 1, female = 0) • Presence of diabetes: Hemoglobin A1c level of 8% or higher (yes = 1, no = 0). The outcome measures used were the British Medical Research Council Scale (MRCS) and Functional Sensory Recovery (FSR), with "good" recovery defined as an MRCS of S3 or higher and an FSR of 1. Factors influencing sensory recovery after lingual nerve reconstruction in patients with nerve injury were examined. Postoperative recovery was evaluated using the MRCS scale and FSR criteria. [Table 1] Statistical Analysis Ordinal logistic regression and multivariate logistic regression analysis were used to evaluate the association between each predictor variable and the postoperative MRCS score. Odds ratios (OR), 95% confidence intervals (CI), and p-values were calculated. All statistical analyses were performed with a two-sided significance level of p < 0.05. All data were statistically analyzed using JMP® 14.2.0 (SAS Institute Inc., North Carolina, USA). Results The age of the patients ranged from 20 to 48 years for males, with a mean of 31.2 years, a median of 29, and a standard deviation of 8.0. For females, the age range was 18 to 63 years, with a mean of 34.7 years, a median of 32, and a standard deviation of 11.3. A Mann-Whitney U test (non-parametric test) revealed no significant difference in the distribution between males and females, with a U value of 71.5 and a P value of 0.111 [Table 2]. The time from lingual nerve injury to nerve repair surgery ranged from a minimum of 2 months to a maximum of 204 months, with a mean of 17.3 months, a median of 6, and a standard deviation of 28.5[Table 3]. The length of the damaged lingual nerve confirmed during surgery (mm) was a minimum of 10 mm and a maximum of 25 mm, with a mean of 14.7 mm, a median of 15 mm, and a standard deviation of 2.93[Table 4]. Since the MRCS score is an ordinal scale, we first attempted ordinal logistic regression analysis. The results of the ordinal logistic regression showed that the time to surgery had a p-value of 0.390, and the nerve gap length had a p-value of 0.328, indicating no association with the improvement of MRCS scores. In this analysis, neither the time to surgery nor the nerve gap distance showed a statistically significant correlation with postoperative recovery based on the MRCS score [Table 5]. Therefore, to clarify the clinical significance, the postoperative MRCS score was re-categorized into a binary outcome of "good prognosis (S3 or higher)" and "poor prognosis (S2 + or lower)". A multivariate logistic regression analysis (with "good prognosis" as the outcome variable) was performed on this binary outcome. Since the cases in this study included extreme outliers for the time to surgery (e.g., 72, 96, and 204 months), a logarithmic transformation (Log Transformation) was applied to the time to surgery to suppress the influence of these outliers and make the distribution closer to a normal distribution. Furthermore, we analyzed the time to surgery (after log transformation), nerve gap length, sex, age, and presence of diabetes as independent variables including confounding factors. As a result, the importance of the time to surgery was clearly demonstrated. The p-value for the log-transformed time to surgery was 0.044, indicating a clear and statistically significant association that a shorter time to surgery leads to a good prognosis, even after statistically adjusting for the effects of age, sex, and diabetes. The odds ratio was 0.304, showing a strong tendency for a longer time to surgery to lead to a poor prognosis. The p-value for the nerve gap length was 0.128, which did not show a significant association. Nerve gap length, age, sex, and presence of diabetes showed no statistically significant association with the postoperative prognosis [Table 6]. Discussion In this retrospective analysis, we examined the functional recovery at one year postoperatively in 67 cases (49 valid cases) of lingual nerve injury who underwent reconstruction using a nerve conduit. The evaluation measures used were the MRCS and FSR, with "good" recovery defined as an MRCS of S3 or higher and an FSR of 1. We investigated factors affecting sensory recovery after lingual nerve reconstruction in patients with nerve injury. Postoperative recovery was evaluated using the MRCS scale and FSR criteria. By combining ordinal logistic regression and multivariate logistic regression, it became possible to handle ordinal categorical variables as an outcome measure while simultaneously adjusting for the effects of multiple explanatory variables. This approach is characterized by its ability to avoid information loss from simple binarization and to perform an analysis that reflects gradual changes in outcomes. Furthermore, by simultaneously correcting for confounding factors such as age, sex, nerve gap distance, and time to surgery, the independent effect of each factor could be estimated more accurately. This is expected to improve statistical power and enhance the reliability and reproducibility of the results, as the obtained odds ratios are clinically interpretable. The ordinal logistic regression analysis did not yield significant results, which may be due to the uneven distribution of cases among the MRCS categories. On the other hand, the multivariate logistic regression analysis, which focused on a clinically relevant outcome, clearly showed that the time to surgery is the most important factor determining the prognosis. This result, obtained after simultaneously adjusting for multiple confounding factors, is considered highly reliable. Although nerve gap distance is generally considered an important factor in determining the prognosis, no significant association was found in this study. This might be due to the limited number of cases, or the effect may have been masked by the more powerful factor of the time to surgery. Statistically, the results were as stated above, but from a review of individual cases, even those with a long time to surgery (e.g., 8 or 17 years) showed good functional recovery postoperatively. Therefore, it cannot be definitively stated to patients preoperatively that a long time since injury will lead to a poor prognosis or that surgery is not indicated. As Robinson stated that nerve repair should be considered regardless of the length of time that has passed since injury [ 8 ]. The debate over what length of nerve gap necessitates the use of a nerve conduit, Perrelle suggested that 15 mm is the limit for using a nerve conduit༻9༽. Numerous reports have conducted animal experiments using the sciatic nerves of small animals (rats, rabbits, etc.), i.e., repairing thin nerves, and have shown that nerve regeneration up to 30 mm has been achieved using artificial nerves alone༻10,11༽. On the other hand, in experiments using large animals (sheep, pigs) and thick median nerves measuring 8 cm in length, nerve regeneration using conduit alone was not observed༻12,13,14༽. When using artificial nerves, the concentration of neurotrophic factors is critical to advancing nerve regeneration, there is a limit of regenerative capacity. In other words, if the regenerative field is V, then the regenerative distance L will inevitably be shorter for nerves with a large diameter. For example, if r is doubled, L will be one-fourth the original length. V = πr 2 x L༻15༽. Nerve grafting with cell suspensions e. g. with Schwann cells shows promising results on small defect sizes over 30 mm in length in animals but is limited on translation to human organism by highly regulated laws for transplantation of human stem cells༻16༽. The diameter of the human lingual nerve is about 3 mm, and it is not thick, so we believe that nerve regeneration using an artificial nerve within 30 mm alone is probably possible. we have a case in our experience with a nerve gap of 25 mm that was left untreated for 6 years, and the patient showed good functional recovery. Clinically, the basic decision of whether the damaged and degenerated nerve was completely excised and the surgeon's technique are largely involved. If a suitable environment for regeneration is reliably secured after the complete excision of the damaged nerve, the prognosis may be good even if the resection distance is slightly extended. This is a highly debated point and a topic that needs to be fully investigated with more experienced cases in the future. Conclusion In this retrospective analysis, the results of the ordinal logistic regression analysis showed that earlier surgical intervention was not significantly associated with improved sensory recovery after lingual nerve repair as measured by the MRCS score. The results of the multivariate logistic regression analysis, however, showed that the time to surgery was a significant independent prognostic factor. Other factors such as age, sex, and diabetes showed no significant trends in either analysis. These findings emphasize the clinical importance of performing surgical repair at an appropriate time and with accurate anatomical knowledge to optimize postoperative outcomes in patients with lingual nerve injury. To confirm these observations and further elucidate prognostic factors, a prospective, multi-institutional study with a larger sample size is needed in the future. Abbreviations Medical Research Council Scale (MRCS), Functional Sensory Recovery (FSR), Clinical Neurosensory Testing (CNT) Declarations Ethic approval and consent to participate This study was performed in accordance with the Declaration of Helsinki for medical protocols and was approved by the Wakayama Medical University Institutional Review Board (Nos.1689) and the North Osaka Housennka Hospital Review Board (Nos.RR040501). General consent was given by the patients Consent for publication Written informed consent for the publication was obtained. Funding There is no funding related to this article. Author Contribution SF read and wrote the manuscript. IT, OS, and SS prepared the retrospective data. SS analyzed and interpreted this data. SF designed and wrote the entire article. All authors read and approved the final manuscript Acknowledgement The study was supported by a grant from the Grant-in-Aida grant for Scientic Research from Japan Society for the promotion of Science (No.18K09751). Data Availability Please contact the author for data requests. References Kipp DP, Goldstein BH, Weiss WW (1980) Dysesthesia after mandibular third molar surgery: a retrospective study and analysis of 1,377 surgical procedures. J Am Dent Assoc 100:185–192 Mason DA (1988) Lingual nerve damage following lower third molar surgery. Int J Oral Maxillofac Surg 17:290–294 Robert RC, Bacchett PB, Pogrel MA (2005) Frequency of trigeminal nerve injuries following third molar removal. J Oral Maxillofac Surg 63:732–735 Susarla SM, Kaban LB, Donoff RB, Dodson TB (2007) Does early repair of lingual nerve injuries improve functional sensory recovery? J Oral Maxillofac Surg 65:1070–1076 Kushnerev E, Yates JM (2015) Evidence-based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review. J Oral Rehabil 42:786–802 Suhaym O, Miloro M (2020) Does early repair of trigeminal nerve injuries influence neurosensory recovery? A systematic review and meta-analysis. Int J Oral Maxillofac Surg 50:820–829 Ghali GE, Epker BN (1989) Clinical neurosensory testing: practical applications. J Oral Maxillofac Surg 47:1074–1078 Robinson PP, Loescher AR, Yates JM, Smith KG (2004) Current management of damage to the inferior alveolar and lingual nerves as a result of removal of third molars. Br J Oral Maxillofac Surg 42:285–292 Perrelle JM, Boreland AJ, Gamboa JM Gowda P(2023)Biomimetic Strategies for Peripheral Nerve Injury Repair: An Exploration of Microarchitecture and Cellularization. Biomed Mater Devices 1: 21–37 Koller R, Rab M, Todoroff BP, Neumayer C (1997) The influence of the graft length on the functional and morphological result after nerve grafting: an experimental study in rabbits. Br J Plast Surg 50:609–614 Saheb-Al-Zamani M, Yan Y, Farber SJ, Hunter DA (2013) Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence. Exp Neurol 247:165–177 Forden J, Xu QG, Khu KJ, Midha R (2011) A long peripheral nerve autograft model in the sheep forelimb. Neurosurgery 68:1354–1362 Atchabahian A, Genden EM, MacKinnon SE, Doolabh VB (1998) Regeneration through long nerve grafts in the Swine model. Microsurgery 18:379–382 Strasberg SR, Mackinnon SE, Genden EM, Bain JR (1996) Long-segment nerve allograft regeneration in the sheep model: experimental study and review of the literature. J Reconstr Microsurg 12:529–537 Deng Pan BS, Mackinnon SE, Wood MD (2020) Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve 61:726–739 Kornfeld TM, Radtke VC (2019) Nerve grafting for peripheral nerve injuries with extended defect sizes. Wien Med Wochenschr 169:240–251 Tables Tables 1 to 6 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.AllofPatientsdata49cases.pdf Table2.BackgroundofpatientsAge.pdf Table.Thetimefromlingualnerveinjurytonerverepair.pdf Table4.Thelengthofthedamagedlingualnerve.pdf Table5.ResultsofOrdinalLogisticRegressionAnalysis.pdf Table6.ResultsofMultivariateLogisticRegressionAnalysis.pdf Cite Share Download PDF Status: Published Journal Publication published 14 Jan, 2026 Read the published version in Maxillofacial Plastic and Reconstructive Surgery → Version 1 posted Editorial decision: Revision requested 22 Oct, 2025 Reviews received at journal 21 Oct, 2025 Reviews received at journal 20 Oct, 2025 Reviews received at journal 19 Oct, 2025 Reviewers agreed at journal 14 Oct, 2025 Reviews received at journal 14 Oct, 2025 Reviews received at journal 14 Oct, 2025 Reviewers agreed at journal 14 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviews received at journal 13 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviews received at journal 12 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviewers agreed at journal 10 Oct, 2025 Reviewers invited by journal 09 Oct, 2025 Editor assigned by journal 06 Oct, 2025 Submission checks completed at journal 06 Oct, 2025 First submitted to journal 27 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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13:48:02","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":99734,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.Thelengthofthedamagedlingualnerve.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7726878/v1/8c965c3d281e56710804b31a.pdf"},{"id":94200285,"identity":"6e28ecf4-3ac6-4834-8f20-4f82d66b9afb","added_by":"auto","created_at":"2025-10-23 13:48:04","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":100297,"visible":true,"origin":"","legend":"","description":"","filename":"Table5.ResultsofOrdinalLogisticRegressionAnalysis.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7726878/v1/d19f9e3f5911bd6934b98990.pdf"},{"id":94200274,"identity":"6822f29f-6780-4776-9887-93606f2e3c8f","added_by":"auto","created_at":"2025-10-23 13:48:02","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":151124,"visible":true,"origin":"","legend":"","description":"","filename":"Table6.ResultsofMultivariateLogisticRegressionAnalysis.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7726878/v1/c9e79feb7756ffd9f4df137e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Factors for Functional Recovery after Lingual Nerve Reconstruction Using an Artificial Nerve Conduit","fulltext":[{"header":"Background","content":"\u003cp\u003ePeripheral nerve injury is a well-known complication of various dental procedures, particularly the extraction of impacted mandibular third molars [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients afflicted with this condition may experience a range of sensory disturbances, including dysesthesia, paresthesia, and numbness in the distribution of the lingual nerve, which can have a significant impact on their quality of life. For patients with persistent severe symptoms, surgical reconstruction of the lingual nerve using a nerve conduit is often considered. However, the degree of recovery varies, and the optimal timing of intervention and the significance of the nerve gap distance remain subjects of clinical debate. Previous studies have suggested that early surgical intervention may lead to better outcomes, but conclusive evidence is lacking and opinions are divided༻4,5,6༽. Furthermore, the extent of nerve recovery is influenced by multiple factors, such as the patient's sex, general health status, and the extent of nerve damage. The purpose of this study is to elucidate the effects of the timing of surgery, nerve gap length, and other potential prognostic factors on postoperative nerve recovery, using MRCS as a standardized measure of sensory function. To achieve this objective, multivariate analysis was used to identify independent factors associated with improvement in MRCS scores after lingual nerve repair surgery.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis study is a retrospective observational study of cases who underwent microsurgical repair of lingual nerve injury using a nerve conduit (Renerve) by the same oral surgeon from 2017 to 2025. The inclusion criteria were as follows: (1) Patients diagnosed with severe lingual nerve injury preoperatively using the Clinical Neurosensory Testing (CNT) method recommended by the American Association of Oral and Maxillofacial Surgeons, and in whom lingual nerve injury was confirmed intraoperatively [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. (2) Patients who underwent microsurgical repair of the lingual nerve using a nerve conduit (Renerve). (3) Patients whose affected sensation was evaluated using the Medical Research Council Scale (MRCS) preoperatively and one year postoperatively. Patients with incomplete records or inadequate follow-up were excluded. Out of 65 cases who underwent surgery in this study, 49 cases (10 male, 39 female) met the selection criteria and were included as valid cases.\u003c/p\u003e\u003cp\u003eEvaluation Items\u003c/p\u003e\u003cp\u003eThe primary outcome measure was postoperative nerve recovery, as assessed by the MRCS sensory score. The MRCS scale classifies sensory recovery into stages S0-S4, and logistic regression analysis was performed. Predictors The explanatory variables were as follows: \u0026bull; Time to surgery (months) \u0026bull; Distance from the injury site to the nerve severance site (mm) \u0026bull; Patient's age (at the time of surgery) \u0026bull; Sex (male\u0026thinsp;=\u0026thinsp;1, female\u0026thinsp;=\u0026thinsp;0) \u0026bull; Presence of diabetes: Hemoglobin A1c level of 8% or higher (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0). The outcome measures used were the British Medical Research Council Scale (MRCS) and Functional Sensory Recovery (FSR), with \"good\" recovery defined as an MRCS of S3 or higher and an FSR of 1. Factors influencing sensory recovery after lingual nerve reconstruction in patients with nerve injury were examined. Postoperative recovery was evaluated using the MRCS scale and FSR criteria. [Table\u0026nbsp;1]\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eOrdinal logistic regression and multivariate logistic regression analysis were used to evaluate the association between each predictor variable and the postoperative MRCS score. Odds ratios (OR), 95% confidence intervals (CI), and p-values were calculated. All statistical analyses were performed with a two-sided significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All data were statistically analyzed using JMP\u0026reg; 14.2.0 (SAS Institute Inc., North Carolina, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe age of the patients ranged from 20 to 48 years for males, with a mean of 31.2 years, a median of 29, and a standard deviation of 8.0. For females, the age range was 18 to 63 years, with a mean of 34.7 years, a median of 32, and a standard deviation of 11.3. A Mann-Whitney U test (non-parametric test) revealed no significant difference in the distribution between males and females, with a U value of 71.5 and a P value of 0.111 [Table\u0026nbsp;2]. The time from lingual nerve injury to nerve repair surgery ranged from a minimum of 2 months to a maximum of 204 months, with a mean of 17.3 months, a median of 6, and a standard deviation of 28.5[Table\u0026nbsp;3]. The length of the damaged lingual nerve confirmed during surgery (mm) was a minimum of 10 mm and a maximum of 25 mm, with a mean of 14.7 mm, a median of 15 mm, and a standard deviation of 2.93[Table\u0026nbsp;4]. Since the MRCS score is an ordinal scale, we first attempted ordinal logistic regression analysis. The results of the ordinal logistic regression showed that the time to surgery had a p-value of 0.390, and the nerve gap length had a p-value of 0.328, indicating no association with the improvement of MRCS scores. In this analysis, neither the time to surgery nor the nerve gap distance showed a statistically significant correlation with postoperative recovery based on the MRCS score [Table\u0026nbsp;5]. Therefore, to clarify the clinical significance, the postoperative MRCS score was re-categorized into a binary outcome of \"good prognosis (S3 or higher)\" and \"poor prognosis (S2\u0026thinsp;+\u0026thinsp;or lower)\". A multivariate logistic regression analysis (with \"good prognosis\" as the outcome variable) was performed on this binary outcome. Since the cases in this study included extreme outliers for the time to surgery (e.g., 72, 96, and 204 months), a logarithmic transformation (Log Transformation) was applied to the time to surgery to suppress the influence of these outliers and make the distribution closer to a normal distribution. Furthermore, we analyzed the time to surgery (after log transformation), nerve gap length, sex, age, and presence of diabetes as independent variables including confounding factors. As a result, the importance of the time to surgery was clearly demonstrated. The p-value for the log-transformed time to surgery was 0.044, indicating a clear and statistically significant association that a shorter time to surgery leads to a good prognosis, even after statistically adjusting for the effects of age, sex, and diabetes. The odds ratio was 0.304, showing a strong tendency for a longer time to surgery to lead to a poor prognosis. The p-value for the nerve gap length was 0.128, which did not show a significant association. Nerve gap length, age, sex, and presence of diabetes showed no statistically significant association with the postoperative prognosis [Table\u0026nbsp;6].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective analysis, we examined the functional recovery at one year postoperatively in 67 cases (49 valid cases) of lingual nerve injury who underwent reconstruction using a nerve conduit. The evaluation measures used were the MRCS and FSR, with \"good\" recovery defined as an MRCS of S3 or higher and an FSR of 1. We investigated factors affecting sensory recovery after lingual nerve reconstruction in patients with nerve injury. Postoperative recovery was evaluated using the MRCS scale and FSR criteria. By combining ordinal logistic regression and multivariate logistic regression, it became possible to handle ordinal categorical variables as an outcome measure while simultaneously adjusting for the effects of multiple explanatory variables. This approach is characterized by its ability to avoid information loss from simple binarization and to perform an analysis that reflects gradual changes in outcomes. Furthermore, by simultaneously correcting for confounding factors such as age, sex, nerve gap distance, and time to surgery, the independent effect of each factor could be estimated more accurately. This is expected to improve statistical power and enhance the reliability and reproducibility of the results, as the obtained odds ratios are clinically interpretable. The ordinal logistic regression analysis did not yield significant results, which may be due to the uneven distribution of cases among the MRCS categories. On the other hand, the multivariate logistic regression analysis, which focused on a clinically relevant outcome, clearly showed that the time to surgery is the most important factor determining the prognosis. This result, obtained after simultaneously adjusting for multiple confounding factors, is considered highly reliable. Although nerve gap distance is generally considered an important factor in determining the prognosis, no significant association was found in this study. This might be due to the limited number of cases, or the effect may have been masked by the more powerful factor of the time to surgery. Statistically, the results were as stated above, but from a review of individual cases, even those with a long time to surgery (e.g., 8 or 17 years) showed good functional recovery postoperatively. Therefore, it cannot be definitively stated to patients preoperatively that a long time since injury will lead to a poor prognosis or that surgery is not indicated. As Robinson stated that nerve repair should be considered regardless of the length of time that has passed since injury [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The debate over what length of nerve gap necessitates the use of a nerve conduit, Perrelle suggested that 15 mm is the limit for using a nerve conduit༻9༽. Numerous reports have conducted animal experiments using the sciatic nerves of small animals (rats, rabbits, etc.), i.e., repairing thin nerves, and have shown that nerve regeneration up to 30 mm has been achieved using artificial nerves alone༻10,11༽. On the other hand, in experiments using large animals (sheep, pigs) and thick median nerves measuring 8 cm in length, nerve regeneration using conduit alone was not observed༻12,13,14༽. When using artificial nerves, the concentration of neurotrophic factors is critical to advancing nerve regeneration, there is a limit of regenerative capacity. In other words, if the regenerative field is V, then the regenerative distance L will inevitably be shorter for nerves with a large diameter. For example, if r is doubled, L will be one-fourth the original length. V\u0026thinsp;=\u0026thinsp;πr\u003csup\u003e2\u003c/sup\u003e x L༻15༽. Nerve grafting with cell suspensions e. g. with Schwann cells shows promising results on small defect sizes over 30 mm in length in animals but is limited on translation to human organism by highly regulated laws for transplantation of human stem cells༻16༽. The diameter of the human lingual nerve is about 3 mm, and it is not thick, so we believe that nerve regeneration using an artificial nerve within 30 mm alone is probably possible. we have a case in our experience with a nerve gap of 25 mm that was left untreated for 6 years, and the patient showed good functional recovery. Clinically, the basic decision of whether the damaged and degenerated nerve was completely excised and the surgeon's technique are largely involved. If a suitable environment for regeneration is reliably secured after the complete excision of the damaged nerve, the prognosis may be good even if the resection distance is slightly extended. This is a highly debated point and a topic that needs to be fully investigated with more experienced cases in the future.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this retrospective analysis, the results of the ordinal logistic regression analysis showed that earlier surgical intervention was not significantly associated with improved sensory recovery after lingual nerve repair as measured by the MRCS score. The results of the multivariate logistic regression analysis, however, showed that the time to surgery was a significant independent prognostic factor. Other factors such as age, sex, and diabetes showed no significant trends in either analysis. These findings emphasize the clinical importance of performing surgical repair at an appropriate time and with accurate anatomical knowledge to optimize postoperative outcomes in patients with lingual nerve injury. To confirm these observations and further elucidate prognostic factors, a prospective, multi-institutional study with a larger sample size is needed in the future.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMedical Research Council Scale (MRCS), Functional Sensory Recovery (FSR), Clinical Neurosensory Testing (CNT)\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthic approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study was performed in accordance with the Declaration of Helsinki for medical protocols and was approved by the Wakayama Medical University Institutional Review Board (Nos.1689) and the North Osaka Housennka Hospital Review Board (Nos.RR040501). General consent was given by the patients\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eWritten informed consent for the publication was obtained.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThere is no funding related to this article.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eSF read and wrote the manuscript. IT, OS, and SS prepared the retrospective data. SS analyzed and interpreted this data. SF designed and wrote the entire article. All authors read and approved the final manuscript\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe study was supported by a grant from the Grant-in-Aida grant for Scientic Research from Japan Society for the promotion of Science (No.18K09751).\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003ePlease contact the author for data requests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKipp DP, Goldstein BH, Weiss WW (1980) Dysesthesia after mandibular third molar surgery: a retrospective study and analysis of 1,377 surgical procedures. J Am Dent Assoc 100:185\u0026ndash;192\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMason DA (1988) Lingual nerve damage following lower third molar surgery. Int J Oral Maxillofac Surg 17:290\u0026ndash;294\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRobert RC, Bacchett PB, Pogrel MA (2005) Frequency of trigeminal nerve injuries following third molar removal. J Oral Maxillofac Surg 63:732\u0026ndash;735\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSusarla SM, Kaban LB, Donoff RB, Dodson TB (2007) Does early repair of lingual nerve injuries improve functional sensory recovery? J Oral Maxillofac Surg 65:1070\u0026ndash;1076\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKushnerev E, Yates JM (2015) Evidence-based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review. J Oral Rehabil 42:786\u0026ndash;802\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuhaym O, Miloro M (2020) Does early repair of trigeminal nerve injuries influence neurosensory recovery? A systematic review and meta-analysis. Int J Oral Maxillofac Surg 50:820\u0026ndash;829\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGhali GE, Epker BN (1989) Clinical neurosensory testing: practical applications. J Oral Maxillofac Surg 47:1074\u0026ndash;1078\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRobinson PP, Loescher AR, Yates JM, Smith KG (2004) 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\u0026ndash;292\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerrelle JM, Boreland AJ, Gamboa JM Gowda P(2023)Biomimetic Strategies for Peripheral Nerve Injury Repair: An Exploration of Microarchitecture and Cellularization. Biomed Mater Devices 1: 21\u0026ndash;37\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoller R, Rab M, Todoroff BP, Neumayer C (1997) The influence of the graft length on the functional and morphological result after nerve grafting: an experimental study in rabbits. Br J Plast Surg 50:609\u0026ndash;614\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaheb-Al-Zamani M, Yan Y, Farber SJ, Hunter DA (2013) Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence. Exp Neurol 247:165\u0026ndash;177\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eForden J, Xu QG, Khu KJ, Midha R (2011) A long peripheral nerve autograft model in the sheep forelimb. Neurosurgery 68:1354\u0026ndash;1362\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAtchabahian A, Genden EM, MacKinnon SE, Doolabh VB (1998) Regeneration through long nerve grafts in the Swine model. Microsurgery 18:379\u0026ndash;382\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStrasberg SR, Mackinnon SE, Genden EM, Bain JR (1996) Long-segment nerve allograft regeneration in the sheep model: experimental study and review of the literature. J Reconstr Microsurg 12:529\u0026ndash;537\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDeng Pan BS, Mackinnon SE, Wood MD (2020) Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve 61:726\u0026ndash;739\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKornfeld TM, Radtke VC (2019) Nerve grafting for peripheral nerve injuries with extended defect sizes. Wien Med Wochenschr 169:240\u0026ndash;251\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 6 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"maxillofacial-plastic-and-reconstructive-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mprs","sideBox":"Learn more about [Maxillofacial Plastic and Reconstructive Surgery](http://jkamprs.springeropen.com/)","snPcode":"40902","submissionUrl":"https://submission.springernature.com/new-submission/40902/3","title":"Maxillofacial Plastic and Reconstructive Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7726878/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7726878/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eLingual nerve injury following dental procedures, such as lower third molar extractions, can cause significant sensory deficits. For patients with persistent severe symptoms, surgical reconstruction of the lingual nerve using a nerve conduit is often considered. However, the degree of recovery varies, the significance of the nerve gap distance and the optimal timing of intervention remain subjects of ongoing debate.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e\u003cp\u003eUsing the Medical Research Council Scale (MRCS) as a standardized measure of sensory function, this study aims to clarify the effects of the timing of surgery, nerve gap length, and other potential prognostic factors on nerve functional recovery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study retrospectively analyzed a cohort of patients who underwent lingual nerve repair surgery. The MRCS score was used as an outcome variable to assess postoperative recovery. Predictors included time to surgery, nerve gap length, age, sex, and the presence or absence of diabetes. Statistical analyses included both ordinal logistic regression and multivariate logistic regression analysis to evaluate the association between each predictor and the postoperative MRCS score.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOrdinal logistic regression analysis showed no statistically significant correlation between the time to surgery or nerve gap length and postoperative recovery based on the MRCS score. Furthermore, to clarify the clinical significance, multivariate logistic regression analysis was performed. The results indicated a statistically significant association between a shorter time to surgery and a favorable prognosis.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eEarly surgical intervention and accurate identification of the injured nerve are considered crucial factors for improving postoperative sensory recovery following lingual nerve injury. 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