Factors influencing outcomes of inferior alveolar nerve repair: a systematic review

Introduction

Background

The inferior alveolar nerve (IAN) provides sensation to the mandibular teeth, gingiva, lower lip, and chin. It plays a crucial role in dental procedures, as its pathway through the infratemporal fossa and mandibular canal is significant for interventions such as local anesthetic nerve blocks, dental implant placement, dental extractions, endodontic procedures, and orthognathic surgery (1-3). Its anatomical variation also makes it susceptible to injury during such procedures, leading to potential neurosensory disturbances (4). Injuries to the IAN can manifest as hypoesthesia, anesthesia, or neuropathic pain in the affected nerve distribution. The severity and duration of these symptoms can vary, ranging from temporary discomfort to permanent sensory and functional impairment (5).

Outcomes of IAN repair are assessed using the Medical Research Council Scale (MRCS) and functional sensory recovery (FSR). MRCS utilizes neurosensory testing to categorize the magnitude of nerve injury that is present and to track sensory improvement after intervention. The scale ranges from S0 (no recovery) to S4 (complete recovery). FSR is defined as achieving greater than S3 on the MRCS (6). On a clinical level, FSR is defined as the return of useful sensory function following nerve injury and is commonly used when assessing the effectiveness of surgical interventions (7).

Rationale and knowledge gap

To date, it is not fully clear what factors including age, sex, time from injury to repair, and method of repair affect outcomes from IAN repair. These factors were selected based on their frequent mention in the literature and measurable impact on FSR. Age and sex were included due to their potential biological influence on nerve regeneration, while time to repair and method of repair were assessed because they are critical variables in surgical outcomes. Other factors, such as nerve defect length, injury etiology, patient comorbidities, and follow-up duration, were not included due to inconsistent reporting across studies. Future research should address these additional variables to provide a more comprehensive understanding of FSR outcomes. Current literature has assessed topics such as evaluating the efficacy of allogeneic nerve grafts for IAN repair after mandibulectomy (8). Other studies have combined IAN and lingual nerve (LN) repair data in their analyses making it difficult to assess IAN outcomes (9,10).

Objective

The purpose of this study is to perform a systematic review of the literature to determine what factors influence IAN repair outcomes. Specifically, age, sex, time to repair, and method of repair will be assessed to see if any influence rate of FSR after IAN repair. The hypothesis was that age, sex, time to repair, and method of repair would have a significant effect on the likelihood of achieving FSR. To the authors’ knowledge, this is the first review conducted specifically to assess IAN repair outcomes and factors that influence FSR rates. We present this article in accordance with the PRISMA reporting checklist (available at https://fomm.amegroups.com/article/view/10.21037/fomm-24-52/rc) (11).

Methods

Study design

The protocol was registered in the PROSPERO (International Prospective Register of Systematic Reviews) database (ID: CRD42024510229). The study followed the PICOS framework: Participants included patients with IAN injuries from iatrogenic, traumatic, or pathological causes with preoperative MRCS scores of S2+ or lower. Interventions involved microsurgical repairs such as neurorrhaphy, autografts, allografts, nerve sliding techniques (NST), and neurolysis. Comparisons were made based on age, sex, timing of repair (early vs. late), and method of repair. The primary outcome was FSR, defined as achieving an MRCS score of S3 or higher. Study designs included retrospective cohort studies and case series with quantitative MRCS outcomes. The following question was created: “What is the effect of age, sex, time from injury to repair, and method of repair on FSR rates of patients who have undergone IAN repair.” The primary outcome was the FSR rate measured as the percentage of patients who achieved a score of S3 on the MRCS. Age, sex, time from injury to repair, and method of repair were chosen for this analysis, as the most data was available for these specific variables. Limited data exists on other variables such as follow-up time, or etiology of injury in relation to achieving FSR. Additional data on etiology of injury were also extracted from each study when available. The study was waived from ethical approval.

Search strategy

An electronic search of PubMed, Scopus, and Cochrane Library databases was conducted on February 15, 2024. The search query utilized was: (inferior alveolar nerve repair OR inferior alveolar nerve regeneration) AND (efficacy OR outcome OR treatment).

Inclusion and exclusion criteria

Inclusion criteria were: (I) full-text availability, (II) studies written in English published after 2010, (III) studies that measured outcomes of IAN nerve repair after iatrogenic, traumatic, or pathological injury, (IV) studies that measured IAN outcomes using the MRCS scale, and (V) studies that recorded preoperative MRCS scores of patients. Articles were excluded if they did not meet the mentioned parameters or were classified as reviews or animal studies.

Screening process

Data from each report were collected by two independent reviewers (S.M. and T.J.) who extracted relevant information on study characteristics, participant demographics, intervention details, and outcomes. A third reviewer (V.B.Z.) verified the extracted data to ensure accuracy and resolve any discrepancies. The reviewers worked independently during the initial data collection phase and subsequently compared their findings. No additional data were obtained from study investigators as the included studies provided sufficient information for analysis. A PRISMA flow chart was created to illustrate the screening methodology, as depicted in Figure 1.

Figure 1 PRISMA chart depicting screening process. MRCS, Medical Research Council Scale.

Study quality assessment

To assess the quality of evidence of the included studies, we utilized the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework as illustrated in Figure 2. The GRADE framework assesses studies in the following 5 categories: (I) risk of bias, (II) imprecision, (III) inconsistency, (IV) indirectness, and (V) publication bias. For each category, included studies were rated as high (green), moderate (yellow), or low (red) quality. High-quality research was defined as having a low risk of bias, consistent findings, direct relevance to the clinical context, and minimal publication bias.

Figure 2 Study quality assessment per GRADE (Grading of Recommendations Assessment, Development and Evaluation).

The Newcastle-Ottawa Scale (NOS) was used to assess the quality of non-randomized studies, such as cohort and case-control studies, in systematic reviews. It evaluates studies in three domains: Selection (representativeness of cohorts, exposure ascertainment), Comparability (control of confounders), and Outcome/Exposure (follow-up and outcome assessment). The purpose of the NOS is to ensure studies included in a review are methodologically sound, reducing bias and increasing the reliability of findings. Higher scores indicate higher quality.

Statistical analysis

A chi-squared (χ²) test of independence was performed to examine the relationship between sex and method of repair and the frequency of FSR. The observed χ² was compared to the critical χ² value at a significance level of 0.05 (α=0.05) to determine if the observed differences were statistically significant (χ²>χ²_critical). For age and time to repair, Pearson’s correlation coefficient was calculated to determine if there was any causal relationship between the two variables and FSR rates. All calculations were conducted using RStudio (Version 2024.04.1+748).

Results

Included studies

From the three databases, a total of 204 articles were screened, of which 51 results originated from PubMed, 126 from Scopus, and 27 from Cochrane Library. Of these, 33 articles were duplicates. After the remaining 171 articles were reviewed, 165 articles were removed as they were not relevant to this study, did not use MRCS/FSR to measure outcomes, did not differentiate between LN and IAN outcomes, were book chapters or review papers, did not report preoperative MRCS scores, or included patients that scored higher than S2+ preoperatively (Figure 1). Only patients who scored S2+ or lower preoperatively were included in this study to control for confounders. A total of 6 articles published between 2012 and 2023 were included in this study and consisted of 5 retrospective cohort studies and 1 case series. A summary of the included studies and extracted data from each study is presented in Table 1.

GRADE analysis

Two studies received a “moderate” rating for the Risk of Bias category, as they did not provide data on the graft length (12,13). Two studies had low quality in “imprecision” due to small sample sizes (14,15). One study received low quality in “publication bias” due to being case series (14). All studies were graded as high quality in the “inconsistency” and “indirectness” categories (Figure 2).

NOS analysis

The NOS assessment evaluated six studies based on selection, comparability, and outcome criteria. Bagheri et al., Sonneveld et al., and Yampolsky et al. scored highest (9/9) due to representative cohorts, detailed exposure assessment, adequate follow-up, and adjustment for confounders (12,13,17). Byun et al. scored 7/9 due to limited confounder adjustments (14). Kang et al. and Lampert et al. scored lower (6/9) due to inconsistent follow-up durations and minimal adjustment for confounders (15,16). All studies used validated MRCS scales for outcome assessment, but some lacked sufficient detail on follow-up loss and confounder control (Table 2).

Age

Among the studies reviewed, 3 analyzed the influence of age on the likelihood of achieving FSR (13,16,17). Bagheri et al. noted a significant negative correlation between increasing age and unfavorable outcomes [odds ratio (OR) =0.97, P=0.02], with a drop in FSR rate after 51 years at a rate of 3% decline per year (17). Similarly, Kang et al. found that among 16 patients (mean age: 56.1±10.1 years), younger patients were more likely to achieve FSR (P=0.04) (16). The study did not define “younger” and “older”. Sonneveld et al. found no statistically significant correlation between age (48.6±13.8 years) and the probability of achieving FSR at 12 months (P=0.82) (13).

Five studies reported the mean age of included patients (13-17). Age and FSR rates were found to be strongly negatively correlated; however, this finding was not statistically significant (P=0.13) (Table 3).

Sex

Bagheri et al. found no significant difference in FSR rates when comparing males and females (17). Yampolsky et al. also found that all patients achieved FSR regardless of sex (12).

From the 3 studies that reported data on sex distribution and FSR rates by sex, 4 males and 31 females were included, of which 1 male and 21 females achieved FSR (13-15). χ² analysis showed that there was no significant association between sex and the number of patients who achieved FSR (χ²=2.77, P=0.09).

Time to repair

Bagheri et al. found that as the interval of injury to repair increased, the chance of achieving FSR decreased linearly by 11% with each passing month (OR =0.898; P=0.001) (17). Byun et al. found that 3 out of 5 patients achieved FSR when undergoing early repair (<60 days), whereas all 4 patients that underwent late repair (>60 days) achieved FSR (14). The early repair group achieved FSR in an average of 198 days, while the late repair group took an average of 241.3 days. This difference was not tested for statistical significance. Lampert et al. reported that 7 patients who suffered IAN injury due to endodontic treatment achieved FSR regardless of the time from injury to repair, which ranged from 1 to 40 weeks (15). Kang et al. found that those who underwent early repair within 60 days were more likely to achieve FSR, although not statistically significant (P=0.07). Approximately 85.7% of the patients in the early-repair group reached FSR, compared to 44.4% in the late group (16). Sonneveld et al. found no significant trend between time elapsed from injury to repair and likelihood of achieving FSR (P=0.14) (13).

Five studies reported the mean time to repair of included patients (13-17). Time to repair and FSR rates were found to be strongly negatively correlated; however, this finding was not statistically significant (P=0.13) (Table 4).

Method of repair

Bagheri et al. directly analyzed the impact of different microsurgical techniques on achieving FSR (17). FSR rates of 85%, 75%, 70.6%, 88.9%, and 87.3% were reported for external neurolysis, internal neurolysis, neuroma excision, direct neurorrhaphy, and autogenous nerve grafts, respectively. Method of repair was not found to have a significant effect on the likelihood of achieving FSR (P=0.20).

The methods of repair used and corresponding FSR rates were primary neurorrhaphy (80.95%), autograft (87.32%), external decompression (85%), neurolysis (77.61%), neuroma excision (70.59%), NST (62.5%), debridement (42.86%), and allogeneic graft (73.68%). No significant association was found between method of repair and FSR rate (χ²=14.05, P=0.08). The most commonly used repair techniques were autografts (71 nerves), neurolysis (67 nerves), and neurorrhaphy (21 nerves).

The length of the nerve defect was inconsistently reported among the studies. Kang et al. noted a mean gap of 7.69 mm (range, 3–15 mm), while Yampolsky et al. included only defects <2 cm (12,16). This inconsistency limits conclusions about its impact on FSR and highlights the need for standardized reporting.

Discussion

The primary aim of this systematic review was to assess factors that could influence outcomes of IAN repair. Age, sex, time from injury to repair, and method of surgical repair were examined to see if any affected the likelihood of achieving FSR. Understanding how such variables impact outcomes can help clinicians optimize their decision making to increase the probability of achieving success. The results of the study showed that age, sex, time from injury to repair, and method of repair had no significant impact on the rate of FSR.

Possible methods of nerve repair include direct neurorrhaphy, connector-assisted repair, use of a nerve autograft, or use of a nerve allograft. Direct neurorrhaphy involves the suturing of the proximal and distal segments of a severed nerve. Connector-assisted repair involves using a conduit to bridge the gap between the proximal and distal nerve stumps to allow for passive re-adaptation (18). Autografts are harvested from another part of the patient’s own body, with the sural, medial, lateral antebrachial cutaneous, and saphenous nerves being the most common sources (19). Allografts are sourced from a human donor and undergo a process of decellularization to diminish their immunogenicity before being utilized (20-23).

Among the studies reviewed, 3 directly assessed the effects of age on FSR outcomes. While our results were not statistically significant, a negative correlation between age and FSR rate was found. Lack of statistically significant evidence may be due to the small sample size of included patients. It is believed that younger patients recover better from nerve injuries because their Schwann cells more effectively support nerve repair, unlike older patients, whose Schwann cells have reduced capacity for myelin clearance and macrophage recruitment. Finally, the regenerative capacity of the peripheral nervous system declines with age, which can be attributed to a reduced ability of aged neurons to initiate repair following injury (24).

Consistent with findings from 3 of the included studies, χ² analysis showed no significant association with sex and FSR rates. Of note, 49 males and 169 females were enrolled across all studies. A possible reason for this discrepancy is that females are more likely to visit the doctor in general than males and to seek medical attention when experiencing pain (25). Estrogen is also thought to play a role in pain modulation, with estrogen receptors present in regions of the nervous system that regulate nociception (26). However, estrogen’s role in pain modulation is complex, as it not only influences pain tolerance but also contributes to inflammation, which may delay nerve healing, particularly in the case of IAN injury (27,28). Further research is required to better understand the role of estrogen in pain modulation, inflammation, and nerve regeneration.

For the assessment of time to repair, Bagheri et al. conducted the largest study and was the only included study that found time to repair had a significant impact on achieving FSR (17). Kang et al. also found that patients who underwent repair within 60 days had higher FSR rates than those who underwent repair after 60 days, although this finding was not statistically significant (16). Three included studies found that FSR rates did not differ based on time between injury and repair. Our statistical analysis showed a negative correlation between FSR rates and time between injury and repair, but this finding was not statistically significant.

Based on these outcomes, it seems that time from injury to repair may affect the likelihood of achieving FSR, though the extent to which it influences functional recovery requires further research (29-32). The lack of statistical significance may be due to the inclusion of studies that are underpowered. A shorter duration between injury and surgery may lead to faster recovery compared to delayed treatment. Earlier intervention may decrease the risk of neuroma formation and lessen neurotoxic effects from injury, thus limiting damage and enhancing speed of recovery (14). Suhaym et al. conducted a meta-analysis analyzing the effect of time from trigeminal nerve injury to repair on outcomes (9). Included studies had varying definitions of early repair, ranging from 2 to 6 months. The study found the FSR rate to be 93.0% for early repairs and 78.5% for late repairs, although the difference was not statistically significant (P=0.59). However, there were significantly higher odds of neurosensory improvement with early repair [OR =5.49, 95% confidence interval (CI): 1.40–21.45 when defined as within 3 months; OR =2.28, 95% CI: 1.05–4.98 when defined as within 6 months] (9).

In this study no significant association was found between method of repair and FSR rate. Likewise, Bagheri et al. directly assessed the relationship between method of repair and the likelihood of achieving FSR and found no correlation (17). Debridement (7 total nerves, 42.86% FSR rate), NST (16 total nerves, and neuroma excision (17 total nerves, 70.59% FSR rate) resulted in lower success rates. The limited effectiveness of debridement could be attributed to its invasive nature, potentially causing further trauma and scar tissue which can hinder nerve regeneration (13). However, the study had a sample size of 7 patients, indicating the need for further research. The NST may be less effective due to post-repair restrictions on nerve mobility, potentially increasing tension at the repair site and impairing functional recovery (33). Despite this, NST presents as a viable alternative for repairing defects up to 15 mm without significant complications (16). Additionally, it eliminates the need for use of nerve allografts or autografts, avoiding possible immunogenic reactions, donor site morbidity, and decreasing the number of required sutures from two to one. Suboptimal outcomes from neuroma excision were likely because the two nerve stumps were left disconnected without integrating other repair methods.

Use of a nerve autograft was the most commonly utilized technique with an FSR rate of 87.32%. Autografts are harvested from another site in the patient’s body, most commonly the sural or auricular nerves. An important consideration is donor site morbidity. FSR rates of the IAN with autografts are typically 75% or higher, in concordance with the results from this study (34,35).

The follow-up times varied significantly across the six studies included in this review. Bagheri et al. did not explicitly report a follow-up duration but assessed sensory recovery during a defined postoperative period (17). Byun et al. reported a follow-up range of 128 to 1,360 days, with a mean duration of approximately 697 days (14). Kang et al. followed patients for a minimum of 3 months, with a median time to FSR of 84.5 days (16). Lampert et al. included patients with at least 3 months of follow-up, assessing final sensory recovery at this interval or later (15). Sonneveld et al. ensured a minimum follow-up of 12 months to evaluate both sensory recovery and pain relief (13). Yampolsky et al. also followed patients for a minimum of 3 months to evaluate the outcomes of nerve graft interventions (12). These differences in follow-up times likely contributed to variability in the reported outcomes and highlight the need for standardization in future research.

This review has several limitations that require consideration. First, the lack of reported graft lengths in studies using allografts for IAN repair limits our ability to assess whether graft length influenced FSR outcomes. Additionally, the small sample sizes in several of the included studies reduce the statistical power of the analysis. Although all nerve injuries were scored S2+ or lower, a wide variety of etiologies were present across the studies, and different mechanisms of injury may have variable effects on repair outcomes. Another notable gap is the absence of consistent follow-up times after surgery across the included studies, which complicates the evaluation of long-term recovery. Follow-up evaluation periods ranged widely across studies, from a minimum of 3 months to 12 months (12,13,16). While most studies used MRCS to assess FSR, the variability in follow-up durations underscores the need for a standardized postoperative evaluation period, ideally 6 to 12 months, to enhance comparability. Finally, while a negative correlation between age and FSR was observed in some studies, the statistical significance of this finding was inconsistent (P=0.13 in our overall analysis). The overall low quality of evidence, primarily due to the inclusion of case series, further limits the strength of the conclusions drawn from this review.

Conclusions

This review has several limitations that require considerations. First, the lack of reported graft lengths in studies using allografts for IAN repair limits our ability to assess whether graft length influenced FSR outcomes. Additionally, the small sample sizes in several of the included studies reduce the statistical power of the study. Although all nerve injuries were scored S2+ or lower, a wide variety of etiologies were present across the studies. Different mechanisms of injury may have variable effects on repair outcomes. The imbalance in sex distribution, with more females than males, limits the ability to generalize results across sexes. Finally, the overall low quality of evidence due to the inclusion of case series, limits the strength of the conclusions.

This study aimed to examine the influence of age, sex, timing from injury to repair, and method of repair on FSR outcomes. Our analysis revealed important trends in IAN repair, although not statistically significant. Age and time to repair have negative correlations with FSR rates, though the strength of this association remains yet to be determined. Sex did not have a significant impact on FSR rates. Method of repair, while varied, did not show a significant association with FSR outcomes, though certain techniques, such as autografts and primary neurorrhaphy, appear to have high FSR rates. Overall, while this review identifies variables that may influence FSR rates of the IAN, the findings highlight the need for further research with larger sample sizes and higher-quality study designs.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://fomm.amegroups.com/article/view/10.21037/fomm-24-52/rc

Peer Review File: Available at https://fomm.amegroups.com/article/view/10.21037/fomm-24-52/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://fomm.amegroups.com/article/view/10.21037/fomm-24-52/coif). V.B.Z. serves as an unpaid editorial board member of Frontiers of Oral and Maxillofacial Medicine from November 2025 to October 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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