The relationship between the auriculotemporal nerve and middle meningeal artery in a sample of the South African population.

BACKGROUND: The interaction between the auriculotemporal nerve and the middle meningeal artery within the infratemporal fossa is vital in the spread of perineural tumours. Knowledge of their morphological and morphometric variations is critical to surgeons approaching the infratemporal fossa. There is a paucity of literature on the relationship between the auriculotemporal nerve and middle meningeal artery in a South African population. Hence, the aim of this study was to document the morphology and morphometry of the auriculotemporal nerve and its relationship to the middle meningeal artery within a South African cohort. MATERIALS AND METHODS: The infratemporal fossae of 32 cadaveric specimens were dissected and the auriculotemporal nerves and middle meningeal arteries were analysed, together with their variations. RESULTS: Nine out of 32 specimens displayed one-root, 14/32 two-root, 7/32 three-root, and 2/32 four-root auriculotemporal nerves. Eighteen auriculotemporal nerves originated from the mandibular nerve, while the rest had at least one communication to the inferior alveolar nerve. The mean distance between the first and second roots of the auriculotemporal nerve was 4.69 mm. There were V-shaped formations found in 23 auriculotemporal nerves. However, the middle meningeal artery only passed through 13/23 V-shapes. The maxillary artery was of a deep course in relation to the lateral pterygoid muscle in 19/32 and superficial in 13/32 of the sample. There were 15 accessory middle meningeal arteries present in 14/32 specimens. The accessory middle meningeal arteries often arose from the middle meningeal artery (46.67%). CONCLUSIONS: The results of this study show a high possibility of variations of the auriculotemporal nerve and middle meningeal artery in the South African population. The variations and interactions should be considered during surgical procedures.

Promotion effect of TGF-ß-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation.

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-ß inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-ß-Zfp423-ApoD pathway.

Promotion effect of TGF-β-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation / 国际口腔科学杂志·英文版

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.

Mandibular nerve schwannoma: a case report.

Benign schwannomas are uncommon and their intraosseous location is even rarer counting for less than 1% of all benign primary bone tumors. They exceptionally occur in the oral cavity with the tongue being the most common site of involvement. We report here a case of intramandibular schwannoma derived from the inferior alveolar nerve, in a 57-year-old patient with a 3 months history of inferior left lip paresthesia. The oral examination showed a firm, painless and non-pulsatile swelling located in the inferior vestibule. The panoramic X-ray revealed a circumscribed and homogeneous radiolucent image. Treatment consisted of total excision of the tumor with preservation of the nerve bundles. The histological examination confirmed the diagnosis of schwannoma. The patient recovered a normal sensory function 6 months post-operatively without any recurrence up to 2 years after surgery. The treatment of intramandibular schwannoma is basically surgical with the conservative approach being the most advocated by majority of authors.

Enlargement of Inferior Alveolar Nerve Canal and Mental Neuropathy Associated With B-Cell Lymphoma: A Case Report and Literature Review.

Enlargement of an inferior alveolar nerve canal (IANC) on radiographic imaging can indicate the presence of a wide variety of pathologic entities. Oral and maxillofacial surgeons have the unique opportunity to regularly examine panoramic radiographs and must exercise proficient clinical judgment when noting abnormal findings on imaging. While malignant processes associated with IANC enlargement are uncommon, these pathologies do occur and may be associated with significant sequelae, especially when accompanied by a delay in diagnosis and in treatment. The purpose of this case report is to describe a case in which a patient presented with mental nerve neuropathy associated with unilateral IANC enlargement on radiography, which was found to be a B-cell lymphoma on biopsy. More importantly, we aim to remind oral and maxillofacial surgeons of this rare presentation of a malignant process so as to promote prompt recognition and referral for appropriate treatment.

Numb chin syndrome secondary to infiltration of inferior alveolar nerve as a presentation of relapse in treated testicular lymphoma-diagnosis on PET/CT and MR neurography.

Numb chin syndrome (NCS) is a rare presentation of primary or recurrent malignant neoplasms among other non-neoplastic causes. The syndrome is characterized by altered sensations in the distribution of the mental nerve and presents with pain and paresthesias along the distribution of the inferior alveolar nerve and its branches. The primary diagnosis is indicated while following up patients through positron emission tomography/computed tomography (PET/CT) when a hypermetabolic focus is seen in the vicinity of the angle of the mandible. Further anatomical localization is performed using magnetic resonance (MR) neurography and postcontrast MR imaging, which demonstrates neural involvement. We hereby describe a case of a 56-year-old man, a treated case of DLBCL (diffuse large B-cell lymphoma), presenting with NCS and diagnosed with perineural invasion through PET/CT and further MR evaluation. To our knowledge, there are no other reports in the literature describing the MR neurography appearance of the inferior alveolar nerve in NCS. We hereby stress on the use of MR neurography followed by postcontrast 3D sequences with multiplanar reformatting for adequate lesion detection.

Sensory denervation increases potential of bisphosphonates to induce osteonecrosis via disproportionate expression of calcitonin gene-related peptide and substance P.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of systematic administration of bisphosphonates (BPs). Sensory innervation is crucial for bone healing. We established inferior alveolar nerve injury (IANI) and inferior alveolar nerve transection (IANT) models characterized by disorganized periosteum, increased osteoclasts, and unbalanced neuropeptide expression. Zoledronate injection disrupted neuropeptide expression in the IANI and IANT models by decreasing calcitonin gene-related peptide (CGRP) and increasing substance P (SP); associated with this, BRONJ prevalence was significantly higher in the IANT model, followed by the IANI model and the sham control. CGRP treatment significantly reduced BRONJ occurrence, whereas SP administration had the opposite effect. In vitro, RAW 264.7 cells were treated with BPs and then CGRP and/or SP to study changes in zoledronate toxicity; combined application of CGRP and SP decreased zoledronate toxicity, whereas CGRP or SP applied alone showed no effects. These results demonstrate that sensory denervation facilitates the occurrence of BRONJ and that CGRP used therapeutically may prevent BRONJ progression, provided that SP is also present. Further studies are necessary to determine the optimal ratio of CGRP to SP for promoting bone healing and to uncover the mechanism by which CGRP and SP cooperate.

High resolution MRI for quantitative assessment of inferior alveolar nerve impairment in course of mandible fractures: an imaging feasibility study.

The purpose of this study was to evaluate a magnetic resonance imaging (MRI) protocol for direct visualization of the inferior alveolar nerve in the setting of mandibular fractures. Fifteen patients suffering from unilateral mandible fractures involving the inferior alveolar nerve (15 affected IAN and 15 unaffected IAN from contralateral side) were examined on a 3 T scanner (Elition, Philips Healthcare, Best, the Netherlands) and compared with 15 healthy volunteers (30 IAN in total). The sequence protocol consisted of a 3D STIR, 3D DESS and 3D T1 FFE sequence. Apparent nerve-muscle contrast-to-noise ratio (aNMCNR), apparent signal-to-noise ratio (aSNR), nerve diameter and fracture dislocation were evaluated by two radiologists and correlated with nerve impairment. Furthermore, dislocation as depicted by MRI was compared to computed tomography (CT) images. Patients with clinically evident nerve impairment showed a significant increase of aNMCNR, aSNR and nerve diameter compared to healthy controls and to the contralateral side (p < 0.05). Furthermore, the T1 FFE sequence allowed dislocation depiction comparable to CT. This prospective study provides a rapid imaging protocol using the 3D STIR and 3D T1 FFE sequence that can directly assess both mandible fractures and IAN damage. In patients with hypoesthesia following mandibular fractures, increased aNMCNR, aSNR and nerve diameter on MRI imaging may help identify patients with a risk of prolonged or permanent hypoesthesia at an early time.

Consequences of Trocar Dynamics on Mental Nerve in Transoral Thyroidectomy.

BACKGROUND: Mental nerve (MN) injuries are reported during transoral endoscopic thyroidectomy vestibular approach. Effect of trocar insertion and position on MN are examined in the present study. MATERIALS AND METHODS: Ten millimeter incision was made at the center of the lower lip oral vestibule. Two 5 mm lateral incisions of the lower lip oral vestibule were made at the junction between the incisor and the canine. These 2 lateral incisions were high, just below the edge of lower lip. Nine pigs (18 MN) were randomly divided into 3 groups and MN dissection was performed. The angle between the lateral ports and median line were changed between 15 and 45 degrees among 3 groups and effect on MN was examined. RESULTS: During dissection when insertion and other ports are in neutral position visual inspection of MNs did not reveal any compression bilaterally. The distance between MN and the ports was 18.2±2.1 mm (16.3 to 21.2 mm). In group I and group II, MNs have no compression by the lateral trocars. In group III (45 degrees), left MNs were all compressed. Two MNs (66.7%) were compressed on the right side. The MN was compressed at its ramification. CONCLUSIONS: The results of the present experimental study, endorse the suggested medial and lateral vestibular incisions for transoral endoscopic thyroidectomy vestibular approach. However, during dynamic modification of the lateral port position/angle, MN compression was observed when the angle was >45 degrees.

Involvement of Satellite Cell Activation via Nitric Oxide Signaling in Ectopic Orofacial Hypersensitivity.

: The mechanical head-withdrawal threshold (MHWT) was significantly reduced following inferior alveolar nerve transection (IANX) in rats. Nitrate and nitrite synthesis was dramatically increased in the trigeminal ganglion (TG) at 6 h after the IANX. The relative number of neuronal nitric oxide synthase (nNOS)-immunoreactive (IR) cells was significantly higher in IANX rats compared to sham-operated and N-propyl-L-arginine (NPLA)-treated IANX rats. On day 3 after NPLA administration, the MHWT recovered considerably in IANX rats. Following L-arginine injection into the TG, the MHWT was significantly reduced within 15 min, and the mean number of TG cells encircled by glial fibrillary acidic protein (GFAP)-IR cells was substantially higher. The relative number of nNOS-IR cells encircled by GFAP-IR cells was significantly increased in IANX rats. In contrast, after NPLA injection into the TG, the relative number of GFAP-IR cells was considerably reduced in IANX rats. Fluorocitrate administration into the TG significantly reduced the number of GFAP-IR cells and prevented the MHWT reduction in IANX rats. The present findings suggest that following IANX, satellite glial cells are activated via nitric oxide (NO) signaling from TG neurons. The spreading satellite glial cell activation within the TG results in mechanical hypersensitivity of face regions not directly associated with the trigeminal nerve injury.

Comparative effects of photobiomodulation therapy at wavelengths of 660 and 808 nm on regeneration of inferior alveolar nerve in rats following crush injury.

The aim of the present study was to investigate the therapeutic effects of 660-nm and 880-nm photobiomodulation therapy (PBMT) following inferior alveolar nerve (IAN) crush injury. Following the nerve crush injuries of IAN, 36 Wistar rats were randomly divided into three groups as follows: (1) control, (2) 660-nm PBMT, and (3) 808-nm PBMT (GaAlAs laser, 100 J/cm2, 70 mW, 0.028-cm2 beam). PBMT was started immediately after surgery and performed once every 3 days during the postoperative period. At the end of the 30-day treatment period, histopathological and histomorphometric evaluations of tissue sections were made under a light and electron microscope. The ratio of the inner axonal diameter to the total outer axonal diameter (g-ratio) and the number of axons per square micrometer were evaluated. In the 808-nm PBMT group, the number of nerve fibers with suboptimal g-ratio ranges of 0-0.49 (p < 0.001) is significantly lower than expected, which indicates better rate of myelinization in the 808-nm PBMT group. The number of axons per square micrometer was significantly higher in the 808-nm PBMT group when compared with the control (p < 0.001) and 660-nm PBMT group (p = 0.010). The data and the histopathological investigations suggest that the PBMT with the 808-nm wavelength along with its settings was able to enhance IAN regeneration after nerve crush injury.

Skeletal Stem Cell-Schwann Cell Circuitry in Mandibular Repair.

Regenerative paradigms exhibit nerve dependency, including regeneration of the mouse digit tip and salamander limb. Denervation impairs regeneration and produces morphological aberrancy in these contexts, but the direct effect of innervation on the stem and progenitor cells enacting these processes is unknown. We devised a model to examine nerve dependency of the mouse skeletal stem cell (mSSC), the progenitor responsible for skeletal development and repair. We show that after inferior alveolar denervation, mandibular bone repair is compromised because of functional defects in mSSCs. We present mSSC reliance on paracrine factors secreted by Schwann cells as the underlying mechanism, with partial rescue of the denervated phenotype by Schwann cell transplantation and by Schwann-derived growth factors. This work sheds light on the nerve dependency of mSSCs and has implications for clinical treatment of mandibular defects.

Unilaterally Enlarged Mandibular Foramina and Canal Associated With Hyperplastic Lymphatic Tissue of Inferior Alveolar Nerve: Case Report and Short Literature Survey.

BACKGROUND: Different phenomena can result in enlargement of mental foramen and mandibular canal. At the foreground of diagnosis is the assessment of the biological properties of the tissue which causes such detailed lesions of the skeleton. CASE REPORT: This report describes a palpable mass at the site of the mental foramen with radiological evidence of an extensive enlargement of the bony portion of the inferior alveolar nerve. These findings were the reason for surgical exploration. Surprisingly, the mass was inflammatory tissue that had proliferated in the canal and foramina. The lesion had grown around the nerve and did not infiltrate it. The diagnosis of lymphatic hyperplasia was made. Other potential causes of the unusual radiological and clinical findings are explained with reference to the literature. CONCLUSION: Imaging does not provide a safe assessment of tumor biology. Surgical exploration with detailed tissue examination of the tumor provides the basis for appropriate therapy.

What Is a Safe Distance for Preservation of the Inferior Alveolar Nerve in Lower Gingival Squamous Cell Carcinoma? A Radiographic and Histopathological Study.

PURPOSE: Involvement of the inferior alveolar nerve (IAN) is important in the prognosis and treatment of gingival squamous cell carcinoma (SCC). METHODS: In this cross sectional study, patients with gingival SCC (T4a), undergoing hemimandibulectomy or subtotal hemimandibulectomy, were examined. The distance between the lesion and inferior alveolar canal (IAC) was measured, using axial computed tomography scans before resection. Following that, histopathological evaluation of IAN was conducted. The receiver operating characteristic curve was plotted to determine the association of IAN involvement in histopathological evaluation with various distances between the lesion and IAC. RESULTS: A total of 29 patients were examined in this study. The mean distance between the lesion and IAC was 9.40 ±â€Š2.21 mm. Nerve involvement was documented in 9 (45%) out of 20 males, while 11 (55%) men showed no involvement. Thirteen (44.82%) patients showed IAN involvement. The receiver operating characteristic curve demonstrated a cut-off point of 9.75 mm for the lesion-IAN distance. The possibility of IAN involvement was 23.33 times higher in patients who reported paresthesia, compared with patients without nerve involvement (odds ratio, 23.33; 95% CL; P = 0.001) CONCLUSION:: It seems that in a CT scan view, a 9.75-mm safe margin is associated with high accuracy for preserving IAN in patients with gingival SCC. Also, neurosensory disturbance can be considered a strong predictor of IAN involvement.

Inferior alveolar nerve transection disturbs innate immune responses and bone healing after tooth extraction.

Coordination between the nervous and innate immune systems to maintain bone homeostasis is largely uncharacterized. The present study investigated the sensory-immune interaction in resting alveolar bone and healing socket by surgical sensory denervation. Bone histomorphometry and immunohistochemistry showed that sensory denervation resulted in moderate suppression of bone remodeling, with a proinflammatory milieu manifested by increased neutrophil recruitment and possible alternations in macrophage phenotypes along the resting bone surface. This denervation effect intensified when bone remodeling was triggered by tooth extraction, as revealed by disrupted temporospatial variations in macrophage subpopulations and neutrophil infiltration, which were closely associated with a dramatic decline in socket bone filling and residual ridge height. Antagonism of calcitonin gene-related peptide (CGRP) brought about similar antianabolic and proinflammatory effects as sensory denervation, suggesting that sensory nerves may monitor the bony milieu by CGRP. Depletion of macrophages, rather than neutrophils, ruled out CGRP effects, illustrating that macrophages were the primary immune mechanism that linked sensory innervation, innate immunity, and bone. The data support that sensory innervation is required for control of innate immune responses and maintenance of bone homeostasis. Sensory neuropeptides, such as CGRP, are a possible target for the development of proanabolic treatments in bone disease by modulating innate immune responses.

Is juxta-apical radiolucency a reliable risk factor for injury to the inferior alveolar nerve during removal of lower third molars?

The aim of this study was to find out if juxta-apical radiolucency (JAR) is a reliable risk factor for injury to the inferior alveolar nerve (IAN) during removal of lower third molars. We designed a cohort study of patients whose dental panoramic tomograms (DPT) had shown JAR before complete removal of lower wisdom teeth. The outcome variable was postoperative permanent neurosensory disturbance of the IAN. A total of 39 patients (50 lower third molars) were identified and screened for permanent neurosensory disturbance. None reported any permanently altered sensation 18 months after the operation. Based on our group, the presence of JAR does not seem to be a reliable predictor of the risk of permanent injury to the IAN during removal of lower third molars.

Semaphorin 3A Inhibits Nerve Regeneration During Early Stage after Inferior Alveolar Nerve Transection.

Neuroma formation at sites of injury can impair peripheral nerve regeneration. Although the involvement of semaphorin 3A has been suggested in neuroma formation, this detailed process after injury is not fully understood. This study was therefore undertaken to examine the effects of semaphorin 3A on peripheral nerve regeneration during the early stage after injury. Immunohistochemistry for semaphorin 3A and PGP9.5, a general neuronal marker, was carried out for clarify chronological changes in their expressions after transection of the mouse inferior alveolar nerve thorough postoperative days 1 to 7. At postoperative day 1, the proximal stump of the damaged IAN exhibited semaphorin 3A, while the distal stump lacked any immunoreactivity. From this day on, its expression lessened, ultimately disappearing completely in all regions of the transected inferior alveolar nerve. A local administration of an antibody to semaphorin 3A into the nerve transection site at postoperative day 3 inhibited axon sprouting at the injury site. This antibody injection increased the number of trigeminal ganglion neurons labeled with DiI (paired t-test, p < 0.05). Immunoreactivity of the semaphorin 3A receptor, neuropilin-1, was also detected at the proximal stump at postoperative day 1. These results suggest that nerve injury initiates semaphorin 3A production in ganglion neurons, which is then delivered through the nerve fibers to the proximal end, thereby contributes to the inhibition of axonal sprouting from the proximal region of injured nerves in the distal direction. To our knowledge, this is the first report to reveal the involvement of Sema3A in the nerve regeneration process at its early stage.

Reconstructive Options for Inferior Alveolar and Lingual Nerve Injuries After Dental and Oral Surgery: An Evidence-Based Review.

PURPOSE: The investigators wanted to evaluate, analyze, and compare the current microsurgical repair modalities (primary repair, autograft, tube conduit, and allograft reconstruction) in achieving functional sensory recovery in inferior alveolar and lingual nerve reconstructions due to injury. METHODS: A literature review was undertaken to identify studies focusing on microsurgical repair of inferior alveolar and lingual nerve injuries. Included studies provided a defined sample size, the reconstruction modality, and functional sensory recovery rates. A Fischer exact test analysis was performed with groups based on the nerve and repair type, which included subgroups of specific nerve gap reconstruction modalities. RESULTS: Twelve studies were analyzed resulting in a sample consisting of 122 lingual nerve and 137 inferior alveolar nerve reconstructions. Among the nerve gap reconstructions for the lingual nerve, processed nerve allografts and autografts were found to be superior in achieving functional sensory recovery over the conduits with P values of 0.0001 and 0.0003, respectively. Among the nerve gap reconstructions for the inferior alveolar nerve, processed nerve allografts and autografts were also found to be superior in achieving functional sensory recovery over the conduits with P values of 0.027 and 0.026, respectively. Overall, nerve gap reconstructions with allografts and autografts for inferior alveolar and lingual nerve reconstruction were superior in achieving functional sensory recovery with a P value of <0.0001. CONCLUSIONS: The data analyzed in this study suggest that primary tension-free repair should be performed in inferior alveolar and lingual nerve reconstructions when possible. If a bridging material is to be used, then processed nerve allografts and autografts are both superior to conduits and noninferior to each other. In addition, allografts do not have the complications related to autograft harvesting such as permanent donor site morbidity. Based on the conclusions drawn from these data, we provide a reproducible operative technique for inferior alveolar and lingual nerve reconstruction.