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.

Lower Facial Nerve Nomenclature Clarification: Cervical Branch Controls Smile-Associated Lower Lip Depression and Dental Display.

OBJECTIVE: In head and neck ablative surgery, traditional teaching is that the key facial nerve branch to preserve along the plane of the lower border of the mandible is the marginal mandibular branch (MMb), which is considered to control all lower lip musculature. The depressor labii inferioris (DLI) is the muscle responsible for pleasing lower lip displacement and lower dental display during natural emotive smiling. STUDY DESIGN: To understand the structure/function relationships of the distal lower facial nerve branches and lower lip musculature. SETTING: In vivo extensive facial nerve dissections under general anesthesia. METHODS: Intraoperative mapping was performed in 60 cases, using branch stimulation and simultaneous movement videography. RESULTS: In nearly all cases, the MMb innervated the depressor anguli oris, lower orbicularis oris, and mentalis muscles. The nerve branches controlling DLI function were identified 2 ± 0.5 cm below the angle of the mandible, originating from a cervical branch, separately and inferior to MMb. In half of the cases, we identified at least 2 independent branches activating the DLI, both within the cervical region. CONCLUSION: An appreciation of this anatomical finding may help prevent lower lip weakness following neck surgery. Avoiding the functional and cosmetic consequences that accompany loss of DLI function would have a significant impact on the burden of potentially preventable sequelae that the head and neck surgical patient frequently carries.

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.

Neuropathic Pain in Lower Lip after Guided Tissue Regeneration: A Case Report.

Post-traumatic trigeminal neuropathic pain is mainly caused by the extraction of third molars or the placement of dental implants. This report describes the treatment of neuropathic pain arising after guided tissue regeneration (GTR). The patient was a 55-year-old woman who had to undergo GTR due to severe periodontitis in the distal aspect of the right mandibular second molar. Postoperatively, the patient had been prescribed mecobalamin for hypesthesia and allodynia in the right lower lip. No improvement was observed in these symptoms after 4 months, however, so she was referred to our Orofacial Pain Center. Preoperative and postoperative cone-beam computed tomography revealed a cyst-like lesion (radiolucent area) close to the right mandibular second molar and canal. Although the results of quantitative sensory examination were normal, rubbing the right lower lip with a cotton swab elicited mechanical allodynia. The diagnosis was post-traumatic trigeminal neuropathic pain for which the patient was given pregabalin and Neurotropin®. The symptoms improved within approximately 32 weeks, with the medication being terminated at 64 weeks. Although hypoesthesia due to nerve injury may suddenly go into remission, allodynia is often intractable. If symptoms show no improvement after 3 months, possible nerve injury should be investigated. Additionally, the distal root of the mandibular molar may be close to the inferior alveolar nerve, necessitating appropriate diagnostic imaging of the operative field. If the lesion or distal root is close to the inferior alveolar nerve, postoperative hypesthesia or neuropathic pain may occur, even without direct trauma.

Effect of concentrated growth factor on lower lip hypoesthesia after osseous genioplasty: a prospective, split-mouth, double-blind randomized controlled trial.

Lower lip hypoesthesia is the most common complication following osseous genioplasty. Concentrated growth factor (CGF) has recently been shown to improve neural regeneration. The aim of this study was to evaluate the effect of concentrated growth factor on neurosensory recovery after osseous genioplasty. Patients who underwent osseous genioplasty between June 2017 and February 2020 were enrolled. CGF was applied to the mental nerve on one side. The treatment side was randomized, and the other side was considered as the control. Lower lip hypoesthesia was assessed preoperatively and postoperatively (1 week, 1, 3, 6, and 9 months) using the two-point discrimination test and a 10-point visual analogue scale (self-reported paresthesia). The assessor was blinded. Twenty-six female patients completed the study. At 1 and 3 months, both the mean two-point discrimination value and mean visual analogue scale score were significantly lower in the CGF group than in the control group (P < 0.001). At 3 months, the percentage of patients with lower lip hypoesthesia in the CGF group was significantly lower than that in the control group (P < 0.001). Both groups showed resolution of lower lip hypoesthesia at 6 months. Concentrated growth factor may accelerate the recovery of long-standing sensory nerve impairment following mental osteotomy.

A case of upper lip necrosis after cosmetic injection of hyaluronic acid soft-tissue filler-Does capillary infarction play a role in the development of vascular compromise, and what are the implications?

Facial rejuvenation with injectable filler substances is a frequently applied outpatient procedure. However, light, moderate, and even severe complications may occur. A case of tissue necrosis at the upper lip after injection of highly cross-linked hyaluronic acid together with the following salvage procedure is presented here. We discuss this complication with respect to relevant anatomy and physicochemical properties of the filler substance and review the recommendations given in literature for decreasing the likelihood of such an adverse event.

Effect of the parasympathetic vasodilation on temperature regulation via trigeminal afferents in the orofacial area.

The skin temperature (Tm) of the orofacial area influences orofacial functions and is related to the blood flow (BF). Marked increases in BF mediated by parasympathetic vasodilation may be important for orofacial Tm regulation. Therefore, we examined the relationship between parasympathetic reflex vasodilation and orofacial Tm in anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited significant increases in BF and Tm in the lower lip. These increases were significantly reduced by hexamethonium, but not atropine. VIP agonist increased both BF and Tm in the lower lip. The activation of the superior cervical sympathetic trunk (CST) decreased BF and Tm in the lower lip; however, these decreases were significantly inhibited by LN stimulation. Our results suggest that parasympathetic vasodilation plays an important role in the maintaining the hemodynamics and Tm in the orofacial area, and that VIP may be involved in this response.

Interference with SRF expression in skeletal muscles reduces peripheral nerve regeneration in mice.

Traumatic injury of peripheral nerves typically also damages nerve surrounding tissue including muscles. Hence, molecular and cellular interactions of neighboring damaged tissues might be decisive for successful axonal regeneration of injured nerves. So far, the contribution of muscles and muscle-derived molecules to peripheral nerve regeneration has only poorly been studied. Herein, we conditionally ablated SRF (serum response factor), an important myofiber transcription factor, in skeletal muscles of mice. Subsequently, the impact of this myofiber-restricted SRF deletion on peripheral nerve regeneration, i.e. facial nerve injury was analyzed. Quantification of facial nerve regeneration by retrograde tracer transport, inspection of neuromuscular junctions (NMJs) and recovery of whisker movement revealed reduced axonal regeneration upon muscle specific Srf deletion. In contrast, responses in brainstem facial motor neuron cell bodies such as regeneration-associated gene (RAG) induction of Atf3, synaptic stripping and neuroinflammation were not overly affected by SRF deficiency. Mechanistically, SRF in myofibers appears to stimulate nerve regeneration through regulation of muscular satellite cell (SC) proliferation. In summary, our data suggest a role of muscle cells and SRF expression within muscles for regeneration of injured peripheral nerves.

Somatotopic organization of corticospinal/corticobulbar motor tracts in controls and patients with tumours: A combined fMRI-DTI study.

OBJECTIVES: To investigate the relative somatotopic organization of the motor corticospinal/corticobulbar foot, hand, lip and tongue fascicles by combining fMRI with DTI and to examine the influence of subjacent intrinsic tumours on these fascicles. METHODS: The study was approved by the local ethics committee. Seven male and three female volunteers (median age: 35 years) and one female and eight male patients with brain tumours (median age: 37 years) were scanned on a 1.5-T MRI scanner. fMRI data, analysed using SPM5, identified the motor task-driven fMRI grey matter activations of the hand, foot, lips and tongue as seed regions for probabilistic tractography. The relationship between the components of the CST was assessed and the distances between them were measured. A statistical comparison was performed comparing these distances in the group of healthy hemispheres with those of the group of non-affected hemispheres and healthy hemispheres. RESULTS: Hand fascicles were identified in all subjects (38/38, 100%), followed by foot (32/38, 84%), lip (31/38, 81%) and tongue fascicles (28/38, 74%). At superior levels, the hand fascicles were anterolateral to the foot fascicles in 77-93% of healthy hemispheres (HH), in 50-71% of non-affected patients' hemispheres (pH) and in 67-89% of affected PH. At inferior levels, the hand fascicles were either anteromedial in 46-45% of HH or anterior in 75% of non-affected PH and in 67-83% of affected PH. Tongue and lip fascicles overlapped in 25-45% of HH, in 10-20% of non-affected PH and in 15-25% of affected PH. No significant difference was found between the group of affected hemispheres and that of healthy and non-affected hemispheres. CONCLUSION: The somatotopy of the hand fascicles in relation to the foot fascicles was anterolateral in patients and volunteers at superior levels but anteromedial in volunteers and mostly anterior in patients at inferior levels. The lip and tongue fascicles generally overlapped. Intracranial tumours displaced the motor fascicles without affecting their relative somatotopy.

Review of Risk Assessment of Major Anatomical Variations in Clinical Dentistry: Accessory Foramina of the Mandible.

Most of the studies of the mandible's anatomical variations have presented the authors' speculations, and only a limited number has provided evidence that demonstrated the actual complications injury to the variant structures caused. To our knowledge, no study has evaluated the risks associated with these variant anatomical structures' injury. We reviewed articles that described clinical cases of the injury to, and anatomical studies of, three anatomical variants of the mandible-the accessory mental, lingual, and retromolar foramina-with which dentists are relatively familiar and that are mentioned often in the context of implant and third molar surgeries, to describe risk assessment methods with which to evaluate potential complications preoperatively. Only a limited number of the clinical reports of injury to the mandible's accessory foramina were available. The potential severe complication of injury of the accessory mental foramen (AMF) is sensory disturbance of the lower lip. Risk of neurosensory disturbance of lower lip can be assessed by AMF/MF ratio and positional relations to the MF. Potential severe complication of injury of the lingual foramen is bleeding and hemorrhage in the oral cavity's floor. Risk of bleeding can be assessed by diameter and positional relation between the mental spine/mylohyoid line. A risk assessment of the retromolar foramen could not be made because of inadequate data. We hope the risk assessments suggested will encourage dentists to predict intraoperative/postoperative complications caused by damaging the mandible's accessory foramina. Clin. Anat. 32:672-677, 2019. © 2019 Wiley Periodicals, Inc.

Evaluation of accuracy and sensory outcomes of mandibular reconstruction using computer-assisted surgical simulation.

PURPOSE: To introduce a modified protocol for mandibular reconstruction and evaluate the protocol using a standardized assessment method. METHOD: This retrospective study involved a case series of nine patients who underwent mandibular reconstruction between 2015 and 2017. The modular protocol comprised three novel modifications in terms of computer-assisted surgical simulation (CASS); surgical template (ST), and surgical procedure. The standardized postoperative evaluation consisted of operation time, part comparison analysis (PCA), facial symmetry, and mechanical quantitative sensory testing. RESULTS: The surgery successfully removed the affected mandible and preserved the inferior alveolar neurovascular bundle (IANB). PCA revealed that the mean error and standard deviation were 0.92 and 0.96 mm, respectively, for all mandibular surface sites. Follow-up results showed good facial symmetry, existence of sensation in lower lip, and no significant differences in pulp vitality between both sides (p = 0.181). Also, the results showed a reduction in the overall operating time. CONCLUSION: The modified mandibular reconstruction method used in this study could repair lateral mandibular defects and preserve the sensory function of the chin and lower lip.

Motor cortex compensates for lack of sensory and motor experience during auditory speech perception.

Listening to speech has been shown to activate motor regions, as measured by corticobulbar excitability. In this experiment, we explored if motor regions are also recruited during listening to non-native speech, for which we lack both sensory and motor experience. By administering Transcranial Magnetic Stimulation (TMS) over the left motor cortex we recorded corticobulbar excitability of the lip muscles when Italian participants listened to native-like and non-native German vowels. Results showed that lip corticobulbar excitability increased for a combination of lip use during articulation and non-nativeness of the vowels. Lip corticobulbar excitability was further related to measures obtained in perception and production tasks showing a negative relationship with nativeness ratings and a positive relationship with the uncertainty of lip movement during production of the vowels. These results suggest an active and compensatory role of the motor system during listening to perceptually/articulatory unfamiliar phonemes.

Operative technique for benign submandibular gland mass without identifying the mandibular branch of the facial nerve.

OBJECTIVE: The marginal mandibular branch of the facial nerve must be protected during surgery for benign diseases of submandibular gland. Methods for protecting the marginal mandibular branch include the nerve identification method and the non-identification method. METHODS: We performed submandibular gland surgery in 138 patients with benign submandibular gland diseases using the non-identification method to preserve the marginal mandibular branch. In brief, the submandibular gland capsule is incised at the inferior border of the gland and detached along the gland parenchyma. The nerve is protected by this procedure without the need for identification. RESULTS: Among 138 patients who underwent this surgical procedure, only 7 patients developed transient paralysis of the lower lip. CONCLUSION: This method of resecting the submandibular gland without identifying the marginal mandibular branch is an effective procedure associated with a low incidence of transient paralysis. Moreover, no patient developed paralysis due to procedural errors.

Numbness of the lower lip does not adversely affect quality of life or patients' satisfaction after mandibular orthognathic surgery.

Measures of patient-reported quality of life (QoL) are increasingly being used to tailor services that are funded by Clinical Commissioning Groups (CCG) in England. Mandibular osteotomies may result in altered sensation of the lower lip, but we know of limited evidence about the resulting effect on QoL. The modified Bristol orthognathic patient outcomes questionnaire was given to patients who had mandibular osteotomies at the Queen Elizabeth Hospital, Birmingham, between March 2006 and April 2016. Questionnaires were collected at the final orthognathic postoperative appointment. The significance of the difference in QoL between those who had altered sensation of the lower lip and those who did not was compared using a two-tailed t test. During this period 170 patients had mandibular orthognathic operations. Completed questionnaires were received from 117 of those patients (69%) during this period, after a follow up of about six months. We found no significant difference between the perceived benefits of treatment between the 41 who had altered sensation and the 74 who did not (p=0.30). Only 5/41 who reported residual numbness six months postoperatively stated that they would not choose to have the same treatment again. In conclusion, orthognathic surgery results in an appreciable improvement in QoL and should continue to be funded by CCG in England. Contrary to the perception of some clinicians, those patients with residual numbness of the lip did not have significantly poorer QoL. Future interpretation of the data will be improved if they are collected both before and after the operation.

Subjective perception of paraesthesia of the lower lip after bilateral sagittal split osteotomy at a district general hospital.

Our aim was to assess patients' perception of paraesthesia of the lower lip after bilateral sagittal split osteotomy (BSSO) at a district general hospital. Patients who had BSSO between August 2013 and August 2014 (n=46) were asked to score their perception of numbness between 0-10 (0=normal sensation. 10=complete loss of sensation/total numbness) one day postoperatively and then weekly for seven weeks, and at three months, 6 months, and one year. Data was collected on score sheets and by regular contact by telephone. Of the 46 operated on, 31 were female and 15 male. Data were available one year postoperatively for 43 patients. Ten of the 92 sides were reported as feeling normal on day 1 postoperatively, three-quarters as feeling normal at six months, and 79 at one year. On multivariate analysis there was no significant difference in postoperative sensation at one year between sides operated on by the registrar (left) and consultant (right) operated (p=0.76). Our results compared favourably with the limited data available in similarly designed studies.

Digital Relief of the Mental Foramen for a CAD/CAM-Fabricated Mandibular Denture.

Relief of the intaglio surface of a denture base is conventionally performed using thin wax and soft metal foil attached to the master cast. The following report highlights a new relief procedure for the mental foramen using a CT double scan technique on the CAD/CAM dentures fabricated for the patient with paresthesia of the left lower lip and chin during mastication.

Effects of ageing on orofacial fine force control and its relationship with parallel change in sensory perception.

PURPOSE: Current theoretical models suggest the importance of a bidirectional relationship between sensation and production in the vocal tract to maintain lifelong speech skills. The purpose of this study was to assess age-related changes in orofacial skilled force production and to begin defining the orofacial perception-action relationship in healthy adults. METHOD: Low-level orofacial force control measures (reaction time, rise time, peak force, mean hold force (N) and force hold SD) were collected from 60 adults (19-84 years). Non-parametric Kruskal Wallis tests were performed to identify statistical differences between force and group demographics. Non-parametric Spearman's rank correlations were completed to compare force measures against previously published sensory data from the same cohort of participants. RESULT: Significant group differences in force control were found for age, sex, speech usage and smoking status. Significant correlational relationships were identified between labial vibrotactile thresholds and several low-level force control measures collected during step and ramp-and-hold conditions. CONCLUSION: These findings demonstrate age-related alterations in orofacial force production. Furthermore, correlational analysis suggests as vibrotactile detection thresholds increase, the ability to maintain low-level force control accuracy decreases. Possible clinical applications and treatment consequences of these findings for speech disorders in the ageing population are provided.

Electrophysiological Evaluation of the Facial Muscles in Congenital Unilateral Lower Lip Palsy.

OBJECTIVES: Congenital unilateral lower lip palsy (CULLP) is a congenital facial asymmetry in which one corner of the mouth does not dip downward symmetrically (Kobayashi, 1979). We analyzed the electrophysiological findings in cases of CULLP to understand the facial nerve mechanisms underlying this pathological condition. METHODS: The electrophysiological findings in 20 patients with CULLP including an electroneuronography (ENoG) of the orbicularis oris muscle, nerve excitability test (NET) results, and the blink reflex (BR) were analyzed. RESULTS: Of 21 patients with CULLP, 20 underwent ENoG, 12 underwent a NET, and 14 underwent a BR examination. Nine of 19 patients with CULLP showed higher ENoG amplitude in the affected side than in the unaffected side. In four patients, the ENoG amplitude in the affected side was similar to that in the unaffected side whereas six patients had higher ENoG amplitude in the unaffected side. All patients showed a normal BR response and only one patient had a left-right difference in the NET response in the marginal mandibular branch. NET also demonstrated that the muscular twitch appeared on the lower lip of the affected side. CONCLUSION: These results suggested that in CULLP, each of the facial nerve branches including the marginal mandibular branch appeared to function within normal parameters. The marginal mandibular branch of the facial nerve, which usually innervates the depressor anguli oris and depressor labii inferioris muscles, may innervate adjacent muscles as well, such as the orbicularis oris muscle, during prenatal development.

Intraoral Observation of the Mentalis and Incisivus Labii Inferioris Muscles.

The mentalis (MT) and the incisivus labii inferioris (ILI), which are accessory muscles of the orbicularis oris (OO) muscle, form an intertwined and three-dimensionally related complex. The purpose of this study is to clarify the relationship between the MT, ILI, and OO muscles via intraoral dissection. Twenty-two sides from 11 fresh adult Caucasian cadaveric heads were used, and the MT, ILI, and OO dissected under the surgical microscope. Next, measurements of the bony attachment were carried out on another 12 sides. The fibers of the MT were separated into 2 parts: a superior and an inferior part with the former coursing anteromedially and joining the inferior part of the OO. The latter coursed anteroinferiorly to the skin of the chin. The ILI traveled anterolaterally and joined the inferior part of the OO. Inferior labial branches of the mental nerves ran on the OO. There was a significant difference (P = 0.0001) between specimens that were edentulous or had severe periodontitis with regard to the distance from the alveolar ridge to the upper side of the quadrangle when compared with specimens with mild periodontitis. However, there was no significant difference (P > 0.05) between specimens that were edentulous or had severe periodontitis specimens with mild periodontitis with regard to the distance from the inferior border of the mandible to the lower side of the quadrangle. We believe that the observations of this study could help surgeons better understand the anatomy of the chin and minimize complications following surgical and other invasive procedures in this area.