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The human body is a complex, integral whole, and disruptions in one organ can lead to dysfunctions in other parts of the organ network. The facial nerve, as the seventh cranial nerve, arises from the brainstem, controls facial expression muscles and plays a crucial role in brain-body communication. This vulnerable nerve can be damaged by trauma, inflammation, tumors, and congenital diseases, often impairing facial expression. Stem cells have gained significant attention for repairing peripheral nerve injuries due to their multidirectional differentiation potential. Additionally, various biomaterials have been used in tissue engineering for regeneration and repair. However, the therapeutic potential of stem cells and biomaterials in treating facial nerve injuries requires further exploration. In this review, we summarize the roles of stem cells and biomaterials in the regeneration and repair of damaged facial nerves, providing a theoretical basis for the recovery and reconstruction of body-brain crosstalk between the brain and facial expression muscles., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest, financial or otherwise., (Copyright © 2024. Published by Elsevier Inc.)

Objective . Engineered nerve conduits must simultaneously enhance axon regeneration and orient axon extension to effectively restore function of severely injured peripheral nerves. The dental pulp contains a population of stem/progenitor cells that endogenously express neurotrophic factors (NTFs), growth factors known to induce axon repair. We have previously generated scaffold-free dental pulp stem/progenitor cell (DPSC) sheets comprising an aligned extracellular matrix (ECM). Through the intrinsic NTF expression of DPSCs and the topography of the aligned ECM, these sheets both induce and guide axon regeneration. Here, the capacity of bioactive conduits generated using these aligned DPSC sheets to restore function in critical-sized nerve injuries in rodents was evaluated. Approach . Scaffold-free nerve conduits were formed by culturing DPSCs on a substrate with aligned microgrooves, inducing the cells to align and deposit an aligned ECM. The sheets were then detached from the substrate and assembled into scaffold-free cylindrical tissues. Main results. In vitro analyses confirmed that scaffold-free DPSC conduits maintained an aligned ECM and had uniformly distributed NTF expression. Implanting the aligned DPSC conduits across critical-sized defects in the buccal branch of rat facial nerves resulted in the regeneration of a fascicular nerve-like structure and myelinated axon extension across the injury site. Furthermore, compound muscle action potential and stimulated whisker movement measurements revealed that the DPSC conduit treatment promoted similar functional recovery compared to the clinical standard of care, autografts. Significance. This study demonstrates that scaffold-free aligned DPSC conduits supply trophic and guidance cues, key design elements needed to successfully promote and orient axon regeneration. Consequently, these conduits restore function in nerve injuries to similar levels as autograft treatments. These conduits offer a novel bioactive approach to nerve repair capable of improving clinical outcomes and patient quality of life., (Creative Commons Attribution license.)

Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves., (© 2024. The Author(s).)

The assessment of facial nerve function plays a crucial role in the diagnosis and treatment of facial nerve disorders.The assessment system for facial nerve function is primarily categorized into subjective and objective systems.While the subjective assessment system is relatively simple, it lacks accuracy as it can be influenced by the subjectivity of evaluator.Whereas, the objective system offers higher precision and stability, providing more quantitative information. In recent years, benefited with advancements in computer vision and artificial intelligence,we have witnessed increasingly accurate,stable and intelligent facial nerve assessment systems gradually implemented in clinical practice.When selecting a specific facial nerve assessment system,factors such as clinical scenarios,assessment objectives,patient characteristics should be considered., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium. The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aims to investigate the current application and the level of knowledge of intraoperative facial nerve monitoring among medical staff in China. Methods: A comprehensive online questionnaire was conducted among medical professionals across different regions in China from October 2022 to February 2023. The survey exclusively targeted departments specializing in otolaryngology, head and neck surgery, neurosurgery, and oral and maxillofacial surgery. The questionnaire covered various aspects including general information, intraoperative facial nerve monitoring practices, training history, indications for monitoring, parameters used during monitoring procedures, as well as factors influencing its implementation. Results: A total of 417 participants from 31 provincial, municipal, and autonomous regions were included. Intraoperative facial nerve monitoring was found to be implemented in 227 (54.4%,227/417) repondents of 53 institutions (24.9%, 53/213). The top three indications for implementing this technique were acoustic neuroma, parotid gland surgery, and modified middle ear surgery (mastoidectomy). Herein 81.1%(184/227) medical staff involved in intraoperative facial nerve monitoring had received relevant training, 57.3%(130/227)-92.1%(209/227) reported a lack of clear description regarding recording thresholds, stimulation currents/frequencies/wave widths. Conclusion: The majority of the institutions surveyed have not yet adopted intraoperative facial nerve monitoring. Furthermore, significant gaps concerning the procedure exist. It is imperative to establish standards or guidelines to promote its better development and application.

Purpose: Intraoperative neuromonitoring (IONM) aims to preserve facial nerve (FN) function during vestibular schwannoma (VS) surgery. However, current techniques such as facial nerve motor evoked potentials (FNMEP) or electromyography (fEMG) alone are limited in predicting postoperative facial palsy (FP). The objective of this study was to analyze a compound fEMG/FNMEP approach., Methods: Intraoperative FNMEP amplitude and the occurrence of fEMG-based A-trains were prospectively determined for the orbicularis oris (ORI) and oculi (OCU) muscle in 322 VS patients. Sensitivity and specificity of techniques to predict postoperative FN function were calculated. Confounding factors as tumor size, volume of intracranial air, or IONM duration were analyzed., Results: A relevant immediate postoperative FP was captured in 105/322 patients with a significant higher risk in large VS. While fEMG demonstrated a high sensitivity (77% and 86% immediately and 15 month postoperative, respectively) for identifying relevant FP, specificity was low. In contrast, FNMEP have a significantly higher specificity of 80.8% for predicting postoperative FP, whereas the sensitivity is low. A retrospective combination of techniques demonstrated still an incorrect prediction of FP in ~ 1/3 of patients., Conclusions: FNMEP and fEMG differ in sensitivity and specificity to predict postoperative FP. Although a combination of IONM techniques during VS surgery may improve prediction of FN function, current techniques are still inaccurate. Further development is necessary to improve IONM approaches for FP prediction., (© 2024. The Author(s).)

Vestibular schwannoma surgery necessitates intraoperative neuromonitoring to secure long-term tumor control by sufficient tumor removal and preservation of neural function. Therein, facial nerve function can be assessed in real-time and quantitatively by intraoperative continuous facial nerve monitoring with repetitive direct stimulation. The ABR and, further, CNAP, are closely monitored for the continuous assessment of the hearing function. In addition, the evoked masseter and extraocular electromyograms, SEP, MEP, and neuromonitoring of the lower cranial nerves are implemented as needed. In this article, we introduce our neuromonitoring techniques during vestibular schwannoma surgery with an illustrative video.

Introduction: Neuromuscular control of the facial expressions is provided exclusively via the facial nerve. Facial muscles are amongst the most finely tuned effectors in the human motor system, which coordinate facial expressions. In lower vertebrates, the extracranial facial nerve is a mixed nerve, while in mammals it is believed to be a pure motor nerve. However, this established notion does not agree with several clinical signs in health and disease., Objectives: To elucidate the facial nerve contribution to the facial muscles by investigating axonal composition of the human facial nerve. To reveal new innervation pathways of other axon types of the motor facial nerve., Methods: Different axon types were distinguished using specific molecular markers (NF, ChAT, CGRP and TH). To elucidate the functional role of axon types of the facial nerve, we used selective elimination of other neuronal support from the trigeminal nerve. We used retrograde neuronal tracing, three-dimensional imaging of the facial muscles, and high-fidelity neurophysiological tests in animal model., Results: The human facial nerve revealed a mixed population of only 85% motor axons. Rodent samples revealed a fiber composition of motor, afferents and, surprisingly, sympathetic axons. We confirmed the axon types by tracing the originating neurons in the CNS. The sympathetic fibers of the facial nerve terminated in facial muscles suggesting autonomic innervation. The afferent fibers originated in the facial skin, confirming the afferent signal conduction via the facial nerve., Conclusion: These findings reveal new innervation pathways via the facial nerve, support the sympathetic etiology of hemifacial spasm and elucidate clinical phenomena in facial nerve regeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Production and hosting by Elsevier B.V.)

This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT SECO ). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion., (© 2022. The Author(s).)

(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.

Background and Purpose: Neurological symptoms and complications associated with coronavirus 2019 (COVID-19) are well known. It was aimed to evaluate the brainstem and trigeminal/facial nerves and the pathways between these structures in COVID-19 using the blink reflex test., Methods: Thirty patients with post COVID-19 (16 males, 14 females) and 30 healthy individuals (17 males, 13 females) were included in this prospective study. Individuals who previously had a positive nose swap polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 and whose previously clinical features were compatible with COVID-19 were included in the post COVID-19 patient group. Neurological examination of the participants should be normal. Blink reflex test was performed on all participants. R1, ipsilateral R2 (IR2), and contralateral R2 (CR2) waves obtained from the test were analyzed., Results: The mean ages of healthy individuals and post COVID-19 patients were 34.0±6.4 and 38.4±10.6 years, respectively. Both age and gender were matched between the groups. R1, IR2, and CR2 latencies/amplitudes were not different between the two groups. The side-to-side R1 latency difference was 0.5±0.3 and 1.0±0.8 ms in healthy individuals and post COVID-19 patients, respectively (p=0.011). One healthy individual and 12 patients with post COVID-19 had at least one abnormal blink reflex parameter (p=0.001)., Conclusion: This study showed that COVID-19 may cause subclinical abnormalities in the blink reflex, which includes the trigeminal nerve, the seventh nerve, the brainstem, and pathways between these structures.

Purpose: Blink reflex (BR) under general anesthesia as an intraoperative neuromonitoring method was used to monitor facial nerves in few studies. This study aimed to test the utility of intraoperative BR during cerebellopontine angle and skull base surgeries, assess its prognostic value for facial nerve functions, and compare it with facial corticobulbar motor evoked potentials (CoMEPs)., Methods: Blink reflex and facial CoMEPs were recorded from 40 patients undergoing skull base surgeries. Subdermal needles were placed in the supraorbital notch for stimulation and in the orbicularis oculi muscle for recording the BR. A double train of 20 to 40 V intensity with an intertrain interval of 40 to 60 milliseconds, an interstimulus interval of 2.5 milliseconds, and a stimulus duration of 0.5 milliseconds were applied. Facial nerve functions were assessed with the House-Brackmann grading system in the postoperative day 1 and third-month period and correlated with intraoperative BR and CoMEPs measurements., Results: Of 40 patients, BR was recordable on the affected side in 32 (80%) and contralateral side in 35 (87.5%) patients. According to our statistical results, BR had a slightly better sensitivity than facial CoMEPs in predicting impairment of facial nerve functions for both postoperative and third-month time points. Blink reflex showed better accuracy for predicting postoperative nerve functions, whereas CoMEPs correlated better in predicting third-month outcome., Conclusions: We suggest that BR is a valuable intraoperative neuromonitoring method that can be used in addition to facial CoMEPs during skull base surgeries to assess real-time facial nerve integrity and predict prognosis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Injury to the facial nerve can occur after different etiologies and range from simple transection of the branches to varying degrees of segmental loss. Management depends on the extent of injury and options include primary repair for simple transections and using autografts, allografts, or conduits for larger gaps. Tissue engineering plays an important role to create artificial materials that are able to mimic the nerve itself without extra morbidity in the patients. The use of neurotrophic factors or stem cells inside the conduits or around the repair site is being increasingly studied to enhance neural recovery to a greater extent. Preclinical studies remain the hallmark for development of these novel approaches and translation into clinical practice. This review will focus on preclinical models of repair after facial nerve injury to help researchers establish an appropriate model to quantify recovery and analyze functional outcomes. Different bioengineered materials, including conduits and nerve grafts, will be discussed based on the experimental animals that were used and the defects introduced. Future directions to extend the applications of processed nerve allografts, bioengineered conduits, and cues inside the conduits to induce neural recovery after facial nerve injury will be highlighted. Impact statement Recovery after facial nerve injury is a complex process, which involves different management options such as primary repair or the use of nerve grafts or conduits. Various tissue-engineered approaches are increasingly studied on preclinical models with limited, but promising, translation to the clinical setting. Herein, preclinical models focusing on different recovery methods after facial nerve injury are comprehensively reviewed based on the experimental animals used. The review provides key insights into current developments and future directions on this highly relevant topic to help researchers further expand the field of tissue engineering and facial nerve recovery.

Facial nerve dysfunction is a common clinical condition that leads to disfigurement and emotional distress in the affected individuals. This study aimed to evaluate whether photobiomodulation can enhance regeneration of crushed facial nerves and attempt to investigate the possible underlying mechanism of neuroprotective function and therapeutic target. Various parameters of photobiomodulation were assigned to the facial nerves and Schwann cells (SCs) separately during crushed injury in rats. Axonal regeneration, functional outcomes, and SC apoptosis, proliferation, and underlying mechanisms of action were evaluated by morphological, histopathological, and functional assessments, flow cytometry, western blotting, real-time PCR, and IncuCyte. The results showed that photobiomodulation improved axonal regeneration and functional recovery, and also promoted proliferation, and inhibited apoptosis of SCs, both of these were considered as the most effective parameters in 250mW group. In addition, the neuroprotective effects of photobiomodulation (500mW) were likely associated with oxidative stress-induced SC apoptosis via activation of the PI3K/Akt signaling pathway. Our results revealed that photobiomodulation significantly promoted axonal regeneration, functional recovery, and regeneration of the facial nucleus, and its mechanism was related to the up-regulation of the PI3K/Akt signaling pathway. These findings provide clear experimental evidence of photobiomodulation as an alternative therapeutic strategy for peripheral nerve damage., (© 2021. The Author(s).)

This study aimed to investigate the effect of charge-balanced transcutaneous electrical nerve stimulation (cb-TENS) in accelerating recovery of the facial function and nerve regeneration after facial nerve (FN) section in a rat model. The main trunk of the left FN was divided and immediately sutured just distal to the stylomastoid foramen in 66 Sprague-Dawley rats. The control group had no electrical stimulus. The other two groups received cb-TENS at 20 Hz (20 Hz group) or 40 Hz (40 Hz group). Cb-TENS was administered daily for seven days and then twice a week for three weeks thereafter. To assess the recovery of facial function, whisker movement was monitored for four weeks. Histopathological evaluation of nerve regeneration was performed using transmission electron microscopy (TEM) and confocal microscopy with immunofluorescence (IF) staining. In addition, the levels of various molecular biological markers that affect nerve regeneration were analyzed. Whisker movement in the cb-TENS groups showed faster and better recovery than the control group. The 40 Hz group showed significantly better movement at the first week after injury (p < 0.0125). In histopathological analyses using TEM, nerve axons and Schwann cells, which were destroyed immediately after the injury, recovered in all groups over time. However, the regeneration of the myelin sheath was remarkably rapid and thicker in the 20 Hz and 40 Hz groups than in the control group. Image analysis using IF staining showed that the expression levels of S100B and NF200 increased over time in all groups. Specifically, the expression of NF200 in the 20 Hz and 40 Hz groups increased markedly compared to the control group. The real-time polymerase chain reaction was performed on ten representative neurotrophic factors, and the levels of IL-1β and IL-6 were significantly higher in the 20 and 40 Hz groups than in the control group (p < 0.015). Cb-TENS facilitated and accelerated FN recovery in the rat model, as it significantly reduced the recovery time for the whisker movement. The histopathological study and analysis of neurotrophic factors supported the role of cb-TENS in the enhanced regeneration of the FN., (© 2022. The Author(s).)

Objectives: This study aimed to determine whether toll-like receptor expression patterns differ in the distal facial nerve during recovery after crushing and cutting injuries., Methods: Adult male Sprague-Dawley rats underwent crushing or cutting injury of the unilateral facial nerve. Their whisker movement and blink reflex were examined. Western blotting was performed with the normal nerve on the left side and the damaged nerve on the right side, four days, 14 days, and 3 months after injury., Results: The scores of whisker movements and blink reflex in the crushing group showed improvements, while the score of the cutting group was significantly lower at 14 days and 3 months (p < 0.05). Western blotting showed that TLRs 11 and 13 increased in the crushing group, and TLRs 1, 2, 3, 4, 5, 8, 10, 11, 12, and 13 increased in the cutting group after 14 days ( p < 0.05). After 3 months, TLRs 10 and 11 increased in the crushing group, and TLRs 1, 4, 5, 8, 11, and 12 increased in the cutting group ( p < 0.05)., Conclusion: TLRs 1, 4, 5, 8, and 12 are related to nerve degeneration after facial nerve injury, and TLRs 10, 11, and 13 are related to recovery from facial palsy.

Objective: To record crossed acoustic reflex thresholds (xART's) postoperatively from patients after surgical repair of unilateral congenital aural atresia (CAA). To seek explanations for when xARTs can and cannot be recorded. We hope to understand the implications for this central auditory reflex despite early afferent deprivation., Methods: Patients who underwent surgery to correct unilateral CAA at a tertiary academic medical were prospectively enrolled to evaluate for the presence of xART. Preoperative ARTs in the normal (non-atretic) ear, and postoperative ipsilateral ARTs (stimulus in the normal ear) and contralateral ARTs (stimulus in the newly reconstructed atretic ear; record in the normal ear) were measured at 500, 1000, and 2000 Hz., Results: Four of 11 patients with normal ipsilateral reflex thresholds preoperatively demonstrated crossed acoustic reflexes postoperatively (stimulus in reconstructed ear; record from normal ear). Four other patients demonstrated normal ipsilateral thresholds preoperatively but did not have crossed reflexes postoperatively. No reflexes (pre- or postoperatively) could be recorded in 3 patients. Crossed reflex threshold is significantly correlated with the postoperative audiometric threshold. There was no correlation between ipsilateral and contralateral reflex thresholds., Conclusion: Crossed acoustic reflexes can be recorded from some but not all postoperative atresia patients, and the thresholds for those reflexes correlate with the postoperative pure tone threshold. The presence of acoustic reflexes implies an intact CN VIII-to-opposite CN VII central reflex arc despite early unilateral sound deprivation.

Objective: The purpose of this study is to determine if different facial muscle groups demonstrate different responses to facial nerve stimulation, the results of which could potentially improve intraoperative facial nerve monitoring (IOFNM)., Methods: IOFNM data were prospectively collected from patients undergoing cochlear implantation. At different stages of nerve exposure, three sites were stimulated using a monopolar pulse. Peak electromyography (EMG) amplitude (μV) in four muscle groups innervated by four different branches of the facial nerve (frontalis-temporal, inferior orbicularis oculi-zygomatic, superior oribularis oris-buccal, and mentalis-marginal mandibular) were recorded., Results: A total of 279 peak EMG amplitudes were recorded in 93 patients. At all three stimulating sites, the zygomatic branch mean peak EMG amplitudes were statistically greater than those of the temporal, buccal, and marginal mandibular branches (P < .05). At stimulating Site C, the marginal mandibular branch mean peak EMG was stronger than the temporal or buccal branches (P < .05). Of the 279 stimulations, the zygomatic branch demonstrated the highest amplitude in 128 (45.9%) trials, followed by the marginal mandibular branch (22.2%)., Conclusions: When utilized, IOFNM should be performed with at least two electrodes, one of which is placed in the orbicularis oculi muscles and the other in the mentalis muscle. However, there is wide variability between patients. As such, in cases of suspected variant nerve anatomy or increased risk of injury (intradural procedures), surgeons should consider using more than two recording electrodes, with at least one in the orbicularis oculi muscle., Level of Evidence: 3 Laryngoscope, 131:E2329-E2334, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective:  The objective of this study was to determine the performance of the standard alarm criterion of motor evoked potentials (MEPs) of the facial nerve in surgeries performed for resections of vestibular schwannomas or of other lesions of the cerebellopontine angle., Methods:  This retrospective study included 33 patients (16 with vestibular schwannomas and 17 with other lesions) who underwent the resection surgery with transcranial MEPs of the facial nerve. A reproducible 50% decrease in MEP amplitude, resistant to a 10% increase in stimulation intensity, was applied as the alarm criterion during surgery. Facial muscular function was clinically evaluated with the House-Brackmann score (HBS), pre- and postsurgery at 3 months., Results:  In the patient group with vestibular schwannoma, postoperatively, the highest sensitivity and negative predictive values were found for a 30% decrease in MEP amplitude, that is, a criterion stricter than the 50% decrease in MEP amplitude criterion, prone to trigger more warnings, used intraoperatively. With this new criterion, the sensitivity would be 88.9% and the negative predictive value would be 85.7%. In the patient group with other lesions of the cerebellopontine angle, the highest sensitivity and negative predictive values were found equally for 50, 60, or 70% decrease in MEP amplitude. With these criteria, the sensitivities and the negative predictive values would be 100.0%., Conclusion:  Different alarm criteria were found for surgeries for vestibular schwannomas and for other lesions of the cerebellopontine angle. The study consolidates the stricter alarm criterion, that is, a criterion prone to trigger early warnings, as found previously by others for vestibular schwannoma surgeries (30% decrease in MEP amplitude)., Competing Interests: None., (Thieme. All rights reserved.)

Objective:  The quantity of A-trains, a high-frequency pattern of free-running facial nerve electromyography, is correlated with the risk for postoperative high-grade facial nerve paresis. This correlation has been confirmed by automated analysis with dedicated algorithms and by visual offline analysis but not by audiovisual real-time analysis., Methods:  An investigator was presented with 29 complete data sets measured during actual surgeries in real time and without breaks in a random order. Data were presented either strictly via loudspeaker (audio) or simultaneously by loudspeaker and computer screen (audiovisual). Visible and/or audible A-train activity was then quantified by the investigator with the computerized equivalent of a stopwatch. The same data were also analyzed with quantification of A-trains by automated algorithms., Results:  Automated (auto) traintime (TT), known to be a small, yet highly representative fraction of overall A-train activity, ranged from 0.01 to 10.86 s (median: 0.58 s). In contrast, audio-TT ranged from 0 to 1,357.44 s (median: 29.69 s), and audiovisual-TT ranged from 0 to 786.57 s (median: 46.19 s). All three modalities were correlated to each other in a highly significant way. Likewise, all three modalities correlated significantly with the extent of postoperative facial paresis. As a rule of thumb, patients with visible/audible A-train activity < 1 minute presented with a more favorable clinical outcome than patients with > 1 minute of A-train activity., Conclusion:  Detection and even quantification of A-trains is technically possible not only with intraoperative automated real-time calculation or postoperative visual offline analysis, but also with very basic monitoring equipment and real-time good quality audiovisual analysis. However, the investigator found audiovisual real-time-analysis to be very demanding; thus tools for automated quantification can be very helpful in this respect., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Facial nerve schwannomas located at internal auditory canal and cerebellopontine angle (IAC/CPA FNS) were diagnosed intraoperatively, it poses a therapeutic dilemma to the surgeon., Objective: To report our experience in managing IAC/CPA FNS and to propose a treatment strategy., Methods: A total of 14 patients with IAC/CPA FNS who were diagnosed intraoperatively and treated by operation between 2015 and 2019 were retrospectively studied., Results: Unilateral hearing loss was the most common symptom and all these patients had normal facial nerve function preoperatively. Surgical approaches used in these patients including translabyrinthine (2 cases), retrosigmoid (RS) (11 cases), and middle cranial fossa (MCF) approach (1 case). Eight patients underwent partial resection, three patients underwent subtotal resection and three patients had complete tumor removal with facial nerve reconstruction. All partial resection patients and two patients underwent subtotal resection achieved a long-term HB grade I facial nerve function. The long-term facial nerve function of patients underwent complete resection and nerve grafting was no better than HB grade III.1 of the eight patients underwent partial resection experienced tumor regrowth during the follow-up., Conclusions: Partial or subtotal resection for IAC/CPA FNS may provide an opportunity of retaining excellent facial nerve function. Regular postoperative imaging is helpful to monitor the recurrence.

Objective: The intraoperative monitoring of cranial nerve function records evoked responses at latencies of a few milliseconds. Unfortunately, these responses may be masked by the electrical artifact of the stimulation pulse. In electrical stimulation, the return discharge of the stimulation pulse significantly contributes to the width of the electrical artifact., Methods: We have generated stimulation pulses with an ISIS Neurostimulator (inomed Medizintechnik GmbH) providing a novel stimulation artifact reduction technique. It delays the return discharge of the stimulating pulse beyond the latency of the expected physiological response. This delayed return discharge is controlled such that no unintended physiological response is evoked., Results: In 21 neurosurgical interventions with motor evoked potentials of the facial nerve (FNMEP), the stimulation method generated a stimulation pulse artifact with reduced tail duration. Compared to conventional stimulation with immediate return discharge, the signal-to-noise ratio of the physiological response may improve with the novel stimulation method. In some surgeries, only the novel stimulation method generated clearly identifiable response signals., Conclusions: The reduced width of the stimulation artifact extends the toolbox of intraoperative monitoring modalities by rendering the interpretation of cranial nerve evoked potentials more reliable., Significance: The novel technique enhances the number of patients for whom intraoperative monitoring may aid in cranial neurosurgery., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [M.T. and M.B are employees of inomed Medizintechnik GmbH. J.S. is member of the inomed scientific advisory board and has received speaker fees for giving presentations at inomed in-house courses on IONM.], (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To identify clinical predictors of facial nerve (FN) outcomes after microsurgical resection of vestibular schwannoma (VS)., Study Design: Prospective cohort study., Setting: Academic medical center., Methods: Consecutive patients undergoing VS resection from November 2017 to October 2019 were included. FN function was evaluated with the House-Brackmann (HB) scale and stratified into good (HB I-II) and poor (HB III-VI) function. Analyses included descriptive statistics, correlation, and logistic regression., Results: Of 256 patients who met criteria (mean age, 47.7 years; 62.5% female), 227 (88.7%) achieved good FN function postoperatively and 238 (93.0%) at latest follow-up (mean, 154.8 days). Operative approaches consisted of translabyrinthine (50.8%), retrosigmoid (25.0%), and middle fossa craniotomies (24.2%). Extent of resection was decided intraoperatively, and gross or near total resection was accomplished in 237 (92.6%) cases. Postoperative HB grade correlated with latest HB grade (0.615, P < .001). Factors associated with good postoperative FN function included small tumor size (≤15 mm; odds ratio [OR], 2.425; P = .042), gross or near total resection (OR, 3.170; P = .041), and ≥100-µV intraoperative FN electromyographic response to a 0.05-mA stimulus (OR, 22.242; P < .001). Factors associated with good FN function at latest follow-up included gross total resection (OR, 7.764; P = .003) and ≥100-µV FN electromyographic response (OR, 8.518; P < .001), accounting for surgical approach and tumor size., Conclusion: Microsurgical resection of VS can be accomplished with excellent FN outcomes. Gross total resection and ≥100-µV intraoperative FN electromyographic response predicted excellent FN outcomes. Immediate postoperative FN function is a prognosticator of long-term FN function.

Objectives/hypothesis: Facial nerve monitoring (FNM) has evolved into a widely used adjunct for many surgical procedures along the course of the facial nerve. Even though majority opinion holds that FNM reduces the incidence of iatrogenic nerve injury, there are few if any studies yielding high-level evidence and no practice guidelines on which clinicians can rely. Instead, a review of the literature and medicolegal cases reveals significant variations in methodology, training, and clinical indications., Study Design: Literature review and expert opinion., Methods: Given the lack of standard references to serve as a resource for FNM, we assembled a multidisciplinary group of experts representing more than a century of combined monitoring experience to synthesize the literature and provide a rational basis to improve the quality of patient care during FNM., Results: Over the years, two models of monitoring have become well-established: 1) monitoring by the surgeon using a stand-alone device that provides auditory feedback of facial electromyography directly to the surgeon, and 2) a team, typically consisting of surgeon, technologist, and interpreting neurophysiologist. Regardless of the setting and the number of people involved, the reliability of monitoring depends on the integration of proper technical performance, accurate interpretation of responses, and their timely application to the surgical procedure. We describe critical steps in the technical set-up and provide a basis for context-appropriate interpretation and troubleshooting of recorded signals., Conclusions: We trust this initial attempt to describe best practices will serve as a basis for improving the quality of patient care while reducing inappropriate variations., Level of Evidence: 4 Laryngoscope, 131:S1-S42, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The aim of this study is to investigate facial nerve outcomes after microsurgical resection in neurofibromatosis type 2 (NF2) compared to sporadic tumors., Study Design: Single institutional retrospective chart review., Setting: Tertiary referral center., Methods: All adult patients with NF2 vestibular schwannoma (VS) or sporadic VS who underwent microsurgical resection from 2008 to 2019 with preoperative magnetic resonance imaging (MRI) and 1 year of postsurgical follow-up were included. The primary outcome measure was postoperative House-Brackmann (HB) facial nerve score measured at first postoperative visit and after at least 10 months., Results: In total, 161 sporadic VSs and 14 NF2 VSs met inclusion criteria. Both median tumor diameter (NF2, 33.5 mm vs sporadic, 24 mm, P = .0011) and median tumor volume (NF2, 12.4 cm 3 vs sporadic, 2.9 cm 3 , P = .0005) were significantly greater in patients with NF2. The median follow-up was 24.9 months (range, 12-130.1). Median facial nerve function after 1 year for patients with NF2 was HB 3 (range, 1-6) compared to HB 1 (range, 1-6) for sporadic VS ( P = .001). With multivariate logistic regression, NF2 tumors (odds ratio [OR] = 13.9, P = .001) and tumor volume ≥3 cm 3 (OR = 3.6, P = .025) were significantly associated with HB ≥3 when controlling for age, sex, extent of tumor resection, translabyrinthine approach, and prior radiation., Conclusion: Tumor volume >3 cm 3 and NF2 tumors are associated with poorer facial nerve outcomes 1 year following microsurgical resection.

The pontine Kölliker-Fuse nucleus (KFn) is a core nucleus of respiratory network that mediates the inspiratory-expiratory phase transition and gates eupneic motor discharges in the vagal and hypoglossal nerves. In the present study, we investigated whether the same KFn circuit may also gate motor activities that control the resistance of the nasal airway, which is of particular importance in rodents. To do so, we simultaneously recorded phrenic, facial, vagal and hypoglossal cranial nerve activity in an in situ perfused brainstem preparation before and after bilateral injection of the GABA-receptor agonist isoguvacine (50-70 nl, 10 mM) into the KFn (n = 11). Our results show that bilateral inhibition of the KFn triggers apneusis (prolonged inspiration) and abolished pre-inspiratory discharge of facial, vagal and hypoglossal nerves as well as post-inspiratory discharge in the vagus. We conclude that the KFn plays a critical role for the eupneic regulation of naso-pharyngeal airway patency and the potential functions of the KFn in regulating airway patency and orofacial behavior is discussed., (Copyright © 2020. Published by Elsevier B.V.)

Endoscopic-assisted techniques have extensively been applied to vestibular schwannoma (VS) surgery allowing to increase the extent of resection, minimize complications, and preserve facial nerve and auditory functions. In this paper, we retrospectively analyze the effectiveness of flexible endoscope in the endoscopic-assisted retrosigmoid approach for the surgical management of VS of various sizes. The authors conducted a retrospective analysis on 32 patients who underwent combined microscopic and flexible endoscopic resection of VS of various sizes over a period of 16 months. Flexible endoscopic-assisted retrosigmoid approach was performed in all cases, and in 6 cases, flexible and rigid endoscopic control were used in combination to evaluate the differences between the two surgical instruments. The surgical results were additionally compared with a previous case series of 141 patients operated for VS of various sizes without endoscopic assistance. Gross-total resection was achieved in 84% of the cases and near-total resection was accomplished in the rest of them. Excellent or good facial nerve function was observed in all except one case with a preoperative severe facial palsy. Hearing preservation surgery (HPS) was attempted in 11 cases and accomplished in 9 (81.8%). A tumor remnant was endoscopically identified in the fundus of the IAC in all cases (100%). Endoscopic assistance increased the rate of total removal and no intrameatal residual tumor was seen at radiological follow-up. Comparative analysis with a surgical cohort of patients operated with the sole microsurgical technique showed a significative association between endoscopic assistance and intracanalicular extent of resection. Combined microsurgical and flexible endoscopic assistance provides remarkable advantages in the pursuit of maximal safe resection of VS and preservation of facial nerve and auditory functions, minimizing the risk of post-operative complications.

Objective: The aim of this study was to investigate the effects of systemic administration of decorin (DC) on facial nerve (FN) regeneration., Methods: A total of 32 female albino Wistar rats were divided into 4 groups: control (C) group: no bilateral FN neurorrhaphy (B-FNN), no DC application, sham-operated group: B-FNN without DC application, DC group: DC application without B-FNN, and B-FNN + DC group: B-FNN and DC application. Nerve conduction studies were performed before and after skin incisions at 1st, 3rd, 5th, and 7th weeks in all groups. The amplitude and latency of compound muscle action potentials were recorded. FN samples were obtained and were investigated under light microscopy and immunohistochemical staining. The nerve and axon diameter, number of axons, H score, Schwann cell proliferation, and myelin and axonal degeneration were recorded quantitatively., Results: In the sham group, the 3rd and 5th postoperative week, amplitude values were significantly lower than those of the B-FNN + DC group (p < 0.05). Nerve diameters were found to be significantly larger in the sham, DC, and B-FNN + DC groups than in the C group (p < 0.05). The number of axons, the axon diameter, and the H scores were found to be significantly higher in the B-FNN + DC group than in the sham group (p < 0.05). The Schwann cell proliferation, myelin degeneration, and axonal degeneration scores were significantly lower in the B-FNN + DC group than in the sham group (p < 0.05)., Conclusion: Electrophysiological and histopathological evaluation revealed the potential benefits provided by DC. This agent may increase FN regeneration., (© 2021 S. Karger AG, Basel.)

Objectives: Initially treating vestibular schwannomas (VSs) with subtotal resection (STR) followed by Gamma Knife radiosurgery (GKRS) for progression of tumor residual is a strategy that balances maximal tumor resection with preservation of neurological function. The effect of timing of GKRS for residual and recurrent VSs remains poorly defined. We developed a simple and practical treatment algorithm for the timing of GKRS after STR of VSs and reviewed our follow-up results to determine outcomes between patients treated with early vs. late GKRS., Patients and Methods: Patients that underwent STR between 1999 and 2017 for a VS at Tufts Medical Center were identified and included in the study cohort. Patients who received GKRS ≤ 12 months after STR were included in the early intervention group. Patients who received GKRS > 12 months after STR or did not have tumor progression on follow-up thus not requiring GKRS were included in the observation/delayed intervention group., Results: STR of VSs was performed on 23 patients. Mean patient age at the time of STR was 53.0 years (range: 20-86.2). The mean follow-up was 4.2 years (range: 1 month-15.5 years). Patients most frequently presented with hearing loss. There were 5 patients (21.7 %) in the early intervention group and 18 (78.3 %) patients in the observation/delayed intervention group. Ten of 23 patients (43.5 %) required GKRS. Thirteen (56.5 %) did not receive GKRS. None of the patients in the early intervention group or the observation/delayed intervention group had changes in House-Brackmann (HB) Grade either after GKRS or at the end of the study period., Conclusions: GKRS of residual or recurrent tumor is safe following STR of VS and appears to carry a low risk of worsening facial nerve function when performed for progressive tumor growth., (Copyright © 2020. Published by Elsevier B.V.)

In this study, we devised a novel cross-facial nerve grafting (CFNG) procedure using an autologous nerve graft wrapped in an adipose-derived stem cell (ADSC) sheet that was formed on a temperature-responsive dish and examined its therapeutic effect in a rat model of facial palsy. The rat model of facial paralysis was prepared by ligating and transecting the main trunk of the left facial nerve. The sciatic nerve was used for CFNG, connecting the marginal mandibular branch of the left facial nerve and the marginal mandibular branch of the right facial nerve. CFNG alone, CFNG coated with an ADSC suspension, and CFNG wrapped in an ADSC sheet were transplanted in eight rats each, designated the CFNG, suspension, and sheet group, respectively. Nerve regeneration was compared histologically and physiologically. The time to reinnervation, assessed by a facial palsy scoring system, was significantly shorter in the sheet group than in the other two groups. Evoked compound electromyography showed a significantly higher amplitude in the sheet group (4.2 ± 1.3 mV) than in the suspension (1.7 ± 1.2 mV) or CFNG group (1.6 ± 0.8 mV; p < .01). Toluidine blue staining showed that the number of myelinated fibers was significantly higher in the sheet group (2,450 ± 687) than in the suspension (1,645 ± 659) or CFNG group (1,049 ± 307; p < .05). CFNG in combination with ADSC sheets, prepared using temperature-responsive dishes, promoted axonal outgrowth in autologous nerve grafts and reduced the time to reinnervation., (© 2020 John Wiley & Sons, Ltd.)

This protocol describes consistent and reproducible methods to study axonal regeneration and inhibition in a rat facial nerve injury model. The facial nerve can be manipulated along its entire length, from its intracranial segment to its extratemporal course. There are three primary types of nerve injury used for the experimental study of regenerative properties: nerve crush, transection, and nerve gap. The range of possible interventions is vast, including surgical manipulation of the nerve, delivery of neuroactive reagents or cells, and either central or end-organ manipulations. Advantages of this model for studying nerve regeneration include simplicity, reproducibility, interspecies consistency, reliable survival rates of the rat, and an increased anatomic size relative to murine models. Its limitations involve a more limited genetic manipulation versus the mouse model and the superlative regenerative capability of the rat, such that the facial nerve scientist must carefully assess time points for recovery and whether to translate results to higher animals and human studies. The rat model for facial nerve injury allows for functional, electrophysiological, and histomorphometric parameters for the interpretation and comparison of nerve regeneration. It thereby boasts tremendous potential toward furthering the understanding and treatment of the devastating consequences of facial nerve injury in human patients.

We developed an attachable magnetic nerve stimulator (AMNS) that connects the metallic instruments to a neurophysiological monitoring unit for monitoring the facial nerve (FN) during ear surgery and present our experiences with intraoperative neuromonitoring (IONM) of the FN using AMNS. The FN in 20 patients who underwent tympanomastoidectomy for chronic ear disease was examined. The electromyography (EMG) amplitudes of the FN using AMNS were assessed. The EMG amplitudes of the FN at 1.00-mA stimulation during drilling were 265 ± 64 µV in the orbicularis oris and 288 ± 57 µV in the orbicularis oculi. The EMG amplitudes using AMNS attached to the surgical instruments under 0.35-mA stimulus at the tympanic segment of the FN were 196 ± 43 µV in the orbicularis oris and 197 ± 41 µV in the orbicularis oculi. The application of continuous stimulation with burr and surgical instruments using the AMNS is feasible and effective for FN stimulation and identification.

Object: Surgery of tumours in the cerebellopontine angle (CPA) can lead to loss of facial nerve function. Different methods of intra-operative nerve monitoring (IOM) (including free-running EMG, direct nerve stimulation and transcranial motor evoked potentials (TcMEP)) have been used to predict facial nerve outcome during surgery. Recent research has shown TcMEP threshold increase and the occurrence of A-trains on the EMG to have great potential in doing so. This study compares these two methods and correlates them to House-Brackmann (HB) scores post-op in patients with tumours in the cerebellopontine angle., Method: Forty-three patients (one was operated twice) with large CPA tumours treated surgically in the Radboud University Medical Center between 2015 and 2019 were included in this study. During surgery, TcMEP threshold increases and A-train activity were measured. Because our treatment paradigm aims at facial nerve preservation (accepting residual tumour), TcMEP threshold increase of over 20 mA or occurrence of A-trains were considered as warning signs and used as a guide for terminating surgery. HB scores were measured post-op, at 6 weeks, 6 months and 1 year after surgery. Spearman's correlation was calculated between the IOM-values and the HB scores for a homogeneous subgroup of 30 patients with vestibular schwannoma (VS) without neurofibromatosis type II (NF-II) and all patients collectively., Results: TcMEP threshold was successfully measured in 39 (90.7%) procedures. In the homogeneous VS non-NFII group, we found a statistically significant moderate-to-strong correlation between TcMEP threshold increase and House Brackmann score immediately post-op, at 6 weeks, 6 months and 1 year after surgery (Spearman's rho of 0.79 (p < 0.001), 0.74 (p < 0.001), 0.64 (p < 0.001) and 0.58 (p = 0.002), respectively). For A-trains, no correlation was found. Similar results were found when including all patients with CPA tumours. A threshold increase of < 20 mA was a predictor of good facial nerve outcome., Conclusion: These results show that TcMEP threshold increases are strongly correlated to post-operative HB scores, while A-trains are not. This suggests TcMEP threshold increases can be a valuable predictor for facial nerve outcome in patients with large tumours when facial nerve preservation is prioritized over total resection. In this study, we found no use for A-trains to prevent facial nerve deficits.

Background/aim: To adapt the Sunnybrook facial grading system (SFGS) into Turkish and perform validation and reliability studies on the Turkish version., Materials and Methods: The original English version of the SFGS was translated into Turkish by performing a linguistic validity study based on international standards. The evaluators comprised 6 physicians. Evaluations were performed twice independently using the video recordings of 65 facial palsy patients. Synchronously, the House-Brackman facial grading system (HBFGS) was filled out to display concurrent validity. The intraclass correlation coefficient (ICC) and Cronbach’s alpha was used for the examination of the inter- and intra-rater reliability. As another indication of reliability, the generalizability (G) was also examined., Results: The ICC for the inter-rater reliability for resting symmetry, symmetry of voluntary movement, synkinesis, and the composite score, which are 4 components of the SFGS, were determined, respectively, as 0.822, 0.956, 0.606, and 0.957 for the first evaluation, and 0.805, 0.965, 0.584, and 0.965 for the second evaluation. For the intra-rater reliability, the ICC were determined as 0.842, 0.956, 0.794, and 0.937, while the Cronbach’s alpha coefficients were determined as 0.809, 0.956, 0.792, and 0.948, respectively. The G coefficient was determined as G = 0.772. For the concurrent validity, a strong correlation was found between the SFGS and HBFGS scores., Conclusion: The present study adapted the SFGS into Turkish, and demonstrated that the adapted scale was valid and reliable. The Turkish version can be used for the evaluation of facial palsy, the follow-up of treatment efficiency, and standardization in reporting outcomes with the international literature., Competing Interests: No conflict of interest was declared by the authors., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Studies on the effects of the pulse waveform used in electrical muscle stimulation on the activations and perceived discomfort of the waveform have been mainly executed on limb muscles with variable results, however, knowledge of these effects on facial muscles is currently lacking. We studied two waveforms, square wave and sinusoidal wavelet, for the activation of the frontalis muscle in 9 individuals with unresolved facial nerve palsy. Both waveforms produced a movement that was greater in amplitude compared with the maximal voluntary movement of the affected side in 8 participants and at least as great as the healthy side's maximal voluntary movement in 4 participants. Both waveforms were equally successful in producing movements, and there was no significant difference in perceived discomfort ratings between the two waveforms. These findings will be useful for the future development of neuroprosthetic applications for reanimating facial muscles using electrical stimulation. Trial registration: ClinicalTrials.gov NCT03496025, registration date March 19, 2018.

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.

Assessing facial nerve function from visible facial signs such as resting asymmetry and symmetry of voluntary movement is an important means in clinical practice. By using image processing, computer vision and machine learning techniques, replacing the clinician with a machine to do assessment from ubiquitous visual face capture is progressing more closely to reality. This approach can do assessment in a purely automated manner, hence opens a promising direction for future development in this field. Many studies gathered around this interesting topic with a variety of solutions proposed in recent years. However, to date, none of these solutions have gained a widespread clinical use. This study provides a comprehensive review of the most relevant and representative studies in automated facial nerve function assessment from visual face capture, aiming at identifying the principal challenges in this field and thus indicating directions for future work.

Objective: Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN., Method: A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS., Results: Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P < 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P < 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P < 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS., Conclusion: Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN., Significance: Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Animal models of nerve function have been subject to extensive study in order to understand and investigate methods which may improve axon regeneration and promote functional outcomes following nerve injury and repair. As the facial nerve is a cranial nerve, there is mounting evidence that cranial nerve regeneration differs from peripheral, and outcome models specifically addressing the facial nerve are required. Murine models are the most commonly utilized, with a variety of methods employed to measure the actions of whisking, eye closure, or ear movement as indicators of facial nerve regeneration. Each method of measurement is reviewed in terms of validity, strengths, limitations, and the specific outcome data provided. The authors propose that prior to choosing an outcome model, the goals and objectives of a planned study should be well defined, as various outcome measures may be useful depending on the information which is desired. The aim of this paper, therefore, is to provide the reader with a concise review which may facilitate project design., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Purpose: The aim of this study was to analyze the utility of various preoperative electrophysiological tests of the facial nerve CNVII in predicting CNVII function after vestibular schwannoma surgery., Methods: This retrospective study included 176 patients who had preoperative facial nerve electroneurography and electrically evoked blink reflex testing. We defined the following variables: axonal degeneration of CNVII (AD-CNVII), trigeminal nerve damage (D-CNV), disturbances in the short-latency pathway of the blink reflex (D-BR), and any changes in electrophysiological test results (A-EMG)., Results: AD-CNVII, D-CNV, D-BR, and A-EMG were noted in 24%, 10%, 64%, and 71% of the patients, respectively. Negative D-CNV correlated with good CNVII function in early (p = 0.005) and long-term follow-up (p = 0.003) but was not an independent prognostic factor for postoperative facial muscles function. D-CNV appeared to be closely related to tumor size. D-BR was related to tumor size and had no predictive value. AD-CNVII (amplitude reduction of 50% or more compared to the healthy side) was an independent factor associated with increased risk of facial muscles weakness (p = 0.015 and p = 0.031 for early and late outcomes, respectively)., Conclusions: Further studies are needed to establish which tests and cut-off values are the most useful for predicting post-surgical facial nerve function., Competing Interests: The authors have declared that no competing interests exist.

Facial paralysis can result in severe implications for the patients. However, stem cell biology has become an important field in regenerative medicine since the discovery and characterization of mesenchymal stem cells. Our aim was to evaluate the regeneration after facial nerve crush injury and application of human immature dental pulp stem cells (iDPSC). For this study 70 Wistar rats underwent a unilateral facial nerve crush injury and were divided into two groups: Group I (GI): Crushed; Group II (GII): Crushed and iDPSC, and distributed into study periods of 3, 7, 14, 21, and 42 postoperative days. Facial nerve regeneration was analyzed via functional recovery of whisker movement, histomorphometric analysis, and immunoblotting assay. The results show that GII had complete functional recovery at 14 days, while GI recovered after 42 days. Also, regarding the facial nerve trunk, GII presented histological improvement, evidencing better axonal and structural organization of the myelin sheath, and exhibited statistically higher values for the outer and inner perimeters and g-ratio. Nevertheless, GI exhibited statistically higher values for the thickness of myelin sheath. In the buccal branch, no differences were observed for all parameters between groups. At 42 days, both groups GI and GII were close to the levels observed for the control group. Concerning nerve growth factor expression, GII exhibited statistically greater values ( p < 0.05) compared with the control group at 7 days. In summary, a single injection of human iDPSC promoted a positive effect on regeneration of the facial nerve trunk after 14 days and provided an alternative to support regeneration following peripheral nerve injury.

Idiopathic Bell's palsy can lead to a serious and, sometimes permanently, disfiguring and emotionally challenging facial palsy. Early diagnosis and treatment with corticosteroids are important, as they significantly improve recovery rates. Bell's palsy is a benign condition that should be diagnosed and managed in primary care. Patients who self-present to the emergency department should be managed and discharged without needing admission. We reviewed all patients referred urgently to our hospital with facial weakness and discharged with a diagnosis of Bell's palsy, to explore whether clinicians were confident in making this diagnosis at initial assessment and, if not, how often they sought a specialist opinion. Furthermore, we assessed the impact of its over-investigation and mistreatment on healthcare resources and the patients., (© 2019 Royal College of Physicians.)

Insufficient recovery after injury of a peripheral motor nerve is due to (1) inappropriate pathfinding as a result of axonal regrowth to inappropriate targets, (2) excessive collateral axonal branching at the lesion site, and (3) polyinnervation of the neuromuscular junctions (NMJs). The rat facial nerve model is often used because of its simple and reliable readout to measure recovery of function (vibrissal whisking). Over the last decades scientists have concentrated their efforts to combat mostly NMJ polyinnervation, because it turned out to be very difficult to reduce collateral axonal branching and impossible to navigate thousands of axons toward the original fascicles. In the past, several groups of scientists concentrated their efforts to reduce the activity-dependent polyinnervation of NMJs by electrical stimulation of the muscles (square 0.1 msec pulses at 5 Hz). The results showed no recovery of functions and a severe reduction in the number of innervated NMJs to approximately one fifth of those observed in intact animals. More recent experiments, however, have shown that motor recovery improved significantly following mechanical stimulation of the denervated facial muscles (vibrissal and orbicularis oculi) and that restored functions could invariably be linked to reduced polyinnervation at the NMJ while the number of innervated NMJ remained the same. These results suggest that clinically feasible and effective therapies could be developed and tested in the near future. Anat Rec, 302:1287-1303, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

The lack of a clinically relevant animal models for research in facial nerve reconstruction is challenging. In this study, we investigated the surgical anatomy of the ovine sural nerve as a potential candidate for facial nerve reconstruction, and performed its histological quantitative analysis in comparison to the buccal branch (BB) of the facial nerve using cadaver and anesthetized sheep. The ovine sural nerve descended to the lower leg along the short saphenous vein. The length of the sural nerve was 14.3 ± 0.5 cm. The distance from the posterior edge of the lateral malleolus to the sural nerve was 7.8 ± 1.8 mm. The mean number of myelinated fibers in the sural nerve was significantly lower than that of the BB (2,311 ± 381vs. 5,022 ± 433, respectively. p = 0.003). The number of fascicles in the sural nerve was also significantly lower than in the BB (10.5 ± 1.7 vs. 21.3 ± 2.7, respectively. p = 0.007). The sural nerve was grafted to the BB with end-to-end neurorrhaphy under surgical microscopy in cadaver sheep. The surgical anatomy and the number of fascicles of the ovine sural nerve were similar of those reported in humans. The results suggest that the sural nerve can be successfully used for facial nerve reconstruction research in a clinically relevant ovine model.

Background: In the present study, we investigated whether blink synkinesis monitoring during microvascular decompression (MVD) is effective for predicting long-term outcomes in patients with hemifacial spasm (HFS)., Methods: This retrospective study included 69 patients who had undergone MVD for HFS at a tertiary hospital. All patients underwent intraoperative monitoring of blink synkinesis, lateral spread responses (LSRs), and facial nerve motor-evoked potentials (FNMEPs). Baseline signals were compared to those obtained following decompression with Teflon, and postoperative outcomes were recorded., Results: A total of 65 patients were observed with complete relief of symptoms after 1 year after MVD, while 61 patients were observed with initial disappearance of blink synkinesis, 57 patients were observed with initial elimination of the LSR, and 45 patients with initial decreases in FNMEP amplitude (>50%). The highest sensitivity and accuracy values were observed for blink synkinesis. Chi-square tests comparing the sensitivity of the three methods revealed that FNMEP monitoring was associated with significantly lower sensitivity values than the remaining methods. Combined use of blink synkinesis and LSRs did not significantly increase sensitivity (61/65 vs 62/65) or accuracy (62/69 vs 63/69)., Conclusion: Our results demonstrate that blink synkinesis monitoring is safe during MVD for HFS. Furthermore, blink synkinesis was associated with the highest sensitivity and predictive values among the three methods evaluated. These findings suggest that blink synkinesis can be regarded as the first choice for intraoperative monitoring during MVD. Concurrent use of blink synkinesis and LSR monitoring may maximize the ability to predict patient prognosis and determine the extent of decompression.