Extracranial transport of brain lymphatics via cranial nerve in human.

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.

[A sampling survey of intraoperative facial nerve monitoring in China].

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.

Predictive value of facial motor-evoked potential and electromyography for facial motor function in vestibular schwannoma surgery.

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.

[Intraoperative Neuromonitoring in Vestibular Schwannoma Surgery].

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.

Newly identified axon types of the facial nerve unveil supplemental neural pathways in the innervation of the face.

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.

Application of intentional facial nerve stimulation during cochlear implantation as an electrophysiological tool to estimate the intracochlear electrode position.

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 (fpVCTSECO). 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.

Effect of Pre-Induced Mesenchymal Stem Cell-Coated Cellulose/Collagen Nanofibrous Nerve Conduit on Regeneration of Transected Facial Nerve.

(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.

COVID-19 can cause blink reflex abnormalities.

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.

Relationship between toll-like receptor expression in the distal facial nerve and facial nerve recovery after injury.

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.

The effect of charge-balanced transcutaneous electrical nerve stimulation on rodent facial nerve regeneration.

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-1ß 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.

Photobiomodulation enhances facial nerve regeneration via activation of PI3K/Akt signaling pathway-mediated antioxidant response.

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.

Intraoperative Neuromonitoring of Blink Reflex During Posterior Fossa Surgeries and Its Correlation With Clinical Outcome.

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.

Facial Nerve Repair: Bioengineering Approaches in Preclinical Models.

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.

Improving intraoperative evoked potentials at short latency by a novel neuro-stimulation technology with delayed return discharge.

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.

Surgical management of intraoperatively diagnosed facial nerve schwannoma located at internal auditory canal and cerebellopontine angle - our experiences of 14 cases.

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.

Optimizing Location of Subdermal Recording Electrodes for Intraoperative Facial Nerve Monitoring.

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.