Electrophysiological and histopathological evaluation of the effectiveness of melatonin and glatiramer acetate for traumatic facial nerve injuries.

AIM: This study aimed to evaluate the effect of systemic/local use of melatonin and glatiramer acetate on regeneration in traumatic nerve injury models. MATERIALS AND METHODS: A total of 42 male Wistar albino rats were randomly divided into 6 groups: healthy control (Group 1), injured control (Group 2), local melatonin (Group 3), systemic melatonin (Group 4), local glatiramer acetate (Group 5), and systemic glatiramer acetate (Group 6). In all groups, electromyography recordings of the facial nerve were obtained after surgery and before sacrifice, and the damaged nerve region was histopathologically examined after sacrifice. RESULTS: In the electrophysiological evaluation, the control group had the greatest decrease in amplitude and extension in latency time following surgery than the treatment groups. Furthermore, a significant decrease in the degenerative axon count, edematous areas, and fibrotic areas as well as a significant increase in axonal surface areas was observed in all the treatment groups compared with the damage control group. CONCLUSIONS: Although both glatiramer acetate and melatonin are beneficial in regeneration in traumatic facial nerve injuries, it can be concluded that systemic use of melatonin can yield more positive results than glatiramer acetate and local use of both two drugs.

Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.

Purpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM). Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes. Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05). Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.

Uptake of gadolinium and dexamethasone in rat inner ear and facial nerve using different administrations.

BACKGROUND: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. OBJECTIVES: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. MATERIALS AND METHODS: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. RESULTS: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p < .01). CONCLUSIONS: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. SIGNIFICANCE: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.

Decompression Surgery in Elderly Patients with Hemifacial Spasm Refractory to Botulinum Toxin.

BACKGROUND: Botulinum toxin is an effective treatment for hemifacial spasm in elderly patients. However, some patients do not tolerate the side effects and frequency of botulinum toxin treatments. OBJECTIVES: The purpose of this study was to evaluate the characteristics and outcomes of a cohort of elderly patients referred by neurologists for surgical decompression of the facial nerve following botulinum toxin treatment. METHODS: In a prospective cohort study, logistic regression was used to detect potential predictors of spasm-freedom after surgical decompression of the facial nerve in elderly patients that received ≤8 and >8 botulinum toxin treatments for hemifacial spasm before surgery. Age, sex, side, preoperative symptom duration, and preoperative botulinum toxin treatment were assessed as potential predictors of spasm-freedom at last follow-up. RESULTS: Of 76 elderly patients with hemifacial spasm treated with botulinum toxin and microvascular decompression, with at least 2-years of follow-up (median, 44.5 months), 84.2% were spasm-free at last follow-up. Age (P = 0.38), sex (P = 0.59), side (P = 0.15), preoperative symptom duration (P = 0.7), and number of preoperative botulinum toxin treatments (P = 0.3) were not predictors of long-term spasm-freedom. Permanent ipsilateral hearing loss was the most frequent complication (3.9%). CONCLUSION: This study provides evidence that elderly patients can undergo botulinum toxin treatment for hemifacial spasm without compromising their likelihood of achieving spasm-freedom with future surgical decompression. Therefore, surgical decompression of the facial nerve is an effective therapy for elderly patients with hemifacial spasm refractory to botulinum toxin.

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.

Is Decorin a Promising New Agent for Facial Nerve Regeneration? An Experimental Study.

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.

The pontine Kölliker-Fuse nucleus gates facial, hypoglossal, and vagal upper airway related motor activity.

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.

Nerve guidance conduit promoted peripheral nerve regeneration in rats.

Nerve growth factor (NGF) is important for peripheral nerve regeneration. However, its short half-life and rapid diffusion in body fluids limit its clinical efficacy. Collagen has favorable biocompatibility and biodegradability, and weak immunogenicity. Because it possesses an NGF binding domain, we cross-linked heparin to collagen tubes to construct nerve guidance conduits for delivering NGF. The conduits were implanted to bridge a facial nerve defect in rats. Histological and functional analyses were performed to assess the effect of the nerve guidance conduit on facial nerve regeneration. Heparin enhanced the binding of NGF to collagen while retaining its bioactivity. Also, the nerve guidance conduit significantly promoted axonal growth and Schwan cell proliferation at 12 weeks after surgery. The nerve regeneration and functional recovery outcomes using the nerve guidance conduit were similar to those of autologous nerve grafting. Therefore, the nerve guidance conduit may promote safer nerve regeneration.

The presence of herpes simplex-1 and varicella zoster viruses is not related with clinical outcome of Bell's Palsy.

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.

The effect of insulin-like growth factor 1 on the recovery of facial nerve function in a guinea pig model of facial palsy.

The efficacy of insulin-like growth factor 1 (IGF-1) in the treatment of peripheral facial nerve palsy was investigated using an animal model. The facial nerve within the temporal bone was exposed and compressed by clamping. The animals were treated with either IGF-1 or saline which was topically administered by a gelatin-based sustained-release hydrogel via an intratemporal route. The recovery from facial nerve palsy was evaluated at 8 weeks postoperatively based on eyelid closure, complete recovery rate, electroneurography and number of axons found on the facial nerve. IGF-1 treatment resulted in significant improvement in the changes of the degree of eyelid closure over the total time period and complete recovery rate. A separate study showed that IGF-1 receptor mRNA was expressed in facial nerves up to 14 days after the nerve-clamping procedure. IGF-1 was thus found to be effective in the treatment of peripheral facial nerve palsy when topically applied using a sustained-release gelatin-based hydrogel via an intratemporal route.

Distinct neurotoxic effects of select local anesthetics on facial nerve injury and recovery.

BACKGROUND: Local anesthetic toxicity has been well-documented to cause neuronal injury, death, and dysfunction, particularly in a susceptible nerve. OBJECTIVE: To determine whether select local anesthetics affect neuron survival and/or functional recovery of an injured nerve. METHODS: This report describes 6 separate experiments that test immediate or delayed application of local anesthetics in 3 nerve injury models. Adult C57/black6 male mice underwent a facial nerve sham, transection, or crush injury. Local anesthetic or saline was applied to the facial nerve at the time of injury (immediate) or 1 day after injury (delayed). Average percent facial motoneuron (FMN) survival was evaluated four-weeks after injury. Facial nerve regeneration was estimated by observing functional recovery of eye blink reflex and vibrissae movement after facial nerve crush injury. RESULTS: FMN survival after: transection + immediate treatment with ropivacaine (54.8%), bupivacaine (63.2%), or tetracaine (66.9%) was lower than saline (85.5%) and liposomal bupivacaine (85.0%); crush + immediate treatment with bupivacaine (92.8%) was lower than saline (100.7%) and liposomal bupivacaine (99.3%); sham + delayed treatment with bupivacaine (89.9%) was lower than saline (96.6%) and lidocaine (99.5%); transection + delayed treatment with bupivacaine (67.3%) was lower than saline (78.4%) and liposomal bupivacaine (77.6%); crush + delayed treatment with bupivacaine (85.3%) was lower than saline (97.9%) and lidocaine (96.0%). The average post-operative time for mice to fully recover after: crush + immediate treatment with bupivacaine (12.83 days) was longer than saline (11.08 days) and lidocaine (10.92 days); crush + delayed treatment with bupivacaine (16.79 days) was longer than saline (12.73 days) and lidocaine (11.14 days). CONCLUSIONS: Our data demonstrate that some local anesthetics, but not all, exacerbate motoneuron death and delay functional recovery after a peripheral nerve injury. These and future results may lead to clinical strategies that decrease the risk of neural deficit following peripheral nerve blocks with local anesthetics.

Repair of facial nerve crush injury in rabbits using collagen plus basic fibroblast growth factor.

Facial nerves are frequently crushed or cut during facial surgery. In this study, the feasibility of repairing facial nerves in rabbits after crush or cut off injury was evaluated using collagen conduits with A collagen-binding domain (CBD)-human basic fibroblast growth factor (bFGF). A total of 39 six-month-old New Zealand White rabbits were randomly divided into four groups of nine rabbits, and bilateral crush or cut off injuries were made on each animal's face. Three rabbits were classified as the healthy control. The facial nerves were cut or crushed and then were either untreated or wrapped with a collagen conduit plus bFGF. At the 15, 30, and 90 days after the injury, three rabbits in each group were sacrificed. Regeneration of the injured facial nerve was evaluated using electrophysiological examination (compound muscle action potentials, CAMPs), scanning electron microscopy, and histological observation. The results suggested that using collagen conduits with recombinant proteins CBD-bFGF to repair facial nerves with crush or cut off injuries promoted functional facial nerve recovery. This treatment, as a possible therapeutic for patients with facial nerve injury, requires further investigation.

Comparison of Myelin-Associated Glycoprotein With Vincristine for Facial Nerve Inhibition After Bilateral Axotomy in a Transgenic Thy1-Gfp Rat Model.

IMPORTANCE: Aberrant synkinetic movement after facial nerve injury can lead to prominent facial asymmetry and resultant psychological distress. The current practices of neuroinhibition to promote greater facial symmetry are often temporary in nature and require repeated procedures. OBJECTIVE: To determine whether myelin-associated glycoprotein (MAG), a specific neuroinhibitor, can prevent neuroregeneration with efficacy comparable with that of vincristine, a well-established neurotoxin. DESIGN, SETTING, AND PARTICIPANTS: Rats transgenic for Thy-1 cell surface antigen-green fluorescent protein (Thy1-Gfp) were randomized into 3 groups. Each rat received bilateral crush axotomy injuries to the buccal and marginal mandibular branches of the facial nerves. The animals received intraneural injection of saline, MAG, or vincristine. MAIN OUTCOMES AND MEASURES: The animals were imaged via fluorescent microscopy at weeks 1, 3, 4, and 5 after surgery. Quantitative fluorescent data were generated as mean intensities of nerve segments proximal and distal to the axotomy site. Electrophysiological analysis, via measurement of compound muscle action potentials, was performed at weeks 0, 3, 4, and 5 after surgery. RESULTS: A total of 12 rats were included in the study. Administration of MAG significantly reduced fluorescent intensity of the distal nerve in comparison with the control group at week 3 (mean [SD], MAG group: 94 [11] intensity units vs control group: 130 [11] intensity units; P < .001), week 4 (MAG group: 81 [19] intensity units vs control group: 103 [9] intensity units; P = .004), and week 5 (MAG group: 76 [10] intensity units vs control group: 94 [10] intensity units; P < .001). In addition, rats treated with MAG had greater fluorescent intensity than those treated with vincristine at week 3 (mean [SD], MAG group: 94 [11] intensity units vs vincristine group: 76 [6] intensity units; P = .03), although there was no significant difference for weeks 4 and 5. At week 5, both MAG and vincristine demonstrated lower distal nerve to proximal nerve intensity ratios than the control group (control group, 0.94; vs MAG group, 0.82; P = .01; vs vincristine group; 0.77; P < .001). There was no significant difference in amplitude between the experimental groups at week 5 of electrophysiological testing. CONCLUSIONS AND RELEVANCE: Lower facial asymmetry and synkinesis are common persistent concerns to patients after facial nerve injury. Using the Thy1-Gfp rat, this study demonstrates effective inhibition of neuroregeneration via intraneural application of MAG in a crush axotomy model, comparable with results with vincristine. By potentially avoiding systemic toxic effects of vincristine, MAG demonstrates potential as an inhibitor of neural regeneration for patients with synkinesis. LEVEL OF EVIDENCE: NA.

Peripheral Nerve Block Efficacy on Refractory Neuralgia Complicating Ramsay Hunt Syndrome: A Case Report.

Several case studies have suggested the usefulness of peripheral nerve blocks in the management of various types of chronic pain that are unresponsive to standard medical treatment. We report here the case of a patient with severe neuralgia, secondary to Ramsay Hunt syndrome that was refractory to standard drug therapy. As a last resort, a block of the terminal branches of nervus intermedius was performed. Despite transient facial paralysis, pain was markedly reduced for 3 months with self-reported improved quality of life. To our knowledge, this block has never been described previously.

Electrophysiologic evaluation of facial nerve functions after oxaliplatin treatment.

PURPOSE: This study analyzes the effect of oxaliplatin treatment on the facial nerve. The facial nerve is the most commonly paralyzed cranial motor nerve because it advances through a long, curved bone canal. Electroneurography and blink reflex are the electrophysiological measurements used for evaluating facial nerve function. Oxaliplatin is a cytotoxic agent used in adjuvant or palliative systemic therapy for colorectal cancer treatment. METHODS: This study was performed on 20 individuals who were at least 18 years old at Hacettepe University Ear Nose Throat Department, Audiology and Speech Disorders Unit, and Neurology Division EMG Laboratory as they received oxaliplatin treatment from Hacettepe University Oncology Hospital. Electroneurography and blink-reflex values were recorded and examined. The parameters taken during the second and fourth months were compared for this purpose. RESULTS: This study shows that the prolongation of distal latencies of compound muscle action potential is statistically significant, the amplitudes showed no difference. The ENoG results were analyzed, the prolongation of latency measurements between pre-treatment and the fourth month after treatment were statistically significant. The blink-reflex results showed that comparison with the baseline values, the prolongation of latencies in R1 measurements between pre-treatment, the second month, and the fourth month were significant. CONCLUSIONS: The facial nerve is affected asymptomatically by oxaliplatin treatment. During oxaliplatin treatment, the evaluation of facial nerve function could be beneficial for patients by improving their quality of life. Electroneurography and blink-reflex tests can be used in the early evaluations of different medicines to determine their neurotoxicity.

Effects of Melatonin and Dexamethasone on Facial Nerve Neurorrhaphy.

OBJECTIVES: To investigate the effects of topical and systemic administrations of melatonin and dexamethasone on facial nerve regeneration. MATERIALS AND METHODS: In total, 50 male albino Wistar rats underwent facial nerve axotomy and neurorrhaphy. The animals were divided into 5 groups: control, topical melatonin, systemic melatonin, topical dexamethasone, and systemic dexamethasone. Nerve conduction studies were performed preoperatively and at 3, 6, 9, and 12 weeks after drug administrations. Amplitude and latency of the compound muscle action potentials were recorded. Coapted facial nerves were investigated under light and electron microscopy. Nerve diameter, axon diameter, and myelin thickness were recorded quantitatively. RESULTS: Amplitudes decreased and latencies increased in both the melatonin and dexamethasone groups. At the final examination, the electrophysiological evidence of facial nerve degeneration was not significantly different between the groups. Histopathological examinations revealed the largest nerve diameter in the melatonin groups, followed by the dexamethasone and control groups (p<0.05). Axon diameter of the control group was smaller than those of the melatonin (topical and systemic) and topical dexamethasone groups (p<0.05). The melatonin groups had almost normal myelin ultrastructure. CONCLUSION: Electrophysiological evaluation did not reveal any potential benefit of dexamethasone and melatonin in contrast to histopathological examination, which revealed beneficial effects of melatonin in particular. These agents may increase the regeneration of facial nerves, but electrophysiological evidence of regeneration may appear later.

Transplantation of Olfactory Stem Cells with Biodegradable Hydrogel Accelerates Facial Nerve Regeneration After Crush Injury.

Olfactory mucosa contains neural stem cells, called olfactory stem cells (OSCs), which produce trophic support required for promoting axonal regeneration after nerve injury. However, the local tissue environment can reduce the viability/function of transplanted cells when placed directly on the injury. Although gelatin hydrogels have been shown to aid cell survival during transplantation, such OSC-hydrogel combinations have not been extensively tested, particularly during recovery from facial nerve palsy. In this study, OSCs were isolated from the olfactory mucosae of newborn mice and were shown to express neural stem cell markers before differentiation, as well as cell-type specific markers after differentiation, confirming their multipotency. The OSCs also secrete growth factors and various cytokines that promote nerve regeneration. To test the effects of OSC transplantation in vivo, Medgel, a biodegradable hydrogel sponge, was applied to retain OSCs around the injury site and to lessen the detrimental effects of the local environment in an established facial nerve palsy mouse model. When OSCs were transplanted into the injury site, accelerated recovery was observed for 1 week. When OSCs were transplanted with Medgel, a higher level and duration of accelerated recovery was observed. OSCs in Medgel also increased peripheral nerve function and increased the number of regenerated nerve fibers. These results suggest that OSCs implanted with Medgel accelerate and enhance recovery from facial palsy in mice. Because human OSCs can be easily obtained from olfactory mucosa biopsies with limited risk, this OSC-Medgel combination is a candidate treatment option for accelerating recovery after facial nerve injury. Stem Cells Translational Medicine 2019;8:169&10.

CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathway.

Facial nerve injury is a clinically common disease accompanied by demyelination of damaged nerves. The remyelination of damaged nerves and the unsatisfactory function recovery are problems that have been plaguing people for a long time. The role that CXCL12 plays after facial nerve injury remains unknown. Our experiments found that the expression of CXCL12 was up-regulated in the early stage of facial nerve injury and decreased after two weeks. Further research found that CXCL12 had no effect on Schwann cells proliferation, apoptosis and cell cycle, while significantly promoted Schwann cells migration. Treatment with CXCL12 decreased the phosphorylation of PI3K, AKT and mTOR, but increased autophagy marker LC3II/I. The CXCL12-induced Schwann cells migration was significantly attenuated by inhibition of autophagy and activation of PI3K pathway through pretreatment with 3-MA and IGF-1 respectively, and this effect was enhanced by PI3K pathway inhibitor LY294002. Animal experiment also confirmed that CXCL12 could improve facial nerve function and myelin regeneration. The findings of this study indicate that CXCL12 can promote the migration of Schwann cells and potentially become a key molecule in the repair of facial nerve injury.