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Correction of lower eyelid retraction is necessary to restore adequate blink in paralytic lagophthalmos. A plethora of static and dynamic surgical techniques have been described for lower eyelid repositioning. This article provides an approach to management of the paralytic lower eyelid, including a summary of existing techniques, case examples, and surgical technique for in-office lower eyelid suspension using a palmaris longus tendon graft.

(1) To compare maximum glottic opening angle (anterior glottic angle, AGA) in patients with bilateral vocal fold immobility (BVFI), unilateral vocal fold immobility (UVFI) and normal larynges (NL), and (2) to correlate maximum AGA with patient-reported outcome measures.Patients wisth BVFI, UVFI, and NL were retrospectively studied. An open-source deep learning-based computer vision tool for vocal fold tracking was used to analyze videolaryngoscopy. Minimum and maximum AGA were calculated and correlated with three patient-reported outcomes measures.Two hundred and fourteen patients were included. Mean maximum AGA was 29.91° (14.40° SD), 42.59° (12.37° SD), and 57.08° (11.14° SD) in BVFI (N = 70), UVFI (N = 70), and NL (N = 72) groups, respectively (p 0.001). Patients requiring operative airway intervention for BVFI had an average maximum AGA of 24.94° (10.66° SD), statistically different from those not requiring intervention (p = 0.0001). There was moderate negative correlation between Dyspnea Index scores and AGA (Spearman r = -0.345, p = 0.0003). Maximum AGA demonstrated high discriminatory ability for BVFI diagnosis (AUC 0.92, 95% CI 0.81-0.97, p 0.001) and moderate ability to predict need for operative airway intervention (AUC 0.77, 95% CI 0.64-0.89, p 0.001).A computer vision tool for quantitative assessment of the AGA from videolaryngoscopy demonstrated ability to discriminate between patients with BVFI, UVFI, and normal controls and predict need for operative airway intervention. This tool may be useful for assessment of other neurological laryngeal conditions and may help guide decision-making in laryngeal surgery.III Laryngoscope, 2022.

BACKGROUND Common donor nerve options in smile reanimation include ipsilateral trigeminal motor or contralateral facial nerve branches. Neurotization preference may be influenced by multiple factors, whose relative importance remains poorly understood. In this article, decision-making in smile reanimation is assessed using a stated preference model. METHODS Qualitative interviews with facial palsy patients identified five relevant attributes for study: smile type ("smile when biting" versus "smile spontaneously" as proxies for trigeminal versus cross-facial neurotization), number of operations, success rates, complication rates, and side effects. Community volunteers (n = 250) completed a discrete-choice experiment relevant to free muscle transfer for smile reanimation. Preoperative and postoperative states were demonstrated through video vignettes, together with explanation of surgical risks, consequences, and benefits. Attribute importance was modeled using hierarchical Bayes estimation. RESULTS Two hundred forty-one responses met quality controls. Attribute importance ranked as follows: chance of success, 37.3 percent; smile type, 21.4 percent; side effects, 13.9 percent; complication rates, 13.8; and number of operations, 13.6 percent. All attributes significantly correlated with decision making (p < 0.0001). An aggregate response model revealed most participants (67.6 percent; standard error, 3.0 percent) preferred smile reanimation by cross-facial (assuming a success rate of 80 percent) as opposed to ipsilateral trigeminal motor branch neurotization. When the success rate for cross-facial neurotization was reduced below 67 percent, trigeminal neurotization was preferred. CONCLUSIONS Despite a higher risk of failure, most respondents preferred a cross-facial as opposed to trigeminal neurotization strategy for smile reanimation. These findings highlight the complexity of decision-making and need for individualized risk tolerance assessment in the field of facial reanimation.

Outcomes following free gracilis muscle transfer have steadily improved during the past decade. Areas for continued improvement include re-creating natural smile vectors, improving midface symmetry, minimizing scarring, improving spontaneity, and increasing reliability using various neural sources. Outcome standardization, pooled data collection, and remote data acquisition methods will facilitate comparative effectiveness research and continued surgical advancements.

Background: Recreation of a spontaneous, emotional smile remains a paramount goal of smile reanimation surgery. However, optimal techniques to reliably restore spontaneity remain unknown. Dual automated machine-learning tools were used to develop an objective tool to analyze spontaneous smiling. The feasibility of this tool was tested in a sample of functional free muscle transfers. Methods: Validated humorous videos were used to elicit spontaneous smiles. Automated facial landmark recognition (Emotrics) and emotion detection software (Affdex) were used to analyze video clips of spontaneous smiling in nine normal subjects and 39 facial reanimation cases. Emotionality quotient was used to quantify the ability of spontaneous smiles to express joy. Results: The software could analyze spontaneous smiling in all subjects. Spontaneous smiles of normal subjects exhibited median 100 percent joy and 0 percent negative emotion (emotional quotient score, +100/0). Spontaneous smiles of facial palsy patients after smile reanimation, using cross-facial nerve graft, masseteric nerve, and dual innervation, yielded median emotional quotient scores of +82/0, 0/-48, and +10/-24 respectively (joy, p = 0.006; negative emotion, p = 0.034). Conclusions: Computer vision software can objectively quantify spontaneous smiling outcomes. Of the retrospective sample of cases reviewed in this study, cross-facial nerve graft-innervated gracilis functional free muscle transfer achieved a greater degree of emotionality during spontaneous smiling than masseteric or dually innervated transfer. Quantification of spontaneous smiling from standard video clips could facilitate future, blinded, multicenter trials with sufficient long-term follow-up to definitively establish the rates of spontaneity from a range of reanimation procedures.

ObjectivesSlow-onset peripheral facial palsy is far less common than acute-onset peripheral facial palsy and necessitates diagnostic evaluation for benign or malignant tumors or other less common etiologies. In the rare scenario in which no clarifying etiology is discovered following long-term evaluation (no radiographic or hematologic abnormalities and an otherwise unremarkable evaluation), a diagnostic and management dilemma occurs. We present a series of patients with this possible new clinical entity: Facial palsy, Radiographic and Other Workup Negative (FROWN) and propose a management strategy for this diagnosis of exclusion.MethodsA series of 3,849 patients presenting with facial palsy to a tertiary facial nerve center was retrospectively assessed to identify those with progressive loss of facial function over at least 1 month. Exclusion criteria were history, physical or hematologic findings indicative of known diseases associated with facial palsy, and radiographic studies demonstrating a benign or malignant tumor.ResultsPatients with slow-onset facial palsy constituted 5% (190 patients) of the cohort and were ultimately diagnosed with either a benign or malignant neoplasm or other facial nerve pathology. Fourteen patients with slow-onset facial palsy remained without a diagnosis following long-term evaluation and serial imaging. Eleven patients underwent dynamic facial reanimation surgery and facial nerve and muscle biopsy, with no clear histopathologic diagnosis.ConclusionPatients with slow-onset facial palsy with negative radiographic and medical evaluations over several years may be characterized as having FROWN, an idiopathic and as yet poorly understood condition, which appears to be amenable to facial reanimation but requires further investigation as to its pathophysiology.

Background: Port-wine stain (PWS) is a congenital capillary malformation occurring commonly in the head and neck. Left untreated, affected areas may darken and hypertrophy over time, resulting in pronounced disfigurement, risk of spontaneous hemorrhage, and functional impairment. The burden of hypertrophic facial PWS and the benefit of laser therapy have not heretofore been well characterized. Herein, the health utility of these two states is assessed among naïve observers. Methods: Naïve observers (n = 262) ranked the utility of four randomized health states (monocular blindness, binocular blindness, hypertrophic facial PWS, and laser-treated facial PWS) by means of visual analogue scale (VAS), standard gamble (SG), and time trade-off (TTO) techniques. Health states are presented using standardized facial photographs. Results: Health utilities (VAS, SG, and TTO) were reported as follows (mean ± standard deviation): monocular blindness (0.73 ± 0.21, 0.86 ± 0.21, 0.87 ± 0.18), binocular blindness (0.51 ± 0.26, 0.72 ± 0.27, 0.69 ± 0.27), hypertrophic facial PWS (0.71 ± 0.24, 0.83 ± 0.23, 0.83 ± 0.21), and laser-treated facial PWS (0.87 ± 0.16, 0.91 ± 0.18, 0.92 ± 0.16). Laser-treated facial PWS showed significantly higher utility measures than the untreated hypertrophic state (p

The lower lip serves pivotal functional and aesthetic roles in the face. Palsy of lower lip musculature may result in oral incompetence, articulation difficulties, and impairment of facial expression. Loss of lower lip sensation may result in unrecognized trauma, sialorrhea, and social embarrassment. Herein, we review therapeutic approaches to lower lip reanimation and sensory neurotization.

Importance: Machine learning (ML) approaches to facial landmark localization carry great clinical potential for quantitative assessment of facial function as they enable high-throughput automated quantification of relevant facial metrics from photographs. However, translation from research settings to clinical applications requires important improvements. Objective: To develop an ML algorithm for accurate facial landmarks localization in photographs of facial palsy patients, and use it as part of an automated computer-aided diagnosis system. Design, Setting, and Participants: Facial landmarks were manually localized in portrait photographs of eight expressions obtained from 200 facial palsy patients and 10 controls. A novel ML model for automated facial landmark localization was trained using this disease-specific database. Model output was compared to manual annotations and the output of a model trained using a larger database consisting only of healthy subjects. Model accuracy was evaluated by the normalized root mean square error (NRMSE) between algorithms' prediction and manual annotations. Results: Publicly available algorithms provide poor results when applied to patients compared to healthy controls (NRMSE, 8.56 +/- 2.16 vs. 7.09 +/- 2.34, p << 0.01). We found significant improvement in facial landmark localization accuracy for the clinical population when using a model trained with a relatively small number patients' photographs (1440) compared to a model trained using several thousand more images of healthy faces (NRMSE, 6.03 +/- 2.43 vs. 8.56 +/- 2.16, p << 0.01). Conclusions: Retraining a landmark detection model with a small number of clinical images significantly improved landmark detection performance in frontal view photographs of the clinical population. These results represent the first steps towards an automatic system for computer-aided assessment in facial palsy., 21 pages, 4 figures, 1 table

Multiphoton microscopy (MPM) employs ultrafast infrared lasers for high-resolution deep three-dimensional imaging of live biological samples. The goal of this tutorial is to provide a practical guide to MPM imaging for novice microscopy developers and life-science users. Principles of MPM, microscope setup, and labeling strategies are discussed. Use of MPM to achieve unprecedented imaging depth of whole mounted explants and intravital imaging via implantable glass windows of the mammalian nervous system is demonstrated.

Objectives Advanced nasal malignancies may require rhinectomy, which can have profound psychosocial impacts. Rhinectomy defects can be rehabilitated through surgery or prosthetics. We seek to understand the health utility of the rhinectomy defect, surgical, and prosthetic reconstruction, which have not been previously studied. Study Design Prospective clinical study Methods Adult naive observers (n = 273) ranked the utility of five randomized health states (monocular blindness, binocular blindness, post-rhinectomy nasal defect, postsurgical reconstruction, and post-prosthetic rehabilitation). Health utilities were measured using visual analogue scale (VAS), standard gamble (SG), and time trade-off (TTO). One-way analysis of variance (ANOVA) with post hoc Scheffe's test and the independent samples T-test for a priori comparisons were performed. Multiple linear regression was performed using participant demographics as independent predictors of utility scores. Results Health utilities (VAS, SG, TTO) were reported as follows (mean +/- SD): monocular blindness (0.71 +/- 0.21, 0.84 +/- 0.20, 0.85 +/- 0.19), binocular blindness (0.48 +/- 0.25, 0.68 +/- 0.28, 0.63 +/- 0.28), post-rhinectomy nasal defect (0.59 +/- 0.24, 0.74 +/- 0.24, 0.74 +/- 0.24), postsurgical reconstruction (0.88 +/- 0.16, 0.90 +/- 0.18, 0.89 +/- 0.13), and post-prosthetic rehabilitation (0.67 +/- 0.22, 0.80 +/- 0.23, 0.82 +/- 0.20). Both surgical reconstruction (P < .001) and prosthetic rehabilitation (P < .001) significantly improved health utility. SG and TTO utility scores were inversely associated with observer age (P < .001) and participants who identified themselves as non-Caucasians (P < .05) in post-rhinectomy nasal defect, post-nasal surgical reconstruction, and post-nasal prosthetic rehabilitation health states, while higher levels of education were directly associated with SG scores (P < .05), respectively. Conclusion This is the first study to demonstrate the significant negative impact of the rhinectomy nasal defect on health utility. Rehabilitation by surgical or prosthetic techniques significantly increases health utility as rated by naive observers. Laryngoscope, 2019

Significance: Means for quantitation of myelinated fibers in peripheral nerve may guide diagnosis and clinical decision making in management of peripheral nerve disorders. Multiphoton microscopy techniques such as the third-harmonic generation enable label-free in vivo imaging of peripheral nerves. Aim: Develop a multiphoton microscope based on a custom high-power infrared fiber laser for label-free imaging of peripheral nerve. Approach: A cost-effective multiphoton microscope employing a single fiber laser source at 1300 nm was designed and used for stain-free multicolor imaging of murine and human peripheral nerve. Results: Second-harmonic generation signal from collagen centered about 650-nm delineated neural connective tissue, whereas third-harmonic general signal centered about 433-nm delineated myelin and other lipids. In sciatic nerve from transgenic reporter mice expressing yellow fluorescent protein within peripheral neurons, three-photon-excitation with emission peak at 527-nm delineated axoplasm. The signal obtained from unlabeled axially sectioned samples was adequate for segmentation of myelinated fibers using commercial image processing software. In unlabeled whole mount specimens, imaging depths over 100-mu m were achieved. Conclusions: A multiphoton microscope powered by a fiber laser enables stain-free histomorphometry of mammalian peripheral nerve. The simplicity of the microscope design carries potential for clinical translation to inform decision making in peripheral nerve disorders. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License.

Conventional histomorphometry of peripheral nerve entails lengthy chemical processing, ultrathin sectioning in resin, and imaging by light or electron microscopy. Multiphoton microscopy techniques exist enabling label-free and in vivo imaging of histological samples. Third-harmonic-generation microscopy has recently been demonstrated effective for imaging the myelin sheath of peripheral nerve axons in animal models. Herein, we characterize use of second and third harmonic generation microscopy for label-free imaging of murine and human peripheral nerve via a novel multicolor multiphoton microscope based on a single excitation wavelength at 1300 nm. Second harmonic generation signal from collagen centered about 650 nm delineates neural connective tissue, while third harmonic general signal centered about 433 nm delineates myelin and other lipids. In transgenic mice expressing yellow fluorescent protein linked to the thy1 promoter, three-photon-excitation with emission peak at 527 nm delineates axoplasm. We compare label-free multiphoton imaging of murine and human peripheral nerve against conventional chemical stains and discuss clinical implications of this approach in guiding intraoperative decision making in nerve transfer procedures.

Peripheral nerve injuries yield devastating consequences, and surgical repair outcomes remain suboptimal. Novel therapeutic strategies such as gene therapy could improve peripheral nerve regeneration. Though adeno-associated virus (AAV) vectors have delivered transgenes to intact peripheral neurons, transduction of transected neurons relevant to management of peripheral nerve injuries has not been reported. Herein, in vivo transduction efficiency of axotomized murine facial neurons using four AAV capsids packaging a fluorescent reporter transgene, tdTomato, is characterized. Proximal stumps of transected facial nerve branches in C57Bl/6J mice were immersed in AAV solutions. Four weeks later, facial motor nuclei were volume-imaged via whole-mount two-photon excitation microscopy, and machine learning-based image segmentation quantified the proportion of transgene expressing neurons. We observed remarkable retrograde transduction efficiency with AAV-PHP.S and AAV-F, with expression levels sufficient to detect intrinsic tdTomato fluorescence. This study confirms successful in vivo retrograde transgene delivery to transected peripheral neurons, an approach that carries potential as a research tool and future therapeutic strategy.

Trigeminal anesthesia may yield blindness and facial disfigurement, secondary to neurotrophic keratopathy and trigeminal trophic syndrome. This article summarizes contemporary medical and emerging surgical approaches for the therapeutic management of this rare and devastating disease state.

Purpose of review Trigeminal anesthesia causes neurotrophic keratopathy, which may yield facial disfigurement and corneal blindness. Recent findings We summarize approaches and evidence for corneal neurotization. Summary Regional sensory nerve transfer appears safe and effective for therapeutic management of neurotrophic keratopathy. Prospective randomized clinical trials are necessary to confirm the utility of corneal neurotization.

Background:The ansa cervicalis is useful for cranial nerve repair, and may be harvested without apparent morbidity. Herein we report an unusual and surgically relevant anatomic variant of the ansa cervicalis.Methods:An adult male with left parotid adenoid cystic carcinoma underwent parotidectomy with upper-division facial nerve resection and planned interposition repair using the ansa cervicalis. The ipsilateral hypoglossal nerve was identified, together with a descending branch producing strap muscle contraction when stimulated. This presumed descendens hypoglossi was unusually large in caliber; further dissection revealed continuity with the vagus nerve.Results:Ansa cervicalis harvest was aborted when its separation from vagus nerve epineurium was not possible. The sural nerve was alternatively harvested. The patient awoke with left vocal fold palsy, which completely resolved within 3 months.Conclusion:Anatomic variants of the ansa cervicalis exist that may preclude graft harvest and place the vagus nerve at risk of inadvertent injury.

Background: Tools to quantify layperson assessments of facial palsy are lacking. In this study, artificial intelligence was applied to develop a proxy for layperson assessments, and compare sensitivity to existing outcome measures.Methods: Artificially intelligent emotion detection software was used to develop the emotionality quotient. The emotionality quotient was defined as the percentage probability of perceived joy over the percentage probability of perceived negative emotions during smiling, as predicted by the software. The emotionality quotient was used to analyze the emotionality of voluntary smiles of normal subjects and unilateral facial palsy patients before and after smile reanimation. The emotionality quotient was compared to oral commissure excursion and layperson assessments of facial palsy patients.Results: In voluntary smiles of 10 normal subjects, 100 percent joy and no negative emotion was detected (interquartile ranges, 0/1). Median preoperative emotionality quotient of 30 facial palsy patients was 15/-60 (interquartile range, 73/62). Postoperatively, median emotionality quotient was 84/0 (interquartile range, 28/5). In 134 smile reanimation patients, no correlation was found between postoperative oral commissure excursion and emotionality quotient score. However, in 61 preoperative patients, a moderate correlation was found between layperson-assessed disfigurement and negative emotion perception (correlation coefficient, 0.516; p Conclusions: Computer vision artificial intelligence software detected less joy and more negative emotion in smiles of facial palsy patients compared with normal subjects. Following smile reanimation, significantly more joy and less negative emotion were detected. The emotionality quotient was correlated with layperson assessments. The simplicity, sensitivity, and objectivity of the emotionality quotient render it an attractive tool to serve as a potential proxy for layperson assessment, an ideal outcome measure in facial palsy.

OBJECTIVES Facial palsy causes variable facial disfigurement ranging from subtle asymmetry to crippling deformity. There is no existing standard database to serve as a resource for facial palsy education and research. We present a standardized set of facial photographs and videos representing the entire spectrum of flaccid and nonflaccid (aberrantly regenerated or synkinetic) facial palsy. To demonstrate the utility of the dataset, we describe the relationship between level of facial function and perceived emotion expression as determined by an automated emotion detection, machine learning-based algorithm. METHODS Photographs and videos of patients with both flaccid and nonflaccid facial palsy were prospectively gathered. The degree of facial palsy was quantified using eFACE, House-Brackmann, and Sunnybrook scales. Perceived emotion during a standard video of facial movements was determined using an automated, machine learning algorithm. RESULTS Sixty participants were enrolled and categorized by eFACE score across the range of facial function. Patients with complete flaccid facial palsy (eFACE

BACKGROUND Donor nerve myelinated axon counts correlate with functional outcomes in reanimation procedures; however, there exists no reliable means for their intraoperative quantification. In this article, the authors report a novel protocol for rapid quantification of myelinated axons from frozen sections, and demonstrate its applicability to surgical practice. METHODS The impact of various fixation and FluoroMyelin Red staining strategies on resolved myelin sheath morphology from cryosections of rat and rabbit femoral and sciatic nerves was assessed. A protocol comprising fresh cryosection and rapid staining was developed, and histomorphometric results were compared against conventional osmium-postfixed, resin-embedded, toluidine blue-stained sections of rat sciatic nerve. The rapid protocol was applied for intraoperative quantification of donor nerve myelinated axon count in a cross-facial nerve grafting procedure. RESULTS Resolution of myelinated axon morphology suitable for counting was realized within 10 minutes of tissue harvest. Although mean myelinated axon diameter appeared larger using the rapid fresh-frozen as compared to conventional nerve processing techniques (mean ± SD; rapid, 9.25 ± 0.62 μm; conventional, 6.05 ± 0.71 μm; p < 0.001), no difference in axon counts was observed on high-power fields (rapid, 429.42 ± 49.32; conventional, 460.32 ± 69.96; p = 0.277). Whole nerve myelinated axon counts using the rapid protocol herein (8435.12 ± 1329.72) were similar to prior reports using conventional osmium processing of rat sciatic nerve. CONCLUSIONS A rapid protocol for quantification of myelinated axon counts from peripheral nerves using widely available equipment and techniques has been described, rendering possible intraoperative assessment of donor nerve suitability for reanimation.

Traditional histopathologic evaluation of peripheral nerve using brightfield microscopy is resource-intensive, necessitating complex sample preparation. Label-free imaging techniques paired with artificial intelligence-based image reconstruction and segmentation may facilitate peripheral nerve histomorphometry.Herein, the utility of label-free phase contrast techniques paired with artificial intelligence-based image processing for imaging of mammalian peripheral nerve is demonstrated.Fresh frozen murine sciatic nerve sections were imaged in transmission modalities using differential interference and phase contrast microscopy and in epifluorescent modality following staining with myelin-specific dye. Deep learning was employed to predict epifluorescent images from transmitted phase contrast images, and machine learning employed for automated segmentation of myelinated axons for reporting of axons counts and g-ratios.Conventional peripheral nerve histomorphometry employs resource intensive resin embedding, ultra-microtome sectioning, and staining steps. Herein we demonstrate feasibility of high-throughput nerve histomorphometry via label-free phase contrast imaging of frozen sections.Clinical applications of label-free phase contrast microscopy paired with deep learning algorithms are discussed.

Management of facial palsy can be daunting. This article presents a conceptual framework for classification and therapeutic management of facial palsy.

Fluoro-Gold is a fluorescent neuronal tracer suitable for targeted deep imaging of the nervous system. Widefield fluorescence microscopy enables visualization of Fluoro-Gold, but lacks depth discrimination. Though scanning laser confocal microscopy yields volumetric data, imaging depth is limited, and optimal single-photon excitation of Fluoro-Gold requires an unconventional ultraviolet excitation line. Two-photon excitation microscopy employs ultrafast pulsed infrared lasers to image fluorophores at high-resolution at unparalleled depths in opaque tissue. Deep imaging of Fluoro-Gold-labeled neurons carries potential to advance understanding of the central and peripheral nervous systems, yet its two-photon spectral and temporal properties remain uncharacterized. Herein, we report the two-photon excitation spectrum of Fluoro-Gold between 720 and 990 nm, and its fluorescence decay rate in aqueous solution and murine brainstem tissue. We demonstrate unprecedented imaging depth of whole-mounted murine brainstem via two-photon excitation microscopy of Fluoro-Gold labeled facial motor nuclei. Optimal two-photon excitation of Fluoro-Gold within microscope tuning range occurred at 720 nm, while maximum lifetime contrast was observed at 760 nm with mean fluorescence lifetime of 1.4 ns. Whole-mount brainstem explants were readily imaged to depths in excess of 450 µm via immersion in refractive-index matching solution.

Traditional histopathologic evaluation of peripheral nerve employs brightfield microscopy with diffraction limited resolution of ~ 250 nm. Though electron microscopy yields nanoscale resolution of the nervous system, it is resource-intensive and incompatible with life. Super-resolution microscopy (SRM) comprises a set of imaging techniques permitting unprecedented resolution of fluorescent objects using visible light. The advent of SRM has transformed biomedical science in establishing non-toxic means for investigation of nanoscale cellular structures. Herein, sciatic nerve sections from GFP-variant expressing mice, and regenerating human nerve from cross-facial autografts labelled with a myelin-specific fluorescent dye were imaged by super-resolution radial fluctuation microscopy, stimulated emission depletion microscopy, and structured illumination microscopy. Super-resolution imaging of axial cryosections of murine sciatic nerves demonstrated robust visualization of myelinated and unmyelinated axons. Super-resolution imaging of axial cryosections of human cross-facial nerve grafts demonstrated enhanced resolution of small-calibre thinly-myelinated regenerating motor axons. The utility of SRM in imaging of mammalian cranial and peripheral nerves is demonstrated. The increase in contrast and structural clarity achievable with super-resolution techniques enables visualization of unmyelinated axons, regenerating axons, cytoskeleton ultrastructure, and neuronal appendages using light microscopes.

Background/aim Picosecond infrared laser (PIRL) was investigated regarding its possible therapeutic application in cutting dental roots. Materials and methods Extracted human teeth were processed in the root area by laser ablations followed by histological evaluation. Dentin adjacent to the cutting surface was evaluated morphometrically. Results PIRL produced clearly defined cutting boundaries in dental roots. At the bottom of the cavity, the ablation surface became slightly concave. Heat development in this scantly hydrated tissue was considerable. We attributed the excess heating effects to heat accumulation due to multiple pulse overlap across a limited scan range imposed by tooth geometries. Conclusion Defined areas of the tooth root may be treated using the PIRL. For clinical translation, it would be necessary to improve beam delivery to facilitate beam steering for the intended oral application (e.g. by using a fiber) and identify optimal repetition rates/scan speeds combined with cooling techniques to minimize accumulated heat within ablation cavities.

Creation of symmetrical nasolabial folds (NLFs) is important in the management of the paralyzed face. Established techniques use a linear incision in the NLF, and technical refinements now allow the linear incision to be omitted.This retrospective case series was conducted in a tertiary care setting from February 2, 2017, to June 7, 2017. Participants were all patients (N = 21) with peripheral facial paralysis who underwent NLF modification that used the minimal nasolabial incision technique at the Massachusetts Eye and Ear Infirmary Facial Nerve Center from February 1, 2015, through August 31, 2016.Patient-reported outcome measures using the validated, quality-of-life Facial Clinimetric Evaluation (FaCE) Scale; clinician-reported facial function outcomes using a validated electronic clinician-graded facial paralysis assessment (eFACE); layperson assessment of the overall aesthetic outcome of the NLF; and expert-clinician scar assessment of the NLF.Of the 21 patients who underwent NLF modification that used the minimal nasolabial incision technique, 9 patients (43%) were female and 12 (57%) were male. The mean age was 41 (range, 9-90) years; 17 patients (81%) were adults (≥18 years) and 4 (19%) were children (18 years). Overall, significant improvements were observed after NLF modification in all outcome measures as graded by both clinicians and patients. The mean (SD) scores for total eFACE were 60.7 (14.9) before the operation and 77.2 (8.9) after the operation (mean difference, 16.5 [95% CI, 8.5-24.2]; P .001). The mean (SD) static eFACE scores were 61.4 (20.6) before the operation and 82.7 (12.4) after the operation (mean difference, 21.3 [95% CI, 10.7-31.9]; P .001). The mean (SD) FaCE quality-of-life scores were 51.3 (20.1) before the operation and 70.3 (12.6) after the operation (mean difference, 19.0 [95% CI, 6.5-31.6]; P = .001). The layperson self-assessment of the overall aesthetic outcome of the NLF modification was higher among the group who had the minimal nasolabial incision than it was for the group who had a historical nasolabial incision (mean [SD], 68.17 [13.59] vs 56.28 [13.60]; mean difference, 11.89 [95% CI, 3.81-19.97]; P .001). Similarly, the expert-clinician scar assessment of the NLF modification was higher for the group who had the minimal nasolabial incision than it was for the group who had a historical nasolabial incision (3.78 [0.91] vs 2.98 [0.81]; mean difference, 0.80 [95% CI, 0.29-1.32]; P = .007).The minimal nasolabial incision technique for NLF modification is effective in rehabilitating the NLF in facial paralysis without adding a long linear scar to the central midface.4.

Though unmyelinated fibers predominate axon counts within peripheral nerves, they are frequently excluded in histomorphometric assessment as they cannot be readily resolved by light microscopy. Herein, we demonstrate stain-free resolution of unmyelinated axons in Sox10-Venus mice by widefield fluorescence imaging of sciatic nerve cryosections. Optional staining of cryosections using a rapid and nontoxic myelin-specific dye (FluoroMyelin Red) enables robust synchronous resolution of myelinated and unmyelinated fibers, comprising a high-throughput platform for neural histomorphometry.

Use of a robust high-resolution instrument for grading of facial symmetry would enhance reporting the outcomes of facial reanimation interventions. The eFACE is one such tool.To determine test-retest reliability of the eFACE tool over time and agreement between eFACE assessments made in person vs those made using video of facial mimetic function.A prospective observational study was conducted among 75 consecutive patients with varying degrees of facial palsy who presented between July 1 and December 31, 2014, to an academic tertiary referral hospital. Facial symmetry of all patients was graded in person and via standardized photographic and video documentation of facial mimetic function at the initial visit. Three months after initial presentation, eFACE scores were reassessed by the same raters using the videos of facial mimetic function documented at the initial visit.Individual and subset eFACE scores assessed by 2 facial reanimation surgeons.Among the 75 patients in the study (mean [SD] age, 48.18 [16.60] years; 30 men and 45 women), agreement between in-person and video assessments of facial function using the eFACE scale was excellent (static subset score: mean difference, 0.19; 95% CI, -1.51 to 1.88; P = .83; intraclass correlation coefficient [ICC], 0.85; 95% CI, 0.80 to 0.89; dynamic subset score: mean difference, -0.51; 95% CI, -1.72 to 0.71; P = .41; ICC, 0.96; 95% CI, 0.94 to 0.97; synkinesis subset score: mean difference, -1.14; 95% CI, -2.87 to 0.59; P = .20; ICC, 0.90; 95% CI, 0.86 to 0.93; and composite score: mean difference, -0.41; 95% CI, -1.30 to 0.47; P = .36; ICC, 0.94; 95% CI, 0.92 to 0.96). Agreement between repeated eFACE assessments of video of facial function was excellent (static subset score: ICC, 0.93; 95% CI, 0.87 to 0.96; dynamic subset score: ICC, 0.88; 95% CI, 0.80 to 0.94; synkinesis subset score: ICC, 0.92; 95% CI, 0.86 to 0.96; and composite score: ICC, 0.96; 95% CI, 0.93 to 0.98).Strong agreement exists between eFACE scores of facial function assessed in person and from video recordings. Test-retest reliability of eFACE scores is high. The eFACE is a reliable instrument for high-resolution assessment of facial mimetic function.NA.

Introduction The incidence of Bell's palsy (BP) is elevated in the late phases of pregnancy. Controversy exists as to whether pregnancy is a risk factor for worse outcomes in BP, and whether such outcomes are the result of factors intrinsic to pregnancy or the tendency to withhold medical therapy in this cohort. Methods Long-term facial function outcomes in cases of pregnancy-associated BP (PABP) were compared against outcomes in cases affecting nonpregnant adult women of child-bearing age by a blinded expert using the electronic clinician-graded facial function scale (eFACE) facial grading system. Results Fifty-one pregnancy-associated cases and 58 nonpregnancy-associated cases were included. Among patients who received early corticosteroid therapy, significantly worse static, synkinesis, and composite facial function eFACE scores were demonstrated among cases of PABP compared to nonpregnancy-associated cases (static median = 86 vs. 92.5, P = 0.005; synkinesis median = 79 vs. 86, P = 0.007; composite median = 78 vs. 84, P = 0.023). Among those not treated with corticosteroids, significantly worse dynamic and composite facial function eFACE scores were demonstrated in cases of PABP compared to those for nonpregnancy-associated cases (dynamic median = 74 vs. 92.5, P = 0.038; composite median = 73 vs. 86.5, P = 0.038). A trend toward improved outcomes was demonstrated within both groups for those treated with corticosteroids compared to those who were not. Conclusion In comparison to cases unrelated to pregnancy, late-term PABP is associated with worse long-term outcomes to a degree that cannot solely be explained by differences in medical therapy. Level of Evidence 4. Laryngoscope, 127:2854–2859, 2017

Aberrant depressor anguli oris (DAO) activity may arise after recovery from acute facial paralysis and restrict movement of the oral commissure.To quantify the degree to which DAO inhibition affects smile dynamics and perceived emotional state.In this prospective, pretest-posttest study performed at an academic tertiary referral hospital, patients with unilateral postparalysis facial palsy were studied from January 16 through April 30, 2016.Local anesthetic injection into the ipsilateral DAO.Healthy- and paretic-side commissure displacements from the midline lower vermillion border referenced to the horizontal plane were calculated from random-ordered photographs of full-effort smile before and after injection, and random-ordered hemifacial photographs of the paretic side were assessed as expressing positive, negative, or indiscernible emotion.Twenty patients were identified as having unilateral postparalysis facial palsy with marked synkinesis of the ipsilateral DAO. Patient mean age was 46 years (range, 24-67 years), with a male to female ratio of 1:3. Mean paretic-side commissure displacement increased from 27.45 mm at 21.65° above the horizontal plane to 29.35 mm at 23.58° after DAO weakening (mean difference, 1.90 mm; 95% CI, 1.26-2.54 mm; and 1.93°; 95% CI, 0.34°-3.51°; P .001 and P = .20, respectively). Symmetry of excursion between sides improved by 2.00 mm (95% CI, 1.16-2.83 mm; P .001) and 2.71° (95% CI, 1.38°-4.03°; P .001). At baseline, observers assessed 7 of 20 paretic hemifaces (35%) as expressing positive emotion; this proportion increased to 13 of 20 (65%) after DAO weakening (P = .03).Ipsilateral DAO weakening results in significant improvements in smile dynamics and perceived expression of positive emotion on the paretic hemiface in postparalysis facial palsy. A trial of DAO weakening should be offered to patients with this disfiguring complication of Bell palsy and similar facial nerve insults.3.

Key PointsQuestionCan a video time-stamping method be used to measure spontaneity of smile after dually innervated gracilis smile reanimation surgery? FindingsIn this cohort study of 25 patients treated with dually innervated gracilis free muscle transfers vs 24 patients treated with masseteric nerve-driven transfers (n=11) or cross-face nerve graft-driven gracilis (n=13), a spontaneous smile was present in a median of 33% of smiles, which was more than was present in masseteric nerve-driven transfers (20%) but less than in cross-face nerve graft-driven smile reanimation surgery (75%). MeaningDual innervation may improve synchronicity compared with masseteric nerve transfer but not to the level of cross-face nerve graft-driven gracilis free muscle transfer.This cohort study assesses the outcomes of dually innervated gracilis free muscle transfers using a novel clinical assessment tool.ImportanceSurgeons have sought to optimize outcomes of smile reanimation surgery by combining inputs from nerve-to-masseter and cross-face nerve grafts. An objective assessment tool could help surgeons evaluate outcomes to determine the optimal neural sources for smile reanimation. ObjectiveTo evaluate the use of a novel video time-stamping method and standard outcome measurement tools to assess outcomes of facial reanimation surgery using various innervation strategies. Design, Setting, and ParticipantsCohort study assessing the outcomes of dually innervated gracilis free muscle transfers vs single-source innervated gracilis transfer performed at a tertiary care facial nerve center between 2007 and 2017 using a novel, video time-stamping spontaneity assessment method. The statistical analyses were performed in 2018. InterventionsDually innervated gracilis free muscle transfers or single-source innervated gracilis transfer. Main Outcomes and MeasuresSpontaneous smiling was assessed by clinicians and quantified using blinded time-stamped video recordings of smiling elicited while viewing humorous video clips. ResultsThis retrospective cohort study included 25 patients (12 men and 13 women; median [range] age, 38.4 [29.3-46.0] years) treated with dually innervated gracilis free functional muscle graft for unilateral facial palsy between 2007 and 2017. Smile spontaneity assessment was performed in 17 patients and was compared with assessment performed in 24 patients treated with single-source innervated gracilis transfer (ie, nerve-to-masseter-driven or cross-face nerve graft-driven gracilis [n=13]) (demographic data not available for NTM and CFNG cohorts). The use of time-stamped video assessment revealed that spontaneous synchronous oral commissure movement in a median percentage of smiles was 33% in patients with dually innervated gracilis (interquartile range [IQR], 0%-71%), 20% of smiles in patients with nerve-to-masseter-driven gracilis (IQR, 0%-50%), and 75% of smiles in patients with cross-face nerve graft-driven gracilis (IQR, 0%-100%). Clinicians graded smile spontaneity in dually innervated cases as absent in 40% (n=6 of 15), trace in 33% (n=5 of 15) and present in 27% (n=4 of 15). No association was demonstrated between clinician-reported spontaneity and objectively measured synchronicity. Conclusions and RelevanceDually innervated gracilis free muscle transfers may improve smile spontaneity compared with masseteric nerve-driven transfers but not to the level of cross-face nerve graft-driven gracilis transfers. Quantifying spontaneity is notoriously difficult, and most authors rely on clinical assessment. Our results suggest that clinicians may rate presence of spontaneity higher than objective measures, highlighting the importance of standardized assessment techniques. Level of Evidence4.

Background Conventional processing of nerve for histomorphometry is resource-intensive, precluding use in intraoperative assessment of nerve quality during nerve transfer procedures. Stimulated Raman scattering (SRS) microscopy is a label-free technique that enables rapid and high-resolution histology. Methods Segments of healthy murine sciatic nerve, healthy human obturator nerve, and human cross-facial nerve autografts were imaged on a custom SRS microscope. Myelinated axon quantification was performed through segmentation using a random forest machine learning algorithm in commercial software. Results High contrast, high-resolution imaging of nerve morphology was obtained with SRS imaging. Automated myelinated axon quantification from cross-sections of healthy human nerve imaged using SRS was achieved. Conclusions Herein, we demonstrate the use of a label-free technique for rapid imaging of murine and human peripheral nerve cryosections. We illustrate the potential of this technique to inform intraoperative decision-making through rapid automated quantification of myelinated axons using a machine learning algorithm.

Objective Microvascular decompression (MVD) may be employed in the management of hemifacial spasm (HFS), wherein a pledget of polytetrafluoroethylene (i.e., Teflon, Chemours, Wilmington DE) is sometimes introduced to separate an offending vessel from the cisternal segment of facial nerve. Rarely, Teflon may cause a granulomatous reaction resulting in nerve palsy. We here present the first case series of facial palsy thought to be secondary to Teflon granuloma following MVD for HFS. Methods A data repository of 1,312 patients with facial palsy was reviewed to identify individuals who had previously undergone MVD for HFS. Data collected include age at time of MVD, age at onset of facial weakness and at presentation, House-Brackmann scores, clinician-graded facial function using the Electronic Facial Paralysis Assessment scale, imaging findings, and therapeutic interventions and outcomes. Results Six patients meeting criteria were identified. Average time between MVD with Teflon placement and onset of facial weakness was 16.1 (±4.9) years (range 9.3-23.3 years). Initial House-Brackmann scores were as follows: four patients with V/VI and one each with III/VI and IV/VI. Interventions included eyelid weight placement (n = 3), chemodenervation (n = 2), static suspension with tensor fascia latae (n = 2), dynamic reanimation with cranial nerves V to VII transfer (n = 1), and temporalis muscle transfer (n = 1). Conclusion Teflon granuloma should be considered in the differential diagnosis for patients presenting with new onset facial weakness with a previous history of MVD for HFS. It remains unknown whether early granuloma extirpation is effective. Prompt diagnosis allows consideration of time-sensitive nerve transfer procedures to reanimate facial function. Level of evidence 4 Laryngoscope, 130:1422-1427, 2020.

Background Masseteric- or deep temporal-to-facial nerve transfer (five-to-seven nerve transfer) is increasingly used in facial reanimation; however, the indications and clinical variables affecting outcomes for five-to-seven nerve transfer have not been defined. The authors describe their early experience with five-to-seven nerve transfer, reporting function and patient-reported outcomes, to identify potential parameters that are predictive of outcome. Methods The authors conducted a retrospective chart review of all patients who underwent five-to-seven nerve transfer for smile reanimation from 2012 to 2017. Age, sex, cause of facial paralysis, onset and duration of paralysis, history of adjuvant chemotherapy and/or radiation therapy, donor nerve used, adjunctive procedures, and final excursion were recorded. Standard photographs and videos, and data regarding clinical facial nerve function and patient-reported quality of life, were obtained preoperatively and postoperatively. Results Sixty patients were identified. Forty-seven had flaccid facial paralysis and 13 had postparalysis facial palsy. Among flaccid facial paralysis patients, masseteric nerve transfer was successful in 30 patients (88 percent) and deep temporal nerve transfer was successful in three cases (60 percent). Among postparalysis facial palsy patients, five-to-seven nerve transfer was successful in two patients (20 percent). Average quality-of-life scores improved significantly from preoperatively (46) to postoperatively (59) among flaccid facial paralysis patients with successful five-to-seven nerve transfer. Conclusions Five-to-seven nerve transfer is a viable option in facial reanimation. Shorter denervation times and preoperative flaccidity are favorable predictors of outcome. Five-to-seven nerve transfer as an adjunct to primary repair appears highly effective for enhancing smile function. Five-to-seven nerve transfer results are not reliable in patients with postparalysis facial palsy. Clinical question/level of evidence Therapeutic, IV.

Stimulated emission depletion (STED) microscopy is a powerful bioimaging technique that theoretically provides molecular spatial resolution while preserving the most important assets of fluorescence microscopy. When combined with two-photon excitation (2PE) microscopy (2PE-STED), subdiffraction resolution may be achieved for thick biological samples. The most straightforward implementation of 2PE-STED microscopy entails introduction of an STED beam operating in continuous wave (CW) into a conventional Ti:sapphire-based 2PE microscope (2PE CW-STED). In this implementation, resolution enhancement is typically achieved using time-gated detection schemes, often resulting in drastic signal-to-noise/-background ratio (SNR/SBR) reductions. Herein, we employ a pixel-by-pixel phasor approach to discard fluorescence photons lacking super-resolution information to enhance image SNR/SBR in 2PE CW-STED microscopy. We compare this separation of photons by lifetime tuning approach against other postprocessing algorithms and combine it with image deconvolution to further optimize image quality.

BACKGROUND: Facial palsy is a devastating condition potentially amenable to rehabilitation by functional electrical stimulation. Herein, a novel paradigm for unilateral facial reanimation via an implantable neuroprosthetic device is proposed and its feasibility demonstrated in a live rodent model. The paradigm comprises use of healthy-side electromyography activity as control inputs to a system whose outputs are neural stimuli to effect symmetric facial displacements. The vexing issue of suppressing undesirable activity resulting from aberrant neural regeneration (i.e., synkinesis) or nerve transfer procedures is addressed using proximal neural blockade. METHODS: Epimysial and nerve cuff electrode arrays were implanted in the faces of Wistar rats. Stimuli were delivered to evoke blinks and whisks of various durations and amplitudes. The dynamic relation between electromyography signals and facial displacements were modelled, and model predictions compared against measured displacements. Optimal parameters to achieve facial nerve blockade by means of high-frequency alternating current were determined, and safety of continuous delivery assessed. RESULTS: Electrode implantation was well-tolerated. Blinks and whisks of tunable amplitudes and durations were evoked by controlled variation of neural stimuli parameters. Facial displacements predicted from electromyography input modelling matched those observed with a variance-accounted-for exceeding 96%. Effective and reversible facial nerve blockade in awake behaving animals was achieved, without detrimental effect noted from long-term continual use. CONCLUSIONS: Proof-of-principal of rehabilitation of hemifacial palsy by means of a neuroprosthetic device has been demonstrated. The use of proximal neural blockade coupled with distal functional electrical stimulation may have relevance to rehabilitation of other peripheral motor nerve deficits.