False-positive results in transcranial motor evoked potentials for outcome prognostication during surgery for supratentorial lesions.

During monitoring of motor evoked potentials (MEP) elicited by transcranial electrical stimulation (TES) for prognostication of postoperative motor deficit, significant MEP changes without postoperative deterioration of motor function represent false-positive results. We aimed to investigate this phenomenon in a large series of patients who underwent resection of supratentorial lesions. TES was applied in 264 patients during resection of motor-eloquent supratentorial lesions. MEP were recorded bilaterally from arm, leg, and/ or facial muscles. The threshold criterion was applied assessing percentage increase in threshold level, which was considered significant if being > 20% higher on affected side than on the unaffected side. Subcortical stimulation was additionally applied to estimate the distance to corticospinal tract. Motor function was evaluated at 24 h after surgery and at 3-month follow-up. Patients with false-positive results were analyzed regarding tumor location, tumor volume, and characteristics of the monitoring. MEP were recorded from 399 muscles (264 arm muscles, 75 leg muscles, and 60 facial muscles). Motor function was unchanged postoperatively in 359 muscles in 228 patients. Among these cases, the threshold level did not change significantly in 354 muscles in 224 patients, while it increased significantly in the remaining 5 muscles in 4 patients (abductor pollicis brevis in all four patients and orbicularis oris in one patient), leading to a false-positive rate of 1.1%. Tumor volume, opening the ventricle, and negative subcortical stimulation did not significantly correlate with false-positive results, while the tumor location in the parietal lobe dorsal to the postcentral gyrus correlated significantly (p = 0.012, odds ratio 11.2, 95% CI 1.8 to 69.8). False-negative results took place in 1.1% of cases in a large series of TES-MEP monitoring using the threshold criterion. Tumor location in the parietal lobe dorsal to the postcentral gyrus was the only predictor of false-positive results.

Ventilatory Drive Withdrawal Rather Than Reduced Genioglossus Compensation as a Mechanism of Obstructive Sleep Apnea in REM Sleep.

Rationale: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. Objectives: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). Methods: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory "drive" (calibrated intraesophageal diaphragm EMG), ventilation (oronasal "ventilation"), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation-drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. Measurements and Main Results: REM sleep (⩾10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], -21.8% [-31.2% to -12.4%] of eupnea; P < 0.0001), with an accompanying reduction in ventilation (-25.8% [-31.8% to -19.8%] of eupnea; P < 0.0001). However, there was no effect of REM sleep on collapsibility (ventilation at eupneic drive), baseline genioglossus EMG activity, or responsiveness. REM sleep was associated with increased OSA severity (+10.1 [1.8 to 19.8] events/h), but this association was not present after adjusting for nadir drive (+4.3 [-4.2 to 14.6] events/h). Drive withdrawal was exacerbated in phasic REM sleep. Conclusions: In patients with OSA, the pharyngeal compromise characteristic of REM sleep appears to be predominantly explained by ventilatory drive withdrawal rather than by preferential decrements in muscle activity or responsiveness. Preventing drive withdrawal may be the leading target for REM sleep OSA.

Selective Facial Muscle Activation with Acute and Chronic Multichannel Cuff Electrode Implantation in a Feline Model.

OBJECTIVES: Facial paralysis is a debilitating condition with substantial functional and psychological consequences. This feline-model study evaluates whether facial muscles can be selectively activated in acute and chronic implantation of 16-channel multichannel cuff electrodes (MCE). METHODS: Two cats underwent acute terminal MCE implantation experiments, 2 underwent chronic MCE implantation in uninjured facial nerves (FN) and tested for 6 months, and 2 underwent chronic MCE implantation experiments after FN transection injury and tested for 3 months. The MCE were wrapped around the main trunk of the skeletonized FN, and data collection consisted of EMG thresholds, amplitudes, and selectivity of muscle activation. RESULTS: In acute experimentation, activation of specific channels (ie, channels 1-3 and 6-8) resulted in selective activation of orbicularis oculi, whereas activation of other channels (ie, channels 4, 5, or 8) led to selective activation of levator auris longus with higher EMG amplitudes. MCE implantation yielded stable and selective facial muscle activation EMG thresholds and amplitudes up to a 5-month period. Modest selective muscle activation was furthermore obtained after a complete transection-reapproximating nerve injury after a 3-month recovery period and implantation reoperation. Chronic implantation of MCE did not lead to fibrosis on histology. Field steering was achieved to activate distinct facial muscles by sending simultaneous subthreshold currents to multiple channels, thus theoretically protecting against nerve damage from chronic electrical stimulation. CONCLUSION: Our proof-of-concept results show the ability of an MCE, supplemented with field steering, to provide a degree of selective facial muscle stimulation in a feline model, even following nerve regeneration after FN injury. LEVEL OF EVIDENCE: N/A.

Prognostic value of EMG genioglossus involvement in amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate the prognostic value of needle electromyography (EMG) genioglossus involvement in patients with amyotrophic lateral sclerosis (ALS) at diagnosis. METHODS: We separately explored the prognostic value of clinical bulbar lower motor neuron (LMN) signs and EMG genioglossus involvement using Cox proportional hazard models adjusted for age, gender, diagnostic delay, presence of bulbar upper motor neuron (UMN) signs, EMG cervical and lumbosacral region involvement, ALSFRS-R score and C9Orf72 gene status. Then, we compared the prognostic value of EMG masseter and genioglossus abnormalities in a subset of patients in whom both muscles were analysed. RESULTS: 103 ALS patients were included in the study. Neurophysiological genioglossus involvement was associated with a shorter survival (p = 0.002), a shorter time to moderate dysphagia (p = 0.0001) and to severe dysarthria (p = 0.012). Its prognostic value was still evident in patients without clinical bulbar LMN signs. Bulbar clinical LMN signs were only associated with an earlier onset of moderate dysphagia (p = 0.0001). EMG masseter abnormalities did not reach statistical significance with regard to all the clinical milestones. CONCLUSIONS: Genioglossus EMG at diagnosis could provide important information about ALS progression rate. The masseter muscle seems to be less involved in ALS. SIGNIFICANCE: EMG genioglossus involvement is a prognostic factor in ALS.

Long-term stable efficacy of botulinum toxin A in facial movement disorders with no need for increasing dose.

ABSTRACT: Botulinum toxin A is considered an effective treatment for involuntary facial movements. We examined whether treatment efficacy maintained or changed over time with two products, Botox and Dysport, in patients with hemifacial spasm, facial synkinesis and benign essential blepharospasm.We retrospectively investigated 87 consecutive patients (51 women, 36 men) who had undergone treatment for ≥6 years. Long-term effects, as well as side effects of Botox or Dysport local injections were evaluated. The first three treatments were considered the titration period and not taken into account when testing for dose changes.Mean treatment duration was 10 years (range 6-11, SD 1.0), 2441 treatments were administered, 1162 with Botox and 1279 with Dysport, the two brands were interchanged as needed. Good to full improvement was seen in 90% of patients both with both brands. Injection doses and treatment responses were consistent during the study with both drugs. No major side effects were reported, and relatively few minor adverse events were reported, with clear reduction from the titration period (6.1%), to the remainder of the study (3.9%).Botulinum toxin (BTX-A) is a satisfactory long-term treatment without need for dose increase over. Both Botox and Dysport were effective when used interchangeably.

The research for the function evaluation of facial nerve and the mechanisms of rehabilitation training.

BACKGROUND: Peripheral facial paralysis (PFP) is a common peripheral neural disease. Acupuncture treatment combined with PFP rehabilitation exercises is a routine method of PFP treatment. This article is to provide a new visual and objective evaluation method for exploring the mechanism and efficacy of acupuncture treatment on PFP, and develop an interactive augmented facial nerve function rehabilitation training system with multiple training models. METHODS: This prospective and observational trial will recruit 200 eligible participants for the following study. In the trial, the laser speckle contrast analysis (LASCA) technology will be applied to monitor the microcirculation of facial blood flow during acupuncture, and real-time monitoring algorithms, data sampling, and digital imaging methods will be conducted by machine learning and image segmentation. Then, a database of patient facial expressions will be built, the correlation between surface blood flow perfusion volume and facial structure symmetry will be analyzed, combined with scale assessment and electrophysiological detection. In addition, we will also explore the objectivity and effectiveness of LASCA in the evaluation of facial paralysis (FP), and the changes in blood flow microcirculation before and after acupuncture treatment will be analyzed. RESULTS: The standard image of the facial target area with facial nerve injury will be manually segmented by the convolutional neural network method. The blood flow images of the eyelid, cheek, and mandible of the patients' affected and healthy side will be compared and evaluated. Laser speckle blood flow symmetry Pr and its changes in FP condition evolution and prognosis outcome will be measured, and relevant characteristic signals values will be extracted. Finally, COX regression analysis method is conducted to establish a higher accuracy prediction model of FP with cross-validation based on laser speckle blood flow imaging technology. CONCLUSIONS: We use modern interdisciplinary high-tech technologies to explore the mechanism of acupuncture rehabilitation training in PFP. And we will provide evidence for the feasibility of using the LASCA technique as a typing diagnosis of FP in the acupuncture rehabilitation treatment of PFP. REGISTRATION NUMBER: ChiCTR1800019463.

The Five-Year Prospective Study of Quality of Life in Hemifacial Spasm Treated with Abo-Botulinum Toxin A.

This study aimed to determine the long-term quality of life (QoL) in hemifacial spasm (HFS) patients after treating with Abo-botulinum toxin A (Abo-BTX). The study assessed the disease-specific QoL (hemifacial spasm questionnaire 30 items; HFS 30), the involuntary movements (abnormal involuntary movement scale; AIMS), general health QoL (Medical Outcomes 36-Item Short Form Health Survey; SF-36), and Depression (the Center of Epidemiologic Studies-Depression questionnaire; CES-D). A total of 74 HFS patients were enrolled from 2012 to 2017. The disease-specific QoL; involuntary movements; and the general health domain of SF 36 were significantly improved after injections of Abo-BTX A in the first few years (p < 0.04), but significantly decreased at the fifth year of treatment without significant clinical resistance observed (p < 0.001). Only the general health domain of SF 36 showed persistent improvement over five years (p = 0.02). In summary, Abo-BTX A can improved quality of life in the first few years; however only the general health domain of SF-36 showed significant improvement over five years (p = 0.02). No clinical resistance was observed.

Effects of Synchronized Neuromuscular Electrical Stimulation (NMES) on the Submental Muscles During Ingestion of a Specified Volume of Soft Food in Patients with Mild-to-Moderate Dysphagia Following Stroke.

BACKGROUND Neuromuscular electrical stimulation (NMES) is a method for producing regular contractions of muscles that have been paralyzed. This study aimed to evaluate the effects of synchronized NMES on the submental muscles during ingestion of a specified volume of soft food in patients with mild-to-moderate dysphagia following stroke. MATERIAL AND METHODS Eighty-three patients with mild-to-moderate dysphagia following stroke were enrolled and randomly divided into 3 groups: conventional training (CT) (n=28), eating training (ET) (n=28), and intensive swallowing training (IST) (n=27). The CT group received conventional swallow training, the ET group was given additional individual feedings with a specified volume of soft food, and the IST group received intensive swallowing training with synchronized NEMS. All of the patients were evaluated before and after the treatment with a modified barium swallow, and the Dysphagia Outcome and Severity Scale (DOSS); the numbers of patients with Stroke-Associated Pneumonia (SAP) and wet voice also were assessed. RESULTS After 6 weeks, DOSS scores improved in patients in all 3 groups, and there were significant differences among the groups in their scores (P<0.001 for both measures). In the CT and ET groups, there was a statistically significant difference in the number of patients with SAP before and after treatment (P=0.010 and P<0.001, respectively). There also were fewer cases in the IST group than in the CT (P=0.042) and ET groups (P=0.011). After completion of treatment, compared with the first treatment, there were significantly fewer patients with wet voices in the CT (P<0.001) and IST groups (P<0.001). CONCLUSIONS Feeding a specified volume of soft food plus synchronized NMES of the submental muscles can improve the swallowing function of patients with mild-to-moderate dysphagia following stroke and it reduces their risk of food aspiration.

Botulinum Toxin Type A to Improve Facial Symmetry in Facial Palsy: A Practical Guideline and Clinical Experience.

Unilateral peripheral facial nerve palsy jeopardizes quality of life, rendering psychological consequences such as low self-esteem, social isolation, anxiety, and depression. Among therapeutical approaches, use of Botulinum toxin type A (BoNT-A) on the nonparalyzed side has shown promising results and improvement of quality of life. Nevertheless, the correct technique is paramount, since over-injection of the muscles can result in lack of function, leading to a "paralyzed" appearance, and even worse, functional incompetence, which may cause greater distress to patients. Therefore, the objective of this article is to provide a practical guideline for botulinum toxin use in facial palsy. To this aim, adequate patient assessment, BoNT-A choice, injection plan and dosage, and injection techniques are covered.

The Effect of Depressor Anguli Oris Muscle Block on Facial Symmetry in Synkinetic Facial Paralysis Patients and Its Role in Preoperative Assessment.

BACKGROUND: Depressor anguli oris muscle hypertonicity in synkinetic facial paralysis patients may have an overpowering antagonistic effect on facial symmetry. Depressor anguli oris muscle block is a crucial diagnostic test before any treatment planning. Presented is the largest patient cohort analysis to date on static and dynamic facial symmetry changes after depressor anguli oris muscle block. METHODS: Unilateral synkinetic patients with depressor anguli oris muscle hypertonicity were included. Resting symmetry and smile modiolus angle, excursion, and exposure of teeth were measured on both synkinetic and healthy hemifaces before and after depressor anguli oris muscle block using Emotrics and FaceGram photographic analyses. RESULTS: Thirty-six patients were included. Before depressor anguli oris block, resting modiolus height was elevated on the synkinetic side (p = 0.047). During open-mouth smile, reduced modiolus angle (p < 0.0001), modiolus excursion (p < 0.0001), and exposure of teeth (p < 0.0001) were observed on the synkinetic hemiface. After depressor anguli oris block, resting modiolus height became symmetric (p = 0.64). During open-mouth smile, modiolus angle and exposure of teeth significantly increased (both p < 0.0001); excursion did not improve on the synkinetic side (p = 0.13) but unexpectedly improved in open-mouth smile on the healthy side (p = 0.0068). CONCLUSIONS: Depressor anguli oris muscle block improved resting symmetry and modiolus angle and exposure of teeth during smile, demonstrating the inhibitory mimetic role of a hypertonic depressor anguli oris muscle in synkinesis. It is a critical diagnostic and communication tool in the assessment and treatment planning of depressor anguli oris muscle hypertonicity, suggesting the potential effects of future depressor anguli oris myectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Intraoperative transcranial facial motor evoked potential monitoring in surgery of cerebellopontine angle tumors predicts early and late postoperative facial nerve function.

OBJECTIVE: We propose a novel method that predicts facial nerve function (FNF) calculated from the drop and recovery of facial motor evoked potential (FMEP) amplitude ratio during the surgery of cerebellopontine angle tumors. METHODS: We enrolled 73 patients with cerebellopontine angle tumor, and used a biphasic, constant current, and suprathreshold stimulation (BCS) protocol to record FMEP of the orbicularis oris. We measured the intraoperative minimum-to-baseline amplitude ratio (MBR), the final-to-baseline amplitude ratio (FBR), and the recovery value (RV). RV was measured by subtracting MBR from FBR. Using those values, we evaluated FNF both at early postoperative (EP) and late postoperative (LP) periods. RESULTS: We successfully obtained 62 FMEP readings. Facial palsies occurred in 22 patients during the EP period, and 14 patients recovered during the LP period. Both MBR and FBR showed a significant correlation with FNF in the EP period. RV showed a good predictive power of FNF recovery during the LP period for the first time. CONCLUSIONS: RV is a new and useful predictor of FNF recovery. MBR can be an intraoperative predictor of FNF in the EP period. SIGNIFICANCE: FNF outcome in the early and late postoperative periods can be predicted by FMEP.

Long-term therapy with botulinum toxin in facial synkinesis: Retrospective data analysis of data from 1998 to 2018.

OBJECTIVES: Treatment with botulinum toxin A (BoNT) is the therapy of choice for many patients with facial synkinesis. Repeated injections relieve hypertonicity and hyperkinesis of reinnervated mimic muscles. Aim of the study was to prove if the injection regime and dosage of BoNT change during long-time therapy. DESIGN: Retrospective analysis of patients´ data, who were treated for synkinesis with BoNT from 1998 to 2018. SETTING: Tertiary referral facial nerve centre. PARTICIPANTS: Injection pattern of BoNT was based on clinical symptoms, observations of the specialist and on previous treatment pattern. Onabotulinumtoxin (OnaBoNT), Incobotulinumtoxin (IncoBoNT) and Abobotulinumtoxin (AboBoNT) were available for treatment. Patients consulted our department for following treatment as soon as the symptoms re-occurred. MAIN OUTCOME MEASURES: Change in dosage and injection pattern, the time intervals between treatments over the entire therapy period. RESULTS: Seventy-three patients were repeatedly injected. The median number of treatments was 18, the median treatment interval was 3.0 months. During the initial treatment, orbicularis oculi and the mentalis muscles were the most frequently injected muscles (94%). During repeated treatment, the number of injected muscles increased significantly (P < .0001), whereas the dose per muscle remained stable. The initial dose was 24 U (95%-CI 22-27 U) for OnaBoNT and IncoBoNT; 69 U for AboBoNT(95%-CI 44-94 U). We observed a significant increase in dosage for OnaBoNT and IncoBoNT (P < .0001) during the long-term therapy. The time intervals between treatments were stable for all three BoNT preparations (P > .05). CONCLUSIONS: We observed significant change in treatment dose and injection pattern of BoNT in patients with facial synkinesis. These results provide an orientation in dose finding and injection regimen of BoNT in the long-term course of therapy.

Synkinetic Unilateral Lower Lip Palsy: Diagnosis and Technical Considerations for Facial Reanimation.

Importance: There are no universally adopted surgical techniques to treat depressor labii inferioris (DLI) dysfunction in patients with postfacial paralysis synkinesis. We describe a novel description of this disorder and technical surgical considerations for reanimation. Objective: To describe a new classification for DLI dysfunction and a surgical option to restore a natural appearing full dentition smile. Design: Surgical pearls-description of novel surgical technique. Setting: A private practice. Participants: Patients who underwent the operation.

Autoantibodies in Japanese patients with ocular myasthenia gravis.

INTRODUCTION: The majority of patients with myasthenia gravis (MG) initially present with ocular symptoms, but it is difficult to predict which cases will remain as ocular MG (OMG) or will progress to generalized MG. Herein we evaluated the serologic profile of Japanese OMG and its relationship with clinical features. METHODS: Seventy-three patients with OMG from five Japanese myasthenia gravis (MG) centers were enrolled. Live cell-based assays (CBAs) were used to determine the presence of autoantibodies (Abs) to clustered adult (2α, ß, δ, ε) and fetal (2α, ß, δ, γ) acetylcholine receptor (AChR) isoforms, muscle-specific receptor tyrosine kinase (MuSK), and lipoprotein receptor-related protein-4 (LRP4). RESULTS: Thirty-four of 73 (46.5%) serum samples were positive for Abs against both the adult-type and fetal-type AChR, as expected, but 7 (9.6%) and 2 (2.7%) were positive only for fetal or adult AChR-Abs, respectively. Four (5.4%) samples were positive for MuSK-Abs, but two of these also contained antibodies to fetal AChR or LRP4. Twenty-six (35.6%) samples were seronegative. DISCUSSION: Abs against fetal-specific AChR, MuSK, and LRP4 are found in some patients with OMG. Future studies attempting to predict conversion from ocular symptoms to generalized MG may benefit from measurement of these antibodies.

Identifying jitter outliers in single fiber electromyography: Comparison of four methods.

BACKGROUND: Little is known about how different outlier estimation methods affect cutoff limits for outliers in single fiber electromyography. METHODS: We compared in a prospective fashion the established 18th jitter value (18thjv) method to three, whole-distribution based, outlier detection methods: the interquartile range (IQR), the log-normal, and the Z-score method. The reference limits were probed in a normal cohort and in myasthenia gravis (MG) patients. RESULTS: Differences in outlier cutoff values between the different methods were in the range of 2 µs. The number of abnormal muscles according to the computed criteria was similar for all four methods in the control group. Classification metrics (sensitivity, specificity, Youden's statistic, and predictive values) were also similar among the different methods. In the MG group, however, the Z-score method failed to identify the abnormal jitter values. Accordingly, Kappa agreement was substantial to perfect (0.658 to 1) between the three methods (18thjv, IQR, and log-normal), but was equivalent to chance between the three methods and the Z-score in the MG group. CONCLUSIONS: The established 18thjv method proved largely robust when compared to whole-distribution based methods, and its use in clinical practice is justified. Simple estimation of outlier limits by adding two SDs to the mean of the data, leads to unacceptable deviations from the true cutoff values. Moreover, in a clinical scenario in which the final electrodiagnosis depends only on the number of outliers, it is meaningful to accept a tolerance zone of about 2 µs, which is the approximate variation range among the different methods.

A novel physiologic marker of bulbar motor involvement in amyotrophic lateral sclerosis: Jaw muscle synergy.

OBJECTIVE: To identify a novel physiologic marker of bulbar motor involvement in amyotrophic lateral sclerosis (ALS) based on jaw muscle synergies. METHODS: Muscle synergies were extracted from the surface electromyographic recordings of five jaw muscles during speech in 11 individuals at the prodromal or symptomatic stages of bulbar ALS and 10 neurologically-healthy controls, using non-negative matrix factorization. The disrupted muscle synergies in ALS were identified; their efficacy in differentiating individuals with ALS from healthy controls and relation to the previously-reported kinematic and functional speech deficits were determined. RESULTS: An antagonist synergy (i.e., masseter × digastric) was significantly disrupted in ALS, which differentiated individuals with ALS from healthy controls with 82% sensitivity and 90% specificity. Such a disruption occurred prodromally and was associated with slowed jaw movement and reduced speaking rate across the range of severity. CONCLUSIONS: The disruption of jaw antagonist synergy in ALS likely reflects the impact of impaired neural drive on the coordinative functioning of bulbar muscles, which may be used to assess bulbar motor involvement. SIGNIFICANCE: Jaw antagonist synergy shows promise as a novel physiologic marker of bulbar motor involvement in ALS, which has the potential to serve as a quantitative measurement tool for bulbar assessment.