The Role for Imaging in the Investigation of Isolated Objective Vestibular Weakness.

OBJECTIVE: Unilateral vestibular weakness has considerable potential etiologies. One source is a vestibular schwannoma. This article evaluates, in the absence of other symptoms and signs, if unilateral vestibular weakness is an analogue to asymmetric sensorineural hearing loss and serves as an indication for lateral skull base imaging. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary center. SUBJECTS AND METHODS: All patients undergoing caloric assessment between January 1, 2012, and June 30, 2018, were investigated. Patients with unilateral vestibular weakness (a left-right difference >25% on electronystagmography) were included in the study. A provincial encompassing image library was surveyed for potential adequate imaging (computed tomography internal auditory canal infused, magnetic resonance imaging [MRI] brain, MRI internal auditory canal) of the target population within the preceding 5 years. Presence/absence of vestibular schwannoma on imaging was determined. RESULTS: Of the 3531 electronystagmography reports reviewed during the period, 864 patients were identified with unilateral vestibular weakness. Of these, 542 had sufficient imaging, and 14 vestibular schwannomas were identified. Only 1 individual had a vestibular weakness in isolation, while the remaining 13 patients also suffered from documented sensorineural hearing loss that would have mandated MRI scanning. CONCLUSION: The results of our study suggest that, in isolation, vestibular weakness is an insufficient indicator for lateral skull base imaging.

Fibrosis, low vascularity, and fewer slow fibers after rotator-cuff injury.

INTRODUCTION: Rotator-cuff injury (RCI) represents 50% of shoulder injuries, and prevalence increases with age. Even with successful tendon repair, muscle and joint function may not return. METHODS: To explore the dysfunction, supraspinatus and ipsilateral deltoid (control) muscles were biopsied during arthroscopic RCI repair for pair-wise histological and protein-expression studies. RESULTS: Supraspinatus showed fiber atrophy (P < 0.0001), fibrosis (by Sirius Red, P = 0.05), reduced vascular density (P < 0.001), and a lower proportion of slow fibers (P < 0.0001) compared with the ipsilateral control muscle. There were also higher levels of atrogin-1 (P = 0.05), vascular endothelial growth factor (VEGF, P < 0.01), and dystrophin (P < 0.008, relative to fiber diameter) versus control. CONCLUSIONS: Adaptive changes in vascular endothelial growth factor and dystrophin were likely associated with reduced vascular supply, fatigue resistance, and fibrosis, accompanied by disuse atrophy from mechanical unloading of supraspinatus after tendon tear. Treatment to promote growth and vascularity in atrophic supraspinatus muscle may help improve functional outcome after surgical repair. Muscle Nerve 55: 715-726, 2017.

Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

BACKGROUND: Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. METHODS AND FINDINGS: Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ) subunit of acetylcholine receptor (γ-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli. CONCLUSIONS: Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest indices including satellite cell responsiveness, atrogin-1, atrophy, and innervation may predict surgical outcome.

Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator-cuff muscle.

The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)-based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alpha-bungarotoxin staining, and the γ:ε subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU+ (activated) Pax7+ satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher γ:ε subunit ratio than deltoid (P = 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO-donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome.