Dysphagia as a predictor of voice handicap and voice restoration in unilateral vocal fold immobility.

OBJECTIVE: Dysphagia is multifactorial in unilateral vocal fold immobility (UVFI). Severe dysphagia could indicate greater functional deficits in UVFI. The purpose of this study is to evaluate the association of dysphagia with the need for surgical voice restoration in patients with UVFI. STUDY DESIGN: Retrospective chart review. SETTING: Single-institution, tertiary referral center. METHODS: Records of UVFI patients from 2008 to 2018 were examined. Dysphagia severity was extracted from patient history. Etiology of UVFI and other relevant variables were analyzed to determine their association with dysphagia. Dysphagia severity and other clinical variables were then analyzed for their association with surgical voice restoration. RESULTS: Eighty patients met selection criteria out of 478 patients with UVFI. There was significant concordance between dysphagia severity extracted from patient history and patient-reported EAT-10 scores (R = 0.59, p = 0.000035). Patients' EAT-10 scores were correlated with VHI-10 scores (R = 0.45, p = 0.011). Severe dysphagia (p = 0.037), high VHI-10 score on presentation (p = 0.0009), and longer duration of hoarseness before presentation (p = 0.008) were associated with surgical voice restoration in UVFI patients. CONCLUSION: In this pilot study, severe dysphagia and increased voice handicap on presentation were associated with the need for surgical voice restoration in UVFI patients. Presenting dysphagia may be an additional variable for clinicians to consider for management of UVFI.

Fluorescent Detection of Vestibular Schwannoma Using Intravenous Sodium Fluorescein In Vivo.

BACKGROUND: Vestibular schwannoma (VS) are intracranial tumors caused by merlin deficiency. Sodium fluorescein (SF) is a fluorescent compound that accumulates in various intracranial tumors, causing tumors to emit green fluorescence after blue light excitation. HYPOTHESIS: Intravenous SF preferentially deposits in VS, helping surgeons differentiate tumor from surrounding tissue. METHODS: Merlin-deficient Schwann cells were grafted onto cochleovestibular nerves of immunodeficient rats. Rats were randomized to receive SF (7.5 mg/kg; n = 5) or saline (n = 3). Tissues were harvested at 1 hour and photographed in white and blue light. Sixteen surgeons identified and marked the tumor-tissue interfaces on images. Fluorescence was measured on tissue specimens using the IVIS imaging system and on tissue cross-sections obtained with confocal microscopy. Western blot was performed to measure levels of organic anion transporting polypeptide (OATP), a drug transporter specific for SF. RESULTS: Under blue light, tumors from SF rats demonstrated bright green fluorescence under direct visualization, higher fluorescence measurements on tissue specimens (p < 0.001), and more SF deposition on tissue cross-sections (p < 0.001), when compared with surrounding tissues and placebo rats. Surgeons were better able to distinguish the tumor-tissue interfaces in SF rats. Furthermore, the expression level of OATP1C1 was significantly higher in tumors than in surrounding tissues (p < 0.0001). CONCLUSION: In a xenograft model of VS, intravenous SF preferentially deposits in tumors, compared with normal surrounding tissue. Under blue light, tumors emit an intense green fluorescence that can help surgeons differentiate tumor from critical structures nearby, which may improve clinical outcomes in complicated VS surgery.

Gene therapy for neurological disorders: challenges and recent advancements.

Major advancements in targeted gene therapy have opened up avenues for the treatment of major neurological disorders through a range of versatile modalities varying from expression of exogenous to suppression of endogenous genes. Recent technological innovations for improved gene sequence delivery have focussed on highly specific viral vector designs, plasmid transfection, nanoparticles, polymer-mediated gene delivery, engineered microRNA and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapeutics. These advanced techniques have profound applications in treating highly prevalent neurological diseases and neurodevelopmental disorders including Parkinson's disease, Alzheimer's disease and autism spectrum disorder, as well as rarer diseases such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, lysosomal storage diseases, X-linked adrenoleukodystrophy and oncological diseases. In this article, we present an overview of the latest advances in targeted gene delivery and discuss the challenges and future direction of gene therapy in the treatment of neurological disorders.

Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Cochlear Function in an Experimental Rat Model.

Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti-inflammatory, anti-apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders such as hair cell damage in response to inflammation. Most of the previous studies have used immunosuppression or the complex surgical techniques to deliver stem cells into the cochlea. However, no information is available regarding the biocompatibility and safety of MSCs in the inner ear in immunocompetent cochlea. The aim of the present study was to determine the effect of non-surgical administration of rodent bone marrow derived MSCs (BM-MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. We observed that the transtympanic administration of BM-MSCs has no significant effect on the hearing thresholds as determined by auditory brainstem response and distortion product otoacoustic emissions. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM-MSCs administrated rats. The results of this study suggest that transtympanic administration of BM-MSCs is safe and can be explored in providing otoprotection against cochlear insults. Anat Rec, 303:487-493, 2020. © 2019 American Association for Anatomy.

Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities.

Hearing loss is the most common neurosensory impairment worldwide. While conductive hearing loss can be managed by surgery, the management of sensorineural hearing loss (SNHL), related to the damage of sensory cells of the inner ear is more challenging to manage medically. Many causes of SNHL such as sudden idiopathic SNHL, Meniere's disease, noise-induced hearing loss, autoimmune hearing loss or hearing loss from exposure to ototoxic substances can benefit from delivery of otoprotective drugs to the inner ear. However, systemic drug delivery through oral, intravenous and intramuscular methods leads to undesirable side effects due to the inner ear's limited blood supply and the relatively poor penetration of the blood-inner ear barrier (BLB). Therefore, there has been an increased interest for the targeted drug delivery to the inner ear using nanoparticles. Drug delivery through nanoparticles offers several advantages including drug stabilization for controlled release and surface modification for specific targeting. Understanding the biocompatibility of nanoparticles with cochlea and developing novel non-invasive delivery methods will promote the translation of nanoparticle-mediated drug delivery for auditory disorders from bench to bedside.