Efficiency of a Dexamethasone Nanosuspension as an Intratympanic Injection for Acute Hearing Loss

Background: Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug for intratympanic injection in acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of dexamethasone nanosuspensions as intratympanic injection because the lipophilicity of drugs can affect their permeation of the round window membrane, an important pathway from the middle ear to the cochlea.Results: Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanocrystals in the three nanosuspensions were between approximately 250 and 350 nm in size. In order to compare the efficiency of Dex-SP and a dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography–mass spectrometry. The dexamethasone nanosuspensions showed significantly higher drug concentrations in perilymph and cochlear tissue than Dex-SP at 6 h; interestingly, animals treated with a nanosuspension showed a 26-fold higher dexamethasone concentration in the cochlear tissue than the Dex-SP group. In addition, the dexamethasone nanosuspension achieved better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo, and in the ototoxic animal model, it showed a significantly better hearing protective effect than Dex-SP against ototoxic drugs. In safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL in an in vivo test.Conclusions: A nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection. In addition, it can be applied in studies on the delivery of various hydrophobic antioxidants to treat acute hearing loss.

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Cryptococcal meningitis presenting with acute hearing loss

Reversible sensorineural hearing loss is a recognised complication of cryptococcal meningitis. Cryptococcal meningitis typically presents with usual symptoms of fever, headache and neck stiffness. This case highlights acute, profound, bilateral hearing loss as the initial symptom and presentation of cryptococcal meningitis in a young woman, who was later diagnosed with AIDS.

Acute Sensorineural Hearing Loss - an Unusual Presentation of Uncontrolled DM

Background: Diabetes mellitus (DM) is a systemic metabolic disorder that possesses macro- and microangiopathic consequences. Studies have demonstrated that a relationship exists between sensorineural hearing loss (SNHL) and DM, particularly in patients of older age, longer disease duration, and uncontrolled DM. The pathophysiology of DM related hearing loss is poorly understood, however proposed mechanisms include ischemia, fibrosis, demyelination, and atrophy of the eighth cranial nerve. We however, present a case of acute, transient sensorineural hearing loss in the setting of diabetic ketoacidosis that resolved with blood glucose control. Clinical Case: A 34-year-old male with type 2 diabetes mellitus (A1c 6.5% -diagnosed 6 months prior), hypertension, hyperlipidemia, and morbid obesity presented with shortness of breath and acute hearing loss without tinnitus, after being treated for pneumonia and otitis media with a course of levofloxacin for 7 days. On presentation, patient was tachypneic and tachycardic. Physical examination was significant for mild erythema of the right tympanic membrane without bulging, fluid level, mastoid tenderness, or discharge. Laboratory values were significant for hyperglycemia with blood glucose of 628 mg/dL(n 70–99 mg/dL), A1c 15.9% (n 4.8–5.6%), bicarbonate 8 mmol/L (21–31 mmol/L), anion gap 37 mmol/L (9–16 mmol/L), beta-hydroxybutyrate 11.7 mmol/L (0.02–0.27 mmol/L). Venous gas was suggestive of metabolic acidosis, urinalysis was positive for moderate ketones and glucose >500 mg/dL. The patient was diagnosed with diabetic ketoacidosis and was started on an insulin drip. An audiogram revealed profound bilateral sensorineural hearing loss. A Computerized tomography (CT) scan of the bilateral temporal bones was negative for abnormalities, and a magnetic resonance imaging (MRI) of the brain was negative for morphologic abnormalities of 7th and 8th cranial nerves. Infectious and rheumatologic etiologies were excluded with normal syphilis FTA-ABs, Lyme PCR, Rheumatoid factor, ANCA, and ANA. The patient received one dose of empiric prednisone. His hearing improved after 2 days with normalization of blood glucose to a range of 100–200 mg/dL. A repeat audiogram and auditory brainstem response showed significant improvement with normal bilateral hearing. Discussion: SNHL in DM typically presents in a gradual progression with bilateral involvement, affecting higher frequencies. In patients with DM, studies show that chronicity (greater than 10 years) is strongly associated with SNHL. Other variables include older age and HbA1c greater than 8%. This is the first case to demonstrate acute bilateral SNHL, associated with uncontrolled type 2 diabetes mellitus, which resolved after blood glucose control. In the appropriate context, clinicians should consider significant hyperglycemia as a possible etiology of acute hearing loss.

Cortical Reorganization in Unilateral Deafness Revealed by Auditory Evoked Response

Profound unilateral deafness reduces the ability to detect the location of sounds, which is achieved with binaural hearing. Furthermore, the findings from previous studies have shown that unilateral deafness can cause a substantial change in the pattern of cortical activation, thereby leading to central reorganization in the whole brain. In the present study, we compared N1/P2 auditory cortical activities and the pattern of hemispheric asymmetry of normal hearing, unilaterally deaf, and simulated acute unilateral hearing loss groups during passively listening to speech sounds at different locations. The results show that P2 latencies were prolonged for left-side stimulation with greater angles in the horizontal plane. In the source analysis, a differential lateralization pattern was revealed such that the N1 source activation in the normal hearing subjects was greater in the left hemisphere, while contralateral activity was found in response to the stimulated side for the right-sided deaf and simulated acute hearing loss groups. However, no hemispheric lateralization was found for the left-sided deaf or simulated acute hearing loss groups. In addition, the cortical N1/P2 activities were inversely related to the duration of deafness in the right auditory region. These findings indicate that the cortical reorganization induced by monaural hearing deprivation differs depending on the side and duration of deafness.

Sudden hearing loss following acute carbon monoxide poisoning: A case report and literature review

Introduction: Acute carbon monoxide (CO) poisoning could lead to headache, dizziness, myocardial injury, neurological sequela, and death. Sudden hearing loss is a rare symptom of acute CO poisoning. Case Presentation: Here, we report a case of a 42-year-old woman who suffered from acute hearing loss after exposure to a suicidal environment of high concentration of CO. Partial recovery of hearing was demonstrated after a combination of corticosteroid and hyperbaric oxygen therapy was given. Discussion: The mechanism of sudden hearing loss caused by acute CO poisoning is not well-established. It is believed to be related with the hypoxic damage to the cochlea. The characteristic of sudden hearing loss caused by acute CO poisoning is that it often affects in high frequency bilaterally. Conclusion: This report would prompt the clinician in early recognition of this sudden hearing loss of uncommon etiology.

Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss

The objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements were made before noise exposure, 1 day and 7 days after noise exposure. Proteomic Isobaric Tags for Relative and Absolute Quantification (iTRAQ) was used to observe changes in proteins of the miniature pig inner ear following noise exposure. Western blot and immunofluorescence were performed for further quantitative and qualitative analysis of proteomic changes. The average ABR-click threshold of miniature pigs before noise exposure, 1 day and 7 days after noise exposure, were 39.4 dB SPL, 67.1 dB SPL, and 50.8 dB SPL, respectively. In total, 2,158 proteins were identified using iTRAQ. Both gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses showed that immune and metabolic pathways were prominently involved during the impairment stage of acute hearing loss. During the recovery stage of acute hearing loss, most differentially expressed proteins were related to cholesterol metabolism. Western blot and immunofluorescence showed accumulation of reactive oxygen species and nuclear translocation of NF-κB (p65) in the hair cells of miniature pig inner ears during the acute hearing loss stage after noise exposure. Nuclear translocation of NF-κB (p65) may be associated with overexpression of downstream inflammatory factors. Apolipoprotein (Apo) A1 and Apo E were significantly upregulated during the recovery stage of hearing loss and may be related to activation of cholesterol metabolic pathways. This is the first study to use proteomics analysis to analyze the molecular mechanisms of acute noise-induced hearing loss and its recovery in a large animal model (miniature pigs). Our results showed that activation of metabolic, inflammatory, and innate immunity pathways may be involved in acute noise-induced hearing loss, while cholesterol metabolic pathways may play an important role in recovery of hearing ability following noise-induced hearing loss.