Endolymphatic Hydrops Reversal following Acetazolamide Therapy: Demonstration with Delayed Intravenous Contrast-Enhanced 3D-FLAIR MRI

López

et al. 2017

Sci Rep

The ultrastructural organization of the blood labyrinthine barrier (BLB) was investigated in the human vestibular endorgan, the utricular macula, using postmortem specimens from individuals with documented normal auditory and vestibular function and surgical specimens from patients with intractable Meniere’s disease. Transmission electron microscopic analysis of capillaries located in the normal human utricular stroma showed vascular endothelial cells with few pinocytotic vesicles, covered by a smooth and uniform basement membrane surrounded by pericyte processes. Meniere’s disease specimens revealed differential ultrastructural pathological changes in the cellular elements of the microvasculature. With moderate degeneration of the BLB, there were numerous vesicles within the vascular endothelial cells (VECs), with increased numbers at the abluminal face, pericyte process detachment and disruption of the perivascular basement membrane surrounding the VECs. With severe degeneration of the BLB, there was severe vacuolization or frank apparent necrosis of VECs and loss of subcellular organelles. A higher severity of BLB degenerative changes was associated with a higher degree of basement membrane thickening and edematous changes within the vestibular stroma. This study presents the first ultrastructural analysis of the capillaries constituting the BLB in the human vestibular macula utricle from normal and Meniere’s disease.

Section: Discussionmentioning

confidence: 99%

The blood labyrinthine barrier in the human normal and Meniere’s disease macula utricle

López

et al. 2017

Sci Rep

“…Until recently, our understanding of cochlear disorders was based on histologic or molecular findings in postmortem and animal studies. With advances in imaging techniques, however, magnetic resonance imaging (MRI) is now being used in the study of endolymphatic hydrops (EH) and SSNHL . Though the mechanism for SSNHL associated with PDE5 inhibitor use remains unknown, it has been recently reported that inhibition of phosphodiesterase in mice results in EH .…”

Section: Introductionmentioning

confidence: 99%

Sudden hearing loss after cialis (tadalafil) use: A unique case of cochlear hydrops

Wester

Ishiyama²,

Karnezis

et al. 2018

The Laryngoscope

We discuss a unique case of sudden sensorineural hearing loss after Cialis (tadalafil) use, a phosphodiesterase 5 (PDE5) inhibitor, and the implication of ipsilateral cochlear hydrops seen on magnetic resonance imaging (MRI). We report a case of a 53-year-old male with unilateral low-frequency sudden sensorineural hearing loss (SSNHL) after ingestion of tadalafil. The SSNHL occurred 1 day after ingestion and was associated with aural fullness and tinnitus. There were no symptoms of vertigo. He received oral prednisone immediately after the onset of hearing loss without improvement. Delayed intravenous contrast-enhanced three-dimensional Fluid-attenuated inversion recovery MRI revealed ipsilateral dilation of the cochlear duct without any hydronic change in the vestibular system. Acetazolamide therapy was initiated, and his symptoms improved. A posttreatment audiogram revealed an increase in threshold of 15 dB. To the best of our knowledge, this is the first case of cochlear hydrops visualized on imaging after a PDE5 inhibitor induced SSNHL. Tadalafil and other PDE5 inhibitors have a known association with SSNHL. Despite several proposed mechanisms, there is inconclusive evidence of a causal relationship. Our presented case suggests that cochlear hydrops may be one possible mechanism of PDE5 inhibitor-associated SSNHL. MRI should be considered in the evaluation of such patients who do not respond to oral steroids as initial treatment. Laryngoscope, 2615-2618, 2018.

“…Milon and colleagues have suggested the possibility of utilizing estrogen signaling pathway effectors for hearing protection (Milon et al, 2018). In the Bmyc regulon, both metformin and acetazolamide have been associated with attenuation of hearing loss in certain settings (H. C. Chen, Chung, Lu, & Chien, 2019;Muri, Le, Zemp, Grandgirard, & Leib, 2019;Sepahdari, Vorasubin, Ishiyama, & Ishiyama, 2016;Wester, Ishiyama, Karnezis, & Ishiyama, 2018). Metformin, which inhibits Ndufb2, may reduce the incidence of sudden sensorineural hearing loss amongst diabetic patients (H. C. Chen et al, 2019;Muri et al, 2019).…”

Section: Pharos Analysis Identifies Druggable Gene Targets In Cell Tymentioning

confidence: 99%

Single cell and single nucleus RNA-Seq reveal cellular heterogeneity and homeostatic regulatory networks in adult mouse stria vascularis

Korrapati

Taukulis

Olszewski

et al. 2019

Preprint

The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.