Focal Degeneration of Vestibular Neuroepithelium in the Cristae Ampullares of Three Human Subjects

Abstract

Background: We report a unique pattern of focal degeneration of the neuroepithelium of cristae ampullares, thick subepithelial extracellular deposits, and neural degeneration in three humans.

Objective: To characterize the pattern of vestibular degeneration and measure the thickness of subepithelial deposits in these three cases and controls.

Methods: The subepithelial deposits of vestibular end organs in three subject cases and controls were studied using hematoxylin and eosin, periotic acid-Schiff, Gomori trichrome staining, and immunostaining for antineurofilament, antimyosin VIIa, and anticollagen 4a1. The thickness of deposit as measured by light microscopy was compared with that of control groups (age-matched controls, patients with unilateral Menière's disease, vestibular neuritis, cupulolithiasis, severe nonfocal degeneration of the vestibular neuroepithelium, and Alport syndrome). The correlation of thickness of deposits with age from 0 to 100 years was also investigated.

Results: Focal loss of hair cells in the neuroepithelium, thick subepithelial deposits, and degeneration of subepithelial dendrites and Scarpa's ganglion were found in all three cristae of three subject cases. Immunostaining demonstrated a decrease of afferent neural fibers in the cristae and focal fragmentation of the basement membrane adjacent to the deposits. The thickness of the subepithelial deposits in three cristae of three subject cases was significantly greater than that of all controls. In the three cristae of normal controls, the thickness of deposits demonstrated a positive correlation with age.

Conclusion: Although both age and degeneration of the vestibular neuroepithelium may be associated with the thickness of the subepithelial deposits, in this unique pattern of degeneration, the thickness of the subepithelial deposits was significantly greater than that in all controls.

Fig. 1.

Cytocochleogram of right and left ears of cases 1–3. Missing cytological elements are shown in black.

Fig. 2

Histopathology of vestibular end organs of subject cases (H&E stain). Crista of the superior semicircular canal of case 1. A subepithelial deposit (SED) was thickest near an area of focal degeneration of hair cells (FD) which resulted in thinning of the neuroepithelium near the summit of the crista (arrow).

Fig. 2B.

Crista of the posterior semicircular canal of case 3. A subepithelial deposit (SED) was seen below an area of focal degeneration of hair cells (FD) resulting in a cellular monolayer near the summit of the crista (arrow).

Fig. 2C.

Macula utriculi of case 1. There was a thin subepithelial deposit (SED) beneath a normal appearing neuroepithelium.

Fig. 3.

Immunostaining, PAS and Gomori trichrome stains. Anti-myosin VIIa immunostaining of posterior semicircular canal of case 3. The stereocilia and cuticular plate (ST) were immunostained. There was focal degeneration (FD) of hair cells near the summit of the crista.

Fig. 3B.

Anti-myosin VIIa immunostaining of crista of lateral semicircular canal in a control case. Staining of the stereocilia and cuticular plates (ST) of hair cells showed minimal degeneration of hair cells.

Fig. 3C.

Anti-neurofilament immunostaining of crista of the lateral semicircular canal in case 1. There were reduced numbers of nerve fibers (NF) which traversed the subepithelial mesenchyme and also fibers (PF) that were parallel to the base of the hair cells.

Fig. 3D.

Anti-neurofilament immunostaining of lateral semicircular canal in a control ear. Compared to Fig. 3C, more neurons (NF) traversed the mesenchyme, particularly near the summit of the crista, and also, more nerve fibers (PF) were present parallel to the base of hair cells.

Fig. 3E.

PAS staining of the ampulla of the posterior semicircular canal of case 1. A subepithelial deposit (SED) and the basement membrane (BM) located in the lateral walls of the crista were prominently stained. Focal degeneration (FD) of the neuroepithelium was demonstrated.

Fig. 3F.

Gomori trichrome staining of the crista of the posterior semicircular canal in case 1. The subepithelial deposit (SED) was prominently stained near the summit of the crista. There was focal degeneration (FD) of the hair cells of the neuroepithelium near the summit of the crista.

Fig. 3G.

Anti-collagen 4a1 immunostaining of the crista of the lateral semicircular canal of case 1. The basement membrane (BM) was distinguishable from the subepithelial deposit (SED) which is only lightly stained. The basement membrane was fragmented in the area near the summit of the crista (arrows).

Fig. 4.

Comparison of the Thickness of the Subepithelial Deposit. SSC = superior semicircular canal; LSC= lateral semicircular canal; PSC= posterior semicircular canal; Ut = utricle; Sac = saccule. The asterisks (*) indicates the statistical significance (*p<0.05; ** p<0.01; *** p<0.001; Mann-Whitney U test). The mean thickness (micrometers) of the subepithelial deposit seen in the three cristae and both maculae of the three study cases verses age-matched controls (n=22; 80 to 99 years old; mean 87.2 years), and Meniere’s disease, vestibular neuritis, cupulolithiasis, severe non-focal vestibular degeneration, and Alport syndrome. The subepithelial deposit was considerably thicker in the three study cases in the three cristae and only slightly thicker in the utricle and saccule. The mean thickness of the subepithelial deposit of affected ears verses unaffected (Meniere’s disease, vestibular neuritis, cupulolithiasis) or age-matched controls (severe non-focal vestibular degeneration, Alport syndrome) in the vestibular end organs. The age-matched controls for the cases of severe non-focal vestibular degeneration and Alport syndrome consisted of 63 ears (range: 42 to 92 years old, mean 68.7 years) and 43 ears (range: 12 to 60, mean 39.1 years), respectively.

Fig. 5.

Scatter plot of aging population without vestibular symptoms (n=111) verses thickness of the subepithelial deposit in vestibular end organs. The subepithelial deposit was consistently thicker in the three study cases (blue dots) in the three cristae and only slightly thicker in the utricle and saccule than in the aging population (red diamonds). Spearman’s correlation coefficient by rank test demonstrated moderate correlation with SSC and PSC, and a weak correlation with LSC between age and thickness.