Introduction: Dizziness is a common disease. However, approximately 10–40% of patients were diagnosed unknown dizziness even though general, neurological, and otological examinations were performed. The aim of this otopathological study was to investigate the histopathology of the peripheral vestibular system of patients who suffered from undiagnosed dizziness. Methods: Eighteen temporal bone specimens from 9 patients with undiagnosed dizziness and 20 temporal bone specimens from age-matched 10 normal controls were selected. Cases with a history of dizziness and vertigo caused by particular peripheral vestibular disease and central etiology were excluded. Specimens of the vestibular system were carefully assessed by light microscopy. The basophilic deposits adhered to cupulae of the semicircular canals and the wall of the labyrinth were investigated. Scarpa’s ganglion cell counts in the vestibular nerves were performed. Results: Fifteen ears of 9 patients had the findings of vestibular pathology such as a basophilic deposit on cupula (8 ears), on canal wall (7 ears), vestibular nerve loss (8 ears), or vestibular atelectasis (2 ears). Unclear pathological findings such as crista neglecta, subepithelial deposits of the crista ampullaris, and adhesion of the cupula to dark cell area were demonstrated. The mean size of basophilic deposits seen in the patients (mean: 191 µm) was larger than that of latent deposits seen in the normal controls (mean: 101 µm; p = 0.01). Conclusions: We demonstrated some peripheral vestibular pathological findings such as deposit within the semicircular canal, vestibular nerve loss, and vestibular atelectasis and suggested the possible diagnosis of dizziness (benign paroxysmal positional vertigo, presbyvestibulopathy, vestibular atelectasis). These findings will provide a better insight into the multiple etiologies of the unknown dizziness in the elderly.

Dizziness is defined as a subjective sensation of disturbed or impaired spatial orientation without a false or distorted sense of motion, which is distinguished from vertigo with spinning sensation [Bisdorff et al., 2009]. Dizziness is a common clinical complaint in outpatient clinics, emergency, and otolaryngology departments. However, the diagnosis of dizziness is not always easy because of the diversity of the etiology [Newman-Toker et al., 2008]. Even though general physical, neurological, and otological examinations were performed, approximately 10–40% of patients were diagnosed unknown [Newman-Toker et al., 2008; Parker et al., 2019; Nishikawa et al., 2021]. Especially in the elder age, presbystasis or presbyvestibulopathy (PVP) is used to describe an age-related disequilibrium that means specific etiology could not be clinically identified [Agrawal et al., 2019]. Although there were several temporal bone studies concerning vestibular diseases such as benign paroxysmal positional vertigo (BPPV) [Schuknecht 1969; Parnes and McClure, 1992; Welling et al., 1997; Parham, 2014], vestibular neuritis [Schuknecht and Kitamura, 1981; Nadol, 1995], Ménière’s disease [Sando et al., 2002], and presbystasis [Merchant and Nadol, 2010b], less is known concerning the histophysiology of undiagnosed dizziness. Herein, the aim of this study is to investigate the histopathology of the peripheral vestibular system of patients with a history of undiagnosed dizziness using light microscopy.

Selection of Cases

To identify cases with a history of “undiagnosed dizziness,” the database of the National Temporal Bone Hearing and Balance Pathology Resource Registry was used. The keyword dizziness was used for the database search. There were 155 cases with the vestibular symptom dizziness in the collection of Otopathology Laboratory at Massachusetts Eye and Ear (total of more than 2,180 temporal bones). The 18 temporal bones from 9 study cases of patients with undiagnosed dizziness (4 men and 5 women, ranging in age from 64 to 92 years; mean 79.8 years) were identified (Table 1). Exclusion criteria (online suppl. Figure; for all online suppl. material, see www.karger.com/doi/10.1159/000526469) included (1) history of diagnosed dizziness and vertigo caused by a vestibular disorder such as BPPV, Ménière’s disease, vestibular neuritis, sudden sensory neural hearing loss, and superior semicircular canal dehiscence (SSCD); (2) otologic surgery involving the middle and/or inner ear such as tympanoplasty and stapedotomy; (3) dizziness by a central origin such as stroke/intracerebral hemorrhage, leukemia, meningitis, and head trauma; (4) history of headache which was suspected vestibular migraine [Vitkovic et al., 2007]; (5) unknown vertigo which was suspected the orthostatic symptom and category of possible BPPV without observable positional nystagmus [von Brevern et al., 2015] from existent medical records; and (6) severe postmortem changes, such as compression artifact or autolysis.

Table 1.

The presence and size of deposit in the labyrinth in the dizziness cases

 The presence and size of deposit in the labyrinth in the dizziness cases
 The presence and size of deposit in the labyrinth in the dizziness cases

Regarding normal controls, the collection of Otopathology Laboratory at Massachusetts Eye and Ear has 121 individual cases without dizziness nor vertigo from the age 0 to 100. Similar cohorts of controls without vestibular disorders have been studied in our previous study [Okayasu et al., 2018]. Age-matched normal cases having both right and left ears were randomly selected as controls. Twenty temporal bones of age-matched 10 control cases without dizziness and vertigo during life (5 men and 5 women ranging in age from 67 to 96 years; mean 80.9 years) were identified (Table 2).

Table 2.

The presence and size of deposit in the labyrinth in normal controls

 The presence and size of deposit in the labyrinth in normal controls
 The presence and size of deposit in the labyrinth in normal controls

Histologic Preparation

All temporal bones were removed after death and fixed in 10% buffered formalin. The specimens were then decalcified in EDTA, dehydrated in graded alcohols, and embedded in celloidin. Serial sections with a thickness of 20 µm were cut in the horizontal (axial) plane. Every tenth section was stained with hematoxylin and eosin (H&E) and mounted on glass slides for study using light microscopy [Merchant and Nadol, 2010a].

Evaluation of Vestibular System

The cupulae of the 3 semicircular canals were carefully observed by light microscopy. In addition, the lumina of the membranous labyrinth was examined for evidence of deposits. Since the presence of cupula deposits in the labyrinth in normal was also reported [Moriarty et al., 1992; Bachor et al., 2002], we investigated the prevalence of asymptomatic deposit in both study cases with dizziness and normal controls. The size of the deposit was classified as large, medium, and small referring to previous reports [Moriarty et al., 1992; Bachor et al., 2002]. Large was defined as a deposit both whose linear width was greater than half the width of the base of the cupula and whose thickness was greater than or equal to the thickness of the sensory epithelium at the apex seen in cross section (Fig. 1). Medium was a deposit which exceeds the parameter of either width or thickness. Small was a deposit which is less than both of the parameters. Moreover, the diameter of each deposit was measured using imaging software Image J (1.52a) (National Institutes of Health, USA). The diameters of deposit were compared between study cases with dizziness and normal using Mann-Whitney U test. The statistical analyses were performed using GraphPad software (GraphPad Prism version 7.02; GraphPad Software, Inc., La Jolla, CA, USA). p < 0.05 is considered significant.

Fig. 1.

Example photograph of cupulolithiasis and definition of the deposit size. This old woman was clinically diagnosed with BPPV. A two-direction arrow (black) indicated the diameter of the deposit (223 μm) on the cupula of the posterior canal ampulla found in the patient of the left ear. A white two-direction arrow (a) indicated the total width of the base of the cupula. The other white two-direction arrow (b) indicated the thickness of the sensory epithelium at the apex of the crista ampullaris. This deposit was classified as large because the liner width and thickness of the deposit were greater than both parameters: (1) half-width of the base of the cupula and (2) thickness of the sensory epithelium. Medium deposit exceeded either parameter. Small deposit was less than both parameters.

Fig. 1.

Example photograph of cupulolithiasis and definition of the deposit size. This old woman was clinically diagnosed with BPPV. A two-direction arrow (black) indicated the diameter of the deposit (223 μm) on the cupula of the posterior canal ampulla found in the patient of the left ear. A white two-direction arrow (a) indicated the total width of the base of the cupula. The other white two-direction arrow (b) indicated the thickness of the sensory epithelium at the apex of the crista ampullaris. This deposit was classified as large because the liner width and thickness of the deposit were greater than both parameters: (1) half-width of the base of the cupula and (2) thickness of the sensory epithelium. Medium deposit exceeded either parameter. Small deposit was less than both parameters.

Close modal

Scarpa’s ganglion cell (ScGC) counts in the superior and inferior vestibular nerves in study cases with dizziness were performed. The number of counted cells in every stained section at a magnification of ×400 multiplied by a correction factor of 0.88 [Velázquez-Villaseñor et al., 2000] and then multiplied by 10 (to account for unstained sections) gave the total count. According to the normative ScGC count for decades that were previously described [Velázquez-Villaseñor et al., 2000], the percentage of ScGC count per mean ScGC of age-matched normative was calculated. Since there is poor consensus between dizziness and the counts of ScGCs, we referred to the category by Knoll et al. [2019, 2020] classified into 4 groups based on the percentage of ScGCs: normal (≥100%), mild (>67%), moderate (67%≥ to >33%), and severe (33%≥). We regarded the moderate and severe degeneration as symptomatic for dizziness.

Case History and Histopathological Findings

Case 1

The woman had undiagnosed dizziness occurring head movement in her thirties. No nystagmus was identified. She died at 68 years. Histologic study of the left ear showed a large mass of basophilic deposit on the top of cupula of crista ampullaris at the posterior semicircular canal, which was a probable causative factor of cupulolithiasis (Fig. 2a, a1). The detachment of the cupula from the crista ampullaris seemed to be artifact for preparation. There was a moderate decrease in the total number of ScGCs compared with age-matched normative (Table 1).

Fig. 2.

Basophilic deposit of cases 1–3. a Basophilic deposit on the cupula of the posterior canal ampulla of the left ear was seen in case 1. a1 A higher magnification of deposit, which was classified as a large deposit in our criteria. The size of the deposit (221 μm) was similar to that of the deposit (223 μm), which caused cupulolithiasis in Fig. 1. b A huge deposit seen in crista ampullaris at the lateral semicircular canal of the right ear in case 2. c Large basophilic deposit with the fragment of cupula attached on the dark-cell area seen in crista ampullar at the lateral semicircular canal of the left ear in case 2. d Large basophilic deposit (221 μm) attached on the dark-cell area and detached cupula with medium basophilic deposit (73 μm) seen in crista ampullar at the posterior semicircular canal of the left ear in case 2. e Detached cupula with large basophilic deposit seen in crista ampullar at the posterior semicircular canal of the left ear in case 3.

Fig. 2.

Basophilic deposit of cases 1–3. a Basophilic deposit on the cupula of the posterior canal ampulla of the left ear was seen in case 1. a1 A higher magnification of deposit, which was classified as a large deposit in our criteria. The size of the deposit (221 μm) was similar to that of the deposit (223 μm), which caused cupulolithiasis in Fig. 1. b A huge deposit seen in crista ampullaris at the lateral semicircular canal of the right ear in case 2. c Large basophilic deposit with the fragment of cupula attached on the dark-cell area seen in crista ampullar at the lateral semicircular canal of the left ear in case 2. d Large basophilic deposit (221 μm) attached on the dark-cell area and detached cupula with medium basophilic deposit (73 μm) seen in crista ampullar at the posterior semicircular canal of the left ear in case 2. e Detached cupula with large basophilic deposit seen in crista ampullar at the posterior semicircular canal of the left ear in case 3.

Close modal

Case 2

The old man complained of the undiagnosed dizziness occurring in head movement. Nystagmus was not identified. He died at the age of 84 years. Histologic study of the right ear showed huge mass including basophilic deposit and membrane tissue, which seems mass of entwined otolith membrane near the base of crista ampullaris at the lateral semicircular canal of the right ear (Fig. 2b). At the crista ampullaris of the lateral semicircular canal of the left ear, an amorphous mass seemed to fragment of cupula with basophilic deposit was attached on the dark-cell area (Fig. 2c). At the crista ampullaris of the posterior semicircular canal, a large mass of basophilic deposit was attached on the dark-cell area and a detached cupula with medium basophilic deposit was seen (Fig. 2d). Before the huge mass with basophilic deposits and the amorphous mass adhere there, the mass could cause canalithiasis. There was a moderate decrease in the total number of ScGCs compared with age-matched normative.

Case 3

The old woman had undiagnosed dizziness and died at 91 years. Histologic study of the left ear showed a small granulose deposit on the top of cupula of the crista ampullaris at the lateral semicircular canal. At the posterior semicircular canal, there was afloating mass that seemed to fragment of cupula with the basophilic deposit (Fig. 2e). Thisfloating mass was a causative factor of canalithiasis. Since there was no cupula on the top of the ampulla, this mass might be a detached cupula. Even if thisfloating mass was artifact, a cupula with a basophilic deposit was a causative factor of cupulolithiasis. The total number of ScGCs showed mild-to-moderate degeneration compared with age-matched normative.

Case 4

The woman had unknown dizziness at the age of 82–87 years. She died at the age of 92 years. Histologic study of the right ear showed adhesion of medium basophilic deposit on the labyrinth wall adjacent to the crista ampullaris of the posterior semicircular canal (Fig. 3a). If the depositfloated within the semicircular canal, it possibly caused canalithiasis. There were smaller granulose deposits on the opposite wall of the dark-cell area where the metabolism of otoconia and endolymph takes place [Igarashi, 1989]. The total number of ScGCs showed mild degeneration compared with age-matched normative.

Fig. 3.

Basophilic deposit of cases 4–6. a Medium basophilic deposit adhered on the labyrinth wall adjacent to the crista ampullaris of the right posterior semicircular canal in case 4. There were little granulose deposits on the wall of the dark-cell area (arrowheads). b Three basophilic deposits (red bars) and the fragment of cupula with basophilic deposit (blue arrow) adhered on the labyrinth wall of the right posterior semicircular canal in case 6. c Macula utricle of left ear in case 7. The granulose deposit on the wall was identified between the macula utricle and the crista ampullaris of the lateral semicircular canal. C1 is the high magnification of the red square. The granulose deposit seemed to be absorbed. d Large basophilic deposit and amorphous mass (arrowhead) adhered on the labyrinth wall of the left superior semicircular canal in case 8.

Fig. 3.

Basophilic deposit of cases 4–6. a Medium basophilic deposit adhered on the labyrinth wall adjacent to the crista ampullaris of the right posterior semicircular canal in case 4. There were little granulose deposits on the wall of the dark-cell area (arrowheads). b Three basophilic deposits (red bars) and the fragment of cupula with basophilic deposit (blue arrow) adhered on the labyrinth wall of the right posterior semicircular canal in case 6. c Macula utricle of left ear in case 7. The granulose deposit on the wall was identified between the macula utricle and the crista ampullaris of the lateral semicircular canal. C1 is the high magnification of the red square. The granulose deposit seemed to be absorbed. d Large basophilic deposit and amorphous mass (arrowhead) adhered on the labyrinth wall of the left superior semicircular canal in case 8.

Close modal

Case 5

The woman had undiagnosed dizziness and died at the age of 80 years. Histologic study of the left ear showed adhesion of medium basophilic granulose deposit on the labyrinth wall adjacent to the crista ampullaris of the lateral semicircular canal. Interestingly, crista neglecta was found at the wall close to the cribriform area of the singular nerve interior to the crista ampullaris of the posterior semicircular canal in the left temporal bone (Fig. 4a). The prevalence of crista neglecta was reported at 0.9–7.6% [Montandon et al., 1970; Okano et al., 1978] in humans. To our knowledge, there had not been a clinical case report of the patients with crista neglecta who complained the dizziness and vertigo. The relationship between crista neglecta and vestibular disorder is unknown [Okano et al., 1978]. The number of ScGCs showed moderate-to-mild degeneration compared with age-matched normative.

Fig. 4.

Other observations with the possibility of pathology. a The posterior semicircular canal of the left ear in case 5. Crista ampulla and crista neglecta (arrowhead) were seen. b The crista ampulla of lateral semicircular canal of the left ear in case 6. An SED was observed below the summit of the crista. Large basophilic deposits were attached on the dark-cell area. c The lateral semicircular canal of the right ear in case 7. Cupula attached to the dark-cell area. c1 and c2 are high magnification of red squares. The adhesion seemed tight and dark cells seemed to proliferate to the cupula. d The lateral semicircular canal of the right ear in case 8. Cupula collapsed and tightly attached to the dark-cell area.

Fig. 4.

Other observations with the possibility of pathology. a The posterior semicircular canal of the left ear in case 5. Crista ampulla and crista neglecta (arrowhead) were seen. b The crista ampulla of lateral semicircular canal of the left ear in case 6. An SED was observed below the summit of the crista. Large basophilic deposits were attached on the dark-cell area. c The lateral semicircular canal of the right ear in case 7. Cupula attached to the dark-cell area. c1 and c2 are high magnification of red squares. The adhesion seemed tight and dark cells seemed to proliferate to the cupula. d The lateral semicircular canal of the right ear in case 8. Cupula collapsed and tightly attached to the dark-cell area.

Close modal

Case 6

From the age of 67 years, the man had undefined dizziness for more than 10 years. An audiogram showed bilateral downsloping sensory neural hearing loss consistent with age. The central cause of dizziness was negative by neurological evaluations and magnetic resonance imaging (MRI). He died at the age of 82 years. Histologic study of the left ear showed medium basophilic granulose deposits and an amorphous large mass (120 µm) that seemed to fragment of cupula on the labyrinth wall because the cupula of crista ampullaris of the lateral semicircular canal was disappeared (Fig. 3b). In the right ear, there were adhesions of large basophilic deposits on the labyrinth wall adjacent to the crista ampullaris of the lateral semicircular canal (Fig. 4b). In all three cristae ampullares of bilateral temporal bones, there were subepithelial amorphous extracellular deposits under the neuroepithelium (Fig. 4b). However, whether these unique subepithelial deposits (SEDs) of cristae ampullares cause disequilibrium or not is unknown. The detail of otopathological evaluation on SED was described in our previous study [Okayasu et al., 2018]. The number of ScGCs showed mild degeneration compared with age-matched normative.

Case 7

The man had undiagnosed dizziness spells related to height and position. He died at the age of 77 years from heart failure. In the histologic study of the left ear, there was a medium granulose deposit on the top of the cupula at the posterior semicircular canal. The absorption of the granulose deposit by the dark cells was identified at the wall between the crista ampulla of the lateral semicircular canal and macula utricle (Fig. 3c, c1). There was afloating mass that seemed to fragment of cupula near the utricle. In the right ear, there was the adhesion of an amorphous mass, which seems fragment of cupula on the dark-cell area (Fig. 4c). At the larger magnification, the dark cells stretched toward amorphous mass (Fig. 4c1, c2), which suggested that the mass had adhered antemortem time. This contact may suggest that the dark cells play a role to absorb the fragment cupula likewise the metabolic system of otoconia. The detail of the metabolic system of the cupula is unknown. The number of ScGCs showed mild degeneration compared with age-matched normative.

Case 8

The woman had occasional dizziness. The etiology was unknown. She died at the age of 64 years from acute myocardial infarction. In the histologic study, there were the adhesion of deposits and amorphous mass on the dark-cell area in the superior (Fig. 3d), lateral, and posterior semicircular canal of the left ear, the translocation of cupula from the summit of the ampulla to the dark-cell area at the lateral semicircular canal of the right ear (Fig. 4d) and the posterior semicircular canal of the left ear. The number of ScGCs in the left ear showed moderate degeneration compared with age-matched normative. The vestibular nerve of the right ear was not identified in the internal auditory canal due to avulsion during the extraction of the temporal bone.

Case 9

At the age of 77 years, this man had undiagnosed dizziness spells occurring once every 2 days, lasting 1–2 min, and related to turning head. Caloric tests using 5 mL cold water gave no action on either side. He died at the age of 80 years from coronary heart disease. In the histologic study of the right ear, there was the near-total collapse of the walls of the superior and posterior ampullae and partial collapse of the lateral ampulla (Fig. 5a–c). In the left ear, there are the partial collapse of the wall of the lateral ampulla (Fig. 5d) and minimal collapse of the superior and posterior ampullae what is called “vestibular atelectasis.” The hair cells of vestibular sensory organs appear normal in both ears. The number of ScGCs in the right ear showed normal to mild degeneration compared with age-matched normative. The inferior vestibular nerve of the left ear was partially avulsed. Merchant and Schuknecht [1988] described that the collapse of the ampullary walls in both inner ears was expected to explain the symptoms of dysequilibrium since those collapses of the labyrinth would interfere with the motion mechanics of the cupula.

Fig. 5.

Vestibular atelectasis. a–c Near-total collapse of the labyrinth walls of the superior (a) and posterior (b) and partial collapse of the lateral semicircular canal (c) in the right ear of case 9. Basophilic deposit attached on the cupula at the posterior semicircular canal (b). d The partial collapse of the lateral semicircular canal was seen in the left ear of case 9.

Fig. 5.

Vestibular atelectasis. a–c Near-total collapse of the labyrinth walls of the superior (a) and posterior (b) and partial collapse of the lateral semicircular canal (c) in the right ear of case 9. Basophilic deposit attached on the cupula at the posterior semicircular canal (b). d The partial collapse of the lateral semicircular canal was seen in the left ear of case 9.

Close modal

Normal Controls

All 10 normal controls (16 of 20 ears) without dizziness and vertigo in their life had the small to large otolithic deposit on the cupula or labyrinth wall. The presence and size of deposits in the labyrinth in the normal controls are shown in Table 2.

Quantitative Assessment of Deposit

The mean diameter of deposit for the study cases with undiagnosed dizziness (mean: 191 µm, median: 145 µm) was greater than that of normal control (mean: 101 µm, median: 73.3 µm; p = 0.01).

This otopathological study has identified some of the peripheral vestibular pathological changes for the 9 patients with unknown dizziness during their life. Various possible etiologies such as BPPV, degeneration of the vestibular nerve, and vestibular atelectasis were speculated.

The otolithic deposits on the cupula or labyrinth wall were commonly seen in temporal bones of both patients with dizziness (72.2%; 13/18 temporal bones) and controls (80%; 16/20 temporal bones) with no dizziness and vertigo. These findings agree with the previous reports that cupular deposits were identified not only in the patients with BPPV but also in normal [Moriarty et al., 1992] and children [Bachor et al., 2002]. It is difficult to prove whether the deposits were made antemortem or postmortem. However, the huge deposit in case 2 (Fig. 2b) was presumed the tangle of membranal tissue caused by convective movement of the endolymph rather than artifact preparing the specimen. This large deposit was similar to the fragment of the otolithic membrane extracted from the posterior semicircular canal during posterior semicircular canal occlusion [Kao et al., 2017]. The adhesion of cupula to dark cells seemed tight (Fig. 4d) and dark cell seemed to proliferate (Fig. 4c1, c2). These histologic features suggested the antemortem formation.

BPPV is believed to be caused by the displacement of particulate matter, likely fragments of otoconia from the utricle, into the semicircular canals. Complete BPPV is diagnosed by the observation of canal-specific positional nystagmus explained by the theory of cupulolithiasis and canalithiasis [von Brevern et al., 2015]. Patients with positional vertigo without positional nystagmus and those who denied the other vestibular disease are diagnosed with possible BPPV [von Brevern et al., 2015] or subjective BPPV [Tirelli et al., 2001; Haynes et al., 2002; Huebner et al., 2013]. Several temporal bone studies reported that the basophilic deposits were resent on the cupula 22–63% [Schuknecht and Ruby, 1973; Moriarty et al., 1992; Naganuma et al., 1996]. Movement of free-floating debris was identified within the semicircular canal in the patients with BPPV [Parnes and McClure, 1992; Welling et al., 1997]. The clinical remission by physical maneuvers [Epley, 1992; Lempert, 1996] and head-up sleep [Horinaka et al., 2019] suits the theory caused by otoconia. A study using the hydrodynamic calculation model reported that larger cupular volume displacement and nystagmus could result from larger and/or multiple otoconia and a deposit with the diameter of 15 µm would cause the nystagmus of order 2º/s, which is approximately the threshold for the sensation of rotation [Squires et al., 2004]. Once the otoconia approach the wall, the pressure on the cupular volume displacement decays. Another study using the physicomathematical model predicted that the mass of particles with the diameter of 39.4 μm and the mass of 0.69 μg contributed the cupulolithiasis [House and Honrubia, 2003]. To our knowledge, this is the first histopathological study of the human temporal bone to compare the size of otolithic deposits quantitatively. The diameter of the deposit in dizziness cases was significantly greater than that of normal control. Moreover, the mean diameter of deposit 191 µm was greater enough than the diameter 15–39.4 µm, which caused the threshold for sensation or cupulolithiasis. Indeed, these findings suggested that the size of the deposit is an important factor of dizziness sensation and remained the possibility that these deposits caused the dizziness in some patients of this study.

Since the total number of the ScGC in 6 dizziness cases (8 temporal bones) tended to be less than that of normal, the degeneration of the vestibular nerve also possibly causes dizziness. However, how much loss of ScGCs causes dizziness is unknown. Another alternative diagnosis is PVP. PVP is a diagnostic criterion defined by the Bárány Society as a chronic vestibular syndrome characterized by unsteadiness, gait disturbance, and/or recurrent falls in the presence of mild bilateral vestibular deficits, with findings on laboratory tests that are between normal [Agrawal et al., 2019]. To diagnose PVP, a vestibular test is needed to confirm the bilaterally reduced function of the vestibulo-ocular reflex. However, there were no medical records of recently developed tests such as video head impulse test.

As seen in case 9, our study cases included a patient with vestibular atelectasis [Merchant and Schuknecht, 1988]. The vestibular atelectasis was the clinically classified primary (paroxysmal or insidious) and secondary type. The primary vestibular atelectasis is also one of the probable causes of dizziness, which is difficult to diagnose. Recently, 3-Tesla MRI after intravenous administration of gadolinium has enabled to evaluate both endolymphatic hydrops [Ito et al., 2016, 2019] and vestibular atelectasis [Eliezer et al., 2019]. As the spreading of the 3-dimensional MRI analysis on the labyrinth, more patients with undiagnosed dizziness could be diagnosed as vestibular atelectasis.

This study included the case with a crista neglecta and SED of crista ampulla, which have not concluded the association with dizziness. To accumulate the temporal bone study, it is expected that a relation between dizziness and these findings is elucidated.

Study Limitations

The study has several limitations. Artifactual changes of the cupula and granulose deposit during histological preparation using EDTA in the decalcification process which dissolved otoconia cannot be completely ruled out. The clinical history of some cases may have been incompletely reported in medical records. The time lag between dizziness and death could have affected modified histopathological changes by various other factors. The dizziness of some cases had resolved. The investigation of the superior semicircular canal between the top and crista ampullaris, which is important for the study about SSCD, might be insufficient. Some temporal bone specimens were missing the section of this part because the top of the superior semicircular canal was trimmed in the preparing process to enhance the infiltration of the fixative solution. At least, this study excluded the temporal bones diagnosed with SSCD in our registry by CT prior to histologic preparation [Kamakura and Nadol, 2017; Lin et al., 2019]. Finally, our sample was small.

This temporal bone study identified some of the peripheral vestibular pathological changes. We have also speculated about possible etiologies causing undiagnosed dizziness in these cases. These findings will provide a better insight into the multiple etiologies and multifactorial system of dizziness in the elderly.

The authors thank Diane Jones, Barbara Burgess, Jennifer O’Malley, and Meng Yu Zhu for their expert preparation of the temporal bone specimen, and Garyfallia Pagonis for helpful technical in creating digitized images of the temporal bone sections.

The study was conducted in accordance with the World Medical Association Declaration of Helsinki. The study was approved by the Institutional Review Board of the Massachusetts Eye and Ear under exemption No. 4. All cases have given written informed consent and approved to the sharing of clinical information and pathological findings.

The authors have no conflicts of interest to disclose. Joseph B. Nadol Jr., an author of this manuscript, is a Section Editor of this journal. Otherwise, the author has no conflicts of interest to declare.

This work was supported by Grant #U24-DC013983 from the National Institute of Deafness and Other Communication Disorders (NIDCD).

Conceived and design of the study, and writing the manuscript and approval: Tadao Okayasu, Takefumi Kamakura, Tadashi Kitahara, and Joseph B. Nadol Jr. Execution and analysis: Tadao Okayasu, Takefumi Kamakura, and Joseph B. Nadol Jr.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further enquiries can be directed to the corresponding author.

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