Clinical Characteristics of Patients With Dizziness/Vertigo Accompanied by Posterior Semicircular Canal Hypofunction

Objective: To investigate the clinical characteristics of patients with dizziness/vertigo accompanied by loss of the posterior canal(s) (LPC). Methods: Clinical data of 23 patients with LPC were collected. We determined video-head-impulse test (vHIT) gains of all six semicircular canals and correlated vHIT findings with other vestibulo-cochlear tests, including caloric test, ocular and cervical vestibular-evoked myogenic potentials (oVEMP, cVEMP), pure tone audiometry (PTA), and analyzed the differences in clinical manifestations of patients with LPC with different etiologies. Results: LPC was identified in 23 patients. At the time of disease onset, most patients presented with dizziness (47.8%) and vertigo (30.4%) only, and some patients (21.7%) complained of unsteadiness. Among these 23 patients with LPC, there were 14 (60.9%) patients of isolated LPC (ILPC), 21 (91.3%) patients of unilateral LPC (ULPC), and 2 (8.7%) patients of bilateral LPC (BLPC). (1) Among 14 patients with ILPC, 13 (92.9%) patients had unilateral ILPC, the rate of ipsilesional impairment on caloric test, or oVEMP/cVEMP test or PTA ipsilesionally was 53.8% (7/13) in patients with unilateral ILPC. The causes of unilateral ILPC were vertigo/dizziness of unclear origin (38.5%), labyrinthine infarction (15.4%), vestibular migraine (15.4%), and other diseases (30.8%); (2) among 21 patients with ULPC, 7 patients (33.3%) were accompanied with horizontal semicircular canal hypofunction ipsilesionally, the abnormal rate of caloric test, or oVEMP/cVEMP tests or PTA ipsilesionally was 57.1%. The causes of ULPC were vertigo/dizziness of unclear origin (33.3%), autoimmune inner ear disease (14.3%), labyrinthine infarction (14.3%), vestibular neuritis (9.5%), vestibular migraine (9.5%), and other diseases (19.0%); (3) among two patients with BLPC, one patient presented with unsteadiness, the causes of BLPC were vestibular paroxysmia and autoimmune inner ear disease. Conclusion: vHIT is a fast and effective method for assessing LPC, which can be used to detect isolated PC dysfunction. The causes of ILPC were peripheral origin or central origin. Patients with ILPC and ULPC mostly presented with dizziness/vertigo, and ULPC was often accompanied by ipsilateral vestibulo-cochlear impairment.

Methods: Clinical data of 23 patients with LPC were collected. We determined video-head-impulse test (vHIT) gains of all six semicircular canals and correlated vHIT findings with other vestibulo-cochlear tests, including caloric test, ocular and cervical vestibular-evoked myogenic potentials (oVEMP, cVEMP), pure tone audiometry (PTA), and analyzed the differences in clinical manifestations of patients with LPC with different etiologies.

INTRODUCTION
Peripheral vestibular disease is the most common cause of vertigo. Clinical evaluation of peripheral vestibular function often relies on vestibulo-cochlear tests, such as caloric irrigation, vestibular-evoked myogenic potential (VEMP) test and pure tone audiometry (PTA) (1), however, these tests cannot evaluate the function of the posterior semicircular canal(s) (PSCC). With the introduction of video-head-impulse test (vHIT), it is now possible to detect the function of vertical semicircular canals (SCCs). Due to the lack of diagnostic methods and the anatomical proximity of PSCC (2,3) and based on clinical experience, the loss of the posterior canal (s) (LPC) is clinically uncommon. In terms of anatomy, PSCC is indirectly connected to the inferior vestibular nerve and its accompanying blood vessels, the space that the inferior vestibular nerve travels through is relatively broader than the vestibular nerve trunk, as well as the superior vestibular nerve and its accompanying blood vessels. And the bony channel of the superior vestibular nerve is more than seven times longer than the bony channel of the inferior vestibular nerve, it is speculated that the superior vestibular nerve is more susceptible to vascular and inflammatory factors (4,5), but the PSCC is innervated by the inferior vestibular nerve, so LPC is clinically rare. The clinical manifestations are extremely heterogeneous across patients with LPC, LPC can be accompanied by spontaneous, downbeat nystagmus in positional, or head-shaking test. Diagnosing LPC may be extremely difficult because there are no other characteristic symptoms except dizziness or vertigo (6). Therefore, in order to diagnose and treat patients more effectively, the clinical characteristics and possible etiology in patients with LPC need to be further clarified.
Here we included patients with dizziness/vertigo who were diagnosed with LPC by vHIT, collected the clinical baseline data, results of videonystagmograph, caloric irrigation, ocular and cervical VEMP (oVEMP, cVEMP), and PTA, evaluated the vestibulo-cochlear function of these patients and explored the possible etiology of LPC, with hope of improving diagnosis and treatment for LPC.

Clinical Data Collection
The following data were collected from patients' medical records: sex, age, current medical history (course of disease, symptoms during attack, duration of attack, factors induced the attacks, triggering factors, and accompanying symptoms), underlying diagnosis (including labyrinthine infarction, dizziness/vertigo of unclear origin, vestibular neuritis, autoimmune inner ear disease, Ménière's disease, vestibular migraine, otitis media, vestibular paroxysmia, labyrinthine concussion, intralabyrinthine hemorrhage) (Figure 1), results of physical examination upon admission, and auxiliary examinations (such as immune-related laboratory tests, MRI and CT of the brain). Regarding the diagnosis of the above-mentioned underlying diagnosis, labyrinthine infarction, vestibular neuritis, labyrinthine concussion and intralabyrinthine hemorrhage are diagnosed according to patients' medical history, cochleovestibular evaluation and neurovascular imaging (8)(9)(10)(11), vestibular migraine, Ménière's disease and vestibular paroxysmia are diagnosed based on the diagnostic criteria suggested by Barany society (12)(13)(14), autoimmune inner ear disease is diagnosed according the medical history, vestibulocochlear evaluation and immune-related laboratory tests (15,16), otitis media is diagnosed according to the criteria reported by Gates et al. (17).

Vestibulo-Cochlear Tests
vHIT (Interacoustics, Middelfart, Denmark) was used to assess the function of all the six SCCs by measuring the gain of the vestibulo-ocular reflex. The instrument comprises an inertial measurement unit to measure movements of the head and an infrared camera to record eye movements. vHIT can calculate the mean gain value (ratio of eye to head velocity) for each of the six SCCs, and also detect covert or overt saccades. During the test, goggles were secured firmly to patients' head to ensure that the goggles did not slip from the face during head movement. Patients sat ∼1.5 m in front of a wall on which a visual target was affixed. Before testing, head movement and eye movement were calibrated according to the manufacturer's instructions. Patients were told about the detailed test process to ensure that the patient can cooperate with the examination, and patients were asked to sit in upright posture and keep their eyes fixed on the target on the wall while the examiner applies passive, unpredictable, low amplitude and high acceleration head impulses in the planes of stimulation (horizontal plane, rightanterior-left-posterior plane, left-anterior-right-posterior plane) (18). At least 20 acceptable head impulses for each SCC were required. According to manufacture recommendations, normal gain values are expected to range between 0.80 and 1.20 for horizontal canals (19,20), and 0.70-1.20 for vertical canals (7). Pathological saccades and gain values below the normal range were recorded.
In order to assess the function of the otolithic organs, air conduction oVEMP (Interacoustics, Middelfart, Denmark) was used to assess utricle and superior vestibular nerve function (24), and air conduction cVEMP (Interacoustics, Middelfart, Denmark) was used to assess saccular and inferior vestibular nerve function (25).

Statistical Analysis
All data are expressed as the mean ± SD. Enumeration data are expressed as percentage. The chi-square test was used to compare count data between groups. Yates's correction for continuity or the Fisher exact test was used if necessary. All data were analyzed by a two-tailed test, and a level of P < 0.05 was considered statistically significant. All the analyses were performed using SPSS 22.0 software.
Vertigo was presented in 8 (34.8%) patients, including seven patients with ULPC, and 1 patient with BLPC, dizziness was presented in 15 (65.2%) patients, including 14 patients with ULPC, and one patient with BLPC. And among all patients with LPC, 5 (21.7 %) patients presented with gait unsteadiness, including four patients with ULPC, and one patient with BLPC.

Caloric Irrigation and Eye Movement Measurements Results
Among 21 patients with ULPC, a CP value of >25% was found in 9 (42.9%) patients. Of these nine patients, ipsilesional responses to caloric irrigation were impaired in 8 (88.9%) patients. Among different underlying diagnoses, the rates of ipsilesional impairment on caloric irrigation were different, being highest for vertigo/dizziness of unclear origin (4/7, 57.1%, Table 2). Among 13 patients with ILPC, CP value of >25% was found in 5 (38.5%) patients. And of these five patients, ipsilesional responses to caloric irrigation were impaired in 4 (80%) patients ( Table 3). Among 21 patients with ULPC, SN was found in seven patients (2 patients with ipsilesional beating nystagmus, three patients with contralesional beating nystagmus, one patient with down-beating nystagmus, one patient with up-beating nystagmus), and HSN was found in 11 patients (four patients with ipsilesional beating nystagmus, five patients with contralesional beating nystagmus, two patients with down-beating nystagmus). All 21 patients had normal results of gaze-evoked nystagmus, saccades, smooth pursuit, and optokinetic tests.
Among two patients with BLPC, CP value of >25% was found in one patient with ILPC (right HSCC hypofunction), the other patient showed normal caloric test ( Table 5). SN and HSN were found in all patients (down-beating nystagmus). And all patients had normal results of gaze-evoked nystagmus, saccades, smooth pursuit, and optokinetic tests.

oVEMP and cVEMP Results
Among 21 patients with ULPC, two patients showed ipsilesionally reduced oVEMPs, one patient showed contralesionally reduced oVEMPs, 17 patients showed normal oVEMPs, and the remaining one patient did not undergo oVEMP test. While among two patients with BLPC, one patient showed unilaterally reduced oVEMPs, one patient showed normal oVEMPs.
Among 21 patients with ULPC, one patient showed ipsilesionally reduced cVEMPs, four patients showed contralesionally reduced cVEMPs, 15 patients showed normal oVEMPs, respectively, 1 patient did not undergo cVEMP test. Among two patients with BLPC, normal cVEMPs were observed in both patients. Rates of reduced oVEMP and cVEMP in patients with ULPC and BLPC who had different underlying diagnoses were shown in Tables 2-5.

PTA Results
Among 21 patients with ULPC, hearing loss was identified in 10 (52.4%) patients. Of these 10 patients, four patients showed hearing loss ipsilesionally as ULPC, five patients showed bilateral hearing loss, one patient showed hearing loss on the opposite side as ULPC ( Table 2). Among 13 patients with unilateral ILPC, hearing loss was identified in five patients, two patients showed hearing loss ipsilesionally as ILPC, two patients showed bilateral hearing loss, one patient showed hearing loss on the opposite side as ILPC ( Table 3). Vestibulo-cochlear test results for patients with ILPC and non-ILPC were shown in Tables 2-5.
Among two patients with BLPC, bilateral hearing loss was noted in non-ILPC patient, normal PTA finding was observed in one patient with ILPC ( Table 5).

DISCUSSION
Based on the video-head-impulse test, we detected vestibular function in 448 patients with dizziness/vertigo/unsteadiness, LPC was identified in 23 patients, among these patients, ILPC was noted in 14 patients, accounting for 3.1% of all patients studied, and ULPC was more common than BLPC, this result is similar to the previous findings of Tarnutzer et al. (2), suggesting that LPC is uncommon in patients with dizziness/vertigo, vHIT has important value in the diagnosis of LPC (1), which deserves further attention from clinicians.  Table 3). Murofushi et al. (26) reported that patients with vestibular migraine had lesions in the central nervous system or in the peripheral vestibular system, suggesting that the causes of ILPC can be peripheral origin or central origin.

Clinical Characteristics and Etiology of ILPC
The etiologies of ILPC in our study are different from the findings of Tarnutzer et al. (2), they showed that the most frequent underlying diagnoses were Menière's disease, vestibular neuritis, and vestibular schwannoma. In this study, only one patient had Ménière's disease, the reason may be that all patients included in the study were from Vertigo center of Neurology department, they were admitted with chief complaint of vertigo and dizziness, most of patients with Menière's disease experienced hearing loss who visited out-patient clinic were not included. We further compared the differences between patients with unilateral ILPC and unilateral non-ILPC (Table 5), and found that: (1) at the time of disease onset, dizziness/vertigo were more commonly seen in both patients with unilateral ILPC and unilateral non-ILPC (92.3 vs. 62.5 %, p > 0.05); (2) except vHIT, ipsilateral impairment of any of the tests (caloric irrigation, cVEMP, oVEMP, or PTA) was observed in both patients with unilateral ILPC and unilateral non-ILPC (53.8 vs. 62.5%, p > 0.05); (3) diagnoses were clear in most of patients with unilateral ILPC and unilateral non-ILPC (61.5 vs. 75%, p > 0.05). The results suggested that since it is difficult to distinguish between unilateral ILPC and unilateral non-ILPC based on the clinical characteristics of patients, vHIT is the only diagnostic test to distinguish between patients with unilateral ILPC and unilateral non-ILPC.

Clinical Characteristics and Etiology of ULPC
At present, few studies have focused on the clinical characteristics and etiology of ULPC. We found that patients with ULPC most often presented with dizziness/vertigo (17/21, 81.0%), and few patients presented with unsteadiness (4/21, 19.0%). ULPC may be associated with atherosclerosis, inflammation and immunity: (1) in this study, in addition to about 1/3 of  patients with vertigo/dizziness of unclear origin, atherosclerosisassociated factors were the main causes of LPC. The previous studies indicate that patients with labyrinthine infarction are often accompanied by atherosclerosis-related factors, and LPC can occur in patients with labyrinthine infarction. The reason may be that vascular lesions of the branch of internal auditory artery, i.e., the posterior vestibulocochlear artery, may affect the function of posterior canal ampulla and the inferior portion of the saccule (27,28). The above findings are consistent with results of our study showing that the occurrence of LPC may be closely related to atherosclerosis-related risk factors; (2) in addition to possible atherosclerosis-related factors, we found that inflammation can also invade the inferior vestibular nerve and cause ULPC, the cause of ULPC was vestibular neuritis in 9.5% (2/21) patients. Vestibular neuritis mainly affects the vestibular nerve and superior portion of the vestibular labyrinth, and the inferior vestibular nerve is less affected (29). Our result is consistent with the findings of a study by Kim et al. (30), showing that the occurrence of ULPC may be related to inferior vestibular neuritis; (3) in this study, we found that the diagnosis was autoimmune inner ear disease in four patients with LPC, ULPC was noted in three out of these four patients, suggesting that autoimmune inner ear disease may also cause ULPC. Das et al. (16) showed that the typical clinical presentation of autoimmune inner ear diseases is progressive fluctuating hearing loss, both ears and one ear can be involved, and peripheral cochlear function can be affected, but the study did not use vHIT to further investigate the function of the involved vestibular organs and semicircular canals. Our results suggest that the occurrence of LPC may be related to autoimmune diseases. In this study, results of vestibulo-cochlear tests in patients with ULPC showed that except vHIT, ipsilateral impairment of any of the other vestibular-cochlear tests (caloric test, cVEMP, oVEMP, and PTA) was observed in 57.1% (12/21) patients with ULPC (Figure 3). This result is similar to the findings of previous study by Tarnutzer et al. (2), indicating that ULPC is mostly accompanied by vestibulo-cochlear impairment on multiple tests, and there is no significant difference between unilateral ILPC and unilateral non-ILPC (LPC+LHC). In this study, the number of patients who showed normal cVEMPs was high, we speculated that this may be due to that patients were in mild condition and non-acute phase, most patients (78.3%) had disease duration of > 2 weeks, in addition, we only performed air-conduction cVEMP testing in patients, and did not perform bone-conduction VEMP testing, this may also cause low incidence of cVEMPs abnormality.

Clinical Characteristics of BLPC
In this study, we identified 2 (2/23, 8.7%) patients with BLPC. Dizziness with unsteadiness and vertigo are the main complaints of the patients with BLPC. Our results suggest that the occurrence of BLPC may be associated with autoimmune diseases and vascular factors, which can affect bilateral inferior vestibular nerve, causing down beating spontaneous nystagmus, and down beating head-shaking nystagmus (31). Although the HSCC function detected by both vHIT and caloric tests did not meet the diagnostic criteria for bilateral vestibular vestibulopathy (BVP), however, these patients had a vHIT gain of <0.70 for bilateral PSCC, with main complaints of vertigo/dizziness and unsteadiness, which can be used as complementary methods for diagnosing BVP. With the application of new evaluation methods, future research will further refine and improve the diagnostic criteria for subtypes of BVP.

Study Limitations
LPC are relatively rare in clinical practice, so the sample size of the study is small. Further studies with larger sample size are needed to confirm the results. In addition, this study only included patients admitted to our hospital, patients attending outpatient clinics are needed to be included in future studies.

CONCLUSION
vHIT is a fast and effective method for assessing LPC, which can be used to detect isolated PC dysfunction. The causes of ILPC were peripheral origin or central origin. Patients with ILPC and ULPC mostly presented with dizziness/vertigo, and ULPC was often accompanied by ipsilateral vestibulocochlear impairment.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.