Vestibular schwannoma (VS) is the most common (>90%) benign cerebellopontine angle tumor originating from Schwann cells of the 8th cranial nerve (vestibulocochlear nerve). The incidence of VS is 19/1000000 per year, showing no sexual prevalence [1,2]. Over the last four decades, the incidence of VS has increased and the size of the tumor at the time of diagnosis tends to decrease thanks to familiar usage of radiographic imaging for clinical purpose [2,3]. Although MRI shows great sensitivity for VS, it is difficult to use it as a screening test because of its high financial burden and time consuming procedure. Moreover, the report that only 3% of asymmetric sensorineural hearing loss (ASNHL) patients who receive MRI are diagnosed to VS raises a question about the practicality of MRI [4].

Since the late 1970s, the efficacy of auditory brainstem response (ABR) has been supported by many studies. Koors, et al. [5] have performed a meta-analysis of ABR in VS and calculated that the average sensitivity of ABR is 93.4% with an average specificity of 82%, supporting that ABR is a useful diagnostic tool for patients with clinically suspected VS. However, a significant number of patients with high level of hearing loss did not show wave response after auditory stimulation [6-10]. Moreover, for small intracanalicular tumors, ABR showed noteworthy false negative outcomes [6]. Therefore, a new screening test for VS in ASNHL patients which can also be applied to patients with severe to profound hearing loss without false negative, which is easy to perform, and which is cost-effective, is needed.

It is generally accepted that head shaking nystagmus (HSN) is caused by an asymmetrical peripheral vestibular input or an overcompensation of central velocity storage mechanism [11]. HSN can be biphasic sometimes, meaning that the direction of nystagmus after head shaking changes before the nystagmus disappears. After the first announcement of the presence of biphasic HSN [12], generally accepted assumption of biphasic HSN is that it is a result of prolonged vestibular adaption after completion of peripheral vestibular adaption or by central vestibular disturbance [11,13]. Although there are some reports of HSN beating toward lesional side primarily after head shaking, no single satisfactory explanation of this phenomenon has been presented [14-20].

Herein, the authors devised a nystagmus based screening system (NBSS) for VS in ASNHL patients. The NBSS is composed of four different types of nystagmus: vertical spontaneous nystagmus (SN) and direction changing gaze evoked nystagmus (GEN), which are previously studied central sign nystagmus [21-24], and two types of HSN which firstly show ipsilesional nystagmus after head shaking. We also compared the sensitivity and specificity of NBSS with ABR and confirmed the usefulness of the new screening system.

Of 90 patients in the VS group and 90 patients in the non-VS group, 46 and 76 patients passed our exclusion criteria, respectively. PTA, WRS, ABR, bedside vestibular exam (SN, GEN, and HST), and internal auditory canal MRI were performed for every enrolled patient. All data were retrospectively analysed. Table 1 shows demographic and clinical data of patients.

Because the VS usually grows slowly and gradually compresses the nearby structure, there is a sufficient time for human’s vestibular compensation system to fully adjust. This might explain the reason why there is a significant number of patients with VS complain of asymmetric hearing loss rather than acute exacerbation of dizziness. However, since the vestibule-cochlear nerve is an origin of the tumor, there should always be an inherent vestibular dysfunction in patients with VS. The dysfunction might be the result of long-term accumulation of vestibular compensation. Inspired by the concept of interpreting biphasic HSN with adaptation in vestibular nerve [11], it has been proposed that larger loss of vestibular function promotes greater neural adaptation which would be shown as strong compensatory nystagmus after a head shaking test [27]. By extending the previous idea, the authors hypothesized that in a situation when vestibular compensation had been steadily progressed for a long time, the momentary potential of compensation would also increase and the result would be seen as a strong immediate release of excitatory stimuli by ipsilesional side after head shaking. We thought that this concept of vestibular overcompensation could also be applied to VS. Furthermore, to not miss a certain central sign, we included vertical nystagmus and direction changing GEN in our screening system which are known to be the nystagmus occurring by disorganization of neural integrator or impairment of cerebellar gaze-holding mechanism [21,22].

In our study, sensitivity and specificity of presence of nystagmus after head shaking test (positive HSN) were 84.8% and 51.3%, respectively. They were significantly different from previous studies of HSN [14,15], which proposed lower sensitivity of HSN for detecting VS. Humphriss, et al. [14] have reported a sensitivity of 22% as a result of 22 positive HSN among 102 subjects. Asawavichiangianda, et al. [15] have reported a sensitivity of 47.6% calculated by 10 positive HSN among 21 subjects. This discrepancy might be explained by the fact that our study considered positive HSN as the occurrence of more than three beats of nystagmus without any lower limit of degree, while previous studies defined a positive HSN as 5 or more beats with at least 3 degree of slow phase velocity [14] or when at least 5 degree of slow phase velocity occurred [15]. Moreover, no study has suggested the high prevalence of ipsilesional nystagmus (I-Mono and IC-Bi) in VS like us (17 of 39 patients, 43.6%). Rather, the ipsilesional nystagmus was considered as a minor phenomenon violating the Ewald’s second law [14-20]. This difference might have occurred by the setting of the patient that we included in our study. Unlike previous studies which enrolled patients suffering from dizziness, we selected patients who complained of ASNHL regardless of the prevalence of dizziness. Because the majority of the VS arises from vestibular portion of 8th cranial nerve [28,29], those with subjectively detected unilateral hearing loss could be interpreted that the tumor had advanced enough to press the cochlear nerve. Because the VS is a slow growing tumor, it would take a long period for the cochlear nerve to be compressed. Thus, it would have provided sufficient time for vestibular compensation to be accumulated. This inference could explain the high rate of ipsilesional nystagmus by vestibular overcompensation after head shaking in ASNHL patients. Moreover, considering that only 31.8% (7 out of 22) of patients who showed ipsilesional nystagmus after head shaking had subjective dizziness at the time when asymmetric hearing loss was recognized, we assume that vestibular overcompensation could mask the subjective dizziness in VS patients. It could also explain the discrepancy of our result of patients with ASNHL from previous dizziness targeting studies [15-20].

In the patients who showed analysable wave response in ABR, the NBSS alone showed lower sensitivity (45%) than ABR (80%). The ABR has better performance in screening VS compare to NBSS alone when there is a presence of wave response at which the abnormal ABR criteria is applicable. The NBSS alone showed low sensitivity in screening VS. Though we hypothesized the increased momentary potential of vestibular compensation in VS patients, still there were many patients of VS who showed contralateral HSN after head shaking. We expected that momentary potential of vestibular compensation would be increase proportionately to the long term accumulation of vestibular compensation, but this result implies that there might be some other mechanisms affecting the vestibular compensation potential.

When we applied ABR and NBSS together in the patients who showed analysable wave response in ABR, the specificity was the lowest (44%) compared to ABR (52%) and NBSS (88%) alone. Previous study of ABR’s diagnostic performance in VS also showed low specificity (10%-50%) of the ABR [5]. Lowest (44%) result of specificity in combination of ABR and NBSS implies that NBSS was not able to screen the non-VS patient who showed abnormal responses in ABR. There is no single clear explanation to support this, but since the vestibule and cochlear system is not independent pathways, it is acceptable that test using cochlear response (ABR) and vestibular response (NBSS) were not complementary to each other. We would like to emphasize that the strength of NBSS are mainly in the situation when the physician cannot utilize the patients’ auditory system, like the patients with severe to profound hearing loss, as we mentioned above. However, such interpretation should be cautious because there is not enough data of patients and absence of normal control group in this study.

We confirmed that our NBSS could be used as a helpful supplementary material for ABR in detecting ASNHL caused by VS. Additionally, our data showed that a significant number of patients visiting the clinic who were finally diagnosed as VS had severe to profound hearing loss. The ABR was insufficient to screen patients with severe to profound hearing loss, because there was a high rate of absent wave responses after sufficient acoustic stimuli. Our NBSS can be a useful alternative screening method for patients with severe to profound hearing loss without dropped-out cases. However, since there are diverse abnormal criteria of ABR for detecting VS [5], evaluating the efficacy of ABR by single abnormal criteria should be interpreted cautiously. Diverse sensitivity and specificity of ABR in detecting VS had been reported under the different abnormal criteria [5]. Moreover, since the ABR showed unsatisfactory results for small and intracanalicular tumors [5,6], number of such cases involved in different studies could be applied as a bias in evaluating the diagnostic performance of ABR.

Concerning the low cost-effectiveness (low diagnostic yield with high financial burden) and time-consuming process of MRI, the need for alternative screening protocol before imaging has been advocated [30]. To the best of our knowledge, no previous study has analyzed biphasic patterns of HSN in VS or proposed a nystagmus based screening tool using the concept of increased momentary excitatory potential in long termed vestibular overcompensation. Considering that the evaluation of vertical SN, direction changing GEN, and HSN could be completed in a single step approach with little financial burden, we believe that the NBSS could practically help many physicians who has hesitation of managing ASNHL patients in their clinics. The highest sensitivity (84.8%) for VS was adopted in positive HSN result. When we applied the abnormal criteria of ABR and NBSS simultaneously, the satisfactory sensitivity and specificity balance (76.1% and 53.9% for each) were obtained. Therefore, the authors recommend to check the HSN first. If the result is positive, then the physician can continue to proceed ABR and/or the NBSS. The physician can utilize our NBSS as a supplementary method to ABR for diagnosing VS in ASNHL patients.

There are some limitation in this study. First, this is a retrospective study using 1:1 allocation of the VS and non-VS group. Considering the low incidence of VS, there is a worrisome of selection bias that severely effecting the result of this study. Second, there is a significant difference in the duration of hearing loss between the VS and non-VS group. Since this study used a concept of the accumulation of vestibular compensation, difference in hearing loss duration might imply different amount of accumulation between the two groups, which could influenced the direction of HSN. Third, sensitivity and specificity of ABR, NBSS and simultaneous application of ABR and NBSS were relatively low in this study. Therefore, the efficacy of NBSS as a screening tool for VS could be debatable. However, the advantage of this study is in the proposal of nystagmus based screening test for the VS. For the patients with severe to profound hearing loss, ABR seemed unsatisfactory for screening because of the high rate (75%) of absent wave responses. However, since the NBSS is independent of individual’s hearing threshold, it could be helpful especially in those without wave responses in ABR.