The clinical application of head-shaking test combined with head-shaking tilt suppression test in distinguishing between peripheral and central vertigo at bedside vs. examination room

Highlights • Combined HST and the HSTS test have a higher specificity than HST alone.• Repressible horizontal HSN usually suggests a peripheral vertigo specifically.• Findings of the bedside HST + HSTST are consistent with those of VNG.


Introduction
Head-Shaking Nystagmus (HSN) is induced by rapidly shaking and immediately ceasing the head in the horizontal plane; it is a commonly used test to identify the asymmetry between the horizontal Vestibulo-Ocular Reflex (VOR). It is generally agreed that HSN is caused when the central velocity storage system, which includes vestibular nuclei, nucleus prepositus hypoglossi, nodulus and ventral uvula, releases low-frequency and low-velocity vestibular signals generated during the shaking motion. 1 It has been reported that tilting forward may inhibit the horizontal HSN (hHSN). The possible mechanism behind this is that tilting forward excites the otolith organs, which elicit the signals in the direction of gravity 2---4 thus inhibiting the velocity storage system and hHSN. The Head-Shaking Test (HST) and Head-Shaking Tilt Suppression Test (HSTST) can be used in discerning central and peripheral vertigo, respectively; however, their combined use to distinguish between peripheral and central vertigo has been seldom reported. HST and HSTST can be performed at the bedside and in the examination room. Whether the tests performed at the bedside are as reliable as those performed in the examination room needs discussion and support, and to our knowledge, this topic remains unexplored. This study was designed to investigate the clinical value of HST + HSTST in the identification of central and peripheral vertigo and to analyze the consistency of the results of the two tests at the bedside and in the examination room.

Participants
We retrospectively analyzed patients who presented with central or peripheral vertigo at the Balance Center, Department of Otolaryngology-Head and Neck Surgery in Peking Union Medical College Hospital from July 2019 to July 2021. The inclusion criteria were as follows: (1) Either peripheral or central vertigo, suspicious combination of peripheral and central vertigo was excluded by a series of neuroelectrophysiological examinations, physical examinations, and clinical symptoms; (2) Complete clinical data; (3) Completed HST and the HSTS test results at the bedside and in the examination room; and (4) HSN was elicited. The demographic characteristics, diagnosis, and results of HST and the HSTST at the bedside and in the examination, room were collected. The diagnosis was made according to the systematic evaluation of medical history, auditory tests, vestibular examinations, and radiological findings. All patients were divided into the peripheral vertigo group and central vertigo group. This study was exempted from the Institutional Review Board review by the Medical Ethics Committee of Peking Union Medical College Hospital owing to its retrospective design (S-K1760).

HST and HSTST
For HST, patients were made to sit in the clinic room and instructed to wear a video goggle (SRM-PNG, Sireimei Medical Technologies Company, China). The portable goggle has the capacity to block visual fixation but cannot measure the slow-phase eye velocity. Their heads were inclined forward by 30 • and rotated passively in the horizontal plane for 30 cycles at a speed of 2Hz ---3 Hz with the approximate amplitude of head-centered axes of ±10 • by the same physician. Once they were sufficiently relaxed and the nystagmus disappeared, the patients undertook the HSTST. The head was rotated in the same way as in the HST; however, after rotation, patients were immediately instructed to tilt their head forward, rest their chin against the thorax. When the shaking stopped, the direction and intensity of the patient's nystagmus were recorded until it ceased.
All patients were then made to wear a video nystagmograph (VNG, VisualEyes, system2000, Micromedical Technologies, USA) and HST and HSTST were reexamined. The direction and the velocity of the patient's nystagmus were recorded using VNG. The examination room tests were finished by another physician.
HSN may be horizontal (hHSN), vertical, or combined (both horizontal and vertical). HHSN includes unidirectional and bidirectional subtypes. The bidirectional hHSN means that leftward and rightward nystagmus are introduced in succession after shaking the head, and the former nystagmus is recorded as phase I, while the latter is recorded as phase II. Vertical and combined nystagmus are defined as perverted HSN (pHSN), which shows vertical movements of the eyes while shaking the head horizontally. 5 The Tilt Suppression Index (TSI) was calculated according to the velocity of the patient's nystagmus as determined by VNG using the following formula: TSI(%) = slow−phase eye velocity of HSTST slow−phase eye velocity of HST × 100, where TSI < 80% was consid- ered as inhibition, 80% ≤ TSI ≤ 120% was considered as no change, and TSI > 120% was considered as enhancement. 6

Statistical analysis
Data were analyzed using SPSS v. 23.0 (Chicago, IL, USA), and a p value of <0.05 (two-tailed) was considered to indicate statistical significance. Continuous variables that conformed to a normal distribution were reported as mean ± standard deviation and a parameter test was used. Data that did not conform to a normal distribution were reported as median (interquartile range) and a non-parametric test was used. Categorical variables were reported as number (percentage) and were analyzed using the 2 or Fisher's exact test. Receiver Operating Characteristic (ROC) curves were generated to analyze the sensitivity and specificity of HST and HSTST as screening tools at the bedside as well as in the examination room. The kappa statistic test was used to determine the concordance between bedside and examination room results, with a kappa value < 0.4 being inconsistent, and a kappa value ≥ 0.4 being consistent.
In the central vertigo group, 9 (27.3%) patients had hHSN, and 24 (72.7%) had pHSN. Notably, hHSN was much more likely to occur in the peripheral vertigo group than in the central vertigo group (p < 0.001). The inhibition rate of horizontal eye movement by HSTST was much lower in the central vertigo group than in the peripheral vertigo group (p < 0.001). The velocities of hHSN and pHSN in the central vertigo group were not reduced by HSTST (p = 0.238; p = 0.073; p = 0.090, respectively) ( Fig. 2A and Table 1). Fig. 3 shows one case each of peripheral and central vertigo groups.

HST and HSTST results at the bedside
The bedside results of HST + HSTST were quite similar to the results by VNG in the examination room. In the peripheral vertigo group, 35 (79.5%) patients had unidirectional hHSN, which could be suppressed by HSTST in 32 (91.4%) patients. Phase I of bidirectional hHSN was suppressed in all patients, whereas phase II could not be suppressed in any patient. In the central vertigo group, 11 (33.3%) patients had hHSN, which was irrepressible in 9 (77.8%) patients. The majority of the patients had pHSN (66.6%, 22 cases), which could not be suppressed by HSTST (Fig. 2B).

HST vs. HST + HSTST
When VNG was used to screen for peripheral vertigo, the sensitivity and specificity of HST alone were 93.6% and 72.7% and those of HST + HSTST were 80.9% and 93.9%, respectively. The combination showed a >20% higher specificity than HST alone. The bedside results were in agreement with examination room results. The sensitivity declined because the criteria were stricter with the conditions of being horizontal as well as repressible (Table 2 and Fig. 4).

The consistency between bedside and examination room results
The bedside HST results were concordant with examination room results (kappa = 0.658, p < 0.001). The consistency between the results of HST + HSTST at the bedside and those of VNG was also confirmed by the kappa test (kappa = 0.650, p < 0.001) ( Table 3).

Discussion
HST is reportedly a useful, simple, and time-saving test for identifying vestibular disorders. 7---9 HSN may be inhibited when the head tilts forward during HSTST. 10,11 HST and HSTST can be performed either at the bedside or in the examination room; however, to our knowledge, limited studies have reported the consistency between them. The findings of this study supported that the combination of HST and HSTST resulted in an improved specificity over HST alone in differential diagnoses of peripheral and central vertigo. Furthermore, this study assessed the concordance between HST + HSTS performed at the bedside and in the examination room.
In the present study, most HSN in the peripheral vertigo group was horizontal (both examination room and bedside: 93.6%), among which, a small proportion was bidirectional (examination room: 29.5%; bedside: 20.5%). The majority of unidirectional and bidirectional phase I hHSN could be suppressed by HSTST. However, phase II hHSN was rarely  suppressed. This can be explained by the mechanism of HST and HSTST. As mentioned in the introduction, HSN is induced by the central velocity storage system which stimulates nystagmus in the shaking plane, which is in compliance with Ewald's second law. 1,12 Thus, shaking head axially usually generates hHSN. Unidirectional hHSN often originates from acute unilateral peripheral defects, whereas bidirectional hHSN is widely considered an indicator of a transitional phase from acute to compensatory vertigo in unilateral peripheral defects. Phase II is believed to be the result of the compensation of the Central Nervous System (CNS) in response to the asymmetric input signals from bilateral vestibular organs. 7 Tilting the head forward may excite the otolith organs in the gravitational direction but may not work on the compensatory mechanism. 13 Therefore, unidirectional and phase I of bidirectional HSN can  be easily suppressed, but phase II cannot be suppressed by HSTST.
In the central vertigo group, fewer patients (examination room: 27.3%; bedside: 33.3%) had hHSN compared with the peripheral vertigo group (p < 0.001), and bidirectional nystagmus was not observed in the central vertigo group. Higher incidence of pHSN was a characteristic of central group (examination room: 72.7%; bedside: 66.7%), which is in agreement with previous reports. 14---16 Typically, pHSN has been observed in various diseases of the CNS, particularly in migrainous vertigo 17,18 and those closely associated with the cerebellum. 19---21 There are two hypotheses about the mechanism of pHSN. (1) It could be attributed to incorrect connections and projections between the nucleus prepositus hypoglossi and the interstitial nucleus of Cajal, which participate in the horizontal and vertical VOR; (2) It could be attributed to the injured flocculus reducing the inhibition from the CNS to the superior semicircular canal, resulting in the enhanced input signals originating from the superior canal and leading to vertical nystagmus. 17,22---24 In the present study, the hHSN and pHSN were less susceptible to be inhibited in the central vertigo group than in the peripheral vertigo group (p < 0.001), concurring with the previous literature. 8 Lesions damage the velocity storage system located in the brainstem and cerebellum may failed to be suppressed by HSTST as mentioned above.
It seemed that suppressed hHSN could specifically predict peripheral vertigo, whereas pHSN, even with HSTST, was not robust enough to identify central vertigo. Therefore, we studied the possibility of using suppressed hHSN to screen for peripheral vertigo. The solitary HST had high sensitivity but relatively low specificity in the differentiation of peripheral and central vestibular diseases. When used in combination with HSTST, the specificity of the HST was markedly improved by over 20%, indicating that HST + HSTST was more accurate in identifying peripheral vertigo. Considering the sensitivity of HST + HSTST was reduced by 13% compared with HST alone, the results of HST and HST + HSTST were recommended to considered together to complement each other, which was easily completed and applied in the clinic.
This study also compared bedside and examination room results, and consequently, the bedside outcomes were consistent with those of the VNG in the examination room (HST: kappa = 0.658, p < 0.001; HST+HSTST: kappa = 0.650, p < 0.001). The results suggested that bedside HST + HSTST is as capable as VNG in the examination room in identifying peripheral vertigo. The combination of HST and HSTST can be a useful and primary method in the differential diagnosis of vertigo in the clinic.

Conclusion
HST + HSTST can be used to distinguish between peripheral and central vertigo, and suppressed hHSN often suggests a peripheral disease with a relatively high sensitivity and specificity. Furthermore, findings of HST + HSTST at the bedside have good consistency with those of VNG in the examination room, which provides preliminary information and reference for doctors to distinguish between peripheral and central vertigo in the clinic.

Funding
This work was supported by Beijing Natural Science Foundation (7222313) and Key Program of Central HPB, National Health and Family Planning Commission of the People's Republic of China (W2016ZD03).

Availability of data and material
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval
This study was exempted from the Institutional Review Board (IRB) review by the Medical Ethics Committee of Peking Union Medical College Hospital (S-K1760).

Conflicts of interest
The authors declare no conflicts of interest.