Study design and Participants
The study was approved by Ethics Committee of Beijing Tainan Hospital and performed according to the Declaration of Helsinki guidelines. Informed consent was obtained from the participants. We reviewed the medical data of 1002 dizziness/vertigo patients who registered in vertigo/balance disorder registration database of the Clinical Center for Vertigo and Balance Disturbance of Beijing Tiantan Hospital. The definition of dizziness and vertigo was in accordance with the Bárány Society consensus[11]. The eligible patients who met the following criteria for inclusion in this study were: 1) 18≤age≤80 years; 2) complaint of dizziness or vertigo symptom; 3) ability to walk independently without assistance; 4) complete Romberg test, videonystagmography (VNG) and limits of stability (LOS) of computed dynamic posturography (CDP). Exclusion criteria were as follows: 1) contraindication of VNG; 2) any disease history that precludes patients from evaluating of balance state and vestibular function including dementia, visual impairment, acute stroke, movement disorders, musculoskeletal disease, and disease of extraocular muscle. The detailed flowchart figure was shown in the supplementary material.
Demographic and clinical characteristics
Comprehensive history taking questionnaires including demographic and clinical characteristics was performed on all participants. The demographic information was consisted of age and gender. The clinical characteristics referred to symptoms, medical history, and risk factors for atherosclerosis (AS). The medical history included benign paroxysmal positional vertigo (BPPV), Ménière’s disease (MD), sudden deafness, vestibular neuronitis (VN), motion sickness, migraine, hyperthyroidism, anemia, orthostatic hypotension, obstructive sleep apnea-hypopnea syndrome (OSAHS), and traumatic brain injury (TBI). The AS risk factors included age≥60 years, hypertension, diabetes, hyperlipemia, coronary heart disease (CHD), and stroke.
Neurological examination and Romberg test
All participants underwent detailed neurological examination including consciousness, speech, cranial nerve, sensory, and motor. Cerebellum function was assessed: index-nose test, heel-knee test, and Romberg test. The patient was required to stand erect with their feet 10cm apart, and arms raised forward with shoulder-width apart. The definition of subjective imbalance was patients complained of postural symptoms (one of unsteadiness, directional pulsion, balance-related near fall, and balance-related fall) when performing the Romberg test (whether eyes open or close).
Vestibular function evaluation-VNG
All enrolled patients adopted VNG to evaluate the vestibular function. The VNG test (Micro-medical, VisualEyes 20178624, America) included spontaneous nystagmus test, gaze test, saccade test, tracking test, head shaking test, optokinetic nystagmus test, positional test (Roll test or Dix-Hallpike test), and caloric test. To test spontaneous nystagmus, the subject is seated in the upright position with looking straight ahead. The eye movements are recorded for at least 20-30 seconds under two conditions: open eyes in normal bright room and dark room. The subject looked at the four eccentric optotypes in turn, respectively 30 degrees on the left/right and up/down 25 degrees to test gaze. Each direction was recorded for at least 20 seconds. When nystagmus occurred, the observation record was 60s. Spontaneous nystagmus with slow phase velocity (SPV) >3°/sec and gaze-evoked nystagmus >6°/sec were considered abnormal. To test saccade, the subject took a sitting position with head fixed in the middle position, and eyes were 1.2 meters away from the visual target. The subject was asked to look at the target and record their eye movements. Each test lasts at least 1 minute. The visual tracking test was divided into four types: I and II were considered normal, III and IV are abnormal. To test optokinetic nystagmus, the subject sits and looks directly at the front horizontal sight target. The target point is a continuous series of moving light spots at a speed of 20°/s. The subject is required to follow any one of the targets, moving from one end of the sight target to the other end. Bilateral asymmetry is considered abnormal. Head-shaking nystagmus was considered to be present when at least five consecutive beats of nystagmus with a low-phase velocity of at least 2°/sec were detected. To test positional test, the patient was placed in a supine position and the head was turned 90 degrees to the right, returned to a central position, and turned 90 degrees to the other side. To test Dix-Hallpike, the patient sited on the examination table. The examiner turned the patient’s head 45 degrees to the right, keeping the above head position unchanged. Meanwhile, it quickly changed the posture to the supine position, with the head hanging backwards outside the bed at 30 degrees to the horizontal. BPPV patients showed a few seconds of the incubation period, short-term dizziness and vertical rotation nystagmus occurrence. Caloric test was performed with the head supine and tilted forward 30°. Two methods were applied to perform caloric test. One irrigated the right and left ears with cold water (30°C) and hot water (44°C). The other irrigated the right and left ears, respectively with cold air (24℃) and hot air (50℃). The canal paresis (CP) value greater than 25% was defined as abnormal according to the Jongkees Index formula calculation.
Dynamic Balance function evaluation-LOS
The dynamic balance function evaluation was performed using the SMART EquiTest balance assessment system (NeuroCom International, Clackamas, OR, USA). The LOS test can evaluate an individual’s ability to move their center of gravity (COG) to the given eight direction in space., There is a stick figure in the system screen representing the subject’s live-time dynamic center of pressure (COP). The figure is surrounded by eight targets that represent the maximal theoretical stability of patients. When the COP of patients moves, the figure on the screen will move accordingly. Once the voice prompt sounds, subjects need to move their body to the target that appears on the screen and keep balance as much as possible. A total of eight trials were measured, each with 8 seconds. Every trial was incorporated in the equation of the following measurements, which are mean composite (eight directions/trials averaged) scores: 1) Reaction time (RT) is the time from the start of trial to patient’s first movement (seconds); 2) Movement velocity (MVL) is the mean speed of COG movement (degrees/second); 3) Endpoint excursion (EXE) is the distance of COP displacement when initial lean towards target ( % of maximal LOS); 4) Maximum excursion (MXE) is farthest distance of COP displacement during the eight trials ( % of maximal LOS); 5) Directional control (DCL) is a comparison of the amount of movement in the planned direction (towards the target) to the amount of extraneous movement (away from the target). When the MVL, DCL, one of the EXE and MXE were both abnormal according to the results of LOS, we considered it as balance disorder.
Statistical analysis
Continuous variable namely age is described as mean ± standard deviation (SD). Categorical variables are presented as frequency and percentage. Baseline characteristics between normal balance and balance disorder were compared with chi-squared test for categorical and Mann-Whitney U test for age. Multivariable logistic regression analysis was adopted to analyze the risk factors related balance disorder. We incorporated the variable of P<0.2 in the univariate analysis into the multivariable analysis. The receiver operating characteristic (ROC) curve were performed to evaluate sensitivity and specificity of regression model. The “optimum” cut-off value for ROC curve was defined as the value associated with the maximal sum of sensitivity and specificity. Statistical analysis was performed in SPSS 24.0 (IBM, Chicago, IL, USA). Values with P<0.05 were regarded as statistically significant.