GRAPHICAL ABSTRACT

INTRODUCTION

Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterized by autonomic failure, parkinsonism, and cerebellar and pyramidal signs. Along with Parkinson’s disease (PD) and dementia with Lewy bodies showing alpha-synucleinopathy in neurons, MSA is thought to be caused by the accumulation of aggregated alpha-synuclein in oligodendrocytes [1]. The diagnosis is often challenging, especially in the early stages, owing to the overlap in the clinical phenotype with other alpha-synucleinopathies. Therefore, MSA can often be misdiagnosed as PD, especially in the early stages.

In such cases, catching the slight differences in their clinical feature can aid in the differential diagnosis. In addition to parkinsonism, patients with MSA usually exhibit dysarthria, dysphagia, recurrent falls, and profound autonomic failure without the psychiatric side effects of antiparkinsonian drugs [2]. Furthermore, ancillary diagnostic modalities such as brain magnetic resonance imaging, ^[18F]-fluorodeoxyglucose positron emission tomography, and ^[123I]-metaiodobenzylguanidine cardiac scintigraphy can be helpful [3,4]. However, imaging findings often overlap without a generally accepted cutoff point for differentiation between the two pathologies; this further contributes to only 25% of patients being correctly diagnosed at initial presentation [5], and 20%–38% of patients are diagnosed otherwise on autopsy [6].

In addition to these diagnostics, vestibular-evoked myogenic potentials (VEMPs) provide valuable information regarding the involvement of the central vestibular system and the extent of brainstem dysfunction in neurodegenerative disorders [7,8]. The vestibular system is highly interconnected with the autonomic nervous system. Accordingly, VEMPs may be relevant in the development of orthostatic hypotension (OH) [9,10], a core feature both in MSA and PD patients.

It is largely agreed upon that VEMP responses can be altered in PD [11]. Defining this can be important since VEMP abnormalities can be related to compromised balance, risk of falling, or severe rapid eye movement sleep behavior disorders [12]. However, the prevalence and pattern of VEMP abnormalities in MSA remain largely unknown.

The pattern of VEMP responses has been reported as anecdotal evidence; however, some discrepancies remain. Some researchers have reported that cervical VEMP (cVEMP) is mostly preserved in MSA [13]. Conversely, another study has reported that ocular VEMP (oVEMP) is usually delayed and decreased [14]. In this study, we systematically compared the prevalence and clinical implications of cVEMP and oVEMP abnormalities between MSA and PD patients; we also assessed their diagnostic yield for differentiating MSA from PD and their relevance in the development of OH.

MATERIALS & METHODS

Patients

We retrospectively reviewed the medical records of 30 patients with MSA and 59 patients with de novo PD who underwent neurotologic evaluation between January 2021 and March 2023 at the Korea University Medical Center. We defined “de novo” as an individual newly diagnosed, not yet taking prescribed PD-specific medication at and prior to presentation. MSA and PD were diagnosed according to the Movement Disorder Society criteria [15,16]. All patients with PD met at least one supportive criterion for diagnosis, with no absolute exclusion criteria present. In addition, none of the patients developed red flag signs suggesting atypical parkinsonian syndrome initially or during follow-up (median follow-up period = 2 years, interquartile range [IQR] = 20–26 months).

We excluded patients with a history of central or vestibular disorders, including vestibular neuritis (n = 5), posterior circulation stroke (n = 4), Meniere’s disease (n = 2), and vestibular migraine (n = 2), which may have affected the VEMP results. Electrophysiologic studies (oVEMP, cVEMP, and head-up tilt [HUT]) were conducted before the administration of PD-specific medication in all patients.

Finally, 24 patients with MSA (18 with clinically established MSA and six with clinically probable MSA; 16 with MSA-cerebellar type and eight with MSA-parkinsonian type) and 52 patients with de novo PD were included in the analyses.

This study followed the tenets of the Declaration of Helsinki and was performed according to the guidelines of the Institutional Review Board of Korea University Anam Hospital (2023 AN0442). The written informed consent was obtained from all participants.

oVEMP and cVEMP

oVEMPs and cVEMPs were recorded by one examiner using a Nicolet Viking Select unit (Nicolet-Biomedical, Madison, WI, USA) as described previously [9].

oVEMPs were elicited by tapping the hairline at the AFz using an electric reflex hammer (VIASYS Healthcare, Conshohocken, PA, USA). Bilateral responses were recorded simultaneously after applying the tapping stimuli. Up to 60 tapping stimuli were applied at a 2 Hz frequency and approximately 0.45 g of force. The responses were averaged for each test, and the average latency of the initial negative peak (n1) and n1–p1 amplitude were determined. oVEMP responses were obtained at least twice, and the mean was calculated. The interaural difference (IAD, %) of the oVEMP amplitudes was calculated as [100 × (A_Right − A_Left)/(A_right + A_left)], where A is the n1–p1 amplitude.

cVEMPs were recorded with the patient lying supine on a bed, with the head raised by approximately 30° and rotated to one side to contract the sternocleidomastoid muscle (SCM). A short burst of alternating tone (110 dB nHL, 123.5 dB SPL, 500 Hz, rise time = 2 ms, plateau = 3 ms, and fall time = 2 ms) was applied at a 2.1 Hz frequency monoaurally via headphones. The signal was sampled (48 kHz), amplified, and bandpass-filtered at 30–1,500 Hz. No rectification or smoothing was performed while the cVEMP responses were recorded. cVEMP responses for up to 80 stimuli were averaged for each test. Responses were obtained at least twice for each ear, and the mean values were calculated.

Absolute cVEMP amplitudes were normalized and divided by the mean tonic activation of the SCM during recording. To compare the normalized p13–n23 amplitudes of cVEMP between the right and left sides, the IAD (%) was calculated. The peak latency of p13 was also calculated. To determine the reference ranges, oVEMP and cVEMP responses of 16 healthy participants (nine men, mean age ± standard deviation [SD] = 65 ± 9 years) with no prior history of auditory or vestibular disorders (reference range for oVEMP: n1 latency < 8.32 ms, IAD < 23.9%; reference range for cVEMP: p13 latency < 19.4 ms, normalized p13–n23 amplitude > 1.1 μV, IAD for cVEMP < 31.0%) were used [17].

For statistical analysis, the average values of both sides (right + left/2) were calculated for n1 and p13 peak latencies and n1–p1 and p13–n23 amplitudes. For IAD, the absolute values were used for statistical analyses. Patients with no VEMP responses on either side were excluded from the correlation analyses between amplitudes/latencies and Finometer parameters.

HUT test using the Finometer

The HUT test was performed as described previously [9]. Any medications that may affect the results of the autonomic function tests were discontinued for at least 48 hours before the test in all patients. To monitor the continuous changes in blood pressure (BP) during tilting, beat-to-beat BP was measured via a Finometer (Finapres Medical System BV, Amsterdam, The Netherlands). Predefined 5-s time averaging was applied via Beatscope software (Finapres Medical System BV) [18]. We measured the maximum changes in systolic BP (SBP) and diastolic BP (DBP) at 15 s (∆SBP_15s, ∆DBP_15s), 3 min (∆SBP_3min, ∆DBP_3min), and 10 min (∆SBP_10min, ∆DBP_10min) after the initiation of the tilt.

OH was categorized into initial, classic, and delayed types according to the decrease in BP [19,20]. Neurogenic OH was diagnosed when there was a blunted increase in heart rate (HR) relative to a ∆HR_3min/∆SBP_3min ratio < 0.5 or HR_3min < 17 bpm [21]. Classic OH was defined as a sustained BP drop of at least 20 mmHg or 10 mmHg in SBP or DBP, respectively, within 3 min after tilting the table. Delayed OH was defined as a sustained drop in BP that occurred >3 min after tilting the table. For patients with supine hypertension, a drop in BP of at least 30 mmHg was required because the magnitude of orthostatic BP decrease is dependent on the baseline BP. Initial OH was defined as a transient decrease of >40 mmHg in SBP or 20 mmHg in DBP within 15 s upon standing.

Assessment of ataxia and parkinsonism

The severity of ataxia in patients with MSA was evaluated using the semiquantitative ataxia scale (Scale for the Assessment and Rating of Ataxia [SARA]) and the Unified Multiple System Atrophy Rating Scale (UMSARS) I and II. The severity of motor disability in patients with PD and MSA was assessed using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS motor part) and Hohen and Yahr (H&Y) stages.

Statistical analysis

Nominal/independent variables were compared using the χ² test or Fisher’s exact test. Continuous/independent variables were compared using the Student’s t-test (parametric variables such as n1, p13, and p23 latencies, baseline SBP, baseline DBP, HR, body weight, ∆SBP_{15s, 3min, 10min}, and ∆DBP_{15s, 3min, 10min}), the Mann–Whitney U test (nonparametric variables such as n1–p1 and p13–n23 amplitudes, Composite Autonomic Scoring Scale [CASS], and Composite Autonomic Symptom Score 31 [COMPASS 31]), and Spearman’s correlation. For regression analysis, age, sex, and variables with a p value < 0.2 in univariate analysis were included in the multivariate analysis. In addition, other variables of interest (oVEMP and cVEMP abnormalities and neurogenic OH) were included in the analysis. A p < 0.05 was considered significant in multivariable analysis.

Statistical analyses were performed using the R software package (version 3.4.0; http://www.r-project.org), and the significance level was set at two-tailed p < 0.05.

RESULTS

Clinical characteristics

The clinical profiles of the patients are summarized in Table 1. A total of 24 patients with MSA (mean age ± SD = 65 ± 10 years, 15 men) and 52 with PD (69 ± 12 years, 27 men) were included in the analyses. The MDS-UPDRS-III (median [IQR] = 38 [27–53] vs. 27 [22–33], p = 0.079), CASS (4 [3–5] vs. 4 [2–6], p = 0.796), and COMPASS-31 (22 [12–29] vs. 19 [9–31], p = 0.973) scores did not differ between the two groups. However, patients with MSA had higher H&Y stages than those with PD (2.5 [2.5–3] vs. 2.0 [2.0–2.5], p = 0.002). Hypertension (p = 0.011) and diabetes mellitus (p = 0.026) were more commonly observed in patients with PD than in those with MSA.

oVEMPs

oVEMP values were abnormal in 37 patients (37/76, 49%), unilaterally in 19 (13 during left ear stimulation), and bilaterally in 18. Among the 55 ears (37 patients) whose results were abnormal, n1 responses were absent in 38 ears, delayed in 10 ears, and decreased in 9 ears (including two ears with both decreased and delayed responses). The frequency of oVEMP abnormalities did not differ between patients with MSA versus PD (p = 0.127) (Table 2). The n1 latency (7.0 ± 1.6 ms vs. 7.0 ± 1.3 ms, p > 0.999) and n1–p1 amplitude (7.7 ± 6.3 μV vs. 8.2 ± 6.4 μV, p = 0.733) did not differ between patients with PD and those with MSA. IAD also did not differ between the two groups (7.2% [2.4%–38.9%] vs. 10.0% [3.5%–15.5%], p = 0.717).

cVEMPs

cVEMP values were abnormal in 24 patients (24/69, 35%, excluding seven patients with poor SCM contraction [four with MSA and three with PD]), bilaterally in 14 patients and unilaterally in the other 10 patients (four during right ear stimulation). Among the 38 ears (24 patients) whose results were abnormal, normalized p13–n23 responses were decreased in 24 ears, absent in 14 ears, and delayed in nine ears (nine ears showing both decreased and delayed responses). The frequency of cVEMP abnormalities did not differ between patients with MSA and those with PD (p = 0.510) (Table 2). Further, there were no differences in p13 (15.1 ± 3.8 ms vs. 15.9 ± 2.3 ms, p = 0.321), normalized p13–n23 amplitude (1.7 ± 1.5 μV vs. 2.1 ± 1.2 μV, p = 0.219), or IAD (7.1% [2.1%–39.4%] vs. 10.0% [3.5%–15.5%], p = 0.142) between patients with MSA and those with PD (Table 2).

HUT with the Finometer

Neurogenic OH, including classic OH (n = 36), initial OH (n = 1), and delayed OH (n = 2), was observed in 39 patients (39/76, 51%). The frequency of OH was similar between the two groups (p = 0.185) (Table 3). The Finometer parameters were also not different between the two groups, except for a higher baseline DBP in patients with MSA than in those with PD (74 ± 15 mmHg vs. 66 ± 11 mmHg, p = 0.015).

Correlation of VEMP findings with Finometer parameters and clinical findings

The statistics for the correlations between the oVEMP and cVEMP values and the Finometer parameters are listed in Supplementary Tables 1 and 2 (in the online-only Data Supplement).

The n1 latency was negatively correlated with ∆SBP_15s in patients with PD (r = -0.335, p = 0.040) but not in those with MSA (r = 0.277, p = 0.299) (Figure 1 and Supplementary Table 1 in the online-only Data Supplement). The n1–p1 amplitude, normalized p13–n23 amplitude, and IAD were not associated with the Finometer parameters in patients with PD.

p13 latency was positively correlated with ∆SBP_15s in patients with MSA (r = 0.604, p = 0.029) but not in those with PD (r = 0.068, p = 0.670). The normalized p13–n23 amplitude was positively correlated with ∆HR_15s (r = 0.589, p = 0.013), ∆HR_3min (r = 0.636, p = 0.006), and ∆HR_10min (r = 0.685, p = 0.002) in patients with MSA. Similarly, the normalized p13–n23 amplitude was positively correlated with ∆SBP_15s (r = 0.310, p = 0.034), ∆DBP_15s (r = 0.288, p = 0.049), and ∆DBP_3min (r = 0.293, p = 0.045) in patients with PD. The IAD of cVEMP was positively correlated with ∆SBP_15s (r = 0.389, p = 0.008), ∆DBP_15s (r = 0.348, p = 0.018), ∆DBP_3min (r = 0.313, p = 0.034), and ∆DBP_10min (r = 0.318, p = 0.031) in patients with PD (Supplementary Table 2 in the online-only Data Supplement).

The n1–p1 amplitude was negatively correlated with the UMSARS I-II score in patients with MSA (r = -0.571, p = 0.033), whereas it did not correlate with the MDS-UPDRS-III score in patients with PD (r = -0.051, p = 0.687) (Figure 2). The SARA score was not correlated with n1 latency (r = -0.364, p = 0.272) or n1‒p1 amplitude (r = -0.343, p = 0.211) in patients with MSA. The n1 latency was not correlated with UMSARS I-II score in patients with MSA (r = -0.800, p = 0.104) or MDS-UPDRS-III score in patients with PD (r = 0.131, p = 0.476). The normalized p13–n23 amplitudes were not correlated with UMSARS I-II scores in patients with MSA (r = -0.422, p = 0.298) or with MDS-UPDRS-III scores in patients with PD (r = -0.158, p = 0.317). p13 latency was not associated with UMSARS I-II scores in patients with MSA (r = 0.500, p = 0.667) or MDS-UPDRS-III scores in patients with PD (r = -0.107, p = 0.527).

Prediction of MSA compared with PD

Multivariable logistic regression indicated that MSA was associated with bilateral oVEMP abnormalities (odds ratio [95% confidence interval] = 9.19 [1.77–47.76], p = 0.008) (Table 4 and Figure 3).

Subgroup analysis with respect to MSA subtypes

Multivariable logistic regression revealed that MSA-cerebellar type was associated with bilateral oVEMP abnormalities (11.12 [1.76–70.04], p = 0.010) and younger age (0.90 [0.83–0.99], p = 0.025) (Table 5).

MSA-parkinsonian type was not associated with any variables (Table 5).

DISCUSSION

Our findings suggest that 1) bilateral oVEMP abnormalities are a predictor of MSA; 2) n1–p1 amplitudes were negatively correlated with UMSARS I-II scores in patients with MSA but not with MDS-UPDRS-III scores in patients with PD; and 3) ∆SBP_15s was negatively correlated with n1 latency in patients with PD but not in patients with MSA.

Alterations in the otolith-ocular reflex in PD and MSA patients

In addition to VEMP, otolith function can be evaluated via subjective visual vertical (SVV), ocular tilt reaction (OTR), and head heave tests. The SVV and OTR reflect static otolith functions, and the values usually return to normal within weeks to months following a vestibular lesion owing to central compensation [22]. In contrast, VEMP is a measure of the short-latency phasic otolith-ocular reflex, and abnormal values persist even after central compensation [23]. Thus, discrete lesions involving the medial longitudinal fasciculus (for instance, multiple sclerosis, stroke, and tumors) result in alterations in oVEMPs [24].

VEMPs reportedly indicate the degree of brainstem dysfunction in PD [25]. cVEMP values may not differ between patients with PD and healthy participants [26]. However, subsequent studies have reported that approximately 44%–53% of patients exhibit altered cVEMP responses [11]. Furthermore, oVEMP responses exhibit distinct changes compared with relatively preserved cVEMP responses in PD, suggesting the preferential involvement of the upper brainstem by alpha-synuclein pathology [14,27]. The decrease in the cVEMP amplitude can even be reversed by levodopa administration [27].

We also observed cVEMP and oVEMP abnormalities in 31% and 42% of patients with PD, respectively. Nevertheless, our observations show that the abnormal oVEMP response is more profound in patients with MSA. Thus, abnormal oVEMP responses can be an independent predictor of MSA, especially when altered bilaterally. We speculate that these findings represent severely dampened brainstem function in MSA. Our findings agree with previous findings that demonstrated delayed and diminished oVEMP responses in patients with MSA [14]. Furthermore, we demonstrated that the n1–p1 amplitude, a representative indicator of brainstem dysfunction, decreases with neurological deterioration in MSA. These findings suggest that oVEMP has the potential to detect the therapeutic response or clinical decline observed in MSA. The assessment of this otolith function can be clinically significant, as it can be linked to postural instability and falls in patients with MSA [28].

Other neurotologic findings that aid in the differentiation between MSA and PD

In addition to VEMP abnormalities, several neurotologic abnormalities have been reported in patients with MSA [29]. Since the brainstem and cerebellum are profoundly affected, patients with MSA can exhibit downbeat, pendular, gaze-evoked, and central positional nystagmus; opsoclonus; perverted and reversed head-impulse tests; hypermetric saccades; and impaired cancellation of the vestibulo-ocular reflex (VOR) [30].

In contrast, patients with PD rarely exhibit neurotologic abnormalities. A few earlier anecdotes reported mild impairment of the VOR confined to low frequency and detected only on caloric and rotatory chair tests [31,32]. Nevertheless, vestibular dysfunction is negligible and has limited clinical significance. Our observations add to the evidence that oVEMP can aid in differentiating MSA from PD, which has previously drawn little attention.

Mechanism of orthostatic BP regulation, the pathogenesis of OH, and the relevance of VEMP

OH is prevalent both in patients with MSA (60%–84%) and PD (14%–31%) [2,33,34]. However, the early development of neurogenic OH indicates MSA rather than PD; symptomatic OH occurring within one year of disease onset strongly supports the diagnosis of MSA. Contrarily, OH develops approximately 10 years after disease onset in PD [35]. Furthermore, patients with PD generally have milder BP drops than those with MSA [36]. Collectively, although some differences are present in a large scale, cardiovascular autonomic findings in MSA and PD patients overlap and cannot be used to reliably distinguish between these disorders [37].

Orthostatic BP regulation depends on the cardiovascular autonomic reflex, normal blood volume, and defenses against excessive venous pooling [20]; its dysregulation results in cerebral hypoperfusion and, consequently, orthostatic intolerance. OH may ensue depending on the severity of the disruption of the afferent, central, or efferent components of autonomic BP control. Along with the baroreflex, the vestibulo-autonomic reflex contributes to the afferent autonomic BP control during postural changes [38]. Notably, the n1–p1 amplitude was positively associated with ∆SBP_15s but not ∆SBP_3min or ∆SBP_10min in patients with PD. This may be attributed to the rapid adaptation of otolith-autonomic reflexes to orthostasis instead of the slow baroreflex. In this context, the otolithic influence on BP is prominent early during orthostasis [39].

Associations between oVEMP and Finometer parameters in PD and MSA

Some correlations were identified between the VEMP and the Finometer parameters in our patients. For oVEMPs, n1 latency was negatively correlated with ∆SBP_15s in patients with PD but not in those with MSA. For cVEMPs, the normalized p13–n23 amplitude was positively correlated with ∆HR_15s, ∆HR_3min, ∆HR_10min, and ∆SBP_10min in patients with MSA. The normalized p13–n23 amplitude was positively correlated with ∆SBP_15s in patients with PD. These correlations align with the notion that otoliths stabilize BP changes during orthostasis [10]. Therefore, otolithic dysfunction can be associated with the development of OH and postural orthostatic tachycardia syndrome [40]. Likewise, a substantial decrease in BP can be observed in patients with SVV, cVEMP, and oVEMP abnormalities [9].

However, these results should be interpreted with caution. In particular, as cVEMPs are highly dependent on SCM contraction [41], patients with MSA and PD may have difficulty generating cVEMP responses. Furthermore, cVEMP responses to sound stimuli deteriorate with age in healthy participants [41]. Thus, the correlation between cVEMP and the Finometer parameters should be interpreted while other factors are considered. Moreover, n1 latency was positively correlated with ∆SBP_15s in patients with PD but not in those with MSA. As cVEMP responses to bone-conducted stimuli mostly remain unaffected by the aforementioned factors, they can hold statistical significance. Notably, this trend was not as robust as that observed in patients with OH without MSA or PD in our previous study [9]. These findings suggest that despite the frequent occurrence of otolithic dysfunction, it has a limited effect on cardiovascular autonomic control in MSA patients. In contrast, although rarely observed, utricular dysfunction can be associated with the development of OH in PD. We infer that this discrepancy might reflect the difference in the sites of neurodegeneration between MSA and PD patients.

As the utricle is involved in the graviceptive pathway, utricular dysfunction can impair the afferent limb of the neural pathway (otolith-autonomic coupling) responsible for orthostatic tolerance [9,10]. In MSA, autonomic failure results from central autonomic system involvement [42], which includes degeneration of the nucleus solitarius and ambiguus, the dorsal motor nucleus of the vagus, and neurons located in the caudal and rostral ventrolateral medulla [43]. Thus, the integrity of the afferent limb (otolith-ocular reflex or baroreflex) may have a limited effect on the profound degeneration of the central autonomic system. Conversely, degeneration occurs predominantly at the level of postganglionic (i.e., peripheral) sympathetic efferent neurons in PD [44]. Thus, neural substrates in the brainstem are relatively preserved, and the efferent limb of the neural pathway is partially functioning. Accordingly, the integrity of the afferent limb (otolith-autonomic coupling) can influence the regulation of orthostatic BP, although in a slightly more blunted manner than in patients with OH without PD.

Caveats and limitations of our study and suggestions for future studies

Our study had several limitations. First, the influence of cVEMP may have been underestimated. The interpretation of cVEMP must consider patients’ efforts to contract the SCM. Owing to weakness and aging, cVEMPs were not recordable in seven patients (four with MSA and three with PD), which limited the complete assessment of the saccule and sacculocolic reflex. Second, the small sample size limited a thorough analysis of associations between the variables. Differentiating MSA-parkinsonian type poses a challenge in the clinical setting [45,46]. Although the clinical diagnoses of PD and MSA strictly adhere to current diagnostic criteria, a follow-up period of 2 years may be insufficient. The MSA parkinsonian type can initially mimic PD, delaying the diagnosis by an average of 4 years [47]. Thus, the diagnostic utility of oVEMP should be determined on a larger scale and over a longer period in these patient populations. Third, the impact of diabetes mellitus was not explicitly assessed in our data, which should be addressed in future studies to offer a more nuanced understanding of the outcomes.

In conclusion, bilaterally abnormal oVEMP responses may indicate extensive brainstem involvement in MSA. oVEMP reflects the integrity of otolith-autonomic interplay, reliably assists in differentiating between MSA and PD, and helps infer clinical decline.

Supplementary Materials

Notes

Conflicts of Interest

Drs. K.T. Kim, K. Baik, S.U. Lee, E. Park, C.N. Lee, D. Woo, Y. Kim, S. Kwag, and H. Park report no disclosures.

JS Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of Frontiers in Neuro-ophthalmology, Journal of Neuroophthalmology, Journal of Vestibular Research, and Clinical and Translational Neuroscience.

Funding Statement

This study was supported by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by the MSIT (2022 R1A4A1018869).

Author Contributions

Conceptualization: Sun-Uk Lee. Data curation: Kyoungwon Baik, Sun-Uk Lee, Euyhyun Park, Chan-Nyoung Lee, Yukang Kim, Seoui Kwag, Hyunsoh Park. Formal analysis: Keun-Tae Kim, Sun-Uk Lee, Donghoon Woo, Yukang Kim. Funding acquisition: Sun-Uk Lee. Investigation: Kyoungwon Baik, Sun-Uk Lee, Euyhyun Park. Methodology: Kyoungwon Baik, Sun-Uk Lee, Chan-Nyoung Lee. Project administration: Sun-Uk Lee. Resources: Sun-Uk Lee. Supervision: Kyoungwon Baik, Sun-Uk Lee, Chan-Nyoung Lee. Validation: Sun-Uk Lee, Donghoon Woo, Ji-Soo Kim. Visualization: Sun-Uk Lee, Yukang Kim, Seoui Kwag, Hyunsoh Park. Writing—original draft: Keun-Tae Kim, Sun-Uk Lee. Writing—review & editing: Keun-Tae Kim, Sun-Uk Lee, Ji-Soo Kim.

Acknowledgments

None

Figure 1.

Correlation of oVEMP parameters with Finometer parameters. A: The n1 latency shows a negative correlation with ∆SBP_15s in patients with Parkinson’s disease (Spearman’s coefficient = -0.335, p = 0.040). B: On the contrary, it shows no correlation in patients with multiple system atrophy (r = 0.277, p = 0.299). oVEMP, ocular vestibular-evoked myogenic potential; ΔSBP_15s, the maximum changes in systolic blood pressure at 15 s during head-up tilt table test.

Figure 2.

Correlation of clinical disease scales and oVEMP parameters. A: n1–p1 amplitude was negatively correlated with UMSARS I-II in patients with MSA (r = -0.571, p = 0.033). B: Whereas it did not correlate with MDS-UPDRS-III scores in patients with PD (r = -0.051, p = 0.687). oVEMP, ocular vestibular-evoked myogenic potential; UMSARS I-II, Unified Multiple System Atrophy Rating Scale I-II; MDS-UPDRSIII, Movement Society Disorder-Unified Parkinson’s Disease Rating Scale-III score; MSA, multiple system atrophy; PD, Parkinson’s disease.

Figure 3.

Forest plot of the results of logistic regression analysis. Multivariable logistic regression showed that MSA was associated with bilateral oVEMP abnormality (odds ratio [95% confidence interval] = 9.19 [1.77–47.76], p = 0.008]. *p value < 0.05. MSA, multiple system atrophy; cVEMP, cervical vestibular-evoked myogenic potential; oVEMP, ocular vestibular-evoked myogenic potential; OH, orthostatic hypotension.

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