Follow-up observation of eye movements in multiple system atrophy and Parkinson’s disease: a cohort study

Abstract

Objectives

We aimed to explore the changes in oculomotor deficiencies during the follow-up of patients with multiple system atrophy (MSA) and Parkinson’s disease (PD), and to investigate the value of dynamic eye movement examination in their differential diagnosis.

Design

This was a cohort study conducted from 2017 to 2023.

Setting

The Movement Disorders Clinic at a tertiary hospital in Beijing, China.

Participants

56 patients with PD and 13 patients with MSA from an initial cohort of over 1100 with parkinsonism were included in the final longitudinal analysis.

Outcome measures

Multisystem evaluations were performed at baseline. Videonystagmography (VNG) was repeated to assess oculomotor dysfunction at baseline and during follow-up. Abnormalities in the fixation and gaze-holding test, without-fixation test, reflexive and memory-guided saccade tests, smooth pursuit test and optokinetic test were qualitatively and quantitatively recorded and statistically analysed.

Results

The median follow-up time of MSA (16 months) was significantly shorter than that of PD (27 months). In MSA, the incidence of abnormalities in fixation and gaze-holding tests (0% vs 30.8%, p=0.030), reflexive saccade tests (46.2% vs 84.6%, p=0.039, with slow saccades increasing from 7.7% to 46.2%, p=0.027) and smooth pursuit tests (38.5% vs 76.9%, p=0.047) increased significantly from baseline to the end of follow-up. In PD, no significant changes were revealed during follow-up.

Conclusions

MSA exhibited more rapid and prominent changes in fixation and gaze-holding tests, reflexive saccades and smooth pursuit tests than PD. Dynamic observation of oculomotor function may aid in the differential diagnosis of Parkinson’s syndrome.

Correspondence to Dr Guiping Zhao; [email protected]

STRENGTHS AND LIMITATIONS OF THIS STUDY

• The consecutive evaluations made by the same team (consisting of movement disorder neurologists and technicians) ensured the comparability of diagnosis and examination data.

• The longitudinal observation of the cohort minimised selection bias for patients at different disease stages.

• The small sample size in this single-centre study limited statistical power, particularly in the multiple system atrophy group, possibly resulting in undetected significant changes.

• The study was limited to functional tests and lacked information about biomarkers.

Introduction

Both multiple system atrophy (MSA) and Parkinson’s disease (PD) belong to Parkinson’s syndrome. Clinically, the differential diagnosis of MSA and PD can be very challenging, especially for MSA with parkinsonism, and the accuracy varies considerably according to disease duration and is lower at first clinical visit than after longer follow-up.^{1 2}

Eye movement examination is a crucial part of parkinsonism diagnosis. The visuo-oculomotor dysfunction, which can be accurately identified and quantitatively analysed by videonystagmography (VNG), is valuable in the differential diagnosis of MSA and PD.^3–5 For example, the hypermetria and catch-up saccades in smooth-pursuit movement (SPM) associated with cerebellar lesions might be characteristic of MSA, while the multistep pattern in memory-guided saccade (MGS) suggesting disruption in basal ganglia might appear in both PD and MSA.^{4 6} However, due to the wide variation among individuals, the diagnostic efficacy is limited.

Previous studies have shown that the pathological changes in eye movement nuclei in MSA and PD gradually expand in a specific order.⁷ Therefore, the oculomotor function of MSA and PD may demonstrate disease-specific changes with progression, and dynamic observation of these changes may have diagnostic and differential value for MSA and PD. Currently, follow-up studies of oculomotor dysfunction in MSA and PD are seldom reported. We aimed to explore the changes in oculomotor deficiencies during follow-up of these two diseases and to investigate the value of serial eye movement examinations in their differential diagnosis.

Materials and methods

Clinical assessments of participants

This was a cohort study. A total of over 1100 consecutive patients with parkinsonism were screened at Peking University First Hospital (PKUFH) Movement Disorders Clinic between June 2017 and October 2023. Diagnoses were established by three movement disorder neurologists (ZW, WS and JC) according to published criteria for MSA or PD.^{1 2} Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS) or the Unified Parkinson Disease Rating Scale (UPDRS).^{8 9} We collected the clinical data of all individuals who were diagnosed with parkinsonism at their first visit and at every follow-up visit, including their basic information, symptoms and complications. The auxiliary examination mostly included an olfactory examination (the Sniffin Sticks test) with a score range of 0–16,¹⁰ brain MRI and an autonomic nerve assessment (including orthostatic hypotension and/or urogenital dysfunction). All patients with MSA or PD received appropriate treatment if needed, and all patients’ diagnoses were based on the latest clinical follow-up (YS). We selected patients with clinically established MSA or PD who participated in regular follow-up including VNG examination (online supplemental figure 1). We excluded patients who (1) refused to participate in the study or undergo follow-up VNG examinations, (2) could not complete eye movement tests at baseline or follow-up for any reason, including severe visual disturbances, cognitive impairment, motor disorder, etc or (3) had poor-quality recording data at baseline or follow-up.

We also selected 40 healthy individuals (aged±3 years) as controls. All healthy controls (HCs) presented no signs of nervous system disease and were not taking any medication for movement disorder-related diseases. They also had no vestibular system diseases, substance abuse or dependence or psychiatric disorders according to the criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. The Mini-Mental State Examination (MMSE) was used to assess cognitive function.

Protocol of oculomotor examinations

The VNG examinations were scheduled at unmedicated status (in unmedicated individuals, or 0.5 –1 hour before the next dose of L-dopa or dopamine receptor agonist). In each patient, the examinations were performed two to three times, that is, at baseline, and one or two times per year at follow-up. We performed the examinations (HZ and XW) using a binocular EyeLink system (Bao Runtong Research, Beijing, China), as described in our previous studies.^{4 6} In brief, there were six eye movement tests: (1) without-fixation, (2) fixation and gaze-holding, (3) reflexive saccades, (4) SPM, (5) optokinetic nystagmus (OKN) and (6) MGS tests. The following eye movement recording parameters were analysed: quantitative data including (1) latency, peak velocity and accuracy of saccades, and (2) the gains in the SPM and OKN tests (quantitative data were analysed automatically and generated using computer software); and qualitative data including (1) hypometria/hypermetria and saccadic intrusions in reflexive saccades, (2) anticipatory saccades, catch-up saccades and saccadic intrusions in SPM, (3) gaze-evoked nystagmus, square-wave jerks (SWJs) and macro-SWJs in fixation and gaze-holding tests, (4) spontaneous nystagmus and SWJs in the without-fixation test and (5) gains in SPM or OKN lower than 0.60, which were judged as abnormal (qualitative data were judged by three eye movement experts (HZ, XW and GZ)). Any abnormal manifestations of any eye movement type were judged as abnormal in both the quantitative and qualitative analyses.

Statistical analyses

Statistical analyses were performed using SPSS software (V.22.0 for Windows, SPSS, IBM, Armonk, New York, USA). The measurement data were expressed as mean±SD values for normally distributed continuous variables and as median and IQR values for skewed variables. The numerical data were described using proportions. The independent-samples t-test was used to perform intergroup comparisons of normally distributed measurement data. Analysis of variance was used to compare the mean values between multiple groups, and the parameters of two groups were compared if significant differences were determined. The χ² test was used to assess the differences in the distribution of categorical variables according to the diagnosis. We used the Bonferroni method to correct the results for multiple comparisons. Significance was set at p<0.05 (two-tailed).

Patient and public involvement

There was no active patient and public involvement in this study.

Results

This study finally followed-up 13 patients with MSA and 56 with PD (online supplemental figure 1). The MSA group included five patients with MSA-C (multiple system atrophy-cerebellar type), one of whom had the initial diagnosis of pure autonomic failure and eight with MSA-P (multiple system atrophy-parkinsonian type).

The median follow-up time was significantly shorter in the MSA group (16 months) than in the PD group (27 months) (p<0.001). In clinical assessments, the patients with PD showed significantly worse performance in the Sniffin Sticks test than the patients with MSA (p=0.043), while in the MSA group the incidence rate of autonomic dysfunction and abnormal MRI findings were significantly higher than in the PD group (p<0.001). There were no significant differences in age (both at baseline and follow-up periods), gender, disease duration or MMSE score between the two groups (table 1).

Table 1

Clinical information of patients with MSA and PD

Clinical data	MSA	PD	HCs	Test statistics
	N=13	N=56	N=40	χ2/t/F	P value
Age, years (baseline)	61±9 (47⁓72)	62±10 (34⁓84)	63±11 (36⁓83)	0.118	0.889
Age, years (follow-up)	65±9 (49⁓74)	65±10 (35⁓86)	–	0.235	0.815
Gender, male/female	4/9	22/34	14/26	0.661	0.718
Disease duration, months (baseline) (quartile) (min-max)	16 (10–25) (4–48)	28 (8–60) (2–180)	–	229.5	0.155
Follow-up time (months)	16 (6–30)	27 (8–48)	–	3.57	<0.001*
UPDRS/UMSARS score (quartile)	25 (15–39)	12 (7–25)	–	–	–
Hoehn and Yahr stage	–	2.0 (1–2.5)	–	–	–
MMSE score	28±4	28±2	28±1	0.199	0.821
Sniffin Sticks test	11±5	8±4	–	−2.1	0.043*
Abnormal ANS	13	0	–	69	<0.001*
Abnormal MRI	5	0	–	23	<0.001*

*P<0.05.

Bold value used in this Table means the data showed statistical significance with p<0.05.

ANS, autonomic nerve assessment; HCs, heathy controls; MMSE, Mini-Mental State Examination; MSA, multiple-system atrophy; PD, Parkinson’s disease; UMSARS, Unified Multiple System Atrophy Rating Scale; UPDRS, Unified Parkinson’s Disease Rating Scale.

In oculomotor examinations, the comprehensive incidence of abnormalities increased in MSA and decreased in PD during follow-up, but this difference was not statistically significant (table 2 and figure 1). Neither group exhibited definitive disconjugate eye movements.

Table 2

Changes in gaze-holding and without-fixation tests from baseline to latest follow-up in the patients with MSA and PD

Tests		MSA (N=13)		PD (N=56)		HCs (N=40)	Test statistics
		Baseline	Follow-up	Baseline	Follow-up		χ2/t	P value
Comprehensive	Abnormal	11 (84.7%)	13 (100%)	46 (82.1%)	43 (76.8%)	15 (37.5%)	2.17* 0.49†	0.14* 0.48†
Fixation and gaze-holding tests	Abnormal	0	4 (30.8%)	4 (7.1%)	8 (14.3%)	0	4.73* 1.49†	0.03* 0.22†
	Saccadic intrusions (SWJs)	0	3 (23.1%) (2)	4 (7.1%) (2)	7 (12.5%) (4)		3.39* 0.91†	0.07* 0.34†
	Gaze-evoked nystagmus	0	1 (7.7%)	0	0		1.04* †	0.30* †
Without-fixation test	Abnormal	3 (23.1%)	5 (38.5%)	10 (17.9%)	15 (26.8%)	0	0.72* 1.29†	0.39* 0.26†
	Spontaneous nystagmus	0	1 (7.7%)	0	0		1.04*	0.31*
	Saccadic intrusions (SWJs)	2 (15.4%) (2)	4 (30.8%) (3)	10 (17.9%) (9)	13 (23.2%) (13)		0.87* 0.49†	0.35* 0.48†

Data are mean±SD (range), N or median (IQR) values.

Bold figure, p<0.05 between baseline and follow-up.

*MSA.

†PD.

HCs, healthy controls; MSA, multiple-system atrophy; PD, Parkinson’s disease; SWJs, square-wave jerks.

Figure 1. Prevalences of oculomotor abnormalities in patients with MSA and PD. *Significantly increase from baseline to follow-up, p<0.05. MGS, memory-guided saccade; MSA, multiple system atrophy; OKN, optokinetic nystagmus; PD, Parkinson’s disease; SPM, smooth-pursuit movement.

Figure 2. Examples of videonystagmography records in three patients with multiple system atrophy. In patient 1, fixation and gaze-holding tests showed more prominent square wave jerks (arrows) at follow-up (B) than baseline (A), as well as the without-fixation test (C: baseline; D: follow-up). In patient 2, the reflexive saccade test showed more slow saccades (bold arrows) and saccadic intrusions (arrows) at follow-up (F) than baseline (E, dashed arrows showing the original normal saccades). In patient 3, the smooth pursuit test showed more catch-up saccades (hollow and double-head arrows) at follow-up (H) than baseline (G).

Fixation and gaze-holding tests

In MSA, the comprehensive fixation disturbances, including all kinds of saccadic intrusions and gaze-evoked nystagmus, increased significantly from 0% to 30.8% during follow-up (p=0.030). The other abnormalities in MSA and PD showed no significant changes (figures 1 and 2, table 2).

Without-fixation test

The comprehensive abnormalities and saccadic intrusions showed an increasing trend without statistical significance (figures 1 and 2, table 2).

Reflexive saccades

In qualitative analysis, the prevalence of comprehensive saccadic abnormalities (p=0.039) and slow saccades (p=0.027) increased significantly during follow-up in the MSA group. The other abnormalities showed no significant changes in the two groups. The incidence rates of comprehensive saccadic abnormalities (p=0.017) and slow saccades (p=0.012) in MSA at the end of follow-up were significantly higher than those in PD (figures 1 and 2, table 3).

Table 3

Changes in reflexive and memory-guided saccades tests from baseline to follow-up in patients with MSA and PD

Tests		MSA (N=13)		PD (N=56)		HCs (N=40)	Test statistics
		Baseline	Follow-up	Baseline	Follow-up		χ2/t	P value
Reflexive saccades	Abnormal	6 (46.2%)	11 (84.6%)	20 (35.7%)	27 (48.2%)	12	4.25* 1.79†	0.039* 0.18†
	Hypometria	4 (30.8%)	8 (61.5%)	17 (30.4%)	23 (41.1%)	10	2.48* 1.4†	0.12* 0.24†
	Hypermetria	1 (7.7%)	3 (23.1%)	0	0		1.18* †	0.28* †
	Slow saccades	1 (7.7%)	6 (46.2%)	6 (10.7%)	7 (12.5%)	2	4.89* 0.09†	0.027* 0.77†
	Prolonged latency	0	1 (7.7%)	4 (7.1%)	8 (14.3%)	2	1.04* 1.49†	0.31* 0.22†
MGS	Multistep pattern	9 (69.2%)	7 (53.8%)	36 (64.3%)	38 (67.9%)	3	0.65* 0.16†	0.42* 0.69†

Data are mean±SD (range), N or median (IQR) values.

Bold figure, p<0.05 between baseline and follow-up.

*MSA.

†PD.

HCs, healthy controls; MGS, memory-guided saccade; MSA, multiple-system atrophy; PD, Parkinson’s disease.

In quantitative analysis, the latency, velocity and accuracy of saccades showed deteriorating trends, but no significant differences were found (online supplemental tables 1, 2 and figure 2–4).

MGS test

The incidence of multistep saccades in MGS showed no significant changes in MSA or PD during follow-up (figure 2 and table 3).

SPM test

Qualitative analysis revealed a significant increase in the prevalence of comprehensive smooth pursuit deficiency in MSA during follow-up (p=0.047). The other abnormalities showed no significant changes in MSA or PD (figures 1 and 2, table 4).

Table 4

Changes in SPM test from baseline to follow-up in patients with MSA and PD

Tests		MSA (N=13)		PD (N=56)		HCs (N=40)	Test statistics
		Baseline	Follow-up	Baseline	Follow-up		χ2/t	P value
SPM test	Abnormal	5 (38.5%)	10 (76.9%)	25 (44.6%)	29 (51.8%)	4/40	3.94* 0.57†	0.047* 0.449†
	Catch-up saccades	1 (7.7%)	5 (38.5%)	1 (1.8%)	2 (3.6%)	0	3.47* 0.34†	0.06* 0.55†
	Anticipatory saccades	3 (23.1%)	4 (30.8%)	15 (26.8%)	16 (28.6%)	1	0.19* 0.05†	0.66* 0.83†
	Saccadic intrusions	1 (7.7%)	4 (30.8%)	13 (23.2%)	11 (19.6%)	3	2.23* 0.21†	0.14* 0.65†
SPM gain (mean ±SD)	Toward left	0.77±0.14	0.67±0.19	0.79±0.11	0.75±0.13	0.78±0.07	1.48* 1.63†	0.15* 0.11†
	Toward right	0.71±0.14	0.62±0.17	0.75±0.12	0.72±0.14	0.73±0.09	1.50* 1.20†	0.15* 0.23†

Data are mean±SD (range), N or median (IQR) values.

Bold figure, p<0.05 between baseline and follow-up.

*MSA.

†PD.

HCs, healthy controls; MSA, multiple-system atrophy; PD, Parkinson’s disease; SPM, smooth-pursuit movement.

Quantitative analysis showed a decreasing trend in the gains of SPM in both patient groups, but with no significance (table 4).

OKN test

The optokinetic abnormalities and the gain of OKN showed no significant changes during follow-up in MSA or PD (table 5 and figure 1).

Table 5

Changes in optokinetic test from baseline to follow-up in patients with MSA and PD

Tests		MSA (N=13)		PD (N=56)		HCs (N=40)	Test statistics
		Baseline	Follow-up	Baseline	Follow-up		χ2/t	P value
OKN test	Abnormal	3 (23.1%)	4 (30.8%)	3 (5.4%)	4 (7.1%)	0	0.20* 0.15†	0.66* 0.70†
OKN gain (mean ±SD)	Toward left	0.80±0.16	0.68±0.14	0.83±0.12	0.78±0.13	0.85±0.10	1.85* 2.05†	0.08* 0.04†
	Toward right	0.82±0.11	0.71±0.18	0.81±0.12	0.80±0.12	0.82±0.08	1.91* 0.33†	0.07* 0.74†

Data are mean±SD (range), N or median (IQR) values.

*MSA.

†PD.

HCs, healthy controls; MSA, multiple-system atrophy; OKN, optokinetic nystagmus; PD, Parkinson’s disease.

Discussion

Although mild age-related saccadic abnormalities appear occasionally in the healthy population,⁴ oculomotor examination changes are usually related to the severity and pathology of underlying diseases and are not affected by drug exposure. If the patient is able to cooperate, abnormal eye movement findings are often robust and reproducible.¹¹ Linder et al conducted dynamic eye movement observation in patients with Parkinson’s syndrome and reported that few changes in oculomotor functions were observed from baseline to the end of 12-month follow-up.¹² In this study, we performed longer follow-up in patients. Marked oculomotor abnormalities were found in both patients with MSA and PD at baseline, and in contrast to the previous report, these abnormalities tended to deteriorate during follow-up in parallel with clinical progression. Although the MSA group underwent significantly shorter follow-up than the PD group, they showed more oculomotor changes at the end of the observation, indicating more rapid decline of eye movement functions, which reflects the relatively fast-progressing clinical portrait of MSA.

Eye movement dysfunctions in patients with MSA and PD appeared distinct. While dysmetric saccades, reduced SPM gain and multistep saccades occurred in both diseases, hypermetric saccades, prolonged saccade latency, catch-up saccades in SPM and impaired OKN were more common in MSA than in PD^{4 13 14} and slow saccades appeared more frequently in PD than in MSA.¹⁵ It is notable that some inconsistencies existed in previous studies. Anderson et al reported that square wave jerks and spontaneous nystagmus, usually suggesting fixation disturbance, were frequent in MSA and might differentiate it from other neurodegenerative diseases.¹⁵ However, Zhou et al found that the incidence of spontaneous nystagmus was not significantly higher in patients with MSA than in controls, and the incidence of saccadic intrusions in MSA was merely higher than in HCs without significant difference from in PD.¹⁴ In our study, although the fixation disturbance was rare in patients with MSA at baseline, it became more prominent than in PD by the end of follow-up, suggesting that previous conflicting results might reflect selection bias regarding clinical stages. The diagnostic utility of oculomotor examination in parkinsonism should be combined with comprehensive clinical evaluation. For example, a patient exhibiting prominent dyskinesia with relatively mild fixation disturbance more likely has PD than MSA.

The Lewy-related pathology in PD progresses from the medulla to the cerebral cortex following the scheme of Braak staging. Although postural instability may occur in early PD due to pathology involving brainstem structures such as dorsal glossopharyngeus-vagus complex, pedunculopontine nucleus and their thalamic efferents,¹⁶ potential oculomotor abnormalities accompanying mild non-motor symptoms are usually neglected. By the time patients develop significant motor symptoms and receive a clinical diagnosis, pathological changes typically advance to Braak stages 3–6, extensively affecting substantia nigra, thalamus and frontotemporal cortex, leading to eye movement abnormalities associated with executive dysfunction,¹⁷ such as saccadic intrusions, slow saccades, hypometria and anticipatory saccades in SPM.

Therefore, typical oculomotor dysfunction in PD reflects end-stage cerebral dysfunction rather than localised impairment of the cerebellum or brainstem. Supporting this, Vintonyak et al demonstrated that saccadic intrusions in PD correlate with generalised cerebral atrophy rather than regional brain atrophy.¹⁸ Given that late-stage pathological changes show limited progression, we hypothesise that oculomotor deficits identified in patients with clinically diagnosed PD would not deteriorate significantly—a finding confirmed by our study. Although some parameters in the oculomotor examinations showed deteriorating trends, none reached statistical significance. Notably, we observed decreased prevalence of overall oculomotor abnormalities and saccadic intrusions in SPM, possibly reflecting neuroprotective treatment effects.

In MSA, eye movement abnormalities are associated with α-synuclein deposition, neuronal loss and glial cytoplasmic inclusions in the cerebellum, pons and basal ganglia.⁷ Some researchers suggest that MSA-related oculomotor dysfunctions typically manifest as disturbed SPM and catch-up saccades, which are ‘genuine’¹⁷ and reflect localised lesions in the cerebellum and its associated structures, distinct from the executive oculomotor dysfunctions in PD. Our study confirmed prominent SPM impairment, particularly catch-up saccades, in patients with MSA, consistent with prior reports. However, we additionally observed significant progression of fixation disturbance and slow saccades, with prevalence ultimately exceeding that in the PD group by the final follow-up. This finding may reflect pathological spread from local regions such as the cerebellopontine fibres and putamen to cortical areas, subsequently inducing PD-like executive oculomotor dysfunctions.

The oculomotor changes in MSA also provide longitudinal proof to the previous model of the cortical-subcortical network and its clinical correlates in this disease. The decrease of SPM gain in MSA was related to atrophy in the pons, cerebellum and cerebellar vermis, while saccadic intrusions were associated with atrophy in the putamen.¹⁸ Functional MRI studies have demonstrated that decreased SPM gain in patients with MSA significantly correlates with fibre tract disruption in bilateral middle cerebellar peduncles¹⁹ and increased functional connectivity within the ponto-cerebellar network.^{17 20} This subcortical network hyperconnectivity likely represents a compensatory adaptation to the disruption of higher functional networks. When the ongoing cell loss in the cortical ‘default mode’ network reaches a critical point, compensatory mechanisms fail, resulting in a functional disconnection syndrome.^{17 20} Since this network is similarly disrupted in PD and several other neurodegenerative diseases,²⁰ its decompensation in MSA may explain the emergence of comparable oculomotor dysfunctions—particularly fixation disturbances and slow saccades—as documented in our study. The oculomotor examinations may offer a glimpse of the pathological progression in the patients.

The main limitation of this study is the relatively small follow-up cohort, especially in the MSA group. This limited sample size precluded meaningful comparison of oculomotor dysfunction progression between MSA-C and MSA-P subtypes, despite theoretical expectations that earlier and more severe cerebellar pathology in MSA-C should accelerate functional deterioration. While several oculomotor parameters showed non-significant declining trends, larger patient cohorts are needed to establish definite patterns and explore the correlations between the progression of oculomotor dysfunction and motor symptoms (as measured by UPDRS/UMSARS). Although visual symptoms like double or blurred vision are reported in parkinsonism,²¹ we excluded patients with severe visual disturbances that would compromise VNG completion and observed no definitive disconjugacies associated with diplopia. Further studies should incorporate detailed ophthalmological assessments to elucidate the mechanism underlying visual manifestations. In addition, advanced neuroimaging studies are needed to clarify structure-function relationships between oculomotor abnormalities and their pathological mechanisms.

Conclusions

As the disease progresses, MSA demonstrates more pronounced oculomotor deterioration compared with PD, particularly in fixation and gaze-holding tests, reflexive saccades and SPM tests. Dynamic eye movement assessments show clinical value in monitoring MSA progression and differentiating MSA from PD.

We thank all patients for their participation in this study.

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

This study was approved by the ethics committee of Peking University First Hospital (IRB No. 2019210) and was performed in accordance with the principles of the Declaration of Helsinki. All participants were fully aware of the study details and provided written informed consent to participate and publish.

Footnote

YL, HZ and LW contributed equally.

Contributors Conceived the research: YS, FL, WW, LZ, GZ, ZW. Investigation and data curation: ZW, WS, JC, YS, LW, HZ, XW, YL, GZ, YJ. Performed statistical analysis: HZ, YL. Wrote the manuscript: YL, HZ. Revised the manuscript: YL, HZ, GZ. GZ is the guarantor.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

References

¹ Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015; 30: 1591–601. doi:10.1002/mds.26424

² Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord 2022; 37: 1131–48. doi:10.1002/mds.29005

³ Jung I, Kim JS. Abnormal Eye Movements in Parkinsonism and Movement Disorders. J Mov Disord 2019; 12: 1–13. doi:10.14802/jmd.18034

⁴ Zhou H, Wang X, Ma D, et al. The differential diagnostic value of a battery of oculomotor evaluation in Parkinson’s Disease and Multiple System Atrophy. Brain Behav 2021; 11: e02184. doi:10.1002/brb3.2184

⁵ Kassavetis P, Kaski D, Anderson T, et al. Eye Movement Disorders in Movement Disorders. Mov Disord Clin Pract 2022; 9: 284–95. doi:10.1002/mdc3.13413

⁶ Zhou H, Sun Y, Wei L, et al. Quantitative assessment of oculomotor function by videonystagmography in multiple system atrophy. Clin Neurophysiol 2022; 141: 15–23. doi:10.1016/j.clinph.2022.05.019

⁷ Halliday GM, Holton JL, Revesz T, et al. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol 2011; 122: 187–204. doi:10.1007/s00401-011-0852-9

⁸ Wenning GK, Tison F, Seppi K, et al. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord 2004; 19: 1391–402. doi:10.1002/mds.20255

⁹ Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease. The Unified Parkinson’s Disease Rating Scale (UPDRS): Status and recommendations. Mov Disord 2003; 18: 738–50. doi:10.1002/mds.10473

¹⁰ Hummel T, Sekinger B, Wolf SR, et al. ‘Sniffin’ Sticks’: Olfactory Performance Assessed by the Combined Testing of Odour Identification, Odor Discrimination and Olfactory Threshold. Chem Senses 1997; 22: 39–52. doi:10.1093/chemse/22.1.39

¹¹ Frucht SJ, Termsarasab P. Movement Disorders Phenomenology: An Office-Based Approach. 2020; 191–200. doi:10.1007/978-3-030-36975-0_12

¹² Linder J, Wenngren BI, Stenlund H, et al. Impaired oculomotor function in a community-based patient population with newly diagnosed idiopathic parkinsonism. J Neurol 2012; 259: 1206–14. doi:10.1007/s00415-011-6338-9

¹³ Zhou H, Wei L, Jiang Y, et al. Abnormal Ocular Movement in the Early Stage of Multiple-System Atrophy With Predominant Parkinsonism Distinct From Parkinson’s Disease. J Clin Neurol 2024; 20: 37–45. doi:10.3988/jcn.2023.0037

¹⁴ Zhou D, Ma Q, Huang H, et al. Clinical value of video oculomotor evaluation in the differential diagnosis of multiple system atrophy and Parkinson’s disease. Brain Behav 2024; 14: e3510. doi:10.1002/brb3.3510

¹⁵ Anderson T, Luxon L, Quinn N, et al. Oculomotor function in multiple system atrophy: clinical and laboratory features in 30 patients. Mov Disord 2008; 23: 977–84. doi:10.1002/mds.21999

¹⁶ You S, Kim HA, Lee H. Association of Postural Instability with Autonomic Dysfunction in Early Parkinson’s Disease. J Clin Med 2020; 9: 3786. doi:10.3390/jcm9113786

¹⁷ Gorges M, Müller H-P, Kassubek J. Structural and Functional Brain Mapping Correlates of Impaired Eye Movement Control in Parkinsonian Syndromes: A Systems-Based Concept. Front Neurol 2018; 9: 319. doi:10.3389/fneur.2018.00319

¹⁸ Vintonyak O, Gorges M, Müller H-P, et al. Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism. Neurodegener Dis 2017; 17: 117–26. doi:10.1159/000454880

¹⁹ Gorges M, Maier MN, Rosskopf J, et al. Regional microstructural damage and patterns of eye movement impairment: a DTI and video-oculography study in neurodegenerative parkinsonian syndromes. J Neurol 2017; 264: 1919–28. doi:10.1007/s00415-017-8579-8

²⁰ Rosskopf J, Gorges M, Müller H-P, et al. Hyperconnective and hypoconnective cortical and subcortical functional networks in multiple system atrophy. Parkinsonism Relat Disord 2018; 49: 75–80. doi:10.1016/j.parkreldis.2018.01.012

²¹ Sun YR, Beylergil SB, Gupta P, et al. Monitoring Eye Movement in Patients with Parkinson’s Disease: What Can It Tell Us? Eye Brain 2023; 15: 101–12. doi:10.2147/EB.S384763