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Objective:To investigate the clinical characteristics of circadian rhythm disorder of blood pressure and its impact on orthostatic hypotension (OH) in Parkinson′s disease (PD).Methods:A total of 165 PD patients from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to October 2021 were consecutively enrolled. Medical history and scores of motor and non-motor symptoms of patients were collected. Twenty-four-hour ambulatory blood pressure and OH data were collected, and the OH questionnaire was completed. The incidence of each type of circadian rhythm disorder of blood pressure was investigated. The t test, chi-square test and Mann-Whitney U test were used to determine between-group differences of circadian rhythm disorder of blood pressure. The linear trends in clinical characteristics were tested by linear regression analysis. Logistic regression analysis was used to analyze the relationship between different circadian rhythm disorders of blood pressure and OH as well as symptomatic OH (SOH). Results:In 165 PD patients, the incidence of reverse dipping pattern was 39.39% (65/165), nocturnal hypertension was 43.64% (72/165), and awakening hypotension was 31.52% (52/165). Compared with patients without reverse dipping pattern, patients with reverse dipping pattern were older [(71.72±7.81) years vs (65.29±9.68) years, t=-4.491, P<0.001], had later onset age [(66.67±9.10) years vs (62.16±10.66) years, t=-2.809, P=0.006], longer duration [36.00(20.50, 95.50) months vs 24.00(12.00, 41.75) months, Z=-3.393, P<0.001], higher dose of levodopa (LD) [(426.15±267.38) mg/d vs (284.00±235.58) mg/d, t=-3.590, P<0.001], higher levodopa equivalent dose (LED) [(514.80±360.03) mg/d vs (341.44±284.57) mg/d, t=-3.440, P=0.001], higher Unified Parkinson′s Disease Rating Scale (UPDRS)-Ⅱ scores (12.92±6.38 vs 9.54±5.59, t=-3.434, P=0.001), higher UPDRS-Ⅲ scores (28.34±11.60 vs 21.41±12.18, t=-3.508, P=0.001) and higher percentages of hallucinations [18.46% (12/65) vs 7.00% (7/100), χ2 =5.079, P=0.024]. Compared with patients without awakening hypotension, patients with awakening hypotension were older [(70.83±7.09) years vs (66.44±10.16) years, t=-2.811, P=0.006]. Compared with patients without nocturnal hypertension, patients with nocturnal hypertension had longer duration [39.50(15.00, 96.00) months vs 24.00 (12.00, 36.00) months, Z=-2.944, P=0.003], higher LD [(398.61±251.19) mg/d vs (294.62±254.25) mg/d, t=-2.619, P=0.010], higher LED [(493.28±344.02) mg/d vs (345.05±298.59) mg/d, t=-2.959, P=0.004], higher percentages of hallucinations [19.44% (14/72) vs 5.38% (5/93), χ2 =7.882, P=0.005], higher UPDRS-Ⅱ scores (12.08±6.33 vs 10.00±5.86, t=-2.086, P=0.039), higher UPDRS-Ⅲ scores (26.50±11.72 vs 22.42±12.66, t=-2.034, P=0.044), and greater blood pressure variability (BPV) (20.66±5.47 vs 17.44±5.36, t=-3.798, P<0.001). Trend analysis showed that the variety of circadian rhythm was positively correlated with age and duration, use of levodopa and monoamine oxidase B inhibitors and amantidine, morning and daily LD and LED, UPDRS-Ⅱ, UPDRS-Ⅲ and Hamilton Anxiety Scale scores, hallucinations, OH and SOH, and BPV in PD ( P<0.05). Multivariate Logistic regression analysis showed that awakening hypotension ( OR=3.35, 95% CI 1.55-7.22, P=0.002) and nocturnal hypertension ( OR=2.44, 95% CI 1.20-4.97, P=0.014) were risk factors for OH, and LED ( OR=1.21, 95% CI 1.01-1.43, P=0.035), UPDRS-Ⅲ scores ( OR=1.09, 95% CI 1.02-1.16, P=0.009) and w-BPV ( OR=1.14, 95% CI 1.01-1.29, P=0.029) were independent risk factors for SOH. Conclusions:Circadian rhythm disorder of blood pressure was correlated with age, duration, severity of motor symptoms. Awakening hypotension and nocturnal hypertension are independent risk factors for OH in PD.
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Objective:To determine the evolution of gait impairment over the course of Parkinson′s disease (PD) by assessing the changes of gait characteristics in different disease stages, which could be helpful for disease monitoring.Methods:A total of 276 PD patients [PD group, Hoehn-Yahr (H-Y) stage 1-3] and 63 healthy controls (control group) enrolled in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2021 were included in this cross-sectional study. The gait spatiotemporal variables were recorded by a portable inertial measurement unit system. Exploratory factor analysis was performed to obtain gait domains representing different gait characteristics. One way analysis of variance was used to evaluate the differences of gait variables and gait domains among the control group and 3 different H-Y stages of the PD group, as well as the differences among the control group and 2 motor subtypes of PD in different stages. The sensitivity of different gait variables and gait domains in evaluating the severity of gait impairments at different disease stages was compared.Results:Eleven gait spatiotemporal variables were grouped in 4 gait domains: pace (step length, gait speed and stride length), rhythm/phase (cadence, stride time and double support time), pace-related variability/asymmetry [step length coefficient of variation (CV), gait speed CV and step length asymmetry] and rhythm/phase-related variability/asymmetry (swing time CV and swing time asymmetry). As the disease progresses, most evolution trends of the 4 gait domains in the tremor-dominant PD patients were consistent with those in the non-tremor-dominant subtype. Compared with the control group, PD patients at H-Y stage 1 began to show the mild impairment of rhythm/phase-related variability/asymmetry (effect size 0.42; standardized score -0.03±0.69 vs -0.33±0.49, P<0.05), especially swing time asymmetry in tremor-dominant patients; the pace domain was damaged moderately in PD patients at H-Y stage 2 (effect size 0.64; standardized score 0.12±0.80 vs 0.64±0.81, P<0.05), especially in non-tremor-dominant PD patients, but not in PD patients at H-Y stage 1 ( P>0.05). Pace-related variability/asymmetry showed great impairment in PD patients at H-Y stage 3 (effect size 0.62; standardized score 0.27±1.12 vs -0.27±0.52, P<0.05), but not in PD patients at H-Y stages 1 and 2 ( P>0.05). Conclusions:The characteristic impairments of gait in PD evolve in the process of disease progression. The rhythm/phase-related variability/asymmetry domain may be a marker to distinguish early PD from healthy controls. The pace domain and the pace-related variability/asymmetry domain are important markers to evaluate the progression of PD.
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Objective:To investigate whether the presynaptic dopamine neuronal depletion in different striatal subregions predicts future development of wearing-off (WO) in Parkinson′s disease (PD) patients.Methods:A retrospective longitudinal study included 57 PD patients who were referred to the Department of Neurology of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2020, and completed 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane dopamine transporter (DAT) positron emission tomography scans at the initial evaluation and received dopaminergic drugs for at least 12 months during follow-up. The time of starting dopaminergic drug treatment and the occurrence of WO were recorded. After adjusting for clinical related factors, the predictive value of DAT uptake and related parameters in striatal subregions for WO was evaluated by Cox proportional hazards model. Results:During a median follow-up period of 23 months, 10 patients (18.18%) developed WO. Patients with WO exhibited less DAT uptake in the caudate nucleus and anterior putamen nucleus (0.66±0.52 vs 1.08±0.42, t=2.76, P=0.008 and 0.66±0.20 vs 0.87±0.28, t=2.27, P=0.027 respectively), especially in these subregions contralateral to the less-affected side of the body, compared to those without WO. Cox proportional hazard models revealed that after adjusting for gender, age, course of disease, baseline Unified Parkinson′s Disease Rating Scale Ⅲ score and increment of levodopa equivalent dosage, the lower the DAT uptake of the caudate ipsilateral to the less-affected side of the body ( HR=0.20, 95% CI 0.07-0.63, P=0.006), as well as the lower the DAT uptake of the caudate nucleus and posterior putamen nucleus ( HR=0.28, 95% CI 0.11-0.69, P=0.006 and HR=0.08, 95% CI 0.01-0.64, P=0.018 respectively) and the higher the ratio of putamen/caudate contralateral to the less-affected side of the body ( HR=2.33, 95% CI 1.02-5.33, P=0.045), the higher the risk of WO. Conclusion:The presynaptic dopamine neuronal loss, particularly bilateral caudate nucleus dopaminergic depletion at the early stage, has predictive value of development of WO in PD.
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Objective:To identify and quantify spatiotemporal and kinematic gait parameters in a group of early-stage Parkinson′s disease (PD) patients compared with healthy subjects.Methods:Eight patients with PD (PD group, Hoehn-Yahr stage≤2.5) and seven age-matched healthy subjects (control group) were enrolled from the Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2017 and August 2018 for the study. The spatiotemporal and kinematic gait parameters were obtained by Vicon 3D optical motion analysis system under three conditions: single-task walking, dual-task walking and turning. The linear mixed model was used to compare the gait parameters between the two groups and analyze the interactive effects.Results:Arm swing amplitude in the PD group was lower than that in the control group ((0.63±0.15) m vs (0.89±0.27) m in single-task walking, (0.64±0.16) m vs (0.99±0.22) m in dual-task walking, β=-0.353, 95% CI -0.558--0.148, P=0.002). The PD group showed significantly higher arm swing asymmetry than the control group (12.48%±5.48% vs 6.96%±4.39% in single-task walking, 17.13%±4.05% vs 7.67%±5.23% in dual-task walking, β=8.992, 95% CI 4.148-13.836, P=0.001). A notable interactive effect of groups and task factors in arm swing asymmetry was found. The arm swing asymmetry of the PD group increased more than the control group in dual-task walking than in single-task walking (β=3.916, 95% CI 1.367-6.466, P=0.003). As for the gait characteristics of the lower limbs, stride length and step length of the PD group were lower than those of the control group ((1.10±0.17) m vs (1.31±0.10) m in stride length, β=-0.169, 95% CI -0.300--0.038, P=0.015; (0.55±0.09) m vs (0.65±0.04) m in step length, β=-0.081, 95% CI -0.150--0.013, P=0.023). For both groups, statistically significant differences were not observed in step width, stride length and step length between single-task and dual-task walking ( P>0.05). The PD group completed the turning process faster than the control group ((1.66±0.30) s vs (1.37±0.23) s, β=0.302, 95% CI 0.049-0.555, P=0.023). As for the rotation-onset pattern, no statistically significant differences were found between the PD and the control group for the onset of the head, trunk and pelvic rotation ( P>0.05). Participants started to rotate their heads before the pelvis in all groups (β=-0.060, 95% CI-0.107--0.014, P=0.011). Conclusions:The quantified gait parameters can more accurately reflect the gait characteristics of early PD. Patients with PD exhibited smaller arm swing magnitude, greater arm swing asymmetry, shorter stride length, and slower turning speed compared to the controls. Arm swing asymmetry further differs between subjects with early PD and controls under dual-task walking.
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Objective To analyze the characteristic changes of macular thickness in patients with Parkinson's disease by spectral-domain optical coherence tomography (SD-OCT),and find out the association between macular thickness and disease progression,cognitive dysfunction,visuospatial impairment and asymmetry of motor symptoms.Methods Seventy-one Parkinson's disease (PD) patients who were admitted to the Department of Neurology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2016 to May 2018 and sixty-one healthy controls who volunteered to participate for the same period were enrolled and underwent SD-OCT examination.The macular thickness of all retinal quadrant segments,foveal thickness,and macular volume between the two groups were comparatively analyzed.Associations between macular measurements and clinical parameters such as disease duration,Unified Parkinson's Disease Rating Scale part Ⅲ (UPDRS-Ⅲ) scores,Montreal Cognitive Assessment (MoCA) total scores,and visuospatial subscores were analyzed using generalized estimated equation fitted with linear regression models.Results Mean macular thickness in the PD group was significantly reduced compared with those in the control group ((261.94± 12.90) μm vs (270.96± 10.71) μm,B=-8.135,P＜0.01).All quadrants of macular thickness (except fovea and 1 mm central zone) in the PD group were reduced compared with those in the control group.Receiver operating characteristic (ROC) curve analysis revealed that inner superior thickness could predict the presence of PD with an area under ROC of 0.727 (95％CI 0.662-0.792,P＜0.01).UPDRS-Ⅲ scores were negatively correlated with foveal thickness (B=-9.132,P=0.034),1 mm central zone thickness (B=6.963,P=0.036) and all quadrants of the inner ring (superior (B=-7.727,P＜0.01),inferior (B=-5.169,P=0.044),nasal (B=-5.960,P＜0.01) and temporal (B=-5.905,P＜0.01)) macular thickness.The disease duration had no relationship with any quadrant of macular measurements.No statistically significant difference was found between the macula parameters of the hemiretinae corresponding to more and less severely affected cerebral hemisphere.MoCA total scores were positively correlated with all quadrants of the inner ring (superior (B=2.693,P=0.007),inferior (B=3.391,P=0.002),nasal (B=2.609,P=0.001) and temporal (B=2.115,P=0.013)) macular thickness.MoCA visuospatial subscores were positively associated with average macular thickness (B=4.368,P=0.042),macular volume (B=0.161,P=0.004),inferior (B=8.582,6.541),nasal (B=8.130,6.017) and temporal (B=5.938,5.316)quadrants of outer and inner rings macular thickness (all P＜0.05).Conclusions In PD patients,the macular thickness and macular volume were decreased.Asymmetry was not identified between hemiretinae in PD.Some quadrants of macular thickness were associated with disease progression,cognitive dysfunction,and visuospatial impairment.