Postural Instability And Gait Disorder Research Articles

Non‐motor symptoms in early Parkinson's disease with different motor subtypes and their associations with quality of life

The aim of this study was to examine non-motor symptoms in different Parkinson's disease (PD) motor subtypes and their associations with quality of life (QoL). A total of 132 patients with early PD with comprehensive motor examinations and non-motor symptom assessments were included. Motor subtypes were classified based on Stebbins' method. Non-motor symptoms were assessed by the Non-Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson's Disease Questionnaire-8. We identified 66 patients (50%) with tremor-dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non-motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non-motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD. Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non-motor symptoms may improve patients' QoL.

Beta event-related desynchronization can be enhanced by different training programs and is correlated with improved postural control in individuals with Parkinson's disease.

The purpose of this study was to investigate the effects of a specific exercise (SE) training program focusing on balance and muscle strengthening and a turning-based treadmill (TT) training program on cortical desynchronization and postural control in Parkinson's disease (PD). Eighteen patients with PD were recruited and randomly assigned to the SE group, TT training group or control exercise (CE) group and participated in 12 30-min training sessions focusing on balance and strengthening, turning-based treadmill training, or general exercise training, respectively, followed by 10 minutes of over-ground walking in each session for 4 to 6 weeks. The outcomes included alpha event-related desynchronization (ERD), beta ERD, postural control ability indicated by postural instability and gait disorder (PIGD), the step/quick turn test (SQT), and the sensory organization test (SOT). All measurements were assessed at baseline and after training. The results (n=6 for each group) showed that both the SE and TT groups had improved beta ERD, but not alpha ERD, in the Cz area, PIGD score, and turn sway/time in the SQT compared with the CE group. Furthermore, postural control ability was positively correlated with beta ERD in the Cz area. However, there was no significant correlation between SOT total score and alpha ERD in the Cz area. This study showed that beta ERD in the central area and postural control can be improved with balance training, along with lower extremity muscle strengthening exercise and turning-based treadmill training, in patients with PD. Furthermore, improvement in beta ERD in the central area correlated with improvements in postural control ability. This trial was registered at http://www.anzctr.org.au/ (ACTRN12616000198426).

Objective measures of unobstructed walking and obstacle avoidance in Parkinson’s disease subtypes

BackgroundObjective measures of gait in Parkinson's disease (PD) patients according to motor subtypes are not yet fully understood. Although recent advances have been made for unobstructed walking, further work is required on locomotor tasks challenging postural stability, such as obstacle avoidance. Research questionThis study aimed to investigate the influence of PD motor subtypes on objective measures of locomotion during unobstructed walking and obstacle avoidance. MethodsThirty-five PD patients classified as postural instability and gait disorder (PIGD) and 30 as tremor dominant (TD), as well as 45 healthy controls (CG) walked along an 8-m pathway under two conditions: (a) unobstructed walking and (b) obstacle avoidance. Outcome measures included spatiotemporal parameters recorded by an optoelectronic tridimensional system. ResultsDuring unobstructed walking, the PIGD group exhibited shorter stride length, slower velocity, and longer double support phase compared to the TD and CG groups. The TD group also presented slower stride velocity compared to the CG. The PIGD and TD groups presented shorter stride duration than the CG. Regarding obstacle avoidance, the PIGD group exhibited shorter distances for leading foot placement before obstacle, trailing foot placement after obstacle and trailing crossing step length compared to the TD and CG groups. The PIGD group exhibited wider leading crossing step width, lower trailing toe clearance, and slower leading and trailing velocity during obstacle avoidance compared to the CG. SignificancePIGD subtype patients showed worse modifications in objective measures of unobstructed walking and obstacle avoidance. The observed modifications may contribute to increased fall occurrence in PIGD patients.

Deep Brain Stimulation of Pedunculopontine Nucleus for Postural Instability and Gait Disorder After Parkinson Disease: A Meta-Analysis of Individual Patient Data.

Postural instability and gait disorder (PIGD) in Parkinson disease (PD) has been a great challenge in clinical practice because PIGD is closely linked to major morbidity and mortality in PD. Pedunculopontine nucleus (PPN) has been considered as a potential promising target for deep brain stimulation (DBS) in the treatment of PIGD. Ameta-analysis of individual patient data was performed to assess the effects of PPN DBS on PIGD in patients with PD and explore the factors predicting good outcome. According to the study strategy, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, and other sources. After searching the literature, 2 investigators independently screened the literature, assessed the quality of the included trials, and extracted the data. The outcome measures included PIGD, freezing of gait, and falling in PD. Then, individual patient data were incorporated into SPSS software for statistical analyses across series. Six studies reporting individual patient data were included for final analysis. PPN DBS significantly improved PIGD as well as freezing of gait and falling after PD, which was depending on the duration of follow-up and types of outcome measures. In addition, patient age, disease duration, levodopa-equivalent dosage, and the choice of unilateral or bilateral stimulation were similar in groups of patients with PD with or without improvement in PIGD after PPN DBS. Our study provides evidence that PPN DBS may improve PIGD, which should be interpreted with caution and needs further verification before making generalization of our results.

Structural and physiological neurovascular changes in idiopathic Parkinson’s disease and its clinical phenotypes

Neurovascular changes are likely to interact importantly with the neurodegenerative process in idiopathic Parkinson’s disease (IPD). Markers of neurovascular status (NVS) include white matter lesion (WML) burden and arterial spin labelling (ASL) measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). We investigated NVS in IPD, including an analysis of IPD clinical phenotypes, by comparison with two control groups, one with a history of clinical cerebrovascular disease (CVD) (control positive, CP) and one without CVD (control negative, CN). Fifty-one patients with IPD (mean age 69.0 ± 7.7 years) (21 tremor dominant (TD), 24 postural instability and gait disorder (PIGD) and six intermediates), 18 CP (mean age 70.1 ± 8.0 years) and 34 CN subjects (mean age 67.4 ± 7.6 years) completed a 3T MRI scan protocol including T2-weighted fluid-attenuated inversion recovery (FLAIR) and ASL. IPD patients showed diffuse regions of significantly prolonged AAT, small regions of lower CBF and greater WML burden by comparison with CN subjects. TD patients showed lower WML volume by comparison with PIGD patients. These imaging data thus show altered NVS in IPD, with some evidence for IPD phenotype-specific differences.

Structural Brain Alterations in Motor Subtypes of Parkinson's Disease: Evidence from Probabilistic Tractography and Shape Analysis.

Background and ObjectivesThe postural instability and gait disorder (PIGD) and tremor dominant (TD) subtypes of Parkinson’s disease (PD) show different patterns of alterations in functional connectivity (FC) between specific brain regions. This study aimed to investigate the relation between symptomatic heterogeneity in PD and structural alterations underlying these FC changes.Methods68 PD patients classified as PIGD (n = 41) or TD (n = 19) and 19 age-matched controls underwent Magnetic Resonance Imaging (MRI). Diffusion-weighted images were used to assess fractional anisotropy (FA) and mean diffusivity (MD) at the whole-brain level using tract-based spatial statistics (TBSS). In addition, structural connectivity was assessed between regions that previously showed altered FC using probabilistic tractography. Anatomical images were used to determine shape and volume of the putamen, caudate and pallidum.ResultsTBSS revealed widespread FA reductions in PIGD compared to controls involving the superior longitudinal fasciculi and corpus callosum. No such differences were found in TD. Both PD subgroups had increased MD compared to controls in tracts connecting the left caudate with the bilateral ventral putamen. TD patients additionally showed increased MD compared to PIGD and controls in tracts connecting the right inferior parietal lobule with the right premotor and primary motor cortex, which previously showed altered FC. We also found grey matter atrophy in the rostrodorsal head of the caudate in PIGD compared to controls.ConclusionMicrostructural changes in white matter tracts, particularly in those connecting striatal sub-areas, partly underlie FC alterations in PD subtypes. Caudate shape alterations further implicate the striatum in PIGD pathophysiology.

Postural Instability and Gait Disorder (PIGD) in Parkinson’s Disease: Is There Another Target for Deep Brain Stimulation? (P6.381)

Postural Instability and Gait Disorder (PIGD) in Parkinson’s Disease: Is There Another Target for Deep Brain Stimulation? (P6.381)

Functional connectivity alterations in the motor and fronto-parietal network relate to behavioral heterogeneity in Parkinson's disease

BackgroundInsight into the neural mechanisms of postural instability and gait disorder (PIGD) and tremor dominant (TD) subtypes in Parkinson's disease (PD) is indispensable for generating pathophysiology hypotheses underlying this phenotyping. This cross-sectional study aimed to gain insight in specific and brain-wide functional connectivity (FC) and its correlation with motor deterioration and preservation in PD subtypes. Methods68 PD patients classified as PIGD (n = 41), TD (n = 19) or indeterminate (n = 8) and 19 age-matched controls underwent resting-state fMRI while ‘off’ medication to assess FC between regions of interest (ROIs) in the motor and fronto-parietal network and on a whole-brain level using a parcellated template. FC alterations were correlated with quantitative behavioral measures. ResultsROI-analyses showed decreased FC between the caudate and putamen in PIGD compared to TD. This hypo-connectivity was correlated with behavioral impairment. In contrast, TD-specific hyper-connectivity between motor cortical areas and the inferior parietal lobule correlated with less behavioral impairment, suggesting compensatory mechanisms. Both subgroups showed hyper-connectivity between the left supplementary motor area and pedunculopontine nucleus, whereas PIGD-specific right lateralized hyper-connectivity was shown between this nucleus and the premotor cortex. Whole-brain analyses revealed 65% hypo-connectivity and 35% hyper-connectivity in PIGD compared to TD. TD also revealed primarily hypo-connectivity compared to controls, but had more pronounced hyper-connectivity involving temporo-occipital areas. ConclusionThis multilevel analysis showed differential connectivity alterations in large scale neural networks and between motor and cognitive control areas that related to behavioral heterogeneity in PD, underscoring the classic TD-PIGD phenotypical classification.

Cognitive impairment in idiopathic Parkinson's disease.

Cognitive symptoms are common in advanced Parkinson's disease (PD). However, assessment of cognitive impairment is difficult in PD because of accompanying motor symptoms and the coexistence of nonmotor symptoms. Specific subdomains affected in the disease are not reflected in the conventional scales used for assessing cognition. This study was aimed at looking at the spectrum of cognitive impairment in the various phenotypes and stages of PD and the correlation of cognitive impairment with motor and nonmotor symptoms of PD. Fifty PD patients fulfilling the UK PD Society Brain Bank's criteria were selected after obtaining explicit consent. Patients were assessed clinically and by using various scales like Scales for Outcomes in PD-Cognition (SCOPA-COG), mini-mental state examination, and Beck's Depression Inventory and Scoring. The mean age was 58 years, 82% of the patients were male, and the mean modified Hoehn and Yahr staging was 2. The most commonly affected domains were memory and executive functioning. Cognitive impairment was more in those with late-onset disease, more advanced stage of disease, and in the postural instability and gait disorder (PIGD) subgroup. The cognitive function deteriorated with increasing age and duration of the illness. Significant correlation with cognitive impairment was obtained for the manifestations of increased motor disability, presence of coexistent psychotic symptoms and depression. Cognitive impairment was common among PD patients, and it was more prevalent with increasing duration of the disease, in older patients, in late-onset disease, and in the PIGD subgroup. Increasing motor disability and associated psychotic symptoms as well as depression significantly increased the cognitive impairment.

Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors?

Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as “mild” or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life.

Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients

Purpose: This study aimed to explore plasma antioxidant status in de novo Chinese Parkinson's disease (PD) patients and investigate its relationship with specific motor features of PD. Patients and methods: Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinson's disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearman's coefficient. Results: Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. Conclusion: Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.

Distal motor deficit contributions to postural instability and gait disorder in Parkinson's disease

Clinical subtypes in Parkinson's disease (PD) are often based on the presence of clustered motor symptoms. In contrast to the tremor dominant (TD) subtype, the postural instability and gait disorder (PIGD) subtype is characterized by predominantly axial motor involvement and increased cognitive impairment. It is, however, unclear if subtypes represent distinct underlying neuropathological mechanisms or reflect more severe disease progression. We aimed to clarify the validity of PD subtypes by investigating behavioral outcomes at multiple levels. Therefore, spatiotemporal kinematics of gait, upper and lower limb repetitive movements in combination with a balance and cognitive assessment were recorded in 73 patients with PD. We classified patients as PIGD (n=43), TD (n=22) or indeterminate (n=8) while ‘off’ medication and recruited 20 age-matched controls. Surprisingly, differences between PIGD and TD were more prominent during repetitive distal motor tasks than during gait. Gait impairment in PIGD was only shown by reduced step length and gait speed. However, motor scaling and coordination of distal movements were more affected in PIGD than in TD patients. PIGD patients also had impaired postural control compared to TD patients as shown by lower mini-BESTest scores. There were no cognitive differences between patient subgroups. Distal movement was not significantly different in TD patients from controls, except for greater movement asymmetry. The results indicate a widespread impairment within PIGD with more pronounced distal than axial motor deficits. This suggests involvement of different neurotransmitter systems in the neuropathology of PD subtypes, which are at least partially independent of disease progression.

Cognition and gait show a selective pattern of association dominated by phenotype in incident Parkinson's disease.

Reports outlining the association between gait and cognition in Parkinson’s disease (PD) are limited because of methodological issues and a bias toward studying advanced disease. This study examines the association between gait and cognition in 121 early PD who were characterized according to motor phenotype, and 184 healthy older adults. Quantitative gait was captured using a 7 m GAITrite walkway while walking for 2 min under single-task conditions and described by five domains (pace, rhythm, variability, asymmetry, and postural control). Cognitive outcomes were summarized by six domains (attention, working memory, visual memory, executive function, visuospatial function, and global cognition). Partial correlations and multivariate linear regression were used to determine independent associations for all participants and for PD tremor-dominant (TD) and postural instability and gait disorder (PIGD) phenotypes, controlling for age, sex, and premorbid intelligence using the national adult reading test. Cognitive and gait outcomes were significantly worse for PD. Gait, but not cognitive outcomes, was selectively worse for the PIGD phenotype compared with TD. Significant associations emerged for two gait domains for controls (pace and postural control) and four gait domains for PD (pace, rhythm, variability, and postural control). The strongest correlation was for pace and attention for PD and controls. Associations were not significant for participants with the TD phenotype. In early PD, the cognitive correlates of gait are predominantly with fronto-executive functions, and are characterized by the PIGD PD phenotype. These associations provide a basis for understanding the complex role of cognition in parkinsonian gait.

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease

ObjectiveTo assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. MethodsEach subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. InterpretationOur study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program.

CLINICAL PHENOTYPE–SPECIFIC DIFFERENCES IN CEREBRAL HAEMODYNAMICS IN IDIOPATHIC PARKINSON'S DISEASE

IntroductionIdiopathic Parkinson's disease (IPD) exhibits significant heterogeneity in respect of both motor and non motor clinical features. The ‘neurovascular model’ implicates neurovascular mechanisms as key players in the neurodegenerative process.1...

Transcallosal diffusion tensor abnormalities in predominant gait disorder parkinsonism

BackgroundThere have been no previous diffusion tensor imaging (DTI) studies comparing Parkinson's disease (PD) with postural instability and gait disorder (PIGD) parkinsonism. ObjectiveUtilizing DTI with 2-region tractography, we conducted a case control study to determine if different brain regions representing the neural network of the motor system are differentially affected in PIGD compared to PD and controls. MethodsOn a 3 T MR machine, using manual ROI (regions of interest) we determined the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in anatomical brain regions representing the extrapyramidal, pyramidal, and transcallosal tracts, aided by 2-region tractography. FA and ADC were correlated with the Tinetti score (measure of gait and balance). ResultsSixty-five subjects (21 PD, 25 PIGD, 19 controls) were included in the analysis. We demonstrated greater ADC abnormalities in the extrapyramidal, pyramidal and transcallosal motor systems in PIGD compared to controls. Multivariate analysis taking into consideration various clinical variables showed that the FA (p = 0.02) and ADC (p = 0.001) values in the corpus callosum body differentiated PIGD from PD. PIGD with low Tinetti score had a lower FA (p = 0.02) and a higher ADC value (corpus callosum body) (p = 0.03) compared to those with a high score. ConclusionsWe demonstrated for the first time that DTI abnormalities along the transcallosal motor tract in the body of the corpus callosum, but not the substantia nigra, differentiated PIGD from PD, and the degree of corpus callosum body abnormality correlated with the Tinetti score (a measure of risk of falls).

Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

(i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2-3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED₅₀ of 1237 mg day⁻¹ compared with 7-24 mg day⁻¹ for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD.

Postural instability in idiopathic Parkinson's disease: the role of medication and unilateral pallidotomy.

Postural instability (PI) is common in idiopathic Parkinson's disease (IPD). We measured sensory and motor contributions to PI in 50 patients with advanced IPD, off and on medication and in a subset pre- and 3, 6 and 12 months post-unilateral pallidotomy, using computerized dynamic posturography [specifically, the Sensory Organization Test (SOT) and the Unified Parkinson's Disease Rating Scale (UPDRS) subscale PIGD (Postural Instability and Gait Disorder)]. Off medication, all patients had abnormal PIGD scores. The group could be separated into those with normal SOT equilibrium scores (SOTN) and those, the majority, with abnormal postural control when sensory feedback was limited (SOTABN). Medication improved the PIGD scores but worsened the SOT scores in the majority of patients. Increases in spontaneous sway in some patients contributed to the negative effect of medication on SOT scores. However, this could not explain the detrimental effect of medication on SOT scores in at least 40% of patients. On the other hand, pallidotomy improved both PIGD and SOT scores in both groups. A predictor of good outcome from pallidotomy concerning PI was the degree of worsening of the effect that medication had on SOT5 scores. PI in IPD appears to be multifactorial. We propose that the PIGD score reflects sensory and motor aspects of postural control, with normal sensory feedback, while the SOT equilibrium scores measure the sensory organizational process of postural control in the presence of altered sensory inputs. There is a dissociation between the effects of medication and pallidotomy on motor and sensory components of postural control, which may reflect the underlying pathophysiological mechanism responsible for these different components of PI. We suggest that patients with advanced IPD and PI on medication should consider adjuvant surgical treatment for better postural control.