Towards a better understanding of anticipatory postural adjustments in people with Parkinson's disease.

INTRODUCTION: Previous studies have shown that anticipatory postural adjustments (APAs) are altered in people with Parkinson's disease but its meaning for locomotion is less understood. This study aims to investigate the association between APAs and gait initiation, gait and freezing of gait and how a dynamic postural control challenging training may induce changes in these features. METHODS: Gait initiation was quantified using wearable sensors and subsequent straight walking was assessed via marker-based motion capture. Additionally, turning and FOG-related outcomes were measured with wearable sensors. Assessments were conducted one week before (Pre), one week after (Post) and 4 weeks after (Follow-up) completion of a training intervention (split-belt treadmill training or regular treadmill training), under single task and dual task (DT) conditions. Statistical analysis included a linear mixed model for training effects and correlation analysis between APAs and the other outcomes for Pre and Post-Pre delta. RESULTS: 52 participants with Parkinson's disease (22 freezers) were assessed. We found that APA size in the medio-lateral direction during DT was positively associated with gait speed (p<0.001) and stride length (p<0.001) under DT conditions at Pre. The training effect was largest for first step range of motion and was similar for both training modes. For the associations between changes after the training (pooled sample) medio-lateral APA size showed a significant positive correlation with first step range of motion (p = 0.033) only in the DT condition and for the non-freezers only. CONCLUSIONS: The findings of this work revealed new insights into how APAs were not associated with first step characteristics and freezing and only baseline APAs during DT were related with DT gait characteristics. Training-induced changes in the size of APAs were related to training benefits in the first step ROM only in non-freezers. Based on the presented results increasing APA size through interventions might not be the ideal target for overall improvement of locomotion.

The 'Pants-Sign': A Predictor for Falling in People with Parkinson's Disease?

BACKGROUND: A history of falls is the most established predictor of future falls in people with Parkinson's disease (PD). However, predicting a first fall remains challenging. OBJECTIVE: To assess whether experiencing difficulties putting on pants while standing is a viable predictor of future falling, and specifically a first fall, in persons with PD. We define this 'Pants-sign' as people who resort to putting on their pants only while seated. METHODS: 264 persons with PD were included. Information on the Pants-sign, history of falls, disease severity (MDS-UPDRS part III), freezing of gait (N-FOGQ > 0), cognitive function (MoCA), self-reported disability (Schwab & England scale), health-related quality of life (SF-12), Timed-Up-and-Go, and one-legged stance were determined at baseline and after one-year follow-up. The association between the Pants-sign and future falling was examined by univariate logistic regression analysis. A multivariate step-wise logistic regression with forward selection was employed to identify the strongest associations in the entire cohort and a sub-cohort of people without falls in the year prior to baseline. RESULTS: The Pants-sign was univariably associated with a future fall (OR = 2.406, 95% CI [1.313-4.409], p = 0.004]), but was not an independent predictor in the multivariate logistic regression; predictors were higher MDS-UPDRS part III scores (OR = 1.088, 95% CI [1.056-1.121], p < 0.001] and history of falls (OR = 5.696, 95% CI [2.650-12.243], p≤0.001]. For the sub-cohort of people without falls in the previous year (n = 189), the Pants-sign was not associated with future falls. CONCLUSIONS: The Pants-sign is simple to assess and is associated with future falling in PD but is not an independent predictor.

Influence of Crouch Angle on Postural Stability in Quiet Stance and Functional Tasks Among Children with Cerebral Palsy.

The aim of this study is to investigate postural stability and function (functional tasks) in younger (<12 yr) and older (>12 yr) children with lesser (<25°) and greater crouch (>25°) during stance. Postural stability and functional tasks were assessed in 53 ambulatory children with spastic cerebral palsy (CP). Younger and older children with greater crouch angle demonstrated higher displacement of center of pressure compared to children with lesser crouch angle during gait (p < .01). All (younger and older) children with severe crouch angle demonstrated strong association of postural control with stair climb (r = 0.732; p < .05) and timed-up-and-go test (r = 0.84; p < .01). Greater crouch angle demonstrates a moderate association with postural stability (r = 0.528; p < .01) in quiet stance and a strong association with functional tasks in children with CP (r = 0.7-0.84; p < .05).

Freezing of Gait in Parkinson's Disease: Implications for Dual-Task Walking.

BACKGROUND: The simultaneous completion of multiple tasks (dual-tasking, DT) often leads to poorer task performance (DT cost, DTC). People with Parkinson's disease (PwPD) exhibit difficulty with DT, and DTC may be particularly pronounced in PwPD with freezing of gait (FOG). OBJECTIVE: This study assessed the relationship between FOG status and DTC during gait. METHODS: Gait parameters were collected using inertial sensors in 106 PwPD (off-medication), including definite-freezers (dFOG; n = 25), possible-freezers (pFOG; n = 16), and non-freezers (nFOG; n = 65) during single (ST)-and DT walking. RESULTS: PwPD with dFOG had larger (worse) DTC than nFOG for foot-strike angle, stride length, toe-off angle, variability of foot-strike angle, and arm range of motion (ROM). After accounting for covariates, DTC for toe-off angle and stride length remained worse in PwPD who freeze. Worse cognition predicted larger DTC for stride length, gait cycle duration, gait speed, and step duration across groups. Men had larger DTC compared to women for gait speed, variability in foot-strike angle, stride length, and arm ROM. Increased variability in gait speed DTC was associated with increased disease severity. CONCLUSION: These findings provide additional support that PwPD who freeze may rely on greater cortical control for the execution of specific gait metrics. The results also underscore the importance of considering cognition when assessing DT ability in PwPD.

Influence of the percutaneous myofasciotomy on gait of children with spastic cerebral palsy - A short term, retrospective controlled analysis.

BACKGROUND: One of the primary causes in children with cerebral palsy (CP) leading to gait disorders is an increased muscle tone which may secondary result in a shortening of the muscle fascia. Percutaneous myofasciotomy (pMF) is a minimal-invasive surgical intervention correcting the shortened muscle fascia and aims to extend the range of motion. RESEARCH QUESTION: What is the effect of pMF on gait in children with CP three months and one year post-OP? METHODS: Thirty-seven children (f: n = 17, m: n = 20; age: 9,1 ± 3,9 years) with spastic CP (GMFCS: I-III, bilateral (BSCP): n = 24, unilateral (USCP): n = 13) were retrospectively included. All children underwent a three dimensional gait analysis with the Plug-in-Gait-Model before (T0) and three months after pMF (T1). Twenty-eight children (bilateral: n = 19, unilateral: n = 9) underwent a one-year follow-up-measurement (T2). Differences in the Gait Profile Score (GPS), kinematic gait data, gait-related functions and mobility in daily living were statistically analyzed. Results were compared to a control group (CG) matched in age (9,5 ± 3,5 years), diagnosis (BSCP: n = 17; USCP: n = 8) and GMFCS-level (GMFCS I-III). This group was not treated with pMF but underwent two gait analyses in twelve months. RESULTS: The GPS improved significantly in BSCP-pMF (16,46 ± 3,71° to 13,37 ± 3,19°; p < .0001) and USCP-pMF (13,24 ± 3,27° to 10,16 ± 2,06°; p = .003) from T0 to T1 with no significant difference between T1 and T2 in both groups. In CG there was no difference in the GPS between the two analyses. SIGNIFICANCE: PMF may in some children with spastic CP improve gait function three months as well as for one-year post-OP. Medium and long-term effects, however, remain unknown and further studies are needed.

Differential Implications of Cerebral Hypoperfusion and Hyperperfusion in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) exhibit widespread brain perfusion changes. OBJECTIVE: This study investigated whether cerebral regions with hypoperfusion and hyperperfusion have differential effects on motor and cognitive symptoms in PD using early-phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (18 F-FP-CIT) positron emission tomography (PET) scans. METHODS: We enrolled 394 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET scans. Indices reflecting associated changes in regional cerebral hypoperfusion and hyperperfusion on early-phase 18 F-FP-CIT PET scans were calculated as PD[hypo] and PD[hyper] , respectively. The associations of PD[hypo] and PD[hyper] on motor and cognitive symptoms at baseline were assessed using multivariate linear regression. Also, Cox regression and linear mixed models were performed to investigate the effects of baseline PD[hypo] and PD[hyper] on longitudinal outcomes. RESULTS: There was a weak correlation between PD[hypo] and PD[hyper] (γ = -0.19, P < 0.001). PD[hypo] was associated with baseline Unified Parkinson's Disease Rating Scale Part III scores (ß = -1.02, P = 0.045), rapid increases in dopaminergic medications (ß = -18.02, P < 0.001), and a higher risk for developing freezing of gait (hazard ratio [HR] = 0.67, P = 0.019), whereas PD[hyper] was not associated. Regarding cognitive function, PD[hypo] was more relevant to the baseline cognitive performance levels of visuospatial, memory, and frontal/executive function than PD[hyper] . However, greater PD[hyper] was associated with future dementia conversion (HR = 1.43, P = 0.004), whereas PD[hypo] was not associated. CONCLUSIONS: These findings suggest that PD[hypo] and PD[hyper] may differentially affect motor and cognitive functions in patients with PD. © 2023 International Parkinson and Movement Disorder Society.

Added forearm weights for gait pattern normalization in patients with Parkinson's disease.

Patients with Parkinson's Disease presented gait impairment. Applying additional weights to enhancing sensory input may improve gait impairment. We assumed that gait impairment could be improved when patients walked with additional forearm weights, and the gait improvement was associated with clinical characteristic of Parkinson's Disease. Thirty patients with Parkinson's Disease and 30 age-sex matched controls were recruited. Spatiotemporal and joint kinematics parameters were evaluated by a three-dimensional motion capture system in normal walking and walking with sandbags, respectively. The comparisons of spatiotemporal parameters were analyzed using t-test or nonparametric tests. The comparison of joint kinematic data was analyzed using statistical parametric mapping. The correlation between motor symptom and gait parameters changes was analyzed using Pearson's correlation analysis. During normal walking, patients showed deteriorated gait compared with controls. After applying weights to forearms patients increased cadence (p = 0.004), speed (p < 0.001) and step length (p = 0.048), and decreased stride time (p = 0.003). The hip angles significantly increased during 5%-23% and 87%-100% of gait cycle, while knee angles during 9%-25% and 88%-98% of the gait cycle, and ankle angles in 92%-100% of gait cycle. The gait parameters of patients with forearm-loading showed no significant difference compared with healthy subjects walking normally. The change of gait parameters correlated positively with the axial and tremor severity while correlated negatively with the rigidity sub-score. Patients with tremor dominant subtype also showed greater improvement of speed and step time compared with patients with postural instability/gait difficulty subtype. Applying added weights bilaterally to the forearms of patients can normalize gait patterns. Notably, patients with higher scores on axial and tremor and lower rigidity scores gained more benefits.

Feasibility for evaluating motor aspects of Parkinson's disease through video consultations in a resource-limited setting in Southern Brazil.

BACKGROUND: Performing motor evaluations using videoconferencing for patients with Parkinson's disease (PD) is safe and feasible. However, the feasibility of these evaluations is not adequately studied in resource-limited settings. OBJECTIVE: To evaluate the feasibility of performing motor evaluations for patients with PD in a resource-limited setting. METHODS: The examiners rated motor aspects of parkinsonism of 34 patients with PD from the Brazilian public healthcare system through telemedicine with the patient's own means by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating scale. Quality measures of the video meeting were also obtained. The feasibility of rating the motor aspects was the primary outcome whereas the rating of individual motor aspects, video meeting quality and predictors of a complete evaluation served as secondary outcomes. RESULTS: The least assessable parameters were freezing of gait (52.9%), gait (70.6%), leg agility, and rest tremor (both 76.5%). Complete MDS-UPDRS part III was possible in 41.2% of patients and 62 out of 374 motor aspects evaluated (16.6%) were missed. Available physical space for a video evaluation was the worst quality measure. Incomplete evaluations were directly associated with disability (p = 0.048, r = 0.34) and inversely with available physical space (p = 0.003, r = 0.55). CONCLUSION: A significant portion of the MDS-UPDRS part III is unable to be performed during telemedicine-based evaluations in a real-life scenario of a resource-limited setting.

ANTECEDENTES: Realizar avaliações motoras usando videoconferência para pacientes com doença de Parkinson (DP) é seguro e viável. Entretanto, a viabilidade dessas avaliações não é adequadamente estudada em cenários com recursos limitados. OBJETIVO: Identificar a viabilidade de realizar avaliações motoras para pacientes com DP em um ambiente com recursos limitados. MéTODOS: Os examinadores avaliaram os aspectos motores da DP de 34 pacientes do sistema público de saúde brasileiro através da telemedicina com os próprios meios do paciente usando a escala Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Medidas de qualidade da videochamada também foram obtidas. A viabilidade da classificação dos aspectos motores foi o resultado primário, enquanto a classificação dos aspectos motores individuais, a qualidade das videoconferências e os preditores de uma avaliação completa serviram como resultados secundários. RESULTADOS: Os parâmetros menos avaliáveis foram congelamento da marcha (52,9%), marcha (70,6%), agilidade dos membros inferiores e tremor de repouso (ambos 76,5%). A parte III completa da MDS-UPDRS foi possível em 41,2% dos pacientes, mas não foi possível avaliar 62 do total de 374 aspectos motores (16,6%). O espaço físico disponível para uma avaliação em vídeo foi a pior medida de qualidade. As avaliações incompletas foram diretamente associadas ao nível de dependência (p = 0,048, r = 0,34) e inversamente ao espaço físico disponível (p = 0,003, r = 0,55). CONCLUSãO: Uma porção significativa da parte III da MDS-UPDRS é perdida durante as avaliações baseadas em telemedicina em um cenário da vida real com recursos limitados.

Persistent increase in anterior pelvic tilt after hamstring lengthening in children with cerebral palsy.

BACKGROUND: Hamstring lengthening has traditionally been the surgical treatment of choice to correct flexed knee gait in children with cerebral palsy (CP). Improved passive knee extension and knee extension during gait are reported post hamstring lengthening, but concurrent increased anterior pelvic tilt also occurs. RESEARCH QUESTION: Does anterior pelvic tilt increase after hamstring lengthening in children with CP both in the short-term and mid-term, and what predicts increased post-operative anterior pelvic tilt? METHODS: 44 participants were included (age 7.2, SD 2.0 years; 5 GMFCS I, 17 GMFCS II, 21 GMFCS III, 1 GMFCS IV). Mean pelvic tilt was compared between visits, and the effect of potential predictors of change in pelvic tilt was examined using linear mixed models. The relationship of change in pelvic tilt to change in other variables was examined using Pearson correlation. RESULTS: Anterior pelvic tilt increased significantly post-operatively by 4.8° (p < 0.001). It remained significantly higher by 3.8° at 2-15 years follow-up (p < 0.001). Change in pelvic tilt was not affected by sex, age at surgery, GMFCS level, assistance during walking, time since surgery, or baseline values of hip extensor strength, knee extensor strength, knee flexor strength, popliteal angle, hip flexion contracture, step length, walking speed, maximum hip power in stance, or minimum knee flexion in stance. Pre-operative dynamic hamstring length was associated with greater anterior pelvic tilt at all visits but did not affect amount of change in pelvic tilt. Patients in GMFCS I-II showed a similar pattern of change in pelvic tilt to GMFCS III-IV. SIGNFICANCE: When considering hamstring lengthening for ambulatory children with CP, surgeons should weigh increased mid-term anterior pelvic tilt post-operatively with the desired outcome of improved knee extension in stance. Patients with neutral or posterior pelvic tilt and short dynamic hamstring lengths pre-operatively have lowest risk of excessive post-operative anterior pelvic tilt.

Effectiveness of Center of Pressure Trajectory as Anticipatory Postural Adjustment Measurement in Parkinson's Disease With Freezing of Gait History.

BACKGROUND: Evidence showed that patients with Parkinson's disease (PD) who have a history of freezing of gait (FOG) have hypometric anticipatory postural adjustment (APA) during gait initiation (GI) compared to PD without FOG. OBJECTIVES: This study aimed to test the feasibility of center of pressure (COP) displacement during GI as the measure of APA in PD with and without a history of FOG. METHODS: Patients with PD underwent COP trajectory measurements, including duration, length, velocity, and acceleration in different phases of APA (APA1, APA2a, APA2, and LOC), as well as evaluation of New Freezing of Gait Questionnaire (NFOG-Q), Tinetti balance and gait score, and Postural Instability and Gait Difficulty (PIGD) score in the on and off medication states. RESULTS: The duration (seconds) of APA2a, APA2b, and LOC were highest while velocity in mediolateral direction (X) (m/s), including APA1, APA2a, APA2b, and LOC showed lowest in PD with FOG. Velocity in the mediolateral direction in different phases of APA increased in patients with FOG after dopaminergic therapy. APA2a (seconds) and APA2b (X) (m/s) were significantly associated with NFOG-Q part II, APA2b (X) (m/s) was significantly associated with NFOG-Q part III, and APA2a (seconds) was significantly associated with Tinetti balance and gait and PIGD score. CONCLUSIONS: PD with FOG history showed a favorable response of APAs to dopaminergic replacement. The APA parameters by COP trajectory, especially lateral COP shift toward the stance foot (APA2b (X) (m/s) and APA2a (seconds)) are surrogate markers to assess PD with FOG history.

Topological reorganization of functional hubs in patients with Parkinson's disease with freezing of gait.

BACKGROUND AND PURPOSE: Resting-state functional MRI (rs-fMRI) studies in Parkinson's disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks (RSNs). While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity (FC), whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher order functional organization, which could be derived from the "hub" and the "rich-club" organization of the functional networks, could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG. METHODS: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of RSN topology in PD-FOG when compared to those without FOG. We also compared the higher order functional organization derived using the hub and rich-club measures in the FC networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG. RESULTS: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG. CONCLUSIONS: Overall, our findings demonstrate a widespread topological reorganization and disrupted higher order functional network topology in PD-FOG that may further assist in improving our understanding of functional network disturbances associated with PD-FOG.

Associations of striatal dopamine transporter binding with motor and non-motor symptoms in early Parkinson's disease.

Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross-sectional studies indicated certain motor and non-motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed-effect models were respectively conducted to investigate the cross-sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross-sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]-adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR-adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR-adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid-eye-movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR-adjusted p = 0.0120). Furthermore, changes in MDS-UPDRS scores and the State-Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non-motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.

Machine learning approach to gait deviation prediction based on isokinetic data acquired from biometric sensors.

BACKGROUND: Analyzing gait deviation is one of the crucial factors during the diagnosis and treatment of children with Cerebral Palsy (CP). The typical diagnostic procedure requires an expensive and complicated three-dimensional gait analysis system based on visual sensors. In this work, we focus on predicting well-known gait pathology scores using only information collected from the BS4P, the affordable isokinetic dynamometer. Using such equipment, it is possible to determine gait pathological indices such as the gait deviation index (GDI) or the Gillette gait index (GGI). RESEARCH QUESTION: Are there correlations between the results of examining patients with CP on the Biodex Pro 4 device and the gait quality metrics (GDI and GGI)? METHODS: The isokinetic data acquired from biometric sensors (74 records) were analyzed using big data methods. We used several Machine Learning methods to find the correlation between gait deviation and isokinetic data: Adaptive Boosting Regression, K-nearest Neighbor, Decision Tree Regression, Random Forest Regression, and Gradient Boost Regression. RESULTS: In this paper, we provided a detailed comparison of different machine learning regression models in predicting gait quality in patients with CP based only on the data gathered from affordable Biodex 4 Pro device. The best result was obtained using the gradient boosting regression model with Mean Absolute Percentage Error of 6%. However, it was not possible to precisely predict the GGI index using this method. SIGNIFICANCE: The results obtained showed promising results in the evaluation of gait index scores, which gives the possibility of diagnosing patients with CP without the use of expensive optometric systems. Evaluating gait metrics using the approach proposed in this paper could be very helpful for both physicians and physiotherapists in assessing the condition of patients with CP, as well as other diseases related to gait problems.

Impact of GBA variants on longitudinal freezing of gait progression in early Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a common disabling gait disturbance among patients with Parkinson's disease (PD), but the influence of genetic variants on the incidence of FOG has been poorly studied to date. OBJECTIVES: We aimed to evaluate the association of GBA variants with the risk of FOG development in a large early PD cohort. METHODS: This study included 371 early PD patients from the Parkinson's Progression Markers Initiative (PPMI) who were divided into a GBA variant carrier group (GBA-PD group, n = 44) and an idiopathic PD group without GBA variants (iPD group, n = 327). They were followed up for up to 5 years to examine the progression of FOG. The cumulative incidence of FOG and risk factors for FOG were assessed using Kaplan‒Meier and Cox regression analyses. RESULTS: At baseline, the GBA-PD group had lower CSF ß-amyloid 1-42 (Aß42) levels and more severe motor and nonmotor symptoms than the iPD group. During the 5-year follow-up, the GBA-PD group had a higher incidence of FOG than the iPD group, and the FOG progression rate was related to GBA variant severity. In the multivariable Cox model without CSF Aß42, GBA variants were significant predictors of future FOG, and the association remained significant after adding CSF Aß42 to the model. In the subgroup analyses, the effect of GBA variants was not observed in the "low-level" group. However, in the "high-level" group, GBA variants independently increased the risk of FOG, and this association was stronger than the association with CSF Aß42. CONCLUSION: GBA variants are novel genetic risk factors for future FOG development in early PD patients. This association seemed to be mediated by both Aß-dependent pathways and Aß-independent pathways.

[Features of visual, cognitive and neuroimaging changes in Parkinson's disease patients with freezing of gait]. / Osobennosti zritel'nykh, kognitivnykh i neirovizualizatsionnykh izmenenii pri narusheniyakh initsiatsii khod'by u patsientov s bolezn'yu Parkinsona.

OBJECTIVE: To determine visual and cognitive impairments in relation to MRI changes in patients with freezing of Gait (FOG) in Parkinson's disease (PD). MATERIAL AND METHODS: We examined 78 patients with PD without dementia, who were divided into groups according to the presence (FOG«+¼ group) or absence (FOG«-¼ group) of «freezing¼ episodes. RESULTS: A decrease in contrast sensitivity (CS) and retinal photosensitivity was determined in all subjects with PD, but in patients with FOG, the decrease in CS was more pronounced. There was a significant decrease in the volume of the cuneus, lingual gyrus, posterior cingulate gyrus, superior parietal lobe and middle frontal gyrus in the FOG«+¼ group. It was revealed that patients with FOG had cognitive impairments of both the frontal and posterior cortical subtypes, while in the FOG«-¼ group, only visuospatial deficit prevailed. A direct correlation was determined between the severity of FOG and part I of the UPDRS scale, between a decrease in CS and cortical areas related to the dorsal and ventral visual information processing systems. The presence of a negative relationship between the scores of the FOG-Q, Timed Up and Go test and the volume of cortical areas of the frontal lobe responsible for planning and programming of movements indicates their role in the development of FOG in PD. CONCLUSION: Thus, visual impairments associated with PD, along with a heterogeneous profile of cognitive impairment, make a significant contribution to the development of FOG.

Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.

Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.

Traditional Chinese medicine Pingchan granule for motor symptoms and functions in Parkinson's disease: A multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Pingchan granule (PCG) is a traditional Chinese medicine for Parkinson's disease (PD). HYPOTHESIS/PURPOSE: This was the first study aiming to evaluate the efficacy and safety of PCG for motor symptoms, gait impairments and quality of life in PD. STUDY DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants were included and followed for 9 months, randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcome was the severity of motor symptoms assessed by Movement Disorder Society Unified Parkinson's Rating Scale III (MDS-UPDRS-III) motor score. Secondary outcomes included timed up and go test (TUG), functional gait assessment (FGA), freezing of gait (FOG), and quality of life assessed by Parkinson's disease questionnaire (PDQ-39). Assessments were done at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-INR-1,701,194. RESULTS: Generalized estimating equation analyses revealed that PCG group had significantly better improvement in MDS-UPDRS-III motor score than placebo group, as well as its domain scores of axial symptoms, bradykinesia, rigidity, and tremor. Improvements of TUG time, FGA, FOG questionnaire (FOGQ), and PDQ39 scores were also observed. CONCLUSION: PCG had a long-lasting efficacy for motor symptoms and function in PD with good tolerance, supporting that PCG might be a viable alternative in the management of PD.

Freezing of gait is a risk factor for cognitive decline in Parkinson's disease.

BACKGROUNDS: Freezing of gait (FOG) and cognitive impairment are serious symptoms of Parkinson's disease (PD). Understanding the association between FOG and cognition may help formulate specific interventions for PD individuals. OBJECTIVES: We aimed to investigate the associations of cognitive impairment in different domains with FOG status using multiple neuropsychological tests. METHODS: Two cohorts including 691 and 104 participants were recruited from Parkinson's progression markers initiative (PPMI) and central China, respectively. All participants underwent FOG assessment and neuropsychological tests, and 595 individuals from PPMI and 51 from central China were enrolled for longitudinal observation. Cross-sectional and longitudinal associations between cognition and FOG status were evaluated using multivariable-adjusted models. RESULTS: Worse cognitive performances were observed in patients with FOG compared to those without FOG in both cohorts (ß = - 0.020, p < 0.001) using multivariate-adjusted models. Moreover, patients with progressive FOG during follow-up manifested more serious cognitive declines (HR = 1.40, 95% CI = 1.07-1.80). The FOG was mainly associated with the decline of executive, attention, and orientation. Furthermore, FOG was associated with higher levels of cognition-related biomarkers including T-tau, P-tau, and NfL in cerebrospinal fluid (p < 0.050). CONCLUSIONS: FOG is a risk factor for cognitive decline in PD, which emphasizes the need for early detection and monitoring of cognitive changes and interventions on cognitive impairments in PD patients with FOG.

Reduced Short-Latency Afferent Inhibition in Parkinson's Disease Patients with L-dopa-Unresponsive Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD), especially the "L-dopa-unresponsive" subtype, is associated with the dysfunction of non-dopaminergic circuits. OBJECTIVE: We sought to determine whether cortical sensorimotor inhibition evaluated by short-latency afferent inhibition (SAI) related to cholinergic and gamma-aminobutyric acid (GABA)-ergic activities is impaired in PD patients with L-dopa-unresponsive FOG (ONOFF-FOG). METHODS: SAI protocol was performed in 28 PD patients with ONOFF-FOG, 15 PD patients with "off" FOG (OFF-FOG), and 25 PD patients without FOG during medication "on" state. Additionally, 10 ONOFF-FOG patients underwent SAI testing during both "off" and "on" states. Twenty healthy controls participated in this study. Gait was measured objectively using a portable Inertial Measurement Unit system, and participants performed 5-meter Timed Up and Go single- and dual-task conditions. Spatiotemporal gait characteristics and their variability were determined. FOG manifestations and cognition were assessed with clinical scales. RESULTS: Compared to controls, PD patients without FOG and with OFF-FOG, ONOFF-FOG PD patients showed significantly reduced SAI. Further, dopaminergic therapy had no remarkable effect on this SAI alterations in ONOFF-FOG. Meanwhile, OFF-FOG patients presented decreased SAI only relative to controls. PD patients with ONOFF-FOG exhibited decreased gait speed, stride length, and increased gait variability relative to PD patients without FOG and controls under both walking conditions. For ONOFF-FOG patients, significant associations were found between SAI and FOG severity, gait characteristics and variability. CONCLUSION: Reduced SAI was associated with severe FOG manifestations, impaired gait characteristics and variability in PD patients with ONOFF-FOG, suggesting the impaired thalamocortical cholinergic-GABAergic SAI pathways underlying ONOFF-FOG.