Motor imagery ability in patients with functional dystonia.

INTRODUCTION: Motor imagery (MI) involves recreating a movement mentally without physically performing the movement itself. MI has a positive impact on motor performance, motor learning and neural plasticity. We analysed the connection between motor imagination and altered movement execution in individuals with dystonia, a complex sensorimotor disorder. The aim of our study was to examine MI ability in patients with functional dystonia (FD) in comparison to organic dystonia (OD). METHODS: Our case-control study involved 46 patients, 22 with FD and 24 with OD. The assessment consisted of specific questionnaire and standardized motor, cognitive and psychiatric scales. The KVIQ-20 was used to test MI in each patient. RESULTS: Patients with FD scored lower on both global visual and kinaesthetic scales of the KVIQ-20 exam compared to patients with OD (63.1 ± 18.5 vs. 73.7 ± 13.2, and 54.9 ± 21.9 vs. 68.8 ± 18.2, respectively). Patients with FD also exhibited visual and/or kinaesthetic MI impairment in different body segments. The internal perspective when imagining movements was preferred in both patients with FD and OD. CONCLUSION: FD patients showed global dysfunction of visual and kinaesthetic MI abilities. Techniques for MI improvements might have a potential role in dystonia rehabilitation.

Early Screening for the Parkinson Variant of Multiple System Atrophy: A 6-Item Score.

BACKGROUND: A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. OBJECTIVES: To replicate and improve the 4-item MSA-P score. METHODS: We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. RESULTS: The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. CONCLUSIONS: The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.

Long-term outcome of patients with neurological form of Wilson's disease compliant to the de-coppering treatment.

BACKGROUND: A substantial proportion of Wilson's disease (WD) patients exhibit residual neurological symptoms. Data on the prognostic value of initial clinical features and treatment choices in WD patients compliant to the therapy is relatively sparse. AIM: The aim of the present study was to identify predictors of the long-term outcome of patients with WD with good treatment adherence. METHODS: Forty patients with neurological form of WD were evaluated before the de-coppering treatment initiation (based on the medical records) and after mean 15.25 ± 11.24 years of the stable treatment. Severity of neurological symptoms were assessed with a tier two of Global Assessment Scale (GAS) for Wilson's Disease. RESULTS: The most frequent symptoms prior to treatment initiation were dysarthria (90%), tremor (90%), clumsiness (67.5%), depression (67.5%), and gait disturbance (62.5%). Significant decrease in the frequency of dysarthria, clumsiness, tremor, gait disturbance, postural instability and an improvement in school/work performance were observed after the long-term treatment, while frequency of dysphagia, drooling, bradykinesia and rigidity, dystonic and choreatic features did not change. Overall symptom severity decreased over time. Presence of dystonia before treatment initiation was the only identified predictor of worse residual GAS score. Greater severity of residual dystonia was associated with female gender and longer disease duration. CONCLUSION: Although patients with neurological form of WD compliant to de-coppering treatment had favorable disease outcome, a significant burden of residual neurological symptoms was observed after the long-term follow-up. Dystonia at disease onset was the only identified predictor of the worse long-term outcome.

Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing's Syndrome: A Case Report and Review of Literature.

Introduction: Patients with Cushing's syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient's condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient's condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients.

Gait alterations in Parkinson's disease at the stage of hemiparkinsonism-A longitudinal study.

BACKGROUND: Progressive gait impairment in Parkinson's disease (PD) leads to significant disability. Quantitative gait parameters analysis provides valuable information about fine gait alterations. OBJECTIVES: To analyse change of gait parameters in patients with early PD at the stage of hemiparkinsonism and after 1 year of follow up, taking into account clinical asymmetry. METHODS: Consecutive early PD outpatients with strictly unilateral motor features underwent clinical and neuropsychological assessment at the study entry and after 1 year of follow up. Gait was assessed with GAITRite walkway using dual-task methodology. Spatiotemporal gait parameters (step time and length, swing time and double support time) and their coefficients of variation (CV), gait velocity and heel-to-heel base support were evaluated. RESULTS: We included 42 PD patients with disease duration of 1.3 years (±1.13). Progression of motor and non-motor symptoms, without significant cognitive worsening, was observed after 1 year of follow up. Significant shortening of the swing time, prolongation of the double support and increase of their CVs were observed during all task conditions similarly for most parameters on symptomatic and asymptomatic bodysides, except for CV for the swing time under the combined task. CONCLUSION: Alterations of the swing time and double support time are already present even at the asymptomatic body side, and progress similarly, or even at faster pace, at this side, despite dopaminergic treatment These parameters deserve further investigation in larger, prospective studies to address their potential to serve as markers of progression in interventional disease modifying trials with early PD patients.

A Modified Progressive Supranuclear Palsy Rating Scale.

BACKGROUND: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. OBJECTIVE: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. METHODS: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. RESULTS: The modified scale retained 14 items (yielding 0-2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). CONCLUSIONS: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine. © 2021 International Parkinson and Movement Disorder Society.

The Profile and Evolution of Neuropsychiatric Symptoms in Multiple System Atrophy: Self- and Caregiver Report.

OBJECTIVE: Recent research shows that patients with multiple system atrophy (MSA) have significant cognitive and neuropsychiatric comorbidities that can color the clinical presentation of the disease and affect their quality of life. The aims of this study were to determine the neuropsychiatric profile in a cohort of patients with the parkinsonian type of MSA (MSA-P) and their dynamic changes over a 1-year follow-up period and to compare rates of neuropsychiatric symptoms (NPSs) reported by caregivers and the patients themselves. METHODS: Forty-seven patients were assessed at baseline; of these, 25 were assessed again after 1 year. NPS assessment tools included the Neuropsychiatric Inventory (NPI), the Beck Depression Inventory, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Apathy Evaluation Scale. RESULTS: The prevalence of NPSs in patients with MSA-P was very high, with depression, sleep disturbances, apathy, and anxiety being the most frequently occurring features. The evolution of NPSs was found to be independent of motor, autonomic, and cognitive symptoms. None of the scales measuring NPSs, including the NPI, were capable of detecting changes over the 1-year follow-up period. Although the overall prevalence of depression, apathy, and anxiety obtained from caregivers and the patients themselves was similar, reports from these two sources cannot be considered interchangeable. CONCLUSIONS: The progression of neuropsychiatric symptoms was not a subject of rapid change in MSA-P, in contrast to the observed motor, autonomic, and cognitive deterioration. These findings suggest the need to investigate the utility of available instruments in capturing the evolution of NPSs in MSA over time.

Changes of Phenotypic Pattern in Functional Movement Disorders: A Prospective Cohort Study.

Introduction: Functional movement disorders (FMD) refer to a group of movement disorders that present with clinical characteristics incongruent to those due to established pathophysiologic processes, as for example in the case of neurodegeneration or lesions. The aim of this study was to assess clinical features that contribute to the specific phenotypic presentations and disease course of FMD. Methods: The study consisted of 100 patients with FMD treated at Clinic for Neurology, Clinical Center of Serbia, who were longitudinally observed. Comprehensive clinical and psychiatric assessment was performed at the baseline, when initial FMD phenotype was defined. Follow-up assessment of phenotypic pattern over the time and clinical course was done after 3.2 ± 2.5 years at average. Results: We showed that 48% of FMD patients were prone to changes of phenotypic pattern during the disease course. Dystonia had tendency to remains as single and unchanged phenotype over the time (68.2%), while patients initially presented with Tremor, Gait disorder, Parkinsonism and Mixed phenotype were more susceptible to developing additional symptoms (62.5, 50, and 100%, respectively). Higher levels of somatoform experiences (p = 0.033, Exp(B) = 1.082) and higher motor severity (p = 0.040, Exp(B) = 1.082) at baseline assessment were associated with an increased likelihood of further enriching of FMD phenotype with additional functional symptoms. Also, these patients more frequently reported pain, and had higher scores on majority of applied psychiatric scales, together with more frequent presence of major depressive disorder. Conclusion: Results from this prospective study suggested tendency for progression and enrichment of functional symptoms in FMD patients over time. Besides functional core symptoms, other key psychological and physical features (like pain or multiple somatisations) were quite relevant for chronicity and significant dysability of FMD patients.

Copathology in Progressive Supranuclear Palsy: Does It Matter?

BACKGROUND: The influence of concomitant brain pathologies on the progression rate in PSP is unclear. OBJECTIVES: To analyze the frequency and severity of copathologies and their impact on the progression in PSP. METHODS: We analyzed clinic-pathological features of 101 PSP patients. Diagnoses and stages of copathologies were established according to standardized criteria, including Alzheimer's disease-related pathology, argyrophilic grains, Lewy-related pathology, transactive response DNA-binding protein 43 pathology, fused in sarcoma pathology, cerebral amyloid angiopathy, and small vessel disease. Demographic data and major clinical milestones (frequency and latency to onset) were extracted from patients' files. RESULTS: Only 8% of 101 patients presented with pure PSP pathology without any copathology. Alzheimer's disease-related pathology was the most frequent (84%), followed by argyrophilic grains (58%), both occurring as single copathology or in combination with other proteinopathies or cerebrovascular disease. Lewy-related and transactive response DNA-binding protein 43 copathology occurred rarely (8% and 6%, respectively). Fused in sarcoma-positive cases were not found. While being common, copathology was mostly mild in severity, with the exception of frequently widespread argyrophilic grains. Small vessel disease was also frequent (65%). Cerebral amyloid angiopathy occurred only in the presence of Alzheimer's disease-related changes (25%). The copathologies did not have major impact on prevalence and time frame of major disease milestones. CONCLUSIONS: In PSP, concomitant neurodegenerative proteinopathies or cerebrovascular diseases are frequent, but generally mild in severity. Our data confirmed that four repeat tau is still the most relevant target for PSP, whereas the impact of copathologies on progression rate appears to be of less importance. This is relevant information for the development of disease-modifying therapies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Factors associated with deterioration of health-related quality of life in multiple system atrophy: 1-year follow-up study.

The aim of this study was to identify the main contributors to the health-related quality of life (HRQoL) in multiple system atrophy with predominant parkinsonism (MSA-P) and to determine the usefulness of SF-36 in capturing the HRQoL changes over 1-year follow-up. A total of 45 MSA-P and 150 Parkinson's disease (PD) patients were studied. The hierarchical multiple regression analysis was conducted to identify predictors of the SF-36 total score. The magnitude of any change for the HRQoL over 1-year of follow-up, was calculated as an effect size. The average scores for each SF-36 domains, except for the bodily pain, were lower in MSA-P than in PD patients (p < 0.05). The most important predictors of HRQoL in MSA-P, were female gender, older age at onset, SCOPA-AUT score and UMSARS IV, which together with other selected clinical variables accounted for 84% of the variance in the total SF-36 score in the final model in hierarchical analyses. During the 1-year follow-up, the SF 36 was found capable of detecting changes in MSA-P. Our study provided some new insights into potential predictors of the HRQoL and its longitudinal changes in MSA-P, which should be considered when healthcare programs are developed.

Progression of white matter damage in progressive supranuclear palsy with predominant parkinsonism.

INTRODUCTION: Progressive supranuclear palsy with predominant parkinsonism (PSP-P) accounts for 14-35% of all PSP cases. A few cross-sectional MRI studies in PSP-P showed a remarkable white matter (WM) damage. Progression of brain structural damage in these patients remains unknown. METHODS: Longitudinal clinical, cognitive and diffusion tensor (DT) MRI data were obtained over a mean 1.6 year follow up in 10 PSP-P patients. At study entry, patients were compared with 36 healthy controls. Voxelwise statistical analysis of white matter DT MRI data (mean, axial and radial diffusivity, and fractional anisotropy) was carried out using tract-based spatial statistics. RESULTS: During the 1.6 year follow up, PSP-P patients showed significant decline of motor, cognitive and mood disturbances. DT MRI analysis revealed at baseline a widespread pattern of WM alterations. Over time, PSP-P patients exhibited progression of WM damage in supratentorial tracts compared to baseline. No WM changes were detected in cerebellar WM. CONCLUSIONS: In PSP-P patients, WM damage significantly progressed over time. Longitudinal DT MRI measures are a potential in vivo marker of disease progression in PSP-P.

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study.

OBJECTIVES: In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). METHODS: Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. RESULTS: Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. CONCLUSIONS: This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course.

Use of the Neuropsychiatric Inventory to Characterize the Course of Neuropsychiatric Symptoms in Progressive Supranuclear Palsy.

The aim of this study was to determine the neuropsychiatric profile in a cohort of progressive supranucelar palsy (PSP) patients and their dynamic changes over a follow-up period of 1 year. A total of 59 patients were assessed at baseline, while 25 of them were accessible after 1 year of the follow-up. The most common symptoms were apathy and depression, which were also found to be, among other variables, the independent determinants of increased Neuropsychiatric Inventory (NPI) total score. Moreover, apathy deteriorated most profoundly over the follow-up period. The NPI seemed to be a sensitive measure of behavioral changes in PSP.

The utility of FDG-PET in the differential diagnosis of Parkinsonism.

INTRODUCTION: Differential diagnosis of parkinsonian disorders can be difficult on clinical grounds, especially in the early stage. Recent advancements in 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging reveals different patterns of regional glucose metabolism in idiopathic Parkinson's disease (IPD) and atypical parkinsonian syndromes, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), which may help differentiating between these conditions. PURPOSE: To assess the utility of FDG-PET imaging in differential diagnosis of Parkinsonism in clinical practice. METHODS: FDG-PET was performed in 72 patients with parkinsonism (age 34-80 years) referred to our center by movement disorder specialists. FDG-PET diagnosis was obtained by visual assessment of individual scans combined with voxel-based statistical parametric mapping analysis. FDG-PET diagnosis assigned at the time of imaging was compared with the final clinical diagnosis made by the movement disorder specialists after ≥2 years follow-up. RESULTS: FDG-PET findings were consistent with IPD in 27, MSA in 18, PSP in 19 and CBS in 2 patients. The final clinical diagnosis was IPD in 29, MSA in 20, PSP in 21 and CBS in 2 patients. Concordance between the FDG-PET and clinical diagnoses was 92% in the overall sample (IPD 93%, MSA 90%, PSP 91% and CBS 100%). The diagnostic accuracy of FDG-PET was 93% for IPD and MSA and 97% for PSP. CONCLUSION: FDG-PET may help differentiate between IPD, MSA, PSP and CBS among patients presenting with parkinsonian symptoms, which is important for patient counselling and making early decisions about treatment.

Finger tapping analysis in patients with Parkinson's disease and atypical parkinsonism.

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson's disease (PD), progressive supranuclear palsy-Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of -0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (-0.21°/cycle, p=0.032), and particularly from PD (-0.56°/cycle, p=0.001), and MSA-P patients (-1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.

The Pathophysiology of Fatigue in Parkinson's Disease and its Pragmatic Management.

BACKGROUND: Fatigue is 1 of the most common and most disabling symptoms among patients with Parkinson's disease (PD) and has a significant impact on their quality of life. Yet the pathophysiology of fatigue is poorly understood, while its treatment is "limited to an empirical approach based on plausible hypotheses." METHODS: PubMed was searched for articles with the key words "Parkinson's disease" or "parkinsonism" and "fatigue" that were published by or before August 2015. The analysis of articles, which were selected on subjective grounds, was used to review the current knowledge of pathophysiology and treatment outcomes in studies focused on fatigue in PD. CONCLUSIONS: Clinical and experimental findings support the view that fatigue is a primary manifestation of PD. The main hypothesized pathophysiological mechanisms include abnormal basal ganglia (BG)-cortical mechanisms, particularly frontal loops, and an imbalance between neurotransmitters (e.g., dopamine [DA] and serotonin), along with an altered hypothalamus-pituitary-adrenal axis, neuroinflammation, cardiac sympathetic denervation, etc. Pragmatic treatment of fatigue in patients with PD includes various pharmacological (dopaminergic and psychostimulant drugs, antidepressants) and nonpharmacological strategies, although current knowledge suffers from insufficient evidence to support the use of any drug or nondrug therapy.

Mild Cognitive Impairment in Early Parkinson's Disease Using the Movement Disorder Society Task Force Criteria: Cross-Sectional Study in Hoehn and Yahr Stage 1.

BACKGROUND: Mild cognitive impairment (MCI) in Parkinson's disease (PD) is common and confers a higher risk for developing dementia. METHODS: In this cross-sectional study of MCI in PD conducted at a university hospital, a comprehensive neuropsychological battery covering five domains (attention/working memory, executive, verbal, and visual memory, language, and visuospatial) was administered to 111 nondemented PD patients in Hoehn and Yahr stage 1 and to 105 healthy matched control subjects (HC). MCI was diagnosed according to level 2 of the Movement Disorder Society Task Force criteria. RESULTS: Criteria for MCI associated with PD (PD-MCI) were fulfilled by 24% of PD patients in the initial stage of the disease at the z cutoff scores of -1.5 SD in contrast to 7% of HC fulfilling criteria for MCI. Memory and visuospatial domains were the most commonly affected at -1.5 SD. PD-MCI patients mostly had a multiple-domain MCI subtype (78%). They presented a more severe bradykinesia and higher mood and apathy scores in comparison with cognitively normal PD patients. Basic motor scores predicted performance on some cognitive tests and specific cognitive-motor relationships emerged. CONCLUSIONS: MCI, predominantly of a multiple-domain subtype, was quite prevalent even in the initial stage of PD.

Quality of life in patients with progressive supranuclear palsy: one-year follow-up.

The aim of this prospective cohort study that included 46 patients with progressive supranuclear palsy (PSP) was to estimate which demographic and clinical factors were the main contributors to the health-related quality of life (HRQoL) and how did the HRQoL change over a follow-up period of 1 year in these patients. The hierarchical regression analyses showed that the final models demonstrated that gender, included clinical variables and psychiatric/neuropsychological scales, accounted for 68% of the variance in the Physical Composite Score and 73% of the variance of the Mental Composite Score of the 36-item Short Form Health Survey (SF-36). Among variables in both final models, only the score of the Apathy Evaluation Scale showed statistically significant negative predictive value (p < 0.05). Changes in the HRQoL scores were assessed in 28 PSP patients who completed 1-year follow-up period after the baseline examination. Statistically significant decline in the HRQoL was detected for the following scales of the SF-36: physical functioning, vitality, social functioning, and role emotional, as well as in both composite scores (Physical Composite Score and Mental Composite Score). The analyses of magnitude of changes in the HRQoL during 1-year follow-up period showed large effect size (≥0.80) for total scores, as well as for the physical functioning, vitality, and social functioning. In conclusion, despite certain limitations, our study provided some new insights into potential predictors of the HRQoL and its longitudinal changes in patients with PSP.

Attentional set-shifting in Parkinson's disease patients with freezing of gait-acquisition and discrimination set learning deficits at the background?

Cognitive loading aggravates the freezing of gait (FoG), which is observed in approximately 50% of patients with Parkinson's disease (PD) in the advanced stages. To investigate whether a specific pattern of executive deficits, that is, attentional set-shifting and/or inhibitory control, are associated with FoG in PD, 30 PD patients with FoG (PD-FoG+) and 36 PD patients without FoG (PD-FoG-) and 22 control healthy subjects were examined with a comprehensive neuropsychological battery. Intra-Extra Dimensional Set shifting Test (IED) and Stop Signal Task (SST), selected from the Cambridge Automated Neuropsychological Battery (CANTAB battery), were administered to analyze set-shifting and motor inhibition, respectively. The IED task was significantly sensitive for differentiating between PD-FoG+ and PD-FoG- groups (p<.01), as well Adenbrook's clock drawing task (p=.033). By contrast, no differences emerged on any aspect of the SST task and other cognitive tasks. The attrition rate during the IED task showed that the problem in the PD-FoG+ group appeared at the pre-ID level, on the discrimination-learning set; the 32% PD-FoG+ subjects did not achieve the ID level of the task in comparison to negligible 4% of the PD-FoG- patients (p=.011). The logistic regression analysis, indicated the higher the IED stage successfully completed, the less likely presence of FoG in PD subjects. These results demonstrate that the complex cognitive-motor interplay might be responsible for FoG in PD and have had real life implication for the patients.