England Activities Of Daily Living Research Articles

Vastly Different Exercise Programs Similarly Improve Parkinsonian Symptoms: A Randomized Clinical Trial

Objectives: To directly compare the effects of agility exergaming (EXE) and stationary cycling (CYC) exercise training on Parkinson’s disease (PD) patients’ mobility and clinical symptoms. Design: Randomized clinical trial. Setting: Outpatient physiotherapy clinic in a hospital. Participants: Seventy-four stage 2–3, nondemented PD patients were included in this study. Intervention: The groups were as follows: EXE (n = 25), CYC (n = 25), and a wait-listed control group (CON; n = 24). The EXE and CYC groups exercised 5×/week for 5 weeks, matched at 80% of the age-predicted maximal heart rate. Main Outcomes: The primary outcome was the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (UPDRS-II) score. Secondary outcomes were Parkinson’s Disease Quastionnaire-39 (PDQ-39), the Beck Depression Inventory (BDI), the Schwab and England Activities of Daily Living (SE-ADL) scale, Euro-Quality of Life-5 Dimensions (EQ-5D) questionnaire, the Berg Balance Scale (BBS), the Balance Evaluation Systems Test (BESTest), the Tinetti Assessment Tool (TAT), the Dynamic Gait Index, the 6-min walk test (6MWT), and standing posturography. Results: After treatment, UPDRS-II scores improved (mean change: EXE, –4.5 points; CYC, –3.2 points). The results for the other outcomes (EXE and CYC, respectively) were: PDQ, 13 and 17%; BDI, –2.5 and –2.1 points; 6MWT, 129.6 and 141.6 m; and EQ-5D, 12 and 9% (all p < 0.05, but there was no difference between groups). EXE vs. CYC resulted in improved SE-ADL (8.4 and 4.0 points, effect size [ES]: 0.12), BBS (8.8 and 4.2 points, ES: 0.44), and 2 measures of posturography (ES: 0.11 and 0.21) (p < 0.05). BESTtest, TAT, the Dynamic Gait Index, and 4 out of 6 posturography measures did not change (p > 0.05). Conclusion: Two highly different exercise programs resulted in similar improvement of most motor and clinical symptoms in PD patients.

PND124 - HUMANISTIC AND ECONOMIC BURDEN OF PROGRESSIVE SUPRANUCLEAR PALSY: A SYSTEMATIC LITERATURE REVIEW

Progressive supranuclear palsy (PSP) is a rare neurological disease that is characterized by a primary tau pathology. PSP symptoms include early and severe gait instability with falls, slowing of vertical saccadic eye movements, slowed movement, rigidity of the axial musculature, dysphagia, dysarthria, pseudobulbar affect, neuropsychiatric abnormalities, and dementia. There are currently no available treatments for patients with PSP. The objective of this research was to review the available evidence on humanistic and economic burden of PSP, as a foundation work for understanding the unmet needs of this population. A systematic literature review was conducted in 9 databases including Medline and Embase in 2000-2017, supplemented with hand searches of reference lists. Where available, PSP Richardson syndrome (PSP-RS) and other phenotypes were assessed. Health utility (as reported by EQ5D) was measured in 5 studies with a mean utility ranging 0.20-0.41 after mean disease duration of 4.7-6.1 years. PSP patients had the most difficulties with usual activities followed by mobility and self-care. Four studies investigated the gradual worsening of daily activities in the Schwab and England Activities of Daily Living (SEADL) scale and described fast disease progression (annual worsening exceeded 10 points on the 100-point scale). Annual worsening in Clinical Global Impression (CGI) was in the 0.7-0.9 range. Healthcare resource utilization was reported in 5 studies, describing wheelchair dependence, urinary catheterization, tube feeding, hospitalizations, and residential care as important cost drivers. PSP patients typically receive informal care from family members who experienced high psychological strains. Most PSP studies report severely diminished quality of life with rapidly worsening functions. Humanistic and economic burden by PSP disease states or progression levels should be further investigated, to allow subsequent development of health economic models for the value assessment of emerging treatments promising slower PSP progression.

A High-Intensity Multicomponent Agility Intervention Improves Parkinson Patients’ Clinical and Motor Symptoms

ObjectiveTo determine the effects of a high-intensity exercise therapy using sensorimotor and visual stimuli on nondemented Parkinson disease (PD) patients’ clinical symptoms, mobility, and standing balance. DesignRandomized clinical intervention, using a before-after trial design. SettingUniversity hospital setting. ParticipantsA total of 72 PD patients with Hoehn and Yahr stage of 2-3, of whom 64 were randomized, and 55 completed the study. InterventionPD patients were randomly assigned to a no physical intervention control (n=20 of 29 completed, 9 withdrew before baseline testing) or to a high-intensity agility program (15 sessions, 3 weeks, n=35 completed). Main Outcome MeasuresPrimary outcome was the Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) motor experiences of daily living (M-EDL). Secondary outcomes were Beck Depression score, Parkinson Disease Questionnaire-39 (PDQ-39), EuroQoL Five-Dimension (EQ5D) Questionnaire visual analog scale, Schwab and England Activities of Daily Living (SE ADL) Scale, timed Up and Go (TUG) test, and 12 measures of static posturography. ResultsThe agility program improved MDS-UPDRS M-EDL by 38% compared with the 2% change in control (group by time interaction, P=.001). Only the intervention group improved in PDQ-39 (6.6 points), depression (18%), EQ5D visual analog scale score (15%), the SE ADL Scale score (15%), the TUG test (39%), and in 8 of 12 posturography measures by 42%-55% (all P<.001). The levodopa equivalent dosage did not change. ConclusionA high-intensity agility program improved nondemented, stage 2-3 PD patients’ clinical symptoms, mobility, and standing balance by functionally meaningful margins at short-term follow-up.

An 8-Week Low-Intensity Progressive Cycling Training Improves Motor Functions in Patients with Early-Stage Parkinson's Disease.

Background and PurposeThe effects of high-intensity cycling as an adjuvant therapy for early-stage Parkinson's disease (PD) were highlighted recently. However, patients experience difficulties in maintaining these cycling training programs. The present study investigated the efficacy of cycling at a mild-to-moderate intensity in early-stage PD.MethodsThirteen PD patients were enrolled for 16 serial cycling sessions over a 2-month period. Motor function was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III) and Timed Up and Go (TUG) test as primary outcomes. The Montreal Cognitive Assessment (MoCA), modified Hoehn and Yahr Stage (mHYS), total UPDRS, Falls Efficacy Scale, New Freezing of Gait Questionnaire, Schwab and England Activities of Daily Living, 39-item Parkinson's Disease Questionnaire, Patient Global Impression of Change, and gait performance were assessed as secondary outcomes.ResultsThe age and the age at onset were 59.67±7.24 and 53.23±10.26 years (mean±SD), respectively. The cycling cadence was 53.27±8.92 revolutions per minute. The UPDRS III score improved significantly after 8 training sessions (p=0.011) and 16 training sessions (T2) (p=0.001) in the off-state, and at T2 (p=0.004) in the on-state compared to pretraining (T0). The TUG duration was significantly shorter at T2 than at T0 (p<0.05). The findings of MoCA, total UPDRS, double limb support time, and mHYS (in both the off- and on-states) also improved significantly at T2.ConclusionsOur pioneer study has demonstrated that a low-intensity progressive cycling exercise can improve motor function in PD, especially akinesia. The beneficial effects were similar to those of high-intensity rehabilitation programs.

Cathepsin S increases tau oligomer formation through limited cleavage, but only IL-6, not cathespin S serum levels correlate with disease severity in the neurodegenerative tauopathy progressive supranuclear palsy.

Limited cleavage promotes the aggregation propensity of protein tau in neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of patients suffering from tauopathies such as Alzheimer's disease (AD). Furthermore, CatS serum levels correlate with survival in the elderly. The current study investigates whether limited cleavage by CatS promotes tau aggregation, and whether CatS serum levels may correlate with disease severity in tauopathies. Oligomer formation of fluorescently labeled protein tau was monitored by single particle fluorescence spectroscopy after coincubation with CatS. Tau cleavage patterns were investigated by SDS-PAGE. For serum analyses, samples were collected from 42 patients with probable progressive supranuclear palsy (PSP) according to NINDS-PSP criteria. Disease severity was assessed by PSP rating scale (PSP-RS), PSP staging system (PSP-S) and Schwab and England Activities of Daily Living (SEADL). CatS, cystatin C (CysC) and interleukin 6 (IL-6) serum levels were determined by ELISA, ECLIA and turbidimetry, respectively. SDS-PAGE demonstrated a distinct cleavage pattern of protein tau after coincubation with CatS. Furthermore, tau oligomer formation was increased 2.4-fold (p<0.05) after limited cleavage. Serum CatS and CysC levels did not correlate with disease severity in PSP. Of note, IL-6 correlated with PSP-S (r=0.41; 95% CI 0.11-0.65; p=0.008), SEADL (r=-0.37; 95% CI -0.61 to -0.06; p=0.017) and the history and gait/midline subdomains of the PSP-RS. While CatS facilitates tau aggregation in vitro, serum levels of CatS appear not to correlate with disease severity. The observed correlation of IL-6 with disease severity warrants further investigation of inflammatory markers in PSP.

Plasma Cystatin C and High-Density Lipoprotein Are Important Biomarkers of Alzheimer's Disease and Vascular Dementia: A Cross-Sectional Study.

Objectives: Cystatin C (Cys C) and high-density lipoprotein (HDL) play critical roles in neurodegenerative diseases, such as dementia, Alzheimer’s disease (AD) and vascular dementia (VaD). However, whether they can be used as reliable biomarkers to distinguish patients with dementia from healthy subjects and to determine disease severity remain largely unknown.Methods: We conducted a cross-sectional study to determine plasma Cys C and HDL levels of 88 patients with dementia (43 AD patients, 45 VaD patients) and 45 healthy age-matched controls. The severity of dementia was determined based on the Schwab and England Activities of Daily Living (ADL) Scale, the Mini-mental State Examination (MMSE), the Global Deterioration Scale (GDS), the Lawton Instrumental ADL (IADL) Scale, and the Hachinski Ischemia Scale (Hachinski). Receiver operating characteristic (ROC) curves were calculated to determine the diagnostic accuracy of Cys C and HDL levels in distinguishing patients with dementia from healthy subjects.Results: We found that plasma Cys C levels were higher, but HDL levels were lower in AD and VaD patients respectively, compared to healthy control subjects. Yet, Cys C levels were highest among patients with VaD. Interestingly, plasma Cys C levels were significantly correlated with IADL Scale scores. In addition, the ROC curves for Cys C (area under the curve, AUC 0.816 for AD, AUC 0.841 for VaD) and HDL (AUC 0.800 for AD, AUC 0.731 for VaD) exhibited potential diagnostic value in distinguishing AD/VaD patients from healthy subjects. While the ROC curve for the combination of Cys C and HDL (AUC 0.873 for AD, AUC 0.897 for VaD) showed higher diagnostic accuracy in distinguishing AD/VaD patients from healthy subjects than the separate curves for each parameter.Conclusions: Our findings suggest that the inflammatory mediators Cys C and HDL may play important roles in the pathogenesis of dementia, and plasma Cys C and HDL levels may be useful screening tools for differentiating AD/VaD patients from healthy subjects.HighlightsPlasma Cys C levels were higher in patients with AD/VaD than in healthy subjects.Plasma HDL levels were lower in patients with AD/VaD than in healthy subjects.Plasma Cys C levels were significantly correlated with dementia.The ROC curve for the combination of Cys C and HDL showed potential diagnostic value in distinguishing AD/VaD from healthy subjects.

Activities of daily living and manual hand dexterity in persons with idiopathic parkinson disease.

[Purpose] The purpose of this study was to evaluate the relationship between daily activities and manual dexterity in persons with Parkinson disease. [Subjects and Methods] The study participants were 25 patients with idiopathic Parkinson disease. This study used two clinical tools, the box-and-block test and Schwab and England Activities of Daily Living scale, to investigate the relationship between manual dexterity and Schwab and England Activities of Daily Living score. [Results] A positive correlation was observed between the Schwab and England Activities of Daily Living and the box-and-block test scores on the more and less affected sides. Moreover, the Schwab and England Activities of Daily Living score had a greater correlation with the box-and-block test score on the less affected side than that on the more affected side. [Conclusion] Manual dexterity and activities of daily living showed a positive correlation in individuals with Parkinson disease. The results of this study suggest that manual dexterity is an important factor for predicting physical performance in daily living in persons with Parkinson disease.

Disability Rating Scales in Parkinson's Disease: Critique and Recommendations.

PD is associated with impairments that progress over time to disability. A large number of disability scales exist with little information on the best choice in PD. Following methodology adopted by the International Parkinson and Movement Disorder Society Task Force, a review of disability scales used in PD was completed. Based on prespecified criteria, the review categorized scales into: "Recommended"; "Recommended with Further Validation in PD Required" when well-validated scales have not been specifically tested for clinimetric properties in PD; "Suggested"; and "Listed." Twenty-nine disability instruments were identified with nine scales fulfilling criteria for "Recommended" and 7 "Recommended with Further Validation in PD Required." Eight scales are "Suggested" and five scales are "Listed" for use in PD. The nine Recommended scales (Functional Status Questionnaire, Lawton-Brody Activities of Daily Living, Nottingham Activities of Daily Living, Schwab and England Activities of Daily Living, Self-Assessment PD Disability, Short Parkinson's Evaluation Scale/Scales for Outcomes in PD, Unified PD Rating Scale-II: Activities of Daily Living, Movement Disorders Society UPDRS Motor Experiences of Daily Living, PROMIS® and Neuro-QoL Physical Function), and the seven Recommended with Further Validation in PD Required are reviewed. Many disability measures are available and recommended for application in PD. The Task Force does not recommend the development of a new scale. Selection of the most appropriate instrument for a particular objective requires consideration of the characteristics of each scale and the goals of the assessment. © 2016 International Parkinson and Movement Disorder Society.

Postural instability and falls are more frequent in Parkinson’s disease patients with worse trunk mobility

Correlate the occurrence of falls and the activity of rolling over in bed with performance on the Trunk Mobility Scale (TMS) in patients with PD, and determine whether this instrument score can predict the risk of falls. This is a cross-sectional study. Assessed patients reported the frequency of falls in the previous year and whether they had difficulties rolling over in bed. Then, the following scales were applied: TMS, Hoehn and Yahr, Unified Parkinson's Disease Rating Scale-III and Schwab and England Activities of Daily Living. Eighty-five patients were analyzed. Patients with a history of falling showed worse performance in the TMS (p < 0.01). There is a significant correlation between TMS and the activity of rolling over in bed (p < 0.01). PD fallers present worse scores in TMS, and there is a significant correlation between difficulty rolling over in bed and TMS score.

PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.

To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p=0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

Activities of daily living questionnaire from patients' perspectives in Parkinson's disease: a cross-sectional study.

BackgroundThe aim of this study was to develop an assessment tool for activities of daily living (ADL) from the perspective of patients with Parkinson’s disease (PD) and examine the validity and reliability of the assessment.MethodsA preliminary 45-item questionnaire was developed through intensive interviews with 54 patients with PD and administered to another group of 248 patients with PD. Based on clinical and statistical analyses, 20 ADL-items were selected. The final 20-item questionnaire was examined in the other group of 59 patients with PD.ResultsThe new ADL questionnaire showed high internal consistency (Cronbach’s α, 0.962–0.966) and acceptable test-retest reliability (0.632–0.984). Concurrent validity was shown as a significant positive correlation between the new ADL questionnaire and other ADL or clinical instruments. The Hoehn and Yahr stage showed the highest degree of correlation with the new ADL questionnaire, followed by the other ADL scales (Schwab and England ADL and the ADL subscore of the Unified Parkinson’s Disease Rating Scale). Additionally, a regression analysis was conducted with the disease-specific quality of life questionnaire, and the new ADL questionnaire was the most powerful predictor of quality of life among the clinical instruments.ConclusionsThe new ADL questionnaire is a valid tool for assessing ADL from the perspectives of patients with PD.

Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy

IntroductionThere are no effective treatments for progressive supranuclear palsy (PSP). Volumetric MRI (vMRI) may be a useful surrogate outcome measure in PSP clinical trials. The goal of the study was to evaluate the potential of vMRI to correlate with clinical outcomes from an international clinical trial population. MethodsPSP patients (n = 198) from the AL-108-231 trial who had high quality vMRI and Progressive Supranuclear Palsy Rating Scale (PSPRS), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Schwab and England Activities of Daily Living (SEADL), Color Trails Test, Geriatric Depression Screen (GDS) and one year Clinician Global Impression of Change (CGIC) data from the baseline and 52 week visits were included. Linear regression was used to relate baseline values and annual clinical rating scale changes to annual regional vMRI changes (whole brain, ventricular, midbrain and superior cerebellar peduncle volumes). ResultsEffect sizes (Cohen's d) measuring disease progression over one year were largest for vMRI (midbrain [1.27] and ventricular volume [1.31]) but similar to PSPRS (1.26). After multiple comparison adjustment, annual changes in PSPRS, RBANS, SEADL, Color Trails Test, GDS and one year CGIC were modestly correlated with annual vMRI changes (p < 0.05). Baseline neuropsychological status on RBANS (p = 0.019) and Color Trails (p < 0.01) predicted annual midbrain atrophy rates. ConclusionStandard vMRI measurements are sensitive to disease progression in large, multicenter PSP clinical trials, but are not well correlated with clinical changes. vMRI changes may be useful as supportive endpoints in PSP trials.

Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy.

Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. The total PSP-Rating Scale required the least number of patients per group (N = 51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome. © 2016 International Parkinson and Movement Disorder Society.

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.

Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial

In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP. In a double-blind, parallel group, phase 2/3 trial, participants were randomly assigned with permuted blocks in a 1:1 ratio to davunetide (30 mg twice daily, intranasally) or placebo for 52 weeks at 48 centres in Australia, Canada, France, Germany, the UK, and the USA. Participants met the modified Neuroprotection and Natural History in Parkinson Plus Syndrome study criteria for PSP. Primary endpoints were the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England Activities of Daily Living (SEADL) scale at up to 52 weeks. All participants and study personnel were masked to treatment assignment. Analysis was by intention to treat. The trial is registered with Clinicaltrials.gov, number NCT01110720. 313 participants were randomly assigned to davunetide (n=157) or to placebo (n=156), and 241 (77%) completed the study (118 and 156 in the davunetide and placebo groups, respectively). There were no differences in the davunetide and placebo groups in the baseline PSPRS and SEADL. The davunetide and placebo groups did not differ in the change from baseline in PSPRS (median 11·8 [95% CI 10·5 to 13·0] vs 11·8 [10·5 to 13·0], respectively, p=0·41) or SEADL (-0·20 [-0·20 to -0·17] vs -0·20 [-0·22 to -0·17], respectively, p=0·92). 54 serious adverse events were reported in each of the treatment groups, including 11 deaths in the davunetide group and ten in the placebo group. The frequency of nasal adverse events was greater in the davunetide group than in the placebo group (epistaxis 18 [12%] of 156 vs 13 [8%] of 156, rhinorrhoea 15 [10%] vs eight [5%], and nasal discomfort 15 [10%] vs one [<1%]). Davunetide is not an effective treatment for PSP. Clinical trials of disease-modifying treatment are feasible in patients with PSP and should be pursued with other promising tau-directed treatments. Allon Therapeutics.

Different effectiveness of subthalamic deep brain stimulation in Parkinson's disease: A comparative cohort study at 1 year and 5 years

Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to produce long-term symptom improvement in Parkinson's disease. The aim of this study was to identify the target symptoms that show the most improvement at 1 year and at 5 years after STN-DBS. This was a 5-year cohort study of 41 consecutive patients treated with bilateral STN-DBS. Clinical evaluations were performed 1 month prior to surgery and 1 year and 5 years after surgery. The outcome measurements at 1 year and 5 years were the changes compared with the baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts I, II, III, and IV scores, the Hoehn and Yahr stage, and Schwab and England Activities of Daily Living (SEADL) scores in the conditions of off-medication/on-stimulation and off-medication/off-stimulation. Further analysis included changes in the levodopa equivalent daily dose. When compared to the preoperative baseline off-medication condition, significant improvements were observed in the UPDRS parts I, II, III, and IV and SEADL (p<0.001) scores in the off-medication/on-stimulation condition 1 year after STN-DBS. Five years after STN-DBS, improvements in UPDRS scores were observed only for parts II, III, and IV (p<0.001). In the off-medication/off-stimulation condition, no significant improvement was observed. At 5 years, significant deteriorations were observed in scores for the UPDRS part III axial subitem (p=0.005), UPDRS part I (p=0.005), UPDRS part II (p<0.001), and SEADL (p=0.001). The long-term effect of STN-DBS on motor function is promising, although the magnitude of its effectiveness varied over the 5-year period.

Evolution of mild cognitive impairment in Parkinson disease

We examined the development of Parkinson disease (PD)-mild cognitive impairment (MCI) in patients with newly diagnosed PD over 5 years using recently proposed consensus criteria, and we assessed the reliability of the criteria. Patients with PD (n = 123) underwent extensive neuropsychological testing at baseline and after 3 (n = 93) and 5 years (n = 59). Two neuropsychologists independently applied the PD-MCI criteria to examine the interrater and intrarater reliability. At baseline, 35% of patients had PD-MCI. Three years later, 53% of the patients had PD-MCI. At 5-year follow-up, 20 patients who had PD-MCI at an earlier assessment had converted to PD dementia and 50% of the remaining patients without dementia had MCI. The interrater reliability (kappa) was 0.91. The intrarater reliabilities were 0.85 and 0.96. Approximately one-third of patients with newly diagnosed PD fulfill the consensus criteria for PD-MCI; after 5 years, this proportion is approximately 50% of patients without dementia. The criteria have good interrater and intrarater reliability.

Diffusion Tensor Imaging (DTI) and its clinical correlates in drug naïve Wilson’s disease

The purpose is to evaluate white matter (WM) abnormalities in Wilson's disease (WD) using the technique of diffusion tensor imaging (DTI). The prospective case-control study comprised of 15 drug-naïve patients with WD and 15 controls. The phenotype of subjects was evaluated. The DTI/conventional MRI was acquired (3T MRI): Fractional anisotropy (FA) and mean diffusivity (MD) values were extracted from regions of interest placed in pons, midbrain, bilateral frontal and occipital cerebral white matter, bilateral internal capsules (IC), middle cerebellar peduncles (MCP) and corpus callosum (CC). Six patients showed lobar WM signal changes on T(2)-Weighted (T2W)/Fluid attenuation inversion recovery (FLAIR) images while remaining had normal appearing WM. MD was significantly increased in the lobar WM, bilateral IC and midbrain of WD patients. FA was decreased in the frontal and occipital WM, bilateral IC, midbrain and pons. Normal-appearing white matter on FLAIR images showed significantly increased MD and decreased FA values in both frontal and occipital lobar WM and IC compared with those in controls. Correlation of clinical scores and DTI metrics revealed positive correlation between neurological symptom score (NSS) and MD of anterior limb of right internal capsule, Chu stage and MD of frontal and occipital WM. Negative correlation was observed between the Modified Schwab and England Activities of Daily Living (MSEADL) score and MD of bilateral frontal and occipital WM and IC. This is the probably the first study to reveal widespread alterations in WM by DTI metrics in drug naïve WD. DTI analysis revealed lobar WM abnormalities which is less frequently noted on conventional MRI and suggests widespread WM abnormalities in WD. It may be valuable in assessing the true extent of involvement and therefore the severity of the illness.

The clinical impact of precise electrode positioning in STN DBS on three-year outcomes

Few studies have analyzed the clinical impact of subthalamic nucleus (STN) deep brain stimulation (DBS) as a function of the positioning of the inserted electrode. We investigated retrospectively the three-year outcomes in Parkinson's disease (PD) patients following bilateral STN DBS in terms of the electrode positions. Forty-one advanced PD patients were followed up for over three years following bilateral STN DBS. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr staging, Schwab and England Activities of Daily Living (ADL), and the Short Form-36 Health Survey (SF-36) before surgery and one, two, and three years after surgery. The patients were divided into two groups according to the electrode position based on the fused preoperative MRI and postoperative CT images: group I included patients who had both electrodes in the STN (n=30) while group II included patients who had one of the electrodes in the STN (n=11). The UPDRS, the Hoehn & Yahr staging, the Schwab and England ADL, and the SF-36 scores showed significant improvements with decreased l-dopa equivalent daily doses (LEDDs) in both groups as well as in the group as a whole for up to three years following bilateral STN DBS. However, the off-medication UPDRS total and motor (part III) scores significantly deteriorated with increased LEDDs for patients in group II three years after STN DBS compared to that of the group I patients. We conclude that more accurate electrode positioning in the STN leads to better long-term outcomes in advanced PD patients following DBS.

Reliability and validity of a scale for measurement of trunk mobility in Parkinson's disease: Trunk Mobility Scale

Axial rigidity is an important motor manifestation in Parkinson's disease (PD). Trunk mobility impairment can cause gait, balance and postural problems. However, only few instruments analyze the trunk mobility in PD patients. The aim of this study is to present a new Trunk Mobility Scale (TMS) and its validation in PD. The TMS constituted of dynamic tests involving trunk movements in sagittal, transversal and coronal planes. Ninety eight PD patients and 31 normal controls were analyzed. A strong correlation was found between the TMS scores and the Hoehn & Yahr staging scale (r: 0.72; p<0.01), motor Unified Parkinson's Disease Rating Scale (r: 0.84; p<0.01) and Schwab and England Activities of Daily Living (r: -0.72; p<0.01). The scale showed a satisfactory reliability rate (αCronbach: 0.85, ICC: 099). TMS is a simple and reliable instrument to evaluate trunk mobility impairment in patients with PD.