Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, ...and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson’s disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-18F fluorolevodopa positron emission tomography in early and advanced stages of Parkinson’s disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson’s disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin’ Sticks Test. Mean putaminal 6-18F fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson’s disease group showed significant signal changes in the caudate and putamen by 6-18F fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-18F fluorolevodopa uptake (r = −0.52, P < 0.05 and r = −0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson’s Disease Rating Scale motor score (r = −0.48, P < 0.01) and between mean putaminal 6-18F fluorolevodopa uptake and the total odour score (r = 0.58; P < 0.05) as well as the Unified Parkinson’s Disease Rating Scale motor score (r = −0.53, P < 0.05). This study reports a significant association between increased mean diffusivity signal and decreased 6-18F fluorolevodopa uptake, indicating that microstructural degradation of the substantia nigra and the olfactory tract parallels progression of putaminal dopaminergic dysfunction in Parkinson’s disease. Since increases in nigral mean diffusivity signal also correlated with motor dysfunction, diffusion tensor imaging may serve as a surrogate marker for disease progression in future studies of putative disease modifying therapies.
The purpose of the present study was to evaluate the potential of multimodal MR imaging including mean diffusivity (MD), fractional anisotropy (FA), relaxation rates R2 and R2* to detect disease ...specific alterations in Parkinson's Disease (PD). We enrolled 82 PD patients (PD-all) with varying disease durations (≤5 years: PD≤5, n = 43; >5 years: PD>5, n = 39) and 38 matched healthy controls (HC), receiving diffusion tensor imaging as well as R2 and R2* relaxometry calculated from multi-echo T2*-weighted and dual-echo TSE imaging, respectively. ROIs were drawn to delineate caudate nucleus (CN), putamen (PU), globus pallidus (GP) and substantia nigra (SN) on the co-registered maps. The SN was divided in 3 descending levels (SL 1-3). The most significant parameters were used for a flexible discrimination analysis (FDA) in a training collective consisting of 25 randomized subjects from each group in order to predict the classification of remaining subjects. PD-all showed significant increases in MD, R2 and R2* within SN and its subregions as well as in MD and R2* within different basal ganglia regions. Compared to the HC group, the PD≤5 and the PD>5 group showed significant MD increases within the SN and its lower two subregions, while the PD≤5 group exhibited significant increases in R2 and R2* within SN and its subregions, and tended to elevation within the basal ganglia. The PD>5 group had significantly increased MD in PU and GP, whereas the PD≤5 group presented normal MD within the basal ganglia. FDA achieved right classification in 84% of study participants. Micro-structural damage affects primarily the SN of PD patients and in later disease stages the basal ganglia. Iron contents of PU, GP and SN are increased at early disease stages of PD.
Christoph Mueller, Bernadette Pinter, Eva Reiter, Michael Schocke, Christoph Scherfler, Werner Poewe, Klaus Seppi, Innsbruck, Austria: Blazejewska et al.1 identified a hyperintense ovoid area within ...the dorsolateral border of the otherwise hypointense pars compacta of the substantia nigra (SNc) in healthy controls (HC) and the absence of this MRI feature2 in patients with Parkinson disease (PD) using T2*-weighted 7T MRI. Moreover, the postmortem 7T MRI with histopathologic correlations suggested that this MRI feature corresponded to nigrosome 1. We studied this MRI feature in consecutively recruited HC and patients with PD super(3) (16 HC, 53 PD; mean + or - SD age, y: HC 54 + or - 10, PD 67 + or - 8; proportion female: HC 68%, PD 28%; mean + or - SD disease duration, y: 8 + or - 4) using susceptibility-weighted imaging (SWI) at 3T (Siemens Verio MRI scanner, Munich, Germany). Datasets of 2 HC and 18 patients with PD were not of diagnostic quality due to patient motion. In the remaining patients, presence of dorsolateral hyperintensity within the otherwise hypointense SNc was identified in 14/14 HC and 5/35 patients with PD. Absence of this MRI feature resulted in 85.7% sensitivity and 100% specificity to detect PD. We suggest that this MRI feature reported at 7T MRI using T2*-weighted sequences1 can also be detected at 3T using SWI sequences and that absence of this MRI feature might have potential for diagnosing PD.
The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS ...components and HRQoL in a representative international cohort of PD patients.
We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items.
A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue.
This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.
•This is the largest study related to Quality of Life (QoL) in PD so far.•QoL is related especially to MDS-UPDRS Part II (ADLs) and Part I (NMS).•Four out of five most important independent contributors were non-motor items.
Background
The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the ...course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD.
Methods
For this cross‐sectional study, demographic data and MDS‐UPDRS scores were collected, including HY stage. Subscores on MDS‐UPDRS Parts I through IV were analyzed using 1‐way analyses of variance for each HY stage and in 5‐year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states.
Results
The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0–5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS‐UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5‐year increments of disease duration, MDS‐UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states.
Conclusions
MDS‐UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5‐year increments of disease duration in the first 15 years of the disease.
Huntington's disease can present at almost any age but traditionally, those with an onset ≤20 years are described as having juvenile onset Huntington's disease (JOHD). They are more likely to have ...bradykinesia and dystonia earlier in the course of the disease. The Total Motor Score of the Unified Huntington's Disease Rating Scale (UHDRS-TMS) is often used as the principal outcome measure in clinical trials.
To identify a motor scale more suitable for JOHD patients.
A working group reviewed the UHDRS-TMS and modified it by adding four further assessment items. Rasch analysis was used to study the performance of the modified scale in 95 patients with a mean age of 19.4 (SD 6.6) years.
The initial analysis showed a significant overall misfit to the Rasch model and a number of individual items displayed poor measurement properties: all items relating to chorea displayed significant misfit due to under-discrimination. Additionally, a number of items displayed disordered response category thresholds, and a large amount of dependency was present within the item set (96 out of 741 pairwise differences = 13%). An iterative process of scale re-structuring and evaluation was then undertaken, with a view to eliminating the largest sources of misfit and generating a set of items that would conform to Rasch model expectations.
This post-hoc scale restructuring appears to provide a valid motor score that is psychometrically robust in a JOHD population. This scale restructuring offers a pragmatic solution to measuring motor function in a JOHD population, and it could provide the basis for the further iterative development of a more useful clinical rating scale for patients with JOHD.
The purpose of the present study was to evaluate the potential of multimodal MR imaging including mean diffusivity (MD), fractional anisotropy (FA), relaxation rates R2 and R2* to detect disease ...specific alterations in Parkinson's Disease (PD). We enrolled 82 PD patients (PD-all) with varying disease durations ( less than or equal to 5 years: PD less than or equal to 5, n = 43; >5 years: PD>5, n = 39) and 38 matched healthy controls (HC), receiving diffusion tensor imaging as well as R2 and R2* relaxometry calculated from multi-echo T2*-weighted and dual-echo TSE imaging, respectively. ROIs were drawn to delineate caudate nucleus (CN), putamen (PU), globus pallidus (GP) and substantia nigra (SN) on the co-registered maps. The SN was divided in 3 descending levels (SL 1-3). The most significant parameters were used for a flexible discrimination analysis (FDA) in a training collective consisting of 25 randomized subjects from each group in order to predict the classification of remaining subjects. PD-all showed significant increases in MD, R2 and R2* within SN and its subregions as well as in MD and R2* within different basal ganglia regions. Compared to the HC group, the PD less than or equal to 5 and the PD>5 group showed significant MD increases within the SN and its lower two subregions, while the PD less than or equal to 5 group exhibited significant increases in R2 and R2* within SN and its subregions, and tended to elevation within the basal ganglia. The PD>5 group had significantly increased MD in PU and GP, whereas the PD less than or equal to 5 group presented normal MD within the basal ganglia. FDA achieved right classification in 84% of study participants. Micro-structural damage affects primarily the SN of PD patients and in later disease stages the basal ganglia. Iron contents of PU, GP and SN are increased at early disease stages of PD.
BACKGROUND AND PURPOSE—Cognitive impairment occurs in ≤30% of all stroke survivors. However, effective therapies aimed at preventing poststroke cognitive decline are lacking. We assessed the efficacy ...of a multidomain intervention on preventing cognitive decline after stroke.
METHODS—In this randomized, observer-blind trial patients were recruited within 3 months after an acute stroke in 5 Austrian neurological centers. Patients were assigned to a 24-month lifestyle-based multidomain intervention or standard stroke care. Primary outcomes were the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) and occurrence of cognitive decline in the composite scores of at least 2 of 5 cognitive domains at 24 months.
RESULTS—A total of 101 patients were randomized into multi-intervention and 101 into standard care during June 2010 and November 2012. Of them, 76 patients in the intervention group and 83 in the control group were included in the final intention-to-treat analysis. At 24 months, 8 of 76 (10.5%) patients in the intervention group and 10 of 83 (12.0%) patients in the control group showed cognitive decline corresponding to a relative risk reduction of 0.874 (95% confidence interval, 0.364–2.098). The change in ADAS-cog from baseline to 24 months was not different either (median 0 IQR, −1 to 2 in both groups; P=0.808).
CONCLUSIONS—This trial found no benefit of 24-month multidomain intervention with focus on improvement in lifestyle and vascular risk factors on the incidence of poststroke cognitive decline in comparison with standard stroke care. Studies with a larger sample size are needed.
CLINICAL TRIAL REGISTRATION—URLhttp://clinicaltrials.gov. Unique identifierNCT01109836.
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