57 research outputs found
Focus or Neglect on Cognitive Impairment Following the History of Multiple Sclerosis
Cognitive disorders are now considered an integral part of the picture of multiple sclerosis. If we trace the history of the accounts of this disease, from the early descriptions by Jean-Martin Charcot, the first to provide systematic characteristics of multiple sclerosis, to present-day accounts, reports of cognitive disturbances have demonstrated an alternating trend. Cognitive disturbances were identified in the beginning, quite clearly for the times. Then, for a long time, they were considered infrequent or attributed to other factors. Finally, since the 1980s, cognitive disturbances have been the subject of increasingly in-depth studies, and are currently assumed to be a very important consequence of multiple sclerosis. In this work, the history of the description of cognitive disorders of multiple sclerosis will be retraced by analyzing the possible reasons for the differences in attention they have received over time. It emerged from the analysis that, as in the case of other pathologies, various factors have influenced how cognitive disorders have been taken into consideration. Some of these factors are inherent to the very nature of the cognitive impairments present in multiple sclerosis; others are linked to historical periods, or to the different ways of approaching the analysis of the phenomena caused by a disease. The reflections made on these topics should, among other things, increase our awareness of how scientific investigation is invariably placed in the historical context in which it is carried out
Study Protocol: Strategies and Techniques for the Rehabilitation of Cognitive and Motor Deficits in Patients with Multiple Sclerosis
Disruption of neurite morphology parallels MS progression
Objectives: To apply advanced diffusion MRI methods to the study of normal appearing brain tissue in MS and examine their correlation with measures of clinical disability. Methods: A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting (RR-) and 15 with secondary progressive (SP)-MS, and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal appearing brain tissue, and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the two techniques. Results: MS patients showed reduced neurite density and increased orientation dispersion compared to controls in several brain areas (P<0.05), with SPMS patients having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, SPMS patients showed reduced orientation dispersion in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (P<0.05). The association with the MS functional composite score was higher in SPMS compared to RRMS patients. Conclusions: NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps to interpret previous findings of increased anisotropy in the thalamus of MS patients, and are consistent with the degeneration of selective axon populations
Cognitive-motor dual-task training improves dynamic stability during straight and curved gait in patients with multiple sclerosis: a randomized controlled trial
Background: Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating, degenerative disease of the central nervous system and the second most frequent cause of permanent disability in young adults. One of the most common issues concerns the ability to perform postural and gait tasks while simultaneously completing a cognitive task (namely, dual-task DT).Aim: Assessing cognitive-motor dual-task training effectiveness in patients with Multiple Sclerosis (PwMS) for dynamic gait quality when walking on straight, curved, and blindfolded paths.Design: Two-arm single-blind randomized controlled trial. Follow-up at 8 weeks.Setting: Neurorehabilitation Hospital.Population: A sample of 42 PwMS aged 28-71, with a score of 4.00 +/- 1.52 on the Expanded Disability Status Scale were recruited.Methods: Participants were randomized in conventional (CTg) neurorehabilitation and dual-task training (DTg) groups and received 12 sessions, 3 days/week/4 weeks. They were assessed at baseline (T0), after the treatment (T1), and 8 weeks after the end of the treatment (T2) through Mini-BESTest, Tinetti Performance Oriented Mobility Assessment, Modified Barthel Index, and a set of spatiotemporal parameters and gait quality indices related to stability, symmetry, and smoothness of gait extracted from initial measurement units (IMUs) data during the execution of the 10-meter Walk Test (10mWT), the Figure-of-8 Walk Test (Fo8WT) and the Fukuda Stepping Test (FST).Results: Thirty-one PwMS completed the trial at T2. Significant improvement within subjects was found in Mini-BESTest scores for DTg from T0 to T1. The IMU-based assessment indicated significant differences in stability (P<0.01) and smoothness (P<0.05) measures between CTg and DTg during 10mWT and Fo8WT. Substantial improvements (P<0.017) were also found in the inter-session comparison, primarily for DTg, particularly for stability, symmetry, and smoothness measures.Conclusions: This study supports the effectiveness of DT in promoting dynamic motor abilities in PwMS
Viability of a MSQOL-54 general health-related quality of life score using bifactor model
Background MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated. Methods A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald's coefficients (omega, and omega hierarchical). Results The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (>= 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70). Conclusions The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score
Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study
Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance. Methods: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation. Results: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94. Conclusions: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research
Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension
Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen
A comparison of the brief international cognitive assessment for multiple sclerosis and the brief repeatable battery in multiple sclerosis patients
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