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Disability Progression (disability + progression)

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Medical Sciences	100%

Selected Abstracts

Employment, medical absenteeism, and disability perception in Parkinson's disease: A pilot double-blind, randomized, placebo-controlled study of entacapone adjunctive therapy

MOVEMENT DISORDERS, Issue 12 2006
Alexei Korchounov MD
Abstract The objective of this study was to test the impact of entacapone (ENT) addition to levodopa with a decarboxylase inhibitor (LD) in full-time,employed patients with Parkinson's disease (PD), focusing on retirement rates, medical absenteeism, self-perception of disability, as well as motor assessments of parkinsonism, motor fluctuations, and dyskinesias. Thirty full-time,employed PD patients (disease onset before age 60 years) and on optimized monotherapy with LD exhibiting minor motor fluctuations or dyskinesias were entered into a 2-year randomized double-blind placebo-controlled study of ENT adjunctive therapy. The outcome measures were the number of full-time,employed patients at study end, cumulative days of medical absenteeism, patient-completed disability assessments, diary records, and the Unified Parkinson's Disease Rating Scale,based measures of motor fluctuations and dyskinesias. LD + ENT treatment was associated with a lower retirement rate (2 [17%] of 12 vs. 6 [50%] of 12; P = 0.12), lower absenteeism rate (21.5 vs. 43.5 days; P < 0.0001), improved self-perception of disability progression over 2 years (change score 1.0 vs. 4.5; P < 0.0001), and lower scores for both motor fluctuations and dyskinesia assessments compared to LD monotherapy. In this pilot study, LD with ENT adjunctive therapy positively influenced employment rate over 2 years; this effect was associated with reduced motor complications and patient perceptions of stabilized disability. © 2006 Movement Disorder Society [source]

A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis

ANNALS OF NEUROLOGY, Issue 3 2010
Massimiliano Calabrese MD
Objective We assessed the occurrence, extent, and frequency of formation of cortical lesions (CLs) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), and their relationship with cortical atrophy and disability progression. Methods One-hundred seven MS patients (76 RRMS and 31 SPMS), enrolled in a prospective, longitudinal magnetic resonance imaging (MRI) study, were assessed clinically and by brain MRI (including a double inversion recovery sequence) 3 years after study initiation. CL number and volume, T2 white matter (WM) lesion volume, gray matter fraction, and expanded disability status scale (EDSS) were measured. Results At baseline, CLs were detected in 64.4% of RRMS and 74.2% of SPMS patients. During follow-up, 132 new CLs were found in 44 RRMS patients (57.9%; 0.8 new CL/patient/yr) and 61 in 15 SPMS patients (48.4%; 1.0 new CL/patient/yr). Among these patients, only 31 also showed at least 1 new WM lesion. CL number and volume increases were higher in the 52 patients with a clinical worsening compared with those without (p < 0.001). Baseline CL volume correlated with baseline EDSS (r = 0.36, p < 0.001) and EDSS changes over time (r = 0.51, p < 0.001). Baseline CL volume was an independent predictor of EDSS accumulation and GM volume change at follow-up in both patient groups. In SPMS patients, baseline T2 WM lesion volume was another independent predictor of EDSS worsening. Interpretation In relapse-onset MS, CLs accumulate over time and are associated with disability progression. The quantification of CLs might represent an additional useful paraclinical tool to monitor MS evolution. ANN NEUROL 2010;67:376,383 [source]

Elevated Epstein,Barr virus-encoded nuclear antigen-1 immune responses predict conversion to multiple sclerosis

ANNALS OF NEUROLOGY, Issue 2 2010
Jan D. Lünemann MD
Objective The aims of the study were to determine the immune responses to candidate viral triggers of multiple sclerosis (MS) in patients with clinically isolated syndromes (CISs), and to evaluate their potential value in predicting conversion to MS. Methods Immune responses to Epstein,Barr virus (EBV), human herpesvirus 6, cytomegalovirus (HCMV), and measles were determined in a cohort of 147 CIS patients with a mean follow-up of 7 years and compared with 50 demographically matched controls. Results Compared with controls, CIS patients showed increased humoral (p < 0.0001) and cellular (p = 0.007) immune responses to the EBV-encoded nuclear antigen-1 (EBNA1), but not to other EBV-derived proteins. Immunoglobulin G (IgG) responses to other virus antigens and frequencies of T cells specific for HCMV and influenza virus gene products were unchanged in CIS patients. EBNA1 was the only viral antigen with which immune responses correlated with number of T2 lesions (p = 0.006) and number of Barkhof criteria (p=0.001) at baseline, and with number of T2 lesions (p = 0.012 at both 1 and 5 years), presence of new T2 lesions (p = 0.003 and p = 0.028 at 1 and 5 years), and Expanded Disability Status Scale score (p = 0.015 and p = 0.010 at 1 and 5 years) during follow-up. In a univariate Cox regression model, increased EBNA1-specific IgG responses predicted conversion to MS based on McDonald criteria (hazard ratio [95% confidence interval], 2.2 [1.2-4.3]; p = 0.003). Interpretation Our results indicate that elevated immune responses toward EBNA1 are selectively increased in CIS patients and suggest that EBNA1-specific IgG titers could be used as a prognostic marker for disease conversion and disability progression. ANN NEUROL 2010;67:159,169 [source]

Real-life impact of early interferon, therapy in relapsing multiple sclerosis,

ANNALS OF NEUROLOGY, Issue 4 2009
M. Trojano MD
Objective Recent findings support greater efficacy of early vs. delayed interferon beta (IFN,) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFN, treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFN, treatment with regard to the greatest benefits on disability progression. Methods A cohort of 2,570 IFN,-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFN, treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. Results The lowest hazard ratios (HRs) for the three PS quintiles,adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48,0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36,0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. Interpretation Greater benefits on disability progression may be obtained by an early IFN, treatment in RRMS. Ann Neurol 2009;66:513,520 [source]

Gray matter atrophy in multiple sclerosis: A longitudinal study

ANNALS OF NEUROLOGY, Issue 3 2008
Elizabeth Fisher Ph.D.
Objective To determine gray matter (GM) atrophy rates in multiple sclerosis (MS) patients at all stages of disease, and to identify predictors and clinical correlates of GM atrophy. Methods MS patients and healthy control subjects were observed over 4 years with standardized magnetic resonance imaging (MRI) and neurological examinations. Whole-brain, GM, and white matter atrophy rates were calculated. Subjects were categorized by disease status and disability progression to determine the clinical significance of atrophy. MRI predictors of atrophy were determined through multiple regression. Results Subjects included 17 healthy control subjects, 7 patients with clinically isolated syndromes, 36 patients with relapsing-remitting MS (RRMS), and 27 patients with secondary progressive MS (SPMS). Expressed as fold increase from control subjects, GM atrophy rate increased with disease stage, from 3.4-fold normal in clinically isolated syndromes patients converting to RRMS to 14-fold normal in SPMS. In contrast, white matter atrophy rates were constant across all MS disease stages at approximately 3-fold normal. GM atrophy correlated with disability. MRI measures of focal and diffuse tissue damage accounted for 62% of the variance in GM atrophy in RRMS, but there were no significant predictors of GM atrophy in SPMS. Interpretation Gray matter tissue damage dominates the pathological process as MS progresses, and underlies neurological disabillity. Imaging correlates of gray matter atrophy indicate that mechanisms differ in RRMS and SPMS. These findings demonstrate the clinical relevance of gray matter atrophy in MS, and underscore the need to understand its causes. Ann Neurol 2008 [source]

Health-related quality of life in multiple sclerosis: effects of natalizumab

ANNALS OF NEUROLOGY, Issue 4 2007
Richard A. Rudick MD
Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-,-1a) plus natalizumab 300mg (n = 589), or IFN-,-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007 [source]