Department of Neurology, Helsinki University Hospital
The retirement rate due to multiple sclerosis has decreased since 1995- A retrospective study in a Finnish central hospital
Background: Multiple sclerosis (MS) is the most common cause of non-traumatic neurological disability affecting young adults during their best working years. Previous studies have shown that approximately two-thirds of patients with MS (PwMS) are unable to retain employment in the long term, and many retire soon after the diagnosis. However, it is not known, how the rate of retirement has changed over the decades, especially after the introduction of disease modifying therapies (DMTs). The year 1995 was selected as a division point because DMTs have been increasingly available ever since.
Objective: To evaluate the change in retirement rate due to MS and to present risk factors for early retirement.
Methods: A retrospective survey of all PwMS treated at the Department of Neurology, Kanta-Häme Central Hospital, Finland between 1978 and 2015, was conducted. The population was divided into two groups: those diagnosed before year 1995 and those diagnosed thereafter. A Kaplan-Meier analysis was performed to evaluate the time from diagnosis to beginning of a pension in both groups. Crude incidence rates, incidence rate differences as well as age and multivariable adjusted Cox proportional hazard regression analysis were calculated for all pension predictors collected.
Results: A total of 484 PwMS were identified, 140 of whom were diagnosed before the year 1995 and 344 after. Actual retirement rates were 88 (63%) before the year the year 1995 and 111 (32%) after, respectively. The hazard for disability pension diminished in PwMS diagnosed after the year 1995 compared to those diagnosed before, HR 0.41 (95% confidence interval 0.31-0.55). The median time from diagnosis to retirement was 8.3 years in the group diagnosed before year 1995 and 11.1 years in the group diagnosed later. Male sex and age were statistically significant risk factors in relapsing-remitting MS, HR for male sex 1.8 (95% confidence interval 1.18-2.75) and for age 1.1 (95% confidence interval 1.07-1.12). Only age was a risk factor in progressive MS with HR 1.09 (95% confidence interval 1.07-1.11). In subgroup of relapsing-remitting MS, not using disease modifying therapies was a statistically significant risk factor, HR 1.89 (95% confidence interval 1.19-3.01).
Conclusion: The rate of retirement due to MS in Finland has decreased significantly since 1995 and the median time from diagnosis to retirement has become longer. Not using disease modifying therapies for relapsing remitting MS was identified as one risk factor for losing ability to work prematurely.
Department of Neurology, Harvard Medical School, Boston, MA, USA; Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston
Time between expanded disability status scale (EDSS) scores
Background: Although the expanded disability status scale (EDSS) is the most commonly used measure of disability for multiple sclerosis, measurement of disability accumulation is complex due to the unequal steps of the scale.
Objective: To estimate the time between EDSS scores in a large MS cohort from a single center and determine the impact of functional system scores on EDSS transitions.
Methods: 31,394 clinical visits with EDSS scores from 2054 subjects in the CLIMB longitudinal cohort study were included in our analysis. The time to each EDSS score and the time between each EDSS score were calculated using the nonparametric maximum likelihood estimate for interval censored data. For each initial EDSS value, the association between functional status scores and subsequent EDSS value was assessed using a mixed effects linear regression model, and the association with time to EDSS increase was assessed using a Cox proportional hazards model.
Results: The median time until EDSS 2, 3, 4, 5 and 6 in all subjects were 4.8, 15.1, 28.2, 31.2, and 32.4 years, respectively. The time intervals showed that the disability accumulation intervals from EDSS 4 to 6 were much shorter than the accumulation intervals from EDSS 0 to 3 or from EDSS 6 to 8. For EDSS of 1 or 1.5, pyramidal, cerebellar, sensory, bowel-bladder and mental system scores were associated with higher subsequent EDSS values. For higher EDSS values, only pyramidal and bowel-bladder scores maintained the association.
Conclusions: Time between specific EDSS levels varies considerably. Certain functional system scores have greater predictive power for future EDSS-related disability despite same present EDSS level. These findings will assist in adaptation of the EDSS as an outcome measure to assess MS-related disability in clinical trials.
What's remarkable is that this patient had a complete absence of clinical symptoms despite their apparent prolific MRI lesion activity.Petr75 wrote: ↑Sat Aug 15, 2020 8:56 pm
http://www.msdiscovery.org/news/news_sy ... -meets-eye
3 Apr 2012
From the Department of Neurology ,IRCCS (N.B.), Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
Disability Improvement Is Associated with Less Brain Atrophy Development in Multiple Sclerosis
Background and purpose: It is unknown whether deceleration of brain atrophy is associated with disability improvement in patients with MS. Our aim was to investigate whether patients with MS with disability improvement develop less brain atrophy compared with those who progress in disability or remain stable.
Materials and methods: We followed 980 patients with MS for a mean of 4.8 ± 2.4 years. Subjects were divided into 3 groups: progress in disability (n = 241, 24.6%), disability improvement (n = 101, 10.3%), and stable (n = 638, 65.1%) at follow-up. Disability improvement and progress in disability were defined on the basis of the Expanded Disability Status Scale score change using standardized guidelines. Stable was defined as nonoccurrence of progress in disability or disability improvement. Normalized whole-brain volume was calculated using SIENAX on 3D T1WI, whereas the lateral ventricle was measured using NeuroSTREAM on 2D-T2-FLAIR images. The percentage brain volume change and percentage lateral ventricle volume change were calculated using SIENA and NeuroSTREAM, respectively. Differences among groups were investigated using ANCOVA, adjusted for age at first MR imaging, race, T2 lesion volume, and corresponding baseline structural volume and the Expanded Disability Status Scale.
Results: At first MR imaging, there were no differences among progress in disability, disability improvement, and the stable groups in whole-brain volume (P = .71) or lateral ventricle volume (P = .74). During follow-up, patients with disability improvement had the lowest annualized percentage lateral ventricle volume change (1.6% ± 2.7%) followed by patients who were stable (2.1% ± 3.7%) and had progress in disability (4.1% ± 5.5%), respectively (P < .001). The annualized percentage brain volume change values were -0.7% ± 0.7% for disability improvement, -0.8% ± 0.7% for stable, and -1.1% ± 1.1% for progress in disability (P = .001).
Conclusions: Patients with MS who improve in their clinical disability develop less brain atrophy across time compared with those who progress.
Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, São Paulo, Brazil
Neuroinflammation at single cell level: What is new?
Multiple sclerosis is a chronic and demyelinating disease of the central nervous system (CNS), most prevalent in women, and with an important social and economic cost worldwide. It is triggered by self-reacting lymphocytes that infiltrate the CNS and initiate neuroinflammation. Further, axonal loss and neuronal death takes place, leading to neurodegeneration and brain atrophy. The murine model for studying MS, experimental autoimmune encephalomyelitis (EAE), consists in immunizing mice with myelin-derived epitopes. APCs activate encephalitogenic T CD4 and CD8 lymphocytes that migrate mainly to the spinal cord resulting in neuroinflammation. Most of the knowledge on the pathophysiology and treatment of MS was obtained from EAE experiments, as Th17 cells, anti-alpha4 blocking Abs and the role of microbiota. Conversely, recent technology breakthroughs, such as CyTOF and single-cell RNA-seq, promise to revolutionize our understanding on the mechanisms involved both in MS and EAE. In fact, the importance of specific cellular populations and key molecules in MS/EAE is a constant matter of debate. It is well accepted that both Th1 and Th17 T CD4 lymphocytes play a relevant role in disease initiation after re-activation in situ. What is still under constant investigation, however, is the plasticity of the lymphocyte population, and the individual contribution of both resident and inflammatory cells for the progression or recovery of the disease. Thus, in this review, new findings obtained after single-cell analysis of blood and central nervous system infiltrating cells from MS/EAE and how they have contributed to a better knowledge on the cellular and molecular mechanisms of neuroinflammation are discussed.
Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta
Patient-reported financial toxicity in multiple sclerosis: Predictors and association with care non-adherence
Background: Multiple sclerosis (MS) results in considerable financial burdens due to expensive treatment and high rates of disability, which could both impact care non-adherence.
Objective: To measure financial toxicity in MS patients, identify its predictors and association with care non-adherence.
Methods: Adult MS patients visiting neurology clinic (June 2018 to February 2019) were consented to complete a survey. Financial toxicity was measured using Comprehensive Score for Financial Toxicity (COST) (range: 0-44, the lower the score, the worse the financial toxicity). Independent predictors of financial toxicity were identified using linear regression. Associations of COST score with patient outcomes were assessed.
Results: The mean COST score in 243 recruited patients was 17.4 ± 10.2. In response to financial burdens, 66.7% and 34.7% reported life-style altering behaviors or care non-adherence, respectively. Higher financial self-efficacy was associated with less financial toxicity (coefficient, 1.33 (95% confidence interval (CI), 1.02-1.64); p < 0.001). At least one relapse in the last 3 months was associated with greater financial toxicity (coefficient, -3.34 (95% CI, -6.66 to -0.01); p = 0.049). Greater financial toxicity correlated with life-style-altering coping strategy use (p < 0.001), care non-adherence (p = 0.001), and worse health-related quality of life (HRQOL) (p = 0.03).
Conclusion: MS patients with lower financial self-efficacy and prior relapse history are at higher risk for financial toxicity, with associated care non-adherence and lower HRQOL.
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
Feelings of depression, pain and walking difficulties have the largest impact on the quality of life of people with multiple sclerosis, irrespective of clinical phenotype
Background: The symptoms that have the largest impact on health-related quality of life (HRQoL) in people with multiple sclerosis (MS) may vary by MS phenotype (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)). Knowing these symptoms assists in symptom management.
Objective: To examine the associations between 13 common MS symptoms and HRQoL in the total sample and stratified by MS phenotype.
Method: The study included 1985 participants. HRQoL was measured with two multi-attribute utility instruments: assessment of quality of life with eight dimensions (AQoL-8D) and European quality of life with five dimensions and five levels for each dimension (EQ-5D-5L). Multivariable linear regression was used to identify the symptoms that had the largest impact on the HRQoLs.
Results: Feelings of depression, pain, fatigue, and feelings of anxiety were most strongly associated with AQoL-8D and EQ-5D-5L. Walking difficulties additionally contributed to reduced EQ-5D-5L. The strongest single predictors in the multivariable analyses were feelings of depression or pain for AQoL-8D and walking difficulties for EQ-5D-5L, irrespective of MS phenotype.
Conclusion: The strongest single predictors for the AQoL-8D and EQ-5D-5L were feelings of depression, pain and walking difficulties, irrespective of MS phenotype. Reducing these symptoms may have the largest impact on improving HRQoL in all MS phenotypes of people with MS.
Florey Institute of Neuroscience and Mental Health, Florey Department, The University of Melbourne, Parkville, VIC, Australia
Multiple Sclerosis as a Syndrome-Implications for Future Management
We propose that multiple sclerosis (MS) is best characterized as a syndrome rather than a single disease because different pathogenetic mechanisms can result in the constellation of symptoms and signs by which MS is clinically characterized. We describe several cellular mechanisms that could generate inflammatory demyelination through disruption of homeostatic interactions between immune and neural cells. We illustrate that genomics is important in identifying phenocopies, in particular for primary progressive MS. We posit that molecular profiling, rather than traditional clinical phenotyping, will facilitate meaningful patient stratification, as illustrated by interactions between HLA and a regulator of homeostatic phagocytosis, MERTK. We envisage a personalized approach to MS management where genetic, molecular, and cellular information guides management.
Department of Neurology and Neurosurgery, Odessa National Medical University, Odesa, Ukraine
The impairment of the functional system and fatigue at the onset of the disease predict reaching disability milestones in relapsing-remitting multiple sclerosis differently in female and male patients
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with variable types of disability progression (DP). Previous studies, defining different disability milestones (DMs), have reported symptoms at MS onset to be the predictors of DP and sex as a risk factor. Meanwhile, accounting for sex differences in MS, predictors in female and male patients might differ. To investigate whether the symptoms at MS onset predict reaching DMs in patients with relapsing-remitting (RR) MS and whether the predictors vary between different DMs and female and male patients. Data from 128 RR MS patients (84 females, 44 males) was retrospectively studied. EDSS scores 4 and 6 (associated with impaired ambulation) were taken as DMs. Association between symptoms at MS onset and time to reach DMs was assessed with Cox multiple regression model. Pyramidal symptoms and fatigue at MS onset predicted the progression to EDSS 4 in the whole study population (HR 1.84, 95% CI 1.07-3.2, p = 0.028 and HR 2.01, 95% CI 1.12-3.4, p = 0.011, correspondingly). The same symptoms predicted reaching DM in female, but not male patients. Bowel/bladder symptoms predicted reaching EDSS 6 in the whole study population (HR 4.31, 95% CI 1.47-12.6, p = 0.008) and female patients only (HR 3.93, 95% CI 1.04-14.8, p = 0.043). In female patients, fatigue was also the predictor of reaching EDSS 6 (HR 3.54, 95% CI 1.16-10.8, p = 0.026). Impairment of functional symptoms at MS onset can predict reaching DMs in patients with RR-MS, but the predictors for EDSS 4 and EDSS 6 differ in female and male patients.
University of California, Riverside School of Medicine
Abuse and neglect of people with multiple sclerosis: A survey with the North American Research Committee on Multiple Sclerosis (NARCOMS)
Background: An estimated 100,000 Americans with advanced multiple sclerosis (MS) are at risk of mistreatment, yet we lack national prevalence data on abuse and neglect. Our objective was to determine the incidence and prevalence of caregiver abuse and neglect among U.S. adults with advanced MS.
Methods: Through an anonymous telephone survey with the North American Research Committee on Multiple Sclerosis (NARCOMS), we administered the validated Scale to Report Emotional Stress Signs - Multiple Sclerosis (STRESS-MS) and other study measures to 206 U.S. adults who had unpaid caregivers because of MS-related disability.
Results: 54.9% of respondents disclosed undergoing some form of mistreatment since first requiring caregiving by a family member or friend, including psychological abuse (44.2%), financial abuse (25.2%), neglect (16.5%), physical abuse (11.2%) or sexual abuse (8.3%). Many had experienced multiple forms of mistreatment. Mistreated respondents reported less social support, more alcohol use, and higher levels of fatigue and cognitive impairment. Daily caregiving increased mistreatment risk. Caregivers with mental illness were 13 times more likely to be abusive or neglectful. Poor premorbid relationships with caregivers nearly tripled mistreatment risk, while any significant alcohol use history by people with MS or caregivers doubled risk.
Conclusions: In a nationwide survey, over 50% of American adults with advanced MS reported mistreatment by caregivers.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro, Italy
Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors
Background: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available.
Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA).
Methods: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models.
Results: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0.
Sydney Medical School, Save Sight Institute, The University of Sydney, Sydney, NSW, Australia
Expansion of chronic lesions is linked to disease progression in relapsing-remitting multiple sclerosis patients
Background: Slow-burning inflammation is putatively associated with lesion expansion and leads to progressive loss of axons and disability worsening.
Objective: To investigate the incidence and extent of chronic white matter lesion expansion in relapsing-remitting multiple sclerosis (RRMS) patients and to evaluate its relationship with biomarkers of disease progression.
Methods: Pre- and post-gadolinium T1, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor images were acquired from 33 patients. Lesional activity were analysed between baseline and 48 months using custom-designed software.
Results: A total of 569 lesions were identified as chronic at baseline, of which 261 were expanding, 236 were stable and 72 were shrinking. In addition, 139 new lesions (both confluent and free-standing) were observed. Chronic lesion expansion was associated with patient's age and accounted for the bulk (67.3%) of total brain lesion volume increase, while only 32.7% was attributable to new lesion formation. Change in chronic lesion volume correlated with the rate of brain atrophy (r = -0.57, p = 0.001), change of Expanded Disability Status Scale (EDSS; r = 0.38, p = 0.03) and an increase of isotropic diffusivity inside the lesions (r = 0.75, p < 0.001).
Conclusion: Expansion of chronic lesions in RRMS patients is the primary determinant of increased T2 total lesion load. It significantly contributes to disease progression and partially driving axonal loss inside the lesions and brain damage outside of lesional tissue.
Department of Mechanical, Chemical and Materials Engineering, University of Cagliari, Italy
Does Multiple Sclerosis Differently Impact Physical Activity in Women and Man? A Quantitative Study Based on Wearable Accelerometers
In people with multiple sclerosis (pwMS), fatigue, weakness and spasticity may reduce mobility and promote sedentary behavior. However, little is known about the existence of possible differences in the way MS modifies the propensity to perform physical activity (PA) in men and women. The present study aimed to partly close this gap by means of quantitative analysis carried out using wearable sensors. Forty-five pwMS (23 F, 22 M, mean age 50.3) and 41 unaffected age- and sex-matched individuals wore a tri-axial accelerometer 24 h/day for 7 consecutive days. Raw data were processed to calculate average number of daily steps, vector magnitude (VM) counts, and percentage of time spent in sedentary behavior and in PA of different intensities (i.e., light and moderate-to-vigorous, MVPA). Women with MS spent more time in sedentary behavior and exhibited a reduced amount of light intensity activity with respect to men, while MVPA was similar across sexes. However, in comparison with unaffected individuals, the overall PA patterns appear significantly modified mostly in women who, in presence of the disease, present increased sedentary behavior, reduced MVPA, number of daily steps and VM counts. The findings of the present study highlight the urgency of including sex as variable in all studies on PA in pwMS.