Multiple Sclerosis Journal
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An observational study has suggested that relapsing–remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients.
To evaluate the safety and efficacy on MRI activity of treatment with TSO in relapsing MS.
The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24–55) years, disease duration 9 (4–34) years, Expanded Disability Status Scale score 2.5 (1–5.0), and number of relapses within the last two years 3 (2–5). Four patients received no disease modifying therapy, while six patients received IFN-β. After an observational period of 8 weeks, patients received 2500 ova from the helminth Trichuris suis orally every second week for 12 weeks. Patients were followed with serial magnetic resonance imaging, neurological examinations, laboratory safety tests and expression of immunological biomarker genes.
Treatment with Trichuris suis orally was well-tolerated apart from some gastrointestinal symptoms. Magnetic resonance imaging revealed 6 new or enlarged T2 lesions in the run-in period, 7 lesions in the early period and 21 lesions in the late treatment period. Two patients suffered a relapse before treatment and two during treatment. Eight patients developed eosinophilia. The expression of cytokines and transcription factors did not change.
In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect.
Background: Elevated Epstein–Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized.
Objectives: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS.
Methods: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks.
Results: MS risk increased with increasing titers of anti-EBNA complex ( p < 10−9) and anti-EBNA-1 ( p = 5.8 × 10−9) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6–136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6–23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1.
Conclusions: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.
We investigated whether the efficacy of 12-week cognitive rehabilitation in MS patients persists six months after treatment termination and, together with resting state (RS) functional connectivity (FC), changes on neuropsychological performance at follow-up.
Eighteen MS patients with cognitive deficits, assigned randomly either to undergo treatment ( n=9) or not ( n=9), underwent neuropsychological evaluation at baseline (t0), after 12 weeks of rehabilitation (t1) and at six-month follow-up (t2). RS fMRI was obtained at t0 and t1. Changes in neuropsychological performance and their correlations with RS FC modifications were assessed using longitudinal linear models.
At t2 vs. t0, compared with the control group, treated group patients improved in tests of attention, executive function, depression and quality of life (QoL). Neuropsychological scores in these tests at t2 were significantly correlated with RS FC changes in cognitive-related networks and RS FC of the anterior cingulum. RS FC changes in the default mode network predicted cognitive performance and less severe depression, whereas RS FC changes of the executive network predicted better QoL.
Changes in RS FC of cognitive-related networks helps to explain the persistence of the effects of cognitive rehabilitation after several months in relapsing–remitting multiple sclerosis patients and their improvement on depression and QoL scales.
The feasibility and precision of clinical trials for the treatment of MS must be improved Subsequent to the approval by the Food and Drug Administration of the United States of interferon beta-1b as a safe and effective, though not curative, treatment for relapsing-remitting MS, the testing of other agents in this disease has been undertaken or is anticipated. This report summarises the discussions and recommendations of an international workshop held to review critically the elements of current MS therapeutic trials and to identify the most important aspects of clinical evaluation, study design and data analysis that would allow agents for MS to be tested as accurately, rapidly and economically as possible. While acknowledging the many uncertainties about the pathophysiology and natural history of MS, the workshop participants made recommendations about the preferred components to be used in the design of trials which may be different depending on the treatment goal and agent studied. It was concluded that the formulation of a useful clinical trial design must be based on specific guidelines for clinical scales and imaging for which task forces were recommended and subsequently appointed.
Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome suggestive of multiple sclerosis remains uncertain.
The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis.
We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3–6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010).
In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T ( p = 0.005). For patients, this was 4.18 and 4.40, respectively ( p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters.
Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training.
In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated.
This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015.
A total of 1010 patients (mean age = 45 years) participated in Italy. In total, 94% were below retirement age, and of these, 56% were employed. Employment was related to disability, and MS affected productivity at work in 77% of the patients. Overall, 96% and 65% of the patients experienced fatigue and cognitive difficulties as a problem, respectively. Mean utility and total annual costs were 0.735 and €22,900 at Expanded Disability Status Scale (EDSS) of 0–3, 0.534 and €40,100 at EDSS of 4–6.5, and 0.135 and €53,300 at EDSS of 7–9. The mean cost of a relapse was estimated to be €2600.
This study illustrates the burden of MS on Italian patients and provides current data on MS that are important for the development of health policies.
The current focus in multiple sclerosis (MS) is on early diagnosis and drug intervention, with a view to modifying disease progression. Consequently, healthcare costs have shifted from inpatient care and rehabilitation to outpatient care.
This European burden of illness study provides data that can be combined with other evidence to assess whether management approaches provide value to society.
A cross-sectional study was conducted in 16 countries. Patients reported on their disease, health-related quality of life (HRQoL) and resource consumption. Descriptive analyses were performed by disease severity. Costs are reported from a societal perspective in 2015€ PPP (adjusted for purchasing power parity).
The 16,808 participants had a mean age of 51.5 years, and 52% had relapsing–remitting multiple sclerosis (RRMS). Work capacity declined from 82% to 8%, and utility declined from normal population values to less than zero with advancing disease. Mean costs were 22,800€ PPP in mild, 37,100€ PPP in moderate and 57,500€ PPP in severe disease; healthcare accounted for 68%, 47% and 26%, respectively. Fatigue and cognitive difficulties were reported by 95% and 71% of participants, respectively; both had a significant independent effect on utility.
Costs and utility were highly correlated with disease severity, but resource consumption was heavily influenced by healthcare systems organisation and availability of services.
Myelin destruction due to inflammatory oligodendrocyte cell damage or death in conjunction with axonal degeneration are among the major histopathological hallmarks of multiple sclerosis (MS). The majority of available immunomodulatory medications for MS are approved for relapsing–remitting (RR) MS, for which they reduce relapse rate, MRI measures of inflammation, and the accumulation of disability. These medications are, however, of little benefit during progressive MS where axonal degeneration following demyelination outweighs inflammation. This has sparked great interest in the development of new remyelination therapies aimed at reversing the neurodegenerative damage observed in this disease. Remyelination as a result of oligodendrocyte production from oligodendrocyte precursor cells (OPCs) is considered a promising potential target for the treatment of all stages of MS. In this review we present an overview of a) approved medications (some of them FDA-and EMA-approved for other diseases) with a proposed role in regeneration, b) regenerative treatments under investigation in clinical trials, and c) promising future therapeutic approaches aiming specifically at facilitating endogenous repair.
Background: The geographical distribution of multiple sclerosis (MS) means that prevalence rates increase with latitude north or south of the equator. Temporally, a tendency for increased incidences of MS has been observed over the past two decades.
Objectives: Since epidemiological studies of MS in areas close to the Arctic Circle are rare, we evaluated the incidence and prevalence of MS in Northern Ostrobothnia by means of a retrospective cohort study covering the period 1992–2007.
Methods: Patients with a definite clinical diagnosis of MS based on the Poser criteria and the early McDonald criteria of 2001 were identified in the region of Northern Ostrobothnia (population 386,972) and the incidence was calculated at 1-year time intervals, both overall and by gender.
Results: The overall prevalence was 103/100,000 (95% CI, 93–113), with a female/male ratio of 2.17. The mean overall incidence was 6.3/100,000 (95% CI, 5.2–7.2). The incidence shows a tendency to increase over the 16-year period due to a pronounced rise in the female incidence.
Conclusions: Our results show a high prevalence of MS in Northern Ostrobothnia and a disproportional increase in the female MS incidence. These recent epidemiological features may be associated with environmental risk factors such as a vitamin D deficit, low life-long UV radiation and the high-latitude geographical location.
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