Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system. An increase in MS incidence over time is reported in several regions of the world. We aimed to describe the ...evolution of the annual MS incidence in the Lorraine region, France, from 1996 to 2015 and to analyze potential components of a possible change by a temporal effect of age at MS onset, MS onset period, and birth cohort, overall and for each sex. Cases were identified from ReLSEP, a population-based registry of MS cases living in Lorraine, northeastern France, with MS onset between 1996 and 2015. Age-period-cohort modeling was used to describe trends in MS incidence. Annual age- and sex-standardized incidences were relatively stable: 6.76/100 000 population (95%CI 5.76-7.91) in 1996 and 6.78/100 000 (95%CI 5.72-7.97) in 2015. The incidence ratio between women and men was 2.4. For all time periods, the peak incidence occurred between ages 25 and 35 years. Age-period-adjusted cohort and age-cohort-adjusted period analyses did not reveal a period or cohort effect. The incidence of MS remained stable over the study period in Lorraine, and we could not identify any particular effect of disease onset period or birth period on this evolution.
Abstract
Administrative databases are an alternative to disease registries as a research tool to study multiple sclerosis. However, they are not initially designed to fulfill research purposes. ...Therefore, an evaluation of their performance is necessary. Our objective was to assess the performance of the French administrative database comprising hospital discharge records and national health insurance databases in identifying individuals with multiple sclerosis, in comparison with a registry that exhaustively compiles resident multiple sclerosis cases in Lorraine, northeastern France, as reference. We recorded all individuals residing in the Lorraine region who were identified by the administrative database or the registry as having multiple sclerosis from 2011 to 2016. We calculated the Matthews correlation coefficient and other concordance indicators. For identifying individuals with multiple sclerosis, the Matthews correlation coefficient by the administrative database was 0.79 (95% CI 0.78–0.80), reflecting moderate performance. The mean time to identification was 5.5 years earlier with the registry than the administrative database. Administrative databases, although useful to study multiple sclerosis, should be used with caution because results of studies based on them may be biased. Our study highlights the value of regional registries that allow for a more exhaustive and rapid identification of cases.
Objective
To describe the course of disability in patients with benign multiple sclerosis—i.e., with an expanded disability status scale score < 3 10 years after disease onset—for up to 30 years ...after disease onset. We evaluated the proportion of patients remaining in the benign state on the long term and the factor associated with this favorable outcome and determined the pattern of disability course after the loss of the benign status.
Methods
Patients were selected from the ReLSEP, a French population-based registry. We studied the probability (Kaplan–Meier method) and predictors (multivariate Cox model) of remaining < 3 after year 10, and the course of disability after score 3 according to the duration of the benign phase in patients with ≥ 30 years of follow-up (graphs of the course of the mean expanded disability status scale scores in subgroups of patients).
Results
2295/3440 patients had benign multiple sclerosis (66.7%). The probability of remaining benign at year 30 was 0.26 (95% CI 0.26–0.32). A young age at disease onset and a good recovery after the first relapse were associated with remaining benign. Graphs illustrate that those who lost their benign status between years 10 and 30 follow a two-stage course. Beyond score 3, disability accumulation is similar in all but lower disability scores at advanced age are associated with longer benign periods.
Conclusion
The longer a patient remains in the benign state, the lower the final EDSS at advanced age.
The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of ...European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.
Background:
Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far.
Objective:
Explore ...the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods:
A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function.
Results:
At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT).
Conclusion:
Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.
Abstract Objective To review current practice and update guidelines for the methodology of shortening composite measurement scales (CMSs). Study Design and Setting A literature review gathered data ...on 91 shortening processes from 1995 to 2009. The validity of the initial CMS, the shortening methods, and the validity of the derived short-form scales were examined. The results were compared with those from a previous literature review (articles from 1985 to 1995) to develop updated guidelines for CMS shortening. Results The literature review revealed a persisting lack of use of rigorous methodology for CMS shortening. Of the 91 cases of CMS shortening, 36 combined a content approach and a statistical approach; 45 used only a statistical approach and 10 (11%) only a content approach. The updated guidelines deal with the validity and conceptual model of the initial CMS, the preservation of content and psychometric properties during shortening, the selection of items, and the validation of the short form. Conclusion Item reduction based on a rigorous methodology is necessary if the short-form instrument aims to maintain the validity and other measurement properties of the parent instrument, which in turn supports application in research and clinical practice.
Aims
To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable ...immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real‐life setting.
Methods
A population‐based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1–3.5 years of follow‐up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± 95% CI) of ARRt and the odds ratio (OR ± 95% CI) of disability progression, respectively.
Results
Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF‐IMM patients, 1679 DMF‐TERI patients, and 376 DMF‐FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 0.61–0.86) and TERI (0.81 0.68–0.96) and did not show any significant difference when compared with FTY. The risk of the progression of MS‐specific disability was not significantly different for any matched cohorts.
Conclusion
DMF is associated with lower risk of treated relapse for patients with RRMS than other first‐line RRMS agents (TERI and IIM).
The incidence of multiple sclerosis (MS) changes from generation to generation in ethnically different immigrants compared with native-born people. We aimed to determine whether there are ...generational changes in MS phenotypes among North African immigrants in France.
Cohort study with data from a population-based MS registry to compare the clinical characteristics of 80 first (NAG1) and 167 second (NAG2) generation North Africans with MS living in France with 5200 native-born Europeans. Adjusted Cox models were used to test the association between scores of 3 and 6 on the expanded disability status scale (EDSS) and the "origin/generation" variable.
Cox models for EDSS scores 3 and 6 showed a higher risk of score 3 (hazard ratio = 1.738, 95% confidence interval 1.237 to 2.444; P = .002) and 6 (hazard ratio = 2.372, 95% confidence interval 1.626 to 3.462; P<.0001) for NAG1 than Europeans. Being NAG2 was not significantly associated with higher hazards of scores 3 and 6.
We found two different phenotypes among NAG1 and NAG2 MS patients in France. NAG1, but not NAG2, have a higher risk of disability than Europeans. This raises the question of environmental factors in MS expression, and advocates appropriate patient management according to generation in immigrants.
Multiple sclerosis (MS) is an immune-driven demyelinating disease of the central nervous system. Immune cell features are particularly promising as predictive biomarkers due to their central role in ...the pathogenesis but also as drug targets, even if nowadays, they have no impact in clinical practice. Recently, high-resolution approaches, such as mass cytometry (CyTOF), helped to better understand the diversity and functions of the immune system. In this study, we performed an exploratory analysis of blood immune response profiles in healthy controls and MS patients sampled at their first neurological relapse, using two large CyTOF panels including 62 markers exploring myeloid and lymphoid cells. An increased abundance of both a T-bet-expressing B cell subset and a CD206
classical monocyte subset was detected in the blood of early MS patients. Moreover, T-bet-expressing B cells tended to be enriched in aggressive MS patients. This study provides new insights into understanding the pathophysiology of MS and the identification of immunological biomarkers. Further studies will be required to validate these results and to determine the exact role of the identified clusters in neuroinflammation.
Skin biopsy is the most relevant tool to diagnose small-fiber neuropathy. A well-documented normal dataset for intraepidermal nerve fiber in the distal leg is required to improve its diagnostic ...value.
Three hundred healthy subjects were enrolled in the study, after clinical and biological screening to exclude neurological and systemic pathologies. A distal leg biopsy was taken and intraepidermal nerve fiber density after protein gene product-9.5 immunocytochemistry with brightfield microscopy was determined. Morphological variations of intraepidermal nerve fibers, previously described in small-fiber neuropathies, were analyzed. One hundred biopsies were also analyzed at the ultrastructural level.
The median number of fibers was lower in men compared to women and decreased with age. Using statistical modeling taking into account age and gender, we calculated the 5th percentile of intraepidermal nerve fiber density as follows: 7.6156-0.0769 x age (years) + 1.5506 x gender (woman = 1; man = 0). We observed a low frequency of large swellings or horizontal branchings but an increasing frequency of small swellings of intraepidermal nerve fibers and irregular distribution along the dermal-epidermal junction with age. Axonal diameter of unmyelinated fibers of the papillary dermis did not vary with age or gender. Ultrastructural analysis also showed that fiber endings in close apposition to Merkel cells should not be mistaken for small-fiber swellings.
Our dataset allows accurate calculation of the normal density of intraepidermal nerve fibers for each year of age and provides original morphological observations that improve the diagnostic value of skin biopsy in the distal leg for small-fiber neuropathy.
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