Treating Systematic Errors in Multiple Sclerosis Data

Multiple sclerosis (MS) is characterized by high variability between patients and, more importantly here, within an individual over time. This makes categorization and prognosis difficult. Moreover, it is unclear to what degree this intra-individual variation reflects the long-term course of irreversible disability and what is attributable to short-term processes such as relapses, to interrater variability and to measurement error. Any investigation and prediction of the medium or long term evolution of irreversible disability in individual patients is therefore confronted with the problem of systematic error in addition to random fluctuations. The approach described in this article aims to assist in detecting relapses in disease curves and in identifying the underlying disease course. To this end neurological knowledge was transformed into simple rules which were then implemented into computer algorithms for pre-editing disease curves. Based on simulations it is shown that pre-editing time series of disability measured with the Expanded Disability Status Scale (EDSS) can lead to more robust and less biased estimates for important disease characteristics, such as baseline EDSS and time to reach certain EDSS levels or sustained progression

Usages sociaux et politiques de la monnaie en Dordogne dans la première moitié du XIXe siècle

La loi du 7 germinal an XI a pour ambition de poser les bases d’un nouveau système monétaire fondé sur le franc. L’étude sociopolitique de la monnaie dans les campagnes de Dordogne entre 1802 et 1848 rend compte à la fois des enjeux politiques de la mise en place d’une monnaie nationale transformée et d’un vécu monétaire hétérogène où dix pièces de 10 centimes ne « valent » pas un franc… Les pièces étrangères, fausses ou démonétisées concurrencent longtemps la monnaie nationale. Les pratiques afférentes à cette hétérogénéité monétaire permettent d’interroger la monnaie comme enjeu et vecteur de souveraineté, comme outil d’acculturation ou d’intégration des campagnes et comme opérateur d’identification nationale.Political and social uses of money in Dordogne during the first half of the nineteenth century The aim of the “Loi du 7 germinal an XI” was to lay the groundwork for a new monetary system based of the Franc. The sociopolitical study of money in rural Dordogne between 1802 and 1848 takes into account both the political signification of the new national currency, and a heterogenous experience of what money is, where ten coins of 10 centimes are not worth one Franc… Foreign, false or outdated coins remain a serious competition for the national currency. The practices which stem from such a diversity allow us to envision money in its relation to sovereignty, as a mean of acculturation or of integration of rural areas and a agent of national identity

Treating systematic errors in multiple sclerosis data

Multiple sclerosis (MS) is characterized by high variability between patients and, more importantly here, within an individual over time. This makes categorization and prognosis difficult. Moreover, it is unclear to what degree this intra-individual variation reflects the long-term course of irreversible disability and what is attributable to short-term processes such as relapses, to interrater variability and to measurement error. Any investigation and prediction of the medium or long term evolution of irreversible disability in individual patients is therefore confronted with the problem of systematic error in addition to random fluctuations. The approach described in this article aims to assist in detecting relapses in disease curves and in identifying the underlying disease course. To this end neurological knowledge was transformed into simple rules which were then implemented into computer algorithms for pre-editing disease curves. Based on simulations it is shown that pre-editing time series of disability measured with the Expanded Disability Status Scale (EDSS) can lead to more robust and less biased estimates for important disease characteristics, such as baseline EDSS and time to reach certain EDSS levels or sustained progression

Evidence for a two-stage disability progression in multiple sclerosis

It is well documented that disability accumulation in multiple sclerosis is correlated with axonal injury and that the extent of axonal injury is correlated with the degree of inflammation. However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits, remains ambiguous. A hypothesis might be that early focal inflammation could be the pivotal event from which all else follows, suggesting the consideration of multiple sclerosis as a two-stage disease. This prompted us to define two phases in the disease course of multiple sclerosis by using two scores on the Kurtzke Disability Status Scale as benchmarks of disability accumulation: an early phase, ‘Phase 1’, from multiple sclerosis clinical onset to irreversible Disability Status Scale 3 and a late phase, ‘Phase 2’, from irreversible Disability Status Scale 3 to irreversible Disability Status Scale 6. Outcome was assessed through five parameters: Phase 1 duration, age at Disability Status Scale 3, time to Disability Status Scale 6 from multiple sclerosis onset, Phase 2 duration and age at Disability Status Scale 6. The first three were calculated among all patients, while the last two were computed only among patients who had reached Disability Status Scale 3. The possible influence of early clinical markers on these outcomes was studied using Kaplan–Meier estimates and Cox models. The analysis was performed in the Rennes multiple sclerosis database (2054 patients, accounting for 26 273 patient-years) as a whole, and according to phenotype at onset (1609 relapsing/445 progressive onset). Our results indicated that the disability progression during Phase 2 was independent of that during Phase 1. Indeed, the median Phase 2 duration was nearly identical (from 6 to 9 years) irrespective of Phase 1 duration (<3, 3 to <6, 6 to <10, 10 to <15, ≥15 years) in the whole population, and in both phenotypes. In relapsing onset multiple sclerosis, gender, age at onset, residual deficit after the first relapse and relapses during the first 2 years of multiple sclerosis were found to be independent predictive factors of disability progression, but only during Phase 1. Our findings demonstrate that multiple sclerosis disability progression follows a two-stage process, with a first stage probably dependant on focal inflammation and a second stage probably independent of current focal inflammation. This concept has obvious implications for the future therapeutic strategy in multiple sclerosis

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP

Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients

Functional electrical stimulation for foot drop in multiple sclerosis: a systematic review and meta-analysis of the effect on gait speed

Objective: To review the efficacy of functional electrical stimulation (FES) used for foot drop in people with multiple sclerosis (pwMS) on gait speed in short and long walking performance tests. Data sources: Five databases (Cochrane Library, CINAHL, Embase, MEDLINE, Pubmed) and reference lists were searched. Study selection: Studies of both observational and experimental design where gait speed data in pwMS could be extracted were included. Data extraction: Data were independently extracted and recorded. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) tool. Data synthesis: Nineteen studies (described in 20 articles) recruiting 490 pwMS were identified and rated moderate or weak, with none gaining a strong rating. All studies rated weak for blinding. Initial and ongoing orthotic and therapeutic effects were assessed with regards to the impact of FES on gait speed in short and long walking tests. Meta-analyses of the short walk tests revealed a significant initial orthotic effect (t = 2.14, p = 0.016) with a mean increase in gait speed of 0.05 meters per second (m/s) and ongoing orthotic effect (t = 2.81, p = 0.003) with a mean increase of 0.08m/s. There were no initial or ongoing effect on gait speed in long walk tests and no therapeutic effect on gait speed in either short or long walk tests. Conclusions: FES used for foot drop has a positive initial and ongoing effect on gait speed in short walking tests. Further fully-powered randomized controlled trials comparing FES with alternative treatments are required

What Are the Support Needs of Men With Multiple Sclerosis, and Are They Being Met?

Background: Multiple sclerosis (MS) is a chronic, degenerative condition of the central nervous system that can lead to high levels of disability and a range of psychological and social problems. Although considerable research exists on the experience of living with MS and the disease's psychosocial consequences, much of this has focused on women and has seldom considered the male perspective. It is possible, therefore, that men may differ from women in how they experience MS and the type of support or interventions that meet their needs. Methods: A literature review was undertaken to identify the specific support needs of men with MS, describe current support available to men with MS, and evaluate the extent to which these needs are met by current service provision. Results: The literature reviewed suggests that the needs of men with MS are different from those of women in terms of psychological factors such as well-being and mental health and support. Conclusions: If interventions are to be evidence based, then health-care professionals need to take into account the needs, desires, and capabilities of men with MS to inform service development. Further research is required to explore this, both qualitatively and quantitatively, to address the gaps in the evidence base of support needs for men with MS