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Fatigue is common in people with multiple sclerosis (MS). Understanding the relationship between fatigue, physical and neurobehavioural factors is important to inform future research and practice. Few studies explore this explicitly in people with progressive MS (pwPMS).

•Validation of a self declared MS Population with a clinically diagnosed one.•We analysed the UK MS Register for a number of key characteristics. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared epidemiology. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2)•There is a representative population of people with MS in the online element of the UK MS Register – The MS Register can be utilised as a valid cohort for Clinical and PRO research•Kernel Density of the populations for age can be seen in the graphs:

•Multiple sclerosis is diagnosed according to the McDonald Criteria, recently revised in 2017.•Revisions are based on existing evidence, and not expert opinion.•Misdiagnosis in multiple sclerosis remains an issue in recent studies.•High-priority areas of research in multiple sclerosis may influence further diagnostic criteria.

Multiple sclerosis, always challenging, hands down a particular gauntlet with the concept of the radiologically isolated syndrome. This article discusses what it is, recent developments in the field and how these patients should be managed.

OBJECTIVES: To assess the potential contribution of genetic factors to clinical phenotype in multiple sclerosis. METHODS: Using a cohort of 262 pairs of coaffected siblings from 250 families with multiple sclerosis, intersibling concordance analysis was used to explore underlying genetic mechanisms in disease pathogenesis by assessing parameters of disease course, clinical presentation, age and year of onset, and measures of disability and handicap. RESULTS: Adjusted intraclass correlation coefficients were not significant for either age of onset or for year of first symptom. One third of sibling pairs were concordant for presenting symptom (81/262), a result that was non-significant. However, course type was identical in 50% of the sibling pairs (κ=0.17 (95% confidence interval (95% CI) 0.08 to 0.26)) indicating a significant result. Severity of the disease at assessment, using the Kurtzke and CAMBS scales, demonstrated that whereas there was no agreement for relapse rate in the previous year within the sibship, there was significant concordance for measures of disability (κ=0.11 (95% CI 0.04 to 0.19)), progression (κ=0.09 (95% CI 0.01 to 0.18)) and handicap (κ=0.08 (95% CI 0.02 to 0.14)). CONCLUSIONS: Within a sibship, the clinical presentation tends to be different. However, once established, concordance is more likely to be seen for the ultimate course, leading in the end to similar disability and handicap scores. These results are consistent with the hypothesis that genes influence both disease susceptibility and evolution in multiple sclerosis.

Genetic susceptibility to multiple sclerosis is implicated on the basis of classical family studies and phenotype analyses. The only reproducible legacy from the candidate gene approach has been the discovery of population associations with alleles of the major histocompatibility complex. Systematic genome scanning has since been applied using a panel of anonymous markers to identify areas of linkage in co-affected siblings. Here, we describe the principles of genome screening and update the UK survey of multiple sclerosis. This identified 20 regions of potential interest, but in none was there unequivocal linkage. In theory, attempting to replicate these findings in a second set of sibling pair families is the most appropriate way to distinguish true from false positives, but unfortunately the number of families required to do this reliably is prohibitively large. We used three approaches to increase the definition achieved by the screen: (i) the number of sibling pairs types in an identified region of potential linkage was extended; (ii) the information extraction was increased in an identified region; and (iii) a search was made for missed regions of potential linkage. Each of these approaches has considerable limitations. A chromosome-by-chromosome account is given to direct future searches. Although an additional marker placed distal to the 'hit' on chromosome 14q increased linkage in this area, and typing extra sibling pairs increased linkage on chromosomes 6p and 17q, evidence for linkage was more commonly reduced and no additional regions of interest were found. A further refinement of the genome screen was undertaken by conditioning for the presence of HLA-DR15. This produced a surprising degree of segregation among the regions of interest, which divided into two distinct groups depending on DR15 sharing: the DR15-sharing cohort comprised loci on chromosomal areas 1p, 17q and X; and the DR15-non-sharing cohort was made up of loci on 1cen, 3p, 7p, 14q and 22q. This result further highlights the genetic complexity of multiple sclerosis. What can now be inferred is that a gene of major effect is excluded from 95% of the genome and one with a moderate role from 65%, whereas genes which make a very small biological contribution cannot be discounted from any region. The available results suggest that multiple sclerosis depends on independent or epistatic effects of several genes each with small individual effects, rather than a very few genes of major biological importance.Key words: multiple sclerosis; susceptibility genes; major histocompatibility complex; genome screen

Neurofilament Light (NFL) is a promising biomarker of neuroaxonal injury. Its utility may be improved by expression relative to age-matched controls and by adjusting for other covariates, such as body mass index. It has recently been suggested that renal function may modulate the rate of clearance of NFL from circulation, which if confirmed would make renal function an important additional covariate to take into account when interpreting NFL data in research or clinical settings. Here we explore the relationship between renal function and NFL in a cohort of patients with secondary progressive multiple sclerosis (SPMS).

•Large cohorts of people with RRMS have now taken several Disease-Modifying Treatments.•Switching is a distinctive, rapid and emotional decision-making process.•Switching has a different impact on communication for escalation or de-escalation.•Risk perceptions change when new treatments need to be considered.•Patient decision aids should incorporate complexities in consecutive decisions.

ObjectivesDisease modifying treatment for secondary progressive multiple sclerosis (SPMS) represents a major unmet need. We outline here the rationale for the MS-STAT2 trial – a phase 3 study of simvastatin in decreasing clinical progression in SPMS. MS-STAT2 will be a landmark study not only for patients with SPMS, but also for the area of drug repurposing and academically led clinical trials as a whole.DesignMulticentre, double blind, parallel group randomised placebo-controlled trial. It follows the positive outcome from the phase 2 MS-STAT1 trial, which demonstrated a 43% reduction in the annualised rate of brain atrophy compared to placebo.1Subjects1180 patients with SPMS with an expanded disability status scale (EDSS) score of 4.0–6.5. Patients need to show evidence of disease progression over the preceding 2 years.MethodsSubject will be recruited at 28 sites across the UK, and randomised to simvastatin 80 mg or matched placebo and assessed every 6 months over the 3 year trial.ResultsThe primary outcome measure is time to 6 month confirmed disability progression, based on change in Expanded Disability Status Scale (EDSS) scores compared to baseline. Secondary outcomes include assessments of cognition, walking, upper limb function and vision. Sub-studies will include advanced imaging outcomes, ocular coherence tomography and fluid biomarkers.ConclusionsMS-STAT2 is set to be a pivotal trial for SPMS. Recruitment has now commenced and further sites are welcome.ReferenceChataway J, et al. MS-STAT. Lancet2014;383:2213–21.

Identifier les facteurs de risque d’infections urinaires récidivantes chez les patients ayant une SEP.

Background: The combination of both PCR and intrathecal antibody studies is recommended to confirm or refute the diagnosis of herpes simplex encephalitis (HSE). Aim: To investigate the pattern of use of laboratory tests in the diagnosis of suspected cases of HSE, and to determine the final diagnosis in cases proven not to be HSE. Design: Structured audit. Methods: We reviewed the case-notes of all patients who, over a five-year time period, presented with suspected encephalitis; and/or were prescribed aciclovir. Clinical and laboratory criteria were used to categorize the likelihood of HSE. Results: We identified 222 patients: 10 (5%) had definite HSE, 24 (10%) possible HSE, and 144 (65%) a definite alternative diagnosis. In 44 (20%), no final diagnosis was made, but the diagnosis of HSE was excluded. PCR was performed in 68 (31%), intrathecal antibody studies in 24 (11%), and brain biopsy in 17 (8%). A wide range of diseases mimicked HSE, but most common were inflammatory diseases and other infections of the central nervous system. Discussion: Laboratory tests, particularly intrathecal antibody assays, are under-used in the diagnosis of HSE. Although early empirical treatment of suspected HSE is essential, confirmation or exclusion of the diagnosis is equally important to avoid overlooking alternative diagnoses. Identification of the aetiology of encephalitis is of particular importance, given the current concerns of emerging infections and bioterrorism.