The Moulton Foundation [charity number 1109891], Berkeley Foundation [268369], the Multiple Sclerosis Trials Collaboration [1113598], the Rosetrees Trust [298582] and a personal contribution from A Pidgley, UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme.

The emergence of oral disease-modifying therapies in multiple sclerosis (MS) will have a significant impact on the evolving scenario of immunomodulatory treatments in MS where current therapies are all injectable. Reducing relapses in trials translates for individuals with MS into a therapeutic aim of stopping future events. Thus the possible absence of any perceived benefits to the individual together with the long disease course, variable outcome, and a younger age group affected in MS makes side effects the major issue. The use of disease-modifying therapies as a whole needs to be placed in the context of a widening therapeutic indication where the use of these therapies is being justified at an increasingly early stage and in pre-MS syndromes such as clinically isolated and radiologically isolated syndromes where no fixed disability is likely to have accumulated. The five oral therapies discussed (cladribine, fingolimod, laquinimod, BG-12, and teriflunomide) have just completed Phase III studies and some have just been licensed. New oral drugs for MS need to be placed within this evolving marketplace where ease of delivery together with efficacy and side effects needs to be balanced against the known issues but also the known long-term safety of standard injectables.

Asymmetrical sensory ganglionopathies may have an inflammatory basis. Immunomodulatory therapy may be considered early in the disease course, although in this series there was a limited response to treatment.

BackgroundThe recruitment of secondary progressive multiple sclerosis (SPMS) patients to the MS-STAT trial (a double-blind randomised placebo-controlled trial of high dose simvastatin) provided an opportunity to evaluate the frequency and severity of cognitive and neuropsychiatric symptoms at baseline, in this phase of the disease. The study also explored the interaction between frontal lobe function and neuropsychiatric disorders.Methods130 SPMS patients were administered a battery of neuropsychological tests, including the PASAT, the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory.ResultsMean patient age was 50.5 years with mean total MS and SPMS durations of 21.0 years and 7.0 years. Patients demonstrated severe impairment on the PASAT and mild frontal lobe dysfunction. General intelligence, verbal and nonverbal memory, naming and higher visual processing were relatively preserved. 43% of patients had symptoms of depression. There was no association between cognitive and neuropsychiatric test scores or between depression and frontal lobe function.ConclusionImpaired speed of information processing and frontal lobe function were the most prominent cognitive deficits. A high incidence of depression was also noted. These findings have clear implications for the management of early SPMS.

BackgroundTherapeutic options for secondary progressive MS (SPMS) are very limited. Simvastatin is an attractive drug with potentially anti-inflammatory (e.g., reducing leukocyte migration) and neuro-protective effects (e.g., up-regulation of the major cell survival protein bcl-2), in addition to being well tolerated. In trials of early stage MS it is undergoing trials as a single agent or in combination therapy with standard disease modifying treatments. This is the first trial in SPMS.Trial OverviewDouble-blinded/placebo-controlled (1:1) with 80 mg of simvastatin. Two-year follow-up. Entry EDSS 4.0–6.5. Brain atrophy rate as determined from T1-weighted volumetric MRI using the brain boundary shift integral is the primary outcome measure. Secondary outcomes include disability scores, neuropsychological assessments and immunological profiling.Results408 patients were referred, 203 screen failures, 140/140 patients were randomised. Age 52 years (range 35–65), 68% female, MS duration 21 years (8) with a secondary progressive phase of 13 years (7). Median EDSS 6.0 (IQR 0.5). MSFC 10 m walk/s 23.6 (25.6); Nine-hole peg test/s 34.6 (13.2); PASAT/60 35.3 (14.2). MSIS-29ver 2.0 scores: physical 49/80 (11), psychological 20/36 (8), total 69/116 (14). All data as mean (SD) unless stated.ConclusionThis trial is fully recruited and will report in late 2011. ClinicalTrials.gov, number NCT00647348.