Lancet neurology
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Randomized Controlled Trial Comparative Study
Alemtuzumab versus interferon β-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes.
Alemtuzumab is a humanised monoclonal antibody that depletes lymphocytes, causing long-term immunomodulation. In a 3-year, rater-blinded phase 2 study (the CAMMS223 study) in patients with relapsing-remitting multiple sclerosis (RRMS), alemtuzumab reduced relapse rate and the risk of sustained accumulation of disability compared with subcutaneous interferon beta-1a, and the mean expanded disability status scale (EDSS) score of the alemtuzumab cohort improved compared with baseline. Adverse events included infusion-associated reactions, predominantly mild to moderate infections, thyroid disorders, and immune thrombocytopenia. In this study, we further analysed the CAMMS223 data with the aim of determining whether demographic and baseline disease-related characteristics affect the beneficial effects of alemtuzumab. Additionally, we aimed to describe a new outcome measure in multiple sclerosis research: sustained reduction in disability. ⋯ Genzyme and Bayer Schering Pharma.
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On the basis of various clinical and MRI measurements, the phase 3 Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study in patients with relapsing-remitting multiple sclerosis (RRMS) showed that short-course oral treatment with cladribine at cumulative doses of 3·5 and 5·25 mg/kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study. ⋯ Merck Serono SA-Geneva, Switzerland; an affiliate of Merck, Darmstadt, Germany.
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Some patients with early-onset Alzheimer's disease (AD) present with a distinct phenotype. Typically, the first and most salient characteristic of AD is episodic memory impairment. A few patients, however, present with focal cortical, non-memory symptoms, such as difficulties with language, visuospatial, or executive functions. ⋯ Additionally, theAPOE ɛ4 genotype seems to predispose patients to vulnerability in the medial temporal areas, which leads to memory loss. Conversely, patients negative for the APOE ɛ4 allele and with early-onset AD are more likely to be predisposed to vulnerability of cerebral networks beyond the medial temporal lobes. Other factors are probably involved in determining the pattern of atrophy, but these are currently unknown.
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Comparative Study
α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study.
Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are brain disorders characterised by intracellular α-synuclein deposits. We aimed to assess whether reduction of α-synuclein concentrations in CSF was a marker for α-synuclein deposition in the brain, and therefore diagnostic of synucleinopathies. ⋯ American Parkinson Disease Association, Stifterverband für die Deutsche Wissenschaft, Michael J Fox Foundation for Parkinson's Research, National Institutes of Health, Parkinson Research Consortium Ottawa, and the Government of Canada.