Multiple Sclerosis and Related Disorders (2015) 4, 1–2

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Editors' welcome In this issue, we focus largely on the clinical aspects of MS, including the impact of menopause, fatigue and hypothalamic function, the relationship between spinal cord atrophy and disability, useless hand syndrome, and healthrelated quality of life. The validity of potential biomarkers, such as brain-derived neurotrophic factor, melatonin and serotonin, quantitative spinal cord measures, and sensory and motor evoked responses, with patient-outcomes are also presented. Finally, management strategies for leukopenia associated with fingolimod, information about therapeutic adherence, and a new model for “repurposing” therapies for MS are evaluated. In a provocative commentary, Giovannoni et al. propose the “Big Pharma Alternative” (BPA) to enhance development of promising new therapies for conventional Phase 1-III development processes that are not attractive to the pharmaceutical industry. Governmental flexibility, novel study design similar to strategies for rare diseases, and patient-registry models are discussed. The challenges of managing MS treatment during pregnancy, and the potential impact on the fetus, led Alwan et al. to present a thoughtful proposal for a North American MS Patient Pregnancy Registry. Bove et al. explore the severity of MS symptoms in women who have entered or completed menopause. Earlier age of onset and menopause induced by surgery or chemotherapy resulted in greater patient-reported MS severity. The use of hormone replacement therapies did not appear to mitigate these findings. Of particular interest is that the results were collected via “People like me” – a communityempowered self-reporting online site. While such notification methods do not permit complete validation, this approach does access a large patient base and reflects patient-reported features. Further studies are likely to develop from such networks. Amezcua et al. describe the imigration patterns and clinical severity of Hispanic MS patients living in South Carolina. Early immigration chiefly from Mexico into South Carolina was defined as moving prior to age 6 years of age. Later immigrants, who on average settled there in their mid-20s were more likely to have severe MS when compared to those who re-located to 2211-0348/& 2014 Published by Elsevier B.V.

South Carolina in early childhood. The authors discuss factors contributing to greater disability in later settlers that probably reflect access to health care – a major consideration given current changes in health care accessibility. No data are presented about the effect of age at time of migration and risk of subsequent MS, but hopefully this information will be available in a later publication. The term “benign” MS has been ascribed to patients who have Expanded Disability Status Scale (EDSS) scores less than or equal to 3 after a prolonged period of disease. As well known to those familiar with the EDSS, the scale is weighted heavily to deficits in ambulation, and does not assess fully many other aspects such as arm function and cognition. In the paper by Bueno et al., only 30/61 patients remained “benign” (i.e. EDSS o3) when assessed after 25–30 years of disease. Health-related quality of life (HRQoL) was reduced, notably in those reporting fatigue or depression-irrespective of physical status. Physical incapacity did correlate with worsening of HRQoL, and mental health subset scores. Clearly, this paper brings into question the whole concept of “benign” disease. Two studies evaluated spinal cord area. Bernitsas et al., demonstrated that the cross-sectional area of the cord at C2 correlated robustly with EDSS, and allowed relapsing-remitting MS to be distinguished from those with progressive MS. Lui et al. evaluated whether conventional brain MRI images that capture the upper cervical spine in the field of view could serve as a correlate of physical disability. The authors show that the cross-sectional area of the upper spinal cord (approximately at C1) did indeed correlate with disability, and that this relationship was comparable to the more often studied cross-sectional area of the spinal cord at C2/C3. Biomarkers relating to MS biology, outcomes, or therapeutic responsiveness are urgently needed and several manuscripts address this. In a commentary, Schneider reviews the potential relevance of CD20 + T cells to MS pathobiology, and the possible rationale for therapies targeting CD20 + cells. Although epidemiological evidence strongly implicated Epstein Barr Virus (EBV) in the MS causal pathway, the study by Simon et al. that explored polymorphisms associated with infectious mononucleosis found

2 no relationship between any specific polymorphisms and MS. Serum concentrations of brain derived neurotrophic factor (BDNF) also failed to distinguish MS patients from controls, and did not correlate with physical, cognitive, or MRI metrics (Damasceno et al.). Two manuscripts focus on therapy. The TOP study (Therapy Optimization in MS) by Cohen et al. enrolled MS patients through pharmacies, documenting electronic record-based evidence for adherence to glatiramer acetate or interferon beta treatment over a 24 month period. Unsurprisingly, better compliance was associated with a lower relapse rate, emphasizing the adage that “nothing works if you don’t take it”. Another practical Letter by Dr. DeJong, discusses the management, and importantly, the biologic significance of drug-induced

Editorial lymphopenia in MSers. Recommendations are provided for monitoring white blood cell counts specifically for patients treated with Fingolimod. We hope our readers enjoy the current issue, and that the contents assist in the care of persons living with MS.

Editors in Chief Brenda Banwell Gavin Giovannoni Chris Hawkes Fred Lublin

Editors׳ welcome.

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