Alopecia universalis occurring after alemtuzumab treatment for multiple sclerosis. A two-year follow-up of two patients

Alopecia Universalis (AU) is the most severe form of Alopecia Areata and is caused by cytotoxic T-cells reacting with follicular autoantigens, producing complete loss of scalp and body hair. Alemtuzumab is a highly efficacious monoclonal antibody used in the treatment of Multiple Sclerosis (MS), but it causes secondary autoimmunity in up to 40% of patients. Many factors are believed to contribute to this process, but pathogenic mechanisms are not well clear. To date, three cases of AU after treatment with Alemtuzumab have been reported. In this paper we report the cases of two patients who developed AU 12 months after the second cycle of Alemtuzumab, with a review of the literature. One year after the end of the second cycle, two female patients in their thirties experienced complete hair loss. The first case was temporally associated with a significant drop in vitamin D (VD) levels. The second case was accompanied by joint swelling. Both patients had thyroid alterations and showed no hair regrowth after a 2-year follow-up. AU must be considered among the secondary autoimmune manifestations of Alemtuzumab treatment. We emphasize the need for appropriate patient screening and thorough clinical surveillance for factors predisposing patients to secondary autoimmunity

Editorial: Neuroinflammation and the Visual System

The eye is an extension of the central nervous system (CNS) and degenerative diseases of the retina and optic nerve can lead to progressive loss of vision. The causes of degeneration are different and can overlap between genetic predisposition, environmental factors, metabolic alterations, and inflammatory processes. New diagnostic methods and biomarkers are needed to examine and identify the role of neuroinflammation in the degenerative diseases affecting the visual system, not only to aid early diagnosis but also to monitor neuroprotective treatments. The purpose of the present Research Topic was to publish new research describing potential new advances in the diagnosis, treatment, and pathological understanding of conditions that possess inflammatory components affecting the eye and the visual central nervous system

The 412 retrotransposon and the development of gonadal mesoderm in Drosophila

We have shown that the expression of the 412 retrotransposon provides a useful early marker for the development of the gonadal mesoderm in Drosophila embryos. 412 is initially expressed in a set of parasegmentally repeated stripes from parasegments (PS) 2-14 in the mesoderm at the extended germ band stage. During germ band retraction the bulk of 412 expression declines except in dorsolateral clusters of cells in PS10, 11 and 12, where high levels of 412 expression remain. These mesodermal cell clusters are associated with germ cells and subsequently they coalesce, rounding up to form the gonads. The gonadal mesoderm thus appears to originate specifically from three abdominal parasegments, PS10, 11 and 12. We show that the maintenance of high levels of 412 expression in gonadal mesoderm is not induced by contact with germ cells, but rather depends on genetic control by the homeotic genes abdominal-A and Abdominal-B

A novel approach with "skeletonised MTR" measures tract-specific microstructural changes in early primary-progressive MS

We combined tract‐based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract‐specific short‐term changes in early primary‐progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty‐one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM “skeleton,” which represents the tracts that are “common” to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co‐registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a “skeletonised” MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow‐up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal‐appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract‐specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross‐subject and tract‐specific changes in MTR

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS