Corinne Goldsmith Dickinson Center for Multiple Sclerosis

About: Corinne Goldsmith Dickinson Center for Multiple Sclerosis is a based out in . It is known for research contribution in the topics: Multiple sclerosis & Oligodendrocyte. The organization has 86 authors who have published 116 publications receiving 8458 citations.

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

Abstract: The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

New multiple sclerosis phenotypic classification.

Abstract: Background: In 1996, the clinical course of multiple sclerosis (MS) was characterized as relapsing-remitting, primary progressive, secondary progressive or progre

Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial.

Abstract: Summary Background Fingolimod has shown reductions in clinical and MRI disease activity in patients with relapsing-remitting multiple sclerosis. We further assessed the efficacy and safety of fingolimod in such patients. Methods We did this placebo-controlled, double-blind phase 3 study predominantly in the USA (101 of 117 centres). Using a computer-generated sequence, we randomly allocated eligible patients—those aged 18–55 years with relapsing-remitting multiple sclerosis—to receive fingolimod 0·5 mg, fingolimod 1·25 mg, or placebo orally once daily (1:1:1; stratified by study centre). On Nov 12, 2009, all patients assigned to fingolimod 1·25 mg were switched to the 0·5 mg dose in a blinded manner after a review of data from other phase 3 trials and recommendation from the data and safety monitoring board, but were analysed as being in the 1·25 mg group in the primary outcome analysis. Our primary endpoint was annualised relapse rate at month 24, analysed by intention to treat. Secondary endpoints included percentage brain volume change (PBVC) from baseline and time-to-disability-progression confirmed at 3 months. This trial is registered with ClinicalTrilals.gov, number NCT00355134. Findings Between June 30, 2006, and March 4, 2009, we enrolled and randomly allocated 1083 patients: 370 to fingolimod 1·25 mg, 358 to fingolimod 0·5 mg, and 355 to placebo. Mean annualised relapse rate was 0·40 (95% CI 0·34–0·48) in patients given placebo and 0·21 (0·17–0·25) in patients given fingolimod 0·5 mg: rate ratio 0·52 (95% CI 0·40–0·66; p vs placebo; 95% CI 0·61–1·12; p=0·227). Fingolimod 0·5 mg caused more of the following adverse events versus placebo: lymphopenia (27 [8%] patients vs 0 patients), increased alanine aminotransferase (29 [8%] vs six [2%]), herpes zoster infection (nine [3%] vs three [1%]), hypertension (32 [9%] vs 11 [3%]), first-dose bradycardia (five [1%] vs one [ vs seven [2%]). 53 (15%) of 358 patients given fingolimod 0·5 mg and 45 (13%) of 355 patients given placebo had serious adverse events over 24 months, which included basal-cell carcinoma (ten [3%] patients vs two [1%] patients), macular oedema (three [1%] vs two [1%]), infections (11 [3%] vs four [1%]), and neoplasms (13 [4%] vs eight [2%]). Interpretation Our findings expand knowledge of the safety profile of fingolimod and strengthen evidence for its beneficial effects on relapse rates in patients with relapsing-remitting multiple sclerosis. We saw no effect of fingolimod on disability progression. Our findings substantiate the beneficial profile of fingolimod as a disease-modifying agent in the management of patients with relapsing-remitting multiple sclerosis. Funding Novartis Pharma AG.

VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown.

Abstract: Breakdown of the blood-brain barrier (BBB) is an early and significant event in CNS inflammation. Astrocyte-derived VEGF-A has been implicated in this response, but the underlying mechanisms remain unresolved. Here, we identify the endothelial transmembrane tight junction proteins claudin-5 (CLN-5) and occludin (OCLN) as targets of VEGF-A action. Down-regulation of CLN-5 and OCLN accompanied up-regulation of VEGF-A and correlated with BBB breakdown in experimental autoimmune encephalomyelitis, an animal model of CNS inflammatory disease. In cultures of brain microvascular endothelial cells, VEGF-A specifically down-regulated CLN-5 and OCLN protein and mRNA. In mouse cerebral cortex, microinjection of VEGF-A disrupted CLN-5 and OCLN and induced loss of barrier function. Importantly, functional studies revealed that expression of recombinant CLN-5 protected brain microvascular endothelial cell cultures from a VEGF-induced increase in paracellular permeability, whereas recombinant OCLN expressed under the same promoter was not protective. Previous studies have shown CLN-5 to be a key determinant of trans-endothelial resistance at the BBB. Our findings suggest that its down-regulation by VEGF-A constitutes a significant mechanism in BBB breakdown.