Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations

BACKGROUND: Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis (MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses. METHODS: In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone (and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests (ACTH test, combined dexamethasone/CRH test) were additionally analyzed. RESULTS: Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% (p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% (p = 0.32). T2 lesion volume decreased by 21% during treatment (p = 0.001). Monthly plasma prolactin showed a parallel decline (p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged. CONCLUSION: Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS

D2.2 Report on challenges for SCIs

The report discusses the challenges posed by four types of threats -terrorist attacks, cyber attacks, extreme weather and social unrest- on the SmartResilience case studies. The way this analysis was conducted was by assessing these threats using a 5x5 framework matrix. The two axes of the matrix were phases (understand risks, anticipate/prepare, absorb/withstand, respond/recover, adapt/learn) and dimensions (system/physical, information/data, organizational/business, societal/political, cognitive/decision-making). Each individual matrix block was discussed by subject experts who identified specific challenges and implications for each matrix element and rated its relevance (high, medium, low). In terms of the results, the system/physical dimension received the highest number of important challenges. Overall, the most important singular element was to understand risks in the organizational/business dimension. The least importance was attributed to the adapt/learn phase

D5.2 Stress-test and evaluation framework

This report describes the stress-test and evaluation framework to be used by the case studies in tasks 5.3-5.11. It describes how to stress-test the Smart Critical Infrastructures (SCIs), and how to evaluate the results. It introduces the resilience-based approach to stress-testing, and gives a step-by-step description of the stress-test methodology, which is developed in T3.3. The methodology is accompanied with support tools in the database, foremost the creation and use of dynamic checklists (DCLs). A DCL procedure is provided in the report. Each of the nine case studies – ALPHA to INDIA – in tasks 5.3-5.11 have provided one or more specific stress-test scenarios, which will be carried out as an event (workshop, table top simulation, game, or drill), covering one or more of the most relevant type of threats for these smart critical infrastructures (SCIs). Required functionalities and corresponding thresholds (minimum functionality) have been determined in this stress-test framework report – prior to performing the stress-tests. Thus, after conducting the stress-tests, it can be evaluated whether the thresholds or limits have been exceeded or not, i.e. whether the SCIs have failed or passed the stress-tests. The evaluation is documented in the evaluation report, for which a format is provided in this report. This includes an evaluation/feedback on the stress-test methodology and the corresponding support tools