In vivo visualization and analysis of 3-D hemodynamics in cerebral aneurysms with flow-sensitized 4-D MR imaging at 3T

Introduction: Blood-flow patterns and wall shear stress (WSS) are considered to play a major role in the development and rupture of cerebral aneurysms. These hemodynamic aspects have been extensively studied in vitro using geometric realistic aneurysm models. The purpose of this study was to evaluate the feasibility of in vivo flow-sensitized 4-D MR imaging for analysis of intraaneurysmal hemodynamics. Methods: Five cerebral aneurysms were examined using ECG-gated, flow-sensitized 4-D MR imaging at 3T in three patients. Postprocessing included quantification of flow velocities, visualization of time-resolved 2-D vector graphs and 3-D particle traces, vortical flow analysis, and estimation of WSS. Flow patterns were analyzed in relation to aneurysm geometry and aspect ratio. Results: Magnitude, spatial and temporal evolution of vortical flow differed markedly among the aneurysms. Particularly unstable vortical flow was demonstrated in a wide-necked parophthalmic ICA aneurysm (high aspect ratio). Relatively stable vortical flow was observed in aneurysms with a lower aspect ratio. Except for a wide-necked cavernous ICA aneurysm (low aspect ratio), WSS was reduced in all aneurysms and showed a high spatial variation. Conclusion: In vivo flow-sensitized 4-D MR imaging can be applied to analyze complex patterns of intraaneurysmal flow. Flow patterns, distribution of flow velocities, and WSS seem to be determined by the vascular geometry of the aneurysm. Temporal and spatial averaging effects are drawbacks of the MR-based analysis of flow patterns as well as the estimation of WSS, particularly in small aneurysms. Further studies are needed to establish a direct link between definitive flow patterns and different aneurysm geometrie

Altered functional adaptation to attention and working memory tasks with increasing complexity in relapsing-remitting multiple sclerosis patients

As attention, processing speed, and working memory seem to be fundamental for a broad range of cognitive performance, the present study on patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains. To explore subtle neuropsychological changes in either the clinical or fMRI domain, we applied a multistep experimental design with increasing task complexity to investigate global brain activity, functional adaptation, and behavioral responses to typical cognitive processes related to attention and working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9 females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50 years, 6 women) participated. After a comprehensive neuropsychological assessment, participants performed different fMRI experiments testing attention and working memory. In the neuropsychological assessment, patients showed only subtle reduction in learning and memory abilities. In the fMRI experiments, both groups activated the brain areas typically involved in attention and working memory. HC showed a linear in- or decrease in activation paralleling the changing task complexity. Patients showed stronger activation change at the level of the simple tasks and a subsequent saturation effect of (de-)activation at the highest task load. These group/task interaction differences were found in the right parahippocampal cortex and in the middle and medial frontal regions. Our results indicate that, in MS, functional adaptation patterns can be found which precede clinical evidence of apparent cognitive decline

The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients

OBJECTIVE: The objective of this paper is to investigate the relationship between total and regional corpus callosum (CC) atrophy, neuropsychological test performance and fatigue in multiple sclerosis (MS) patients. METHODS: We conducted a cross-sectional study in 113 MS patients: mean age 48±11 years, 75/113 women, 84/113 relapsing-remitting MS, mean disease duration 21±9 years, mean Expanded Disability Status Scale (EDSS) score 3.2±1.7. All patients underwent brain magnetic resonance imaging, standardised neurological assessment and comprehensive cognitive testing including assessments for fatigue and depression. Total and regional CC atrophy was assessed using the corpus callosum index (CCI). RESULTS: CCI correlated more strongly with T2- and T1-lesion volume and whole brain volume than with disease duration or EDSS score. CCI correlated strongly with the verbal fluency test (VFT), Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT). Multivariate regression analysis revealed that atrophy of the posterior CC segment was significantly associated with poor outcome in the PASAT, VFT and SDMT. In contrast, atrophy of the anterior CC segment was significantly associated with fatigue severity and poor outcome in the long-term memory test. CONCLUSIONS: Atrophy of the CC is associated with cognitive impairment and fatigue. Regional CCI results indicate that these associations are partially spatially segregated

Vitamin D as an early predictor of multiple sclerosis activity and progression.

International audienc

Long-term safety and efficacy of daclizumab beta in relapsing–remitting multiple sclerosis

$\bf Objective$ SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED. $\bf Methods$ Eligible participants who completed 1–2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION. $\bf Results$ Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0–24 was 0.21 (0.16–0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time. $\bf Conclusions$ The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED. $\textbf {Trial registration}$ Clinicaltrials.gov NCT01051349; first registered on January 15, 2010