).q RSNA, 2014 Purpose:To evaluate the clinical utility of fast whole-brain macromolecular proton fraction (MPF) mapping in multiple sclerosis (MS) and compare MPF with established quantitative magnetic resonance (MR) imaging measures of tissue damage including magnetization transfer (MT) ratio and relaxation rate (R1). Materials and Methods:In this institutional review board-approved and HIPAAcompliant study, 14 healthy control participants, 18 relapsing-remitting MS (RRMS) patients, and 12 secondary progressive MS (SPMS) patients provided written informed consent and underwent 3-T MR imaging. Threedimensional MPF maps were reconstructed from MTweighted images and R1 maps by the single-point method.Mean MPF, R1, and MT ratio in normal-appearing white matter (WM), gray matter (GM), and lesions were compared between subject groups by using analysis of variance. Results:RRMS patients had lower WM and GM MPF than controls, with percentage decreases of 6.5% (P , .005) and 5.4% (P , .05). MPF in SPMS was reduced relative to RRMS in WM, GM, and lesions by 6.4% (P , .005), 13.4% (P , .005), and 11.7% (P , .05), respectively. EDSS and MSFC demonstrated strongest correlations with MPF in GM (r = 20.74 and 0.81; P , .001) followed by WM (r = 20.57 and 0.72; P , .01) and lesions (r = 20.42 and 0.50; P , .05). R1 and MT ratio in all tissues were significantly less correlated with clinical scores than GM MPF (P , .05). Conclusion:MPF mapping enables quantitative assessment of demyelination in normal-appearing brain tissues and shows primary clinical relevance of GM damage in MS. MPF outperforms MT ratio and R1 in detection of MS-related tissue changes.q RSNA, 2014

Background and Purpose Fast macromolecular proton fraction (MPF) mapping is a recent quantitative MRI method for myelin assessment. The objectives of this study were to evaluate MPF as a measure demyelination in subcortical gray matter (GM) structures in multiple sclerosis (MS) and asses a potential relationship between demyelination and excess iron deposition using MPF and T2* mapping. Materials and Methods MPF and T2* maps were obtained from 12 healthy controls, 18 relapsing-remitting MS (RRMS), and 12 secondary-progressive MS (SPMS) patients using 3T MRI. Parameter values in the caudate nucleus, globus pallidus, putamen, substantia nigra, and thalamus were compared between groups and correlated to clinical data. RESULTS: MPF in all subcortical structures and T2* in the globus pallidus, putamen, and caudate nucleus demonstrated a significant monotonic decrease from controls to RRMS and from RRMS to SPMS. MPF in all subcortical structures significantly correlated with Expanded Disability Status Scale and MS Functional Composite scores with absolute Pearson correlation coefficient (r) values in a range 0.4-0.6. Significant correlations (r=-0.4--0.6) were also identified between MPF and the 9-hole peg test indicating a potential relationship with nigrostriatal pathway damage. Among T2* values, weak significant correlations with clinical variables were found only in the putamen. MPF did not correlate with T2* in any of the studied anatomic structures. Conclusions MPF provides an iron-insensitive measure of demyelination. Myelin loss in subcortical GM structures in MS is unrelated to excess iron deposition. Subcortical GM demyelination is more closely associated with the disease phenotype and disability than iron overload.

Study Design Systematic review. Clinical Questions (1) When used as an assistive device, do wearable exoskeletons improve lower extremity function or gait compared with knee-ankle-foot orthoses (KAFOs) in patients with complete or incomplete spinal cord injury? (2) When used as a rehabilitation device, do wearable exoskeletons improve lower extremity function or gait compared with other rehabilitation strategies in patients with complete or incomplete spinal cord injury? (3) When used as an assistive or rehabilitation device, are wearable exoskeletons safe compared with KAFO for assistance or other rehabilitation strategies for rehabilitation in patients with complete or incomplete spinal cord injury? Methods PubMed, Cochrane, and Embase databases and reference lists of key articles were searched from database inception to May 2, 2016, to identify studies evaluating the effectiveness of wearable exoskeletons used as assistive or rehabilitative devices in patients with incomplete or complete spinal cord injury. Results No comparison studies were found evaluating exoskeletons as an assistive device. Nine comparison studies (11 publications) evaluated the use of exoskeletons as a rehabilitative device. The 10-meter walk test velocity and Spinal Cord Independence Measure scores showed no difference in change from baseline among patients undergoing exoskeleton training compared with various comparator therapies. The remaining primary outcome measures of 6-minute walk test distance and Walking Index for Spinal Cord Injury I and II and Functional Independence Measure–Locomotor scores showed mixed results, with some studies indicating no difference in change from baseline between exoskeleton training and comparator therapies, some indicating benefit of exoskeleton over comparator therapies, and some indicating benefit of comparator therapies over exoskeleton. Conclusion There is no data to compare locomotion assistance with exoskeleton versus conventional KAFOs. There is no consistent benefit from rehabilitation using an exoskeleton versus a variety of conventional methods in patients with chronic spinal cord injury. Trials comparing later-generation exoskeletons are needed.

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Based on the MCID for 6MW, the use of dalfampridine ER 10 mg BID but not 5 mg BID was associated with statistically significant and clinically meaningful improvements in walking relative to placebo. The correlation between improvement on MSWS-12 and the 20% increase in 6MW distance suggests that an improvement on MSWS-12 is clinically relevant. These results, although highlighting a lack of efficacy of dalfampridine ER 5 mg BID, suggest that the 10-mg BID dose is effective for improving walking speed, as observed on short timed-walk tests, and for increasing distance walked over longer timed-walk periods. ClinicalTrials.gov identifier: NCT01328379.