Dataset Information

Intrinsic functional plasticity of the sensorimotor network in relapsing-remitting multiple sclerosis: evidence from a centrality analysis.

ABSTRACT:

Background and purpose

Advanced MRI studies have revealed regional alterations in the sensorimotor cortex of patients with relapsing-remitting multiple sclerosis (RRMS). However, the organizational features underlying the relapsing phase and the subsequent remitting phase have not been directly shown at the functional network or the connectome level. Therefore, this study aimed to characterize MS-related centrality disturbances of the sensorimotor network (SMN) and to assess network integrity and connectedness.

Methods

Thirty-four patients with clinically definite RRMS and well-matched healthy controls participated in the study. Twenty-three patients in the remitting phase underwent one resting-state functional MRI, and 11 patients in the relapsing-remitting phase underwent two different MRIs. We measured voxel-wise centrality metrics to determine direct (degree centrality, DC) and global (eigenvector centrality, EC) functional relationships across the entire SMN.

Results

In the relapsing phase, DC was significantly decreased in the bilateral primary motor and somatosensory cortex (M1/S1), left dorsal premotor (PMd), and operculum-integrated regions. However, DC was increased in the peripheral SMN areas. The decrease in DC in the bilateral M1/S1 was associated with the expanded disability status scale (EDSS) and total white matter lesion loads (TWMLLs), suggesting that this adaptive response is related to the extent of brain damage in the rapid-onset attack stage. During the remission process, these alterations in centrality were restored in the bilateral M1/S1 and peripheral SMN areas. In the remitting phase, DC was reduced in the premotor, supplementary motor, and operculum-integrated regions, reflecting an adaptive response due to brain atrophy. However, DC was enhanced in the right M1 and left parietal-integrated regions, indicating chronic reorganization. In both the relapsing and remitting phases, the changes in EC and DC were similar.

Conclusions

The alterations in centrality within the SMN indicate rapid plasticity and chronic reorganization with a biased impairment of specific functional areas in RRMS patients.

SUBMITTER: Zhuang Y

PROVIDER: S-EPMC4482320 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Intrinsic functional plasticity of the sensorimotor network in relapsing-remitting multiple sclerosis: evidence from a centrality analysis.

Zhuang Ying Y Zhou Fuqing F Gong Honghan H

PloS one 20150625 6

<h4>Background and purpose</h4>Advanced MRI studies have revealed regional alterations in the sensorimotor cortex of patients with relapsing-remitting multiple sclerosis (RRMS). However, the organizational features underlying the relapsing phase and the subsequent remitting phase have not been directly shown at the functional network or the connectome level. Therefore, this study aimed to characterize MS-related centrality disturbances of the sensorimotor network (SMN) and to assess network inte ...[more]

PMID: 26110420

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Project description:Alemtuzumab (previously known as Campath(®)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. Here we explore evidence for its efficacy and safety in relapsing-remitting multiple sclerosis. One Phase II and two Phase III trials of alemtuzumab versus active comparator (interferon beta-1a) have been reported. Two of these rater-blinded randomized studies assessed clinical and radiological outcomes in treatment-naïve patients; one explored patients who had relapsed despite first-line therapy. Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%-74% (P < 0.0001), and in two studies it reduced the risk of sustained disability accumulation by 42%-71% (P < 0.01). In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1), there was no significant difference compared to interferon, perhaps reflecting the surprisingly low frequency of disability events in the comparator group. After alemtuzumab, the Expanded Disability Status Scale score improved by 0.14-1.2 points, culminating in a net advantage with alemtuzumab of 0.41-0.77 points over interferon in the CAMMS223 and CARE-MS2 trials (both P < 0.001). Radiological markers of new lesion formation and brain atrophy following alemtuzumab were significantly improved when compared to interferon in all studies. Adverse events were more common following alemtuzumab than interferon beta-1a (7.2-8.66 versus 4.9-5.7 events per person-year). While infusion reactions are the most common, autoimmunity is the most concerning; within Phase III studies, thyroid disorders (17%-18% versus 5%-6%) and immune thrombocytopenic purpura (1% versus 0%) were reported in patients taking alemtuzumab and interferon beta-1a, respectively. All patients responded to conventional therapy. One patient taking alemtuzumab in the Phase II study suffered a fatal intracranial hemorrhage following immune thrombocytopenic purpura, heralding assiduous monitoring of all patients thereafter. Alemtuzumab has been submitted for licensing in relapsing-remitting multiple sclerosis in the United States and Europe.

Dataset Information

Intrinsic functional plasticity of the sensorimotor network in relapsing-remitting multiple sclerosis: evidence from a centrality analysis.

Background and purpose

Methods

Results

Conclusions

Publications

Intrinsic functional plasticity of the sensorimotor network in relapsing-remitting multiple sclerosis: evidence from a centrality analysis.

Similar Datasets

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