Impaired cortical deactivation during hand movement in the relapsing phase of multiple sclerosis: a cross-sectional and longitudinal fMRI study
ABSTRACT Little is known about the cortical activation changes during clinical relapses in multiple sclerosis (MS).
To assess cross-sectional and longitudinal differences in functional magnetic resonance imaging (fMRI) cortical patterns between the relapsing and stable phases of MS.
We studied 32 patients with relapsing-remitting MS with mild disability: 19 within 48 h of symptom onset of a new relapse (G1) and 13 in the stable phase, relapse-free for at least 6 months (G2). All patients underwent fMRI twice, upon entry (time 1) and 30-50 days later (time 2), during right-hand movement.
No between-group differences were observed in age, disability or T2 lesion load. Between-group analysis showed a significant difference in the ipsilateral precentral gyrus (IPG) activation at time 1. Activity differences in the IPG expressed reduced deactivation in G1 compared with G2. Longitudinal changes in brain activity in the IPG were significantly greater in G1 than G2. G1 patients with a slow clinical recovery (n = 8) showed different activity at baseline and greater activity changes over time in the IPG than patients with a fast recovery (n = 11).
This study shows that the relapsing phase is associated with reduced brain deactivation in the IPG, which is more marked in patients with a slow clinical recovery. Increased cortical excitability associated with inflammation may determine functional modifications within the ipsilateral motor area.
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ABSTRACT: Examination of sensorimotor activation alone in multiple sclerosis (MS) patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation). Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients. 13 relapsing remitting-MS patients (RRMS), 18 secondary progressive-MS patients (SPMS) and 15 healthy controls (HC) underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV) from both T1- and T2-weighted images. Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HC<RRMS<SPMS). Significant deactivation of the ipsilateral cortical sensorimotor areas was reduced in both patient groups with respect to HC. Deactivation of posterior cortical areas belonging to the default mode network (DMN), was increased in RRMS, but not in SPMS, with respect to HC. The amount of activation in the contralateral sensorimotor cortex was significantly correlated with that of deactivation in the DMN in HC and RRMS, but not in SPMS. Both increased activation and decreased deactivation patterns correlated with LV. In RRMS patients, increased cortical activation was associated with increased deactivation of the posterior cortex suggesting a greater resting-state activity in the DMN, probably aimed at facilitating sensorimotor circuit engagement during task performance. In SPMS the coupling between increased sensorimotor activation/increased DMN deactivation was not observed suggesting disorganization between anticorrelated functional networks as a consequence of a higher level of disconnection.PLoS ONE 06/2013; 8(6):e65315. DOI:10.1371/journal.pone.0065315 · 3.53 Impact Factor
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ABSTRACT: Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered ("type A") or jagged-bordered ("type B") pattern. On sagittal FLAIR, the images were evaluated for presence of "Dawson's fingers." Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and "jagged-bordered" periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases.02/2014; 2014:986923. DOI:10.1155/2014/986923
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ABSTRACT: 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. 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. 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. The alterations in centrality within the SMN indicate rapid plasticity and chronic reorganization with a biased impairment of specific functional areas in RRMS patients.PLoS ONE 01/2015; 10(6):e0130524. DOI:10.1371/journal.pone.0130524 · 3.53 Impact Factor