Introduction Despite the increased availability of disease-modifying therapies (DMTs) for treating relapsing-remitting multiple sclerosis (RR-MS), only a few studies have evaluated DMT-associated brain functional changes. Methods We investigated whether significant resting-state functional connectivity (FC) changes occurred in RR-MS patients after 6 and 12 months of dimethyl fumarate (DMF) treatment using both a seed-based and data-driven approach. Results Thirty patients were followed up after 6 months of therapy, and 27 of them reached a 12-month follow-up. Three patients at baseline and only one after 12 months showed gadolinium-enhancing lesions. We did not find any significant FC changes after therapy at either time point. After 12 months of DMF, we observed relatively modest brain volume loss and a significant improvement in Paced Auditory Serial Addition Test 3 s and 25-Foot Walk Test scores. Conclusion The absence of FC changes could be due to the low degree of baseline inflammation in our patients, though we cannot exclude that more time may be required to observe such changes. No FC changes may reflect a beneficial effect of DMF therapy, as supported by conventional MRI findings and clinical improvement.

To evaluate gray matter (GM) and white matter (WM) abnormalities and their clinical correlates in patients with progressive supranuclear palsy (PSP). Sixteen PSP patients and sixteen age-matched healthy subjects underwent a clinical evaluation and multimodal magnetic resonance imaging, including three-dimensional T1-weighted imaging and diffusion tensor imaging (DTI). Volumetric and DTI analyses were computed using SPM and FSL tools. PSP patients showed GM volume decrease, involving the frontal cortex, putamen, pallidum, thalamus and accumbens nucleus, cerebellum, and brainstem. Additionally, they had widespread changes in WM bundles, mainly affecting cerebellar peduncles, thalamic radiations, corticospinal tracts, corpus callosum, and longitudinal fasciculi. GM volumes did not correlate with WM abnormalities. DTI indices of WM damage, but not GM volumes, correlated with clinical scores of disease severity and cognitive impairment. The neurodegenerative changes that occur in PSP involve both GM and WM structures and develop concurrently though independently. WM damage in PSP correlates with clinical scores of disease severity and cognitive impairment, thus providing further insight into the pathophysiology of the disease.

BACKGROUND AND PURPOSE: Studies on functional connectivity in progressive supranuclear palsy have been restricted to the thalamus and midbrain tegmentum. The present study aims to evaluate functional connectivity abnormalities of the subcortical structures in these patients. Functional connectivity will be correlated with motor and nonmotor symptoms of the disease.MATERIALS AND METHODS: Nineteen patients with progressive supranuclear palsy (mean age, 70.93 +/- 5.19 years) and 12 age-matched healthy subjects (mean age, 69.17 +/- 5.20 years) underwent multimodal MR imaging, including fMRI at rest, 3D Ti-weighted imaging, and DTI. fMRI data were processed with fMRI of the Brain Software Library tools by using the dorsal midbrain tegmentum, thalamus, caudate nucleus, putamen, and pallidum as seed regions.RESULTS: Patients had lower functional connectivity than healthy subjects in all 5 resting-state networks, mainly involving the basal ganglia, thalamus, anterior cingulate, dorsolateral prefrontal and temporo-occipital cortices, supramarginal gyrus, supplementary motor area, and cerebellum. Compared with healthy subjects, patients also displayed subcortical atrophy and DTI abnormalities. Decreased thalamic functional connectivity correlated with clinical scores, as assessed by the Hoehn and Yahr Scale and by the bulbar and mentation subitems of the Progressive Supranuclear Palsy Rating Scale. Decreased pallidum functional connectivity correlated with lower Mini-Mental State Examination scores; decreased functional connectivity in the dorsal midbrain tegmentum network correlated with lower scores in the Frontal Assessment Battery.CONCLUSIONS: The present study demonstrates a widespread disruption of cortical-subcortical connectivity in progressive supranuclear palsy and provides further insight into the pathophysiologic mechanisms of motor and cognitive impairment in this condition.

Multiple sclerosis (MS) is a chronic disorder of the central nervous system, pathologically characterized by inflammation, demyelination, and neurodegeneration. In past years, there has been increasing attention paid to its ischemic-vascular aspects because abnormalities in CBF and CBV have been

OPINION article Front. Neurol., 04 March 2015Sec. Multiple Sclerosis and Neuroimmunology Volume 6 - 2015 | https://doi.org/10.3389/fneur.2015.00040

Summary Natalizumab, an anti-alpha4 integrin monoclonal antibody inhibiting the adhesion of lymphocytes to the endothelium, is a widely accepted drug treatment for relapsing–remitting multiple sclerosis (RRMS). A peripheral increase of T and B lymphocytes has already been observed as an early treatment effect. This retrospective observational study was aimed to evaluate the peripheral lymphocyte subsets during a long-term treatment follow-up. We included 23 RRMS patients treated with natalizumab for at least 24–48 months who had pretreatment lymphocyte evaluation. Baseline values of lymphocyte subsets and CD4/CD8 ratio did not differ significantly from the 23 matched healthy subjects. The periodic (every 3–6 months) assessment of immune cell subsets was performed by flow cytometry on peripheral blood collected before drug injection. Therapy with natalizumab was confirmed to be effective during the observational period. For all patients, the increase in lymphocytes during natalizumab therapy compared to baseline at every assessment was significantly higher compared to that of overall white blood cells (2·1- and 1·3-fold, respectively, P < 0·0001). Both T cell subsets were proportionally modified and the CD4/CD8 ratio did not change significantly, while B cells increased significantly compared to T and NK cells (3·2-, 1·88- and 1·92-fold, respectively, P < 0·0001). These changes remained constant throughout the 25–48-month period of therapy. In conclusion, effective natalizumab treatment of RRMS patients was associated with the persistence of its biological effects through a stable increase of peripheral lymphocytes, mainly B cells, and an unchanged proportion of T cell subsets in long-term follow-up.

BACKGROUND AND PURPOSE: Psychiatric symptoms occur in approximately 30% of patients with MS. Such symptoms include OCD, which may interfere heavily with the patient’s daily life. We hypothesized that the widespread involvement of both GM and WM, which characterizes MS, may be responsible for the occurrence of OCD when specific brain structures are affected. The aim of this study was to evaluate the relationship between GM and WM tissue damage and OCD in patients with MS. MATERIALS AND METHODS: We evaluated 16 patients with relapsing-remitting MS who had been diagnosed with OCD on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and 15 age- and sex-matched patients with relapsing-remitting MS with no psychiatric disorders as a CG. The MR study (1.5T) included 3D T1-weighted fast-field echo sequences, DTI (32 directions), and conventional MRI. Images were processed using SPM5, FSL, and Jim 5.0 software to evaluate VBM, TBSS, and global and regional LV, respectively. RESULTS: The VBM analysis revealed a set of clusters of reduced GM volume in the OCD group, compared with the CG, located in the right inferior and middle temporal gyri and in the inferior frontal gyrus. TBSS did not detect any differences in the FA values between the 2 groups; global and regional LV values also did not differ significantly between the 2 groups. CONCLUSIONS: Our study suggests that OCD in MS may be caused by damage in the right frontotemporal cortex.