Ocrelizumab reduces cortical and deep grey matter loss compared to the S1P-receptor modulator in multiple sclerosis

Introduction: Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. Aim: To compare the effect of OCR and FGL on clinical and MRI endpoints. Methods: 95 relapsing-remitting patients (57 OCR, 38 FGL) clinically followed for 36 months underwent a 3-Tesla MRI at baseline and after 24 months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. Results: OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (- 0.12% vs - 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (- 0.45% vs - 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65-0.71), frontal gyrus (d-range = 0.47-0.60), cingulate (d-range = 0.41-0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. Conclusions: When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss

Artery of Percheron stroke from carotid lesion

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Potential neuroprotective effect of Fingolimod in multiple sclerosis and its association with clinical variables

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system affecting both white matter and grey matter in the earliest phases of its course. The crucial role of neurodegeneration in disability progression in MS, regardless of white matter damage, has been confirmed by several imaging and neuropathological studies. Fingolimod is an effective immunomodulator of the sphingosine 1-phosphate receptor, approved in relapsing remitting MS and able to cross the blood-brain barrier and to slow disability progression and brain volume loss. However, it remains unclear whether this neuroprotective action is due to a peripheral anti-inflammatory effect and/or to a direct effect on neuronal cells. Areas covered: In this review, the authors summarize the published preclinical and clinical studies on the effect of Fingolimod in limiting the focal and diffuse grey matter damage in MS. Expert opinion: Fingolimod might have a significant neuroprotective effect on relapsing remitting MS based on its modulatory effect on oligodendroglial cells and astrocytes, and on its direct effect on cortical neurons. Future clinical studies including measures of grey matter damage are required to confirm in vivo such neuroprotective effect

Dimethyl fumarate: A possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events

INTRODUCTION: Among disease-modifying treatments for multiple sclerosis, natalizumab (NTZ) is highly effective, well tolerated and generally safe. Major concerns regard the risk of developing progressive multifocal leukoencephalopathy (PML), and the occurrence of rebounds or disease activity after its discontinuation. The aim of this study was to explore the efficacy of dimethyl fumarate (DMF) in preventing disease reactivation after NTZ discontinuation. METHODS: Thirty-nine patients with relapsing remitting multiple sclerosis, at high risk of PML, were switched from NTZ to DMF and underwent neurological and 3T MRI monitoring for 2 years. Clinical and MRI data regarding the 2-year period preceding NTZ treatment, the 2 years of NTZ treatment and the 2 years of DMF were collected. RESULTS: During the DMF phase, among the 39 patients, one or more relapses occurred in five patients (12.8%), increased disability progression in 4 (10.3%) and MRI activity in 8 (20.5%). Post-NTZ rebound effect was observed only in one patient. Overall, only two dropouts (one rebound activity and one gastrointestinal side effect) were registered and almost 80% of the patients have still no evidence of disease activity at the end of DMF treatment. The multiple linear regression model revealed that the number of relapses and MRI parameters before DMF treatment were good predictors of disease activity during treatment with DMF. DISCUSSION: DMF appeared generally safe and no carryover PML among investigated cases was observed. Although DMF did not eliminate the possibility of disease reactivation, it seems anyway a promising drug for those patients who shall discontinue NTZ. The clinical and radiological activity preceding the DMF treatment might be used as a prognostic marker of therapy response

The effect of fingolimod on focal and diffuse grey matter damage in active MS patients

INTRODUCTION: The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood. METHODS: In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. Each patient underwent a neurological examination every 6 months and a 3T MRI at the beginning of the treatment and after 24 months. The accumulation of new cortical lesions (CLs) and the progression of regional GM atrophy were compared between the two groups. RESULTS: At the end of the study (T24), the percentage of patients with new CLs (13.5 vs. 89%, p\u2009<\u20090.001) and the percentage of GM volume change was lower in the treated group (p\u2009<\u20090.001). The regional analysis revealed that the treated group had also less volume loss in thalamus, caudatus, globus pallidus, cingulate cortex, and hippocampus (p\u2009<\u20090.001), as well as in, cerebellum, superior frontal gyrus, and insular-long gyrus (p\u2009<\u20090.05). Patients with no evidence of disease activity were 60% in the treated group and 10% in the untreated group (p\u2009<\u20090.001). CONCLUSIONS: These results suggest a possible protective effect of fingolimod on focal and diffuse GM damage

Volume changes of thalamus, hippocampus and cerebellum are associated with specific CSF profile in MS

Background: The underlying pathogenesis of surface-in grey matter abnormalities in MS, demonstrated by both neuropathology and advanced MRI analyses, is under investigation and it might be related to CSF-mediated mechanism of inflammation and/or damage. Objective: To examine the link of CSF inflammatory profile with the damage of three regions early-involved in MS and bordering with CSF: thalamus, hippocampus and cerebellum. Methods: In this longitudinal, prospective study, we evaluated, in 109 relapsing-remitting MS patients, at diagnosis and after 2-year follow-up, the association between the baseline CSF level of 19 inflammatory mediators and the volume changes of thalamus, hippocampus, cerebellar cortex and control regions (globus pallidus, putamen). Results: The multivariable analysis showed that the CXCL13 and sCD163 CSF levels at baseline were independent predictors of thalamus (R2model=0.80 ; p &lt; 0.001) and hippocampus (R2model=0.47; p &lt; 0.001) volume change after 2-year follow-up. These molecules, plus CCL25, IFN-γ and fibrinogen, were independent predictors of the cerebellar cortex volume loss (R2model=0.60 ; p &lt; 0.001). No independent predictors of volume changes of the control regions were found. Conclusion: Our results indicate an association between the CSF inflammatory profile and grey matter volume loss of regions anatomically close to CSF boundaries, thus supporting the hypothesis of a surface-in GM damage in MS

Diffusion MRI and silver standard masks to improve CNN-based thalamus segmentation

thalamus segmentatio

Microstructural modulations in the hippocampus allow to characterizing relapsing-remitting versus primary progressive multiple sclerosis

Diffusion MRI for MS patients stratificatio

Unraveling the MRI-Based Microstructural Signatures Behind Primary Progressive and Relapsing-Remitting Multiple Sclerosis Phenotypes

The mechanisms driving primary progressive and relapsing-remitting multiple sclerosis (PPMS/RRMS) phenotypes are unknown. Magnetic resonance imaging (MRI) studies support the involvement of gray matter (GM) in the degeneration, highlighting its damage as an early feature of both phenotypes. However, the role of GM microstructure is unclear, calling for new methods for its decryption