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Mult Scler ; : 1352458519865739, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31339446


BACKGROUND: Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas, and they present the advantage of being extracted from previously acquired clinical magnetic resonance imaging (MRI) scans. SCNs have shown pathophysiological changes in many brain disorders, including multiple sclerosis. OBJECTIVE: To investigate alterations of SCNs at the individual level in patients with clinically isolated syndrome (CIS), thereby assessing their clinical relevance. METHODS: We analyzed baseline data collected in a prospective multicenter (MAGNIMS) study. CIS patients (n = 60) and healthy controls (n = 38) underwent high-resolution 3T MRI. Measures of disability and cognitive processing were obtained for patients. Single-subject SCNs were extracted from brain 3D-T1 weighted sequences; global and local network parameters were computed. RESULTS: Compared to healthy controls, CIS patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections. These disruptions were worse for patients with higher lesion load and worse cognitive processing speed. Alterations of centrality measures and clustering of connections were observed in specific cortical areas in CIS patients when compared with healthy controls. CONCLUSION: Our study indicates that SCNs can be used to demonstrate clinically relevant alterations of connectivity in CIS.

Mult Scler ; : 1352458519845105, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31074686


BACKGROUND: The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated. OBJECTIVE: To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols. METHODS: Nineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients. RESULTS: Patients had lower mean nodal strength ( p = 0.003) and greater network modularity than controls ( p = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load ( p = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones. CONCLUSION: Connectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.

Mult Scler ; : 1352458519851247, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31138052


Fatigue is very common in multiple sclerosis (MS) and is often considered as its most disabling symptom. Over the last 20 years, an increasing number of studies have evaluated the pathogenetic bases of MS-related fatigue. Converging evidence from neurophysiology and neuroimaging research suggests that a dysfunction in a cortico-subcortical pathway, centered on thalamus, is involved in the pathogenesis of fatigue. However, type and significance of such dysfunction remain unknown, and some studies reported an increase in the activity and connectivity within the thalamic network, whereas others suggested its reduction. Hereby, we review the results of neuroimaging studies supporting the different hypotheses about the role of thalamic network in the pathophysiology of MS-related fatigue and discuss limitations and shortcomings of available data, highlighting the key challenges in the field and the directions for future research.

Mult Scler ; : 1352458517751647, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29327668


BACKGROUND: Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome suggestive of multiple sclerosis remains uncertain. OBJECTIVES: The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis. METHODS: We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3-6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010). RESULTS: In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T ( p = 0.005). For patients, this was 4.18 and 4.40, respectively ( p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters. CONCLUSION: Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training.

Eur Neurol ; 71(5-6): 233-41, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24480868


OBJECTIVES: To investigate whether clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) who required a reduction of administration frequency of interferon-beta (IFNB) were similar to those of patients who did not. METHODS: We identified three subgroups of patients under treatment for 24 months with subcutaneous (sc) high-frequency IFNB-1a or -1b: those continuing to receive IFNB according to the drug label (recommended frequency group), those reducing the administration frequency of sc IFNB-1a or -1b (reduced frequency group), and those switched to once weekly intramuscular (im) IFNB (switched group). All patients were followed for further 24 months. The occurrence of relapse, MRI activity and disability worsening were considered as outcome measures. RESULTS: We identified 308 patients, 201 in the recommended frequency group, 70 in the reduced frequency group, and 37 in the switched group. Patients in the reduced frequency group had increased risk for relapses (HR = 1.95, p < 0.001) and MRI activity (HR = 1.41, p < 0.001), while patients in the switched group had increased risk for relapses (HR = 1.67, p = 0.012), but not for MRI activity (HR = 1.26, p = 0.08) than those in the recommended frequency group. Predictors for disease activity re-start after the reduction of IFNB administration frequency were younger age, higher pre-IFNB relapse rate, and reducing sc IFNB frequency to twice weekly rather than switching to im IFNB-1a once weekly. CONCLUSION: Our findings discourage the reduction of sc IFNB administration frequency, especially in younger patients with a higher pre-IFNB relapse rate. However, switching to im IFNB-1a may be considered in some selected cases.

Fatores Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Injeções Intramusculares , Injeções Subcutâneas , Interferon beta-1a , Interferon beta-1b , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Roma , Sensibilidade e Especificidade , Resultado do Tratamento