RESUMEN
Objective: To investigate the rich-club organization in clinically isolated syndrome (CIS) and multiple sclerosis (MS), and to characterize its relationships with physical disabilities and cognitive impairments. Methods: We constructed high-resolution white matter (WM) structural networks in 41 CIS, 32 MS and 35 healthy controls (HCs) using diffusion MRI and deterministic tractography. Group differences in rich-club organization, global and local network metrics were investigated. The relationship between the altered network metrics, brain lesions and clinical variables including EDSS, MMSE, PASAT, disease duration were calculated. Additionally, reproducibility analysis was performed using different parcellation schemes. Results: Compared with HCs, MS patients exhibited a decreased strength in all types of connections (rich-club: pâ¯<â¯0.0001; feeder: pâ¯=â¯0.0004; and local: pâ¯=â¯0.0026). CIS patients showed intermediate values between MS patients and HCs and exhibited a decreased strength in feeder and local connections (feeder: pâ¯=â¯0.019; and local: pâ¯=â¯0.031) but not in rich-club connections. Compared with CIS patients, MS patients showed significant reductions in rich-club connections (pâ¯=â¯0.0004). The reduced strength of rich-club and feeder connections was correlated with cognitive impairments in the MS group. These results were independent of lesion distribution and reproducible across different brain parcellation schemes. Conclusion: The rich-club organization was disrupted in MS patients and relatively preserved in CIS. The disrupted rich-club connectivity was correlated with cognitive impairment in MS. These findings suggest that impaired rich-club connectivity is an essential feature of progressive structural network disruption, heralding the development of clinical disability in MS.
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Encéfalo/diagnóstico por imagen , Enfermedades Desmielinizantes/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Adulto JovenRESUMEN
Background: Diffusion Tensor Imaging (DTI) can evaluate microstructural tissue damage in the optic radiation (OR) of patients with clinically isolated syndrome (CIS), early relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders (NMOSD). Different post-processing techniques, e.g. tract-based spatial statistics (TBSS) and probabilistic tractography, exist to quantify this damage. Objective: To evaluate the capacity of TBSS-based atlas region-of-interest (ROI) combination with 1) posterior thalamic radiation ROIs from the Johns Hopkins University atlas (JHU-TBSS), 2) Juelich Probabilistic ROIs (JUEL-TBSS) and tractography methods using 3) ConTrack (CON-PROB) and 4) constrained spherical deconvolution tractography (CSD-PROB) to detect OR damage in patients with a) NMOSD with prior ON (NMOSD-ON), b) CIS and early RRMS patients with ON (CIS/RRMS-ON) and c) CIS and early RRMS patients without prior ON (CIS/RRMS-NON) against healthy controls (HCs). Methods: Twenty-three NMOSD-ON, 18 CIS/RRMS-ON, 21 CIS/RRMS-NON, and 26 HCs underwent 3â¯T MRI. DTI data analysis was carried out using JUEL-TBSS, JHU-TBSS, CON-PROB and CSD-PROB. Optical coherence tomography (OCT) and visual acuity testing was performed in the majority of patients and HCs. Results: Absolute OR fractional anisotropy (FA) values differed between all methods but showed good correlation and agreement in Bland-Altman analysis. OR FA values between NMOSD and HC differed throughout the methodologies (p-values ranging from pâ¯<â¯0.0001 to 0.0043). ROC-analysis and effect size estimation revealed higher AUCs and R2 for CSD-PROB (AUCâ¯=â¯0.812; R2â¯=â¯0.282) and JHU-TBSS (AUCâ¯=â¯0.756; R2â¯=â¯0.262), compared to CON-PROB (AUCâ¯=â¯0.742; R2â¯=â¯0.179) and JUEL-TBSS (AUCâ¯=â¯0.719; R2â¯=â¯0.161). Differences between CIS/RRMS-NON and HC were only observable in CSD-PROB (AUCâ¯=â¯0.796; R2â¯=â¯0.094). No significant differences between CIS/RRMS-ON and HC were detected by any of the methods. Conclusions: All DTI post-processing techniques facilitated the detection of OR damage in patient groups with severe microstructural OR degradation. The comparison of distinct disease groups by use of different methods may lead to different - either false-positive or false-negative - results. Since different DTI post-processing approaches seem to provide complementary information on OR damage, application of distinct methods may depend on the relevant research question.
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Enfermedades Desmielinizantes/patología , Cápsula Interna/patología , Esclerosis Múltiple Recurrente-Remitente/patología , Neuromielitis Óptica/patología , Sustancia Blanca/patología , Adulto , Anisotropía , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Cápsula Interna/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Neuromielitis Óptica/fisiopatología , Sustancia Blanca/fisiopatologíaRESUMEN
DTI studies in multiple sclerosis (MS) reveal white matter (WM) injury that occurs with disease progression. In the present study we aimed to elucidate the relationship of microstructural WM damage in patients with varying periods of disease duration. DTI scans were acquired from 90 MS patients and 25 healthy controls. Patients were grouped to short (<1 year), moderate (1 up to 6 years) and long (6-10 years) disease duration periods. Statistical analyses of the fractional anisotropy (FA) data were performed using tract-based spatial statistics (TBSS). Whole-brain skeletal FA measurements showed a significant decrease between healthy controls and the short MS disease duration group, as well as between moderate disease duration and long disease duration groups, but failed to show a significant difference between short and moderate disease duration groups. Voxelwise analysis revealed clusters of diffuse FA reductions in 40 WM tracts when comparing healthy controls and MS short disease duration group, with the point of maximal significant difference located in the left inferior longitudinal fasciculus. Comparing short with long disease duration groups, progressive FA reduction was demonstrated across 30 WM tracts, with the point of maximal significant difference migrating to the body of the corpus callosum. A non-linear pattern of WM microstructure disruption occurs in RRMS. Alterations are seen early in the disease course within 1 year from onset, reach a plateau within the next 5 years, and only later additional WM changes are detected. An important period of a possible therapeutic window therefore exists within the early disease stage.
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Imagen de Difusión Tensora/métodos , Progresión de la Enfermedad , Esclerosis Múltiple Recurrente-Remitente/patología , Sustancia Blanca/patología , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: White matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple sclerosis (MS) and in virtually each individual patient. To find a new sensitive and robust marker for WMA we investigated the relationship between cortical surface area, white matter volume (WMV), and whole-brain-surface-averaged rectified cortical extrinsic curvature. Based on geometrical considerations we hypothesized that cortical curvature increases if WMV decreases and the cortical surface area remains constant. METHODS: In total, 95 participants were enrolled: 30 patients with early and advanced relapsing-remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's disease (AD) and 5 patients with clinically isolated syndrome (CIS). RESULTS: 29/30 MS and 5/5 CIS patients showed lower WMV than expected from their intracranial volume (average reduction 13.0%, P < 10(- 10)), while the cortical surface area showed no significant differences compared with controls. The estimated WMV reductions were correlated with an increase in cortical curvature (R = 0.62, P = 0.000001). Discriminant analysis revealed that the curvature increase was highly specific for the MS and CIS groups (96.7% correct assignments between MS and control groups) and was significantly correlated with reduction of white matter fractional anisotropy, as determined by diffusion tensor imaging and the Expanded Disability Status Scale. As expected by the predominant gray and WM degeneration in AD, no systematic curvature increase was observed in AD. CONCLUSION: Whole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV-cortex disproportionality and allows us to assess "pure" WMA without being confounded by intracranial volume. WMA seems to be a characteristic symptom in early MS and can already occur in patients with CIS and should thus be considered in future MS research and clinical studies.