Severity of white matter microstructural damage in a Brazilian relapsing-remitting multiple sclerosis cohort: A possible window to optimize treatment.

BACKGROUND: Multiple sclerosis (MS) is an important cause of acquired neurological disability in young adults, characterized by multicentric inflammation, demyelination, and axonal damage. OBJECTIVE: The objective is to investigate white matter (WM) damage progression in a Brazilian MS patient cohort, using diffusion tensor imaging (DTI) post-processed by tract-based spatial statistics (TBSS). METHODS: DTI scans were acquired from 76 MS patients and 37 sex-and-age matched controls. Patients were divided into three groups based on disease duration. DTI was performed along 30 non-collinear directions by using a 1.5T imager. For TBSS analysis, the WM skeleton was created, and a 5000 permutation-based inference with a threshold of p < .05 was used, to enable the identification of abnormalities in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). RESULTS: Decreased FA and increased RD, MD, and AD were seen in patients compared to controls and a decreased FA and increased MD and RD were seen, predominantly after the first 5 years of disease, when compared between groups. CONCLUSION: Progressive WM deterioration is seen over time with a more prominent pattern after 5 years of disease onset, providing evidence that the early years might be a window to optimize treatment and prevent disability.

Default-mode network and deep gray-matter analysis in neuromyelitis optica patients.

OBJECTIVE: The aim of our study was to detect functional changes in default-mode network of neuromyelitis optica (NMO) patients using resting-state functional magnetic resonance images and the evaluation of subcortical gray-matter structures volumes. MATERIALS AND METHODS: NMO patients (n=28) and controls patients (n=19) were enrolled. We used the integrated registration and segmentation tool, part of FMRIB's Software Library (FSL) to segment subcortical structures including the thalamus, caudate nucleus, putamen, hippocampus and amygdalae. Resting-state functional magnetic resonance images were post-processed using the Multivariate Exploratory Linear Optimized Decomposition into Independent Components, also part of FSL. Average Z-values extracted from the default-mode network were compared between patients and controls using t-tests (P values <0.05 were considered statistically significant). RESULTS: There were areas of increased synchronization in the default-mode network of patients compared to controls, notably in the precuneus and right hippocampus (corrected P<0.01). The frontal area had decreased synchronization in patients compared to controls (corrected P<0.01). There were no observed differences between patients and controls in subcortical volumes or average Z-values values for default-mode network. CONCLUSION: The hyperactivity of certain default-mode network areas may reflect cortical compensation for subtle structural damage in NMO patients.

Sex-specific extent and severity of white matter damage in multiple sclerosis: implications for cognitive decline.

Cognitive dysfunction is common in multiple sclerosis (MS). However, the relationship between white matter (WM) damage and cognition remains insufficiently clear. This study investigates the extent and severity of WM diffusion abnormalities in MS patients and relations with cognition. Diffusion tensor imaging scans were obtained in 131 MS patients (88 women, 6 years postdiagnosis) and 49 age-matched controls (29 women). Patient groups were equal in terms of disease duration, disability, and WM lesion volume. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Post hoc analyses calculated the spatial extent and severity of diffusion abnormalities to relate these to cognitive performance. In controls, 31% of WM voxels showed higher FA in men; therefore, all patient analyses were within-sex. The extent of diffusion changes was higher in male patients than in female patients for all parameters (FA: 24% in women, 53% in men), as was the severity of changes (FA: Z = -0.18 in women, Z = -0.41 in men). Especially the extent of FA abnormalities was strongly related to cognitive performance in all patients (r = -0.42, P < 0.0001). Regionally, thalamic decreases in FA were especially correlated with cognitive performance. Cognitively impaired patients showed greater extent and severity on all diffusion parameters compared to cognitively preserved patients. The WM of male patients was both more extensively and also more severely affected than that of female patients. The extent of WM FA changes, especially in the thalamus, was associated with cognitive performance in this cohort of early MS patients.

Diffusion-weighted imaging and demyelinating diseases: new aspects of an old advanced sequence.

OBJECTIVE: The purpose of this article is to discuss classic applications in diffusion-weighted imaging (DWI) in demyelinating disease and progression of DWI in the near future. CONCLUSION: DWI is an advanced technique used in the follow-up of demyelinating disease patients, focusing on the diagnosis of a new lesion before contrast enhancement. With technical advances, diffusion-tensor imaging; new postprocessing techniques, such as tract-based spatial statistics; new ways of calculating diffusion, such as kurtosis; and new applications for DWI and its spectrum are about to arise.

Subcortical atrophy and cognition: sex effects in multiple sclerosis.

OBJECTIVES: Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS. METHODS: Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains. Stepwise linear regression was used to predict average cognition in the patient group. RESULTS: Most deep GM volumes were reduced in patients, with larger effects on average in men (-11%) than in women (-6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R(2) = 0.31), while lesion volume was not a significant predictor in the model. CONCLUSIONS: Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS.

The role of demyelination in neuromyelitis optica damage: diffusion-tensor MR imaging study.

PURPOSE: To test the hypothesis that white matter damage in neuromyelitis optica (NMO) is more extensive than previously described and likely includes involvement of normal-appearing white matter and to explore by using diffusion-tensor (DT) imaging whether white matter lesions are not only related to wallerian degeneration but are also caused by demyelination. MATERIALS AND METHODS: Seventeen patients with NMO (mean age, 45 years; 14 women) were compared with 17 sex- and age-matched control subjects. The institutional review board approved the study, and all subjects gave written informed consent. In addition to conventional magnetic resonance imaging sequences, DT imaging was performed along 30 noncollinear directions by using a 1.5-T imager. For tract-based spatial statistics (TBSS) analysis, the white matter skeleton was created, and a permutation-based inference with 5000 permutations with a threshold of P less than .05 to enable the identification of abnormalities in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) was used. Partial correlation was applied to identify whether the number of clinical relapses and disease duration were correlated with all TBSS parameters. RESULTS: TBSS showed multiple areas with significant FA decrease in patients with NMO, mainly located in the corona radiata, uncinate fasciculus, corpus callosum, optic radiation, internal and external capsules, and cerebral peduncles. The mean FA, RD, and AD in the abnormal voxels located on the corpus callosum were, respectively, 0.69 ± 0.03 (standard deviation), 0.39 × 10(23) mm(2)/sec ± 0.04, and 1.53 × 10(23) mm(2)/sec ± 0.04 in patients with NMO compared with 0.75 ± 0.02, 0.33 × 10(23) mm(2)/sec ± 0.03, and 1.57 × 10(23) mm(2)/sec ± 0.04 in control subjects (P < .0001, P < .0001, and P = .007, respectively). There was a highly significant inverse correlation between FA and RD (r = 20.976, P < .0001). CONCLUSION: The use of TBSS allowed the identification of extensive white matter damage in patients with NMO. Multiple white matter tracts were involved, including the pyramidal tract, optic radiation, and corpus callosum, likely related to both demyelination and wallerian degeneration.

Diffusion imaging in traumatic brain injury.

Traumatic brain injury is a common cause of death worldwide, affecting mostly young people. The most feasible examination to be performed in the emergency room is computed tomography. Magnetic resonance (MR) imaging is becoming a significant tool in the evaluation of severe brain trauma. Diffusion-weighted imaging is an advanced MR imaging sequence that has been used to detect areas of ischemia and tumor malignancy. This article describes the recent advances in trauma based on diffusion-weighted MR imaging findings and in brain injury from head trauma based on diffusion-weighted MR imaging and diffusion tensor MR imaging findings. Current and potential clinical applications are discussed.