No abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and simultaneous degeneration of upper and lower motor neurons. The pathological process associated to ALS, albeit more pronounced in the motor/premotor cortices and along the corticospinal tracts (CST), does not spare extra-motor brain gray (GM) and white (WM) matter structures. However, it remains unclear whether such extra-motor cerebral abnormalities occur with mildly disabling disease, and how irreversible tissue loss and intrinsic tissue damage are interrelated. To this end, we used an optimized version of voxel-based morphometry (VBM) analysis to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain from mildly disabled patients with ALS. A high-resolution T1-weighted 3D magnetization-prepared rapid acquisition gradient echo and a pulsed gradient spin-echo single shot echo-planar sequence of the brain were acquired from 25 mildly disabled patients with ALS and 18 matched healthy controls. An analysis of covariance was used to compare volumetry and diffusivity measurements between patients and controls. Compared with controls, ALS patients had significant clusters of locally reduced GM density (P < 0.001) in the right premotor cortex, left inferior frontal gyrus (IFG), and superior temporal gyrus (STG), bilaterally. In ALS patients contrasted to controls, we also found significant clusters of locally increased MD (P < 0.001) in the splenium of the corpus callosum and in the WM adjacent to the IFG, STG, and middle temporal gyrus (MTG) of the right hemisphere, and in the WM adjacent to the MTG and lingual gyrus in the left hemisphere. Compared with controls, ALS patients also had significant clusters of locally decreased FA values (P < 0.001) in the CST in the midbrain and corpus callosum, bilaterally. This study supports the notion that ALS is a multisystem disorder and suggests that extra-motor involvement may be an early feature of the disease.

Rehabilitation of attention and information processing and executive functions in RR MS may be effected through enhanced recruitment of brain networks subserving the trained functions.

In multiple sclerosis, the relationship between conventional MRI findings and the clinical evolution of the disease is weak. Magnetization transfer (MT) MRI can provide markers reflecting the more disabling features of multiple sclerosis pathology. The aim of the present study was to assess the value of MT MRI quantities and their short-term changes in predicting the long-term accumulation of disability in multiple sclerosis patients. Conventional and MT MRI scans of the brain were obtained at baseline and after 12 months in 73 patients, who were followed prospectively with clinical visits for a median period of 8 years. At baseline and at 12 months, T2-hyperintense and T1-hypointense lesion volume, normalized brain volume [with grey (GM) and white matter (WM) fractions] and average lesion MT ratio (MTR) were measured. At the two time points, metrics derived from the MTR histograms of the whole-brain parenchyma, GM and normal-appearing WM were also computed. A multivariate analysis, adjusted for follow-up duration, was performed to establish which variables were significant predictors of long-term neurological deterioration. At the end of follow-up, 44 patients (60%) showed a significant disability worsening. A multivariable model included baseline GM MTR histogram peak height [P = 0.029, odds ratio (OR) = 0.97], and average lesion MTR percentage change after 12 months (P = 0.016, OR = 0.88) as independent predictors of disability worsening at 8 years (r2 = 0.28). The discriminating ability of such a model in predicting the individual patients' outcome was 66%. MT MRI provides useful prognostic markers for the prediction of the long-term evolution of multiple sclerosis. This study also suggests that GM damage is one of the key factors associated with disability accumulation in this 'white matter' condition.

Diffusion tensor MRI-based tractography was used to investigate white matter (WM) changes in the major limbic (i.e., fornix and cingulum) and cortico-cortical association pathways [i.e., the uncinate fasciculus, the inferior fronto-occipital fasciculus, the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus, and the corpus callosum] in 25 Alzheimer's disease (AD) patients, 19 amnestic mild cognitive impairment (aMCI) patients, and 15 healthy controls (HC). Mean diffusivity (MD), fractional anisotropy (FA), as well as axial (DA) and radial (DR) diffusivities were measured for each tract, using an atlas-based tractography approach. The association of WM tract integrity with hippocampal volume was also assessed. MD values were significantly different among groups in all WM tracts (P values ranging from 0.002 to 0.03), except in the fornix (P = 0.06) and the inferior fronto-occipital fasciculus (P = 0.09). Conversely, FA was significantly different among groups in the fornix only (P = 0.02). DA values were significantly different among groups in all WM tracts (P values ranging from 0.001 to 0.01), except in the fornix (P = 0.13) and the cingulum (P = 0.29). Significantly different DR values among groups were found in the fornix (P = 0.02) and the ILF (P = 0.01). In the fornix and cingulum, DR was significantly more increased than DA in both patient groups compared to HC. No difference in DA versus DR was found in cortico-cortical WM tracts. DA values in the fornix were significantly correlated with the hippocampal volume. This study demonstrates a different pattern of WM involvement in the limbic and cortico-cortical association pathways in aMCI and AD patients.