Right hemisphere dysfunction and emotional processing in ALS: an fMRI study.

Emotional processing may be abnormal in amyotrophic lateral sclerosis (ALS). Our aim was to explore functional anatomical correlates in the processing of aversive information in ALS patients. We examined the performance of nine non-demented ALS patients and 10 healthy controls on two functional MRI (fMRI) tasks, consisting of an emotional attribution task and a memory recognition task of unpleasant versus neutral stimuli. During the emotional decision task, subjects were asked to select one of three unpleasant or neutral words. During the memory task, subjects were asked to recognize words presented during the previous task. Controls showed, as expected, greater activation in the right middle frontal gyrus during selection of unpleasant than neutral words, and a greater activation mainly in right-sided cerebral areas during the emotional recognition task. Conversely, patients showed a general increase in activation of the left hemisphere, and reduced activation in right hemisphere in both emotional tasks. Such findings may suggest extra-motor neurodegeneration involving key circuits of emotions, mostly negative, commonly involved in FTD.

Widespread cortical thinning characterizes patients with MS with mild cognitive impairment.

BACKGROUND: Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes. METHODS: A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer. RESULTS: Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment. CONCLUSIONS: A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.

Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study.

BACKGROUND: In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS. OBJECTIVE: This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability. METHODS: Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up. RESULTS: At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period. CONCLUSIONS: Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.

Evidence for relative cortical sparing in benign multiple sclerosis: a longitudinal magnetic resonance imaging study.

BACKGROUND: Using double inversion recovery (DIR) MRI, cortical lesions can be seen in the brain of patients with multiple sclerosis (MS). The burden of such lesions seems to be well correlated with the severity of MS-related disability. OBJECTIVE: To investigate whether the extent of cortical damage in patients with benign MS (BMS) might contribute to explain their favorable clinical status. METHODS: Forty-eight patients with BMS (Expanded Disability Status Scale [EDSS] score < or =3.0 and disease duration > or =15 years) and 96 patients with non-disabling, early relapsing-remitting (RR) MS (EDSS score < or =3.0 and disease duration < or =5 years) were studied. Brain MRI, including a DIR and a fluid-attenuated inversion recovery (FLAIR) sequence, was acquired at baseline and after 12 months. On DIR images, intracortical (ICL) and cortical-subcortical lesions (CSL) were identified and their number and volume calculated. Total white matter (WM) lesion volume was quantified on FLAIR images. RESULTS: Compared with early RRMS, patients with BMS had lower number of ICL at both study time points (P < or = 0.001 for both comparisons). At one-year follow-up, a significant increase of ICL and CSL number and total volume was observed only in early patients with RRMS. The number and volume of cortical lesions was not correlated with WM lesion volume. Total ICL number at baseline, total cortical lesion volume at baseline, and total cortical lesion volume change were independent predictors of MS phenotype. CONCLUSION: In patients with BMS, the selective sparing of the cortex from disease-related focal pathology might be one of the factors associated to their favorable clinical status, independently of the (possible) accrual of WM lesions.