MULTIPLE CEREBRAL METASTASES MIMICKING WERNICKE'S ENCEPHALOPATHY IN A CHRONIC ALCOHOLIC

Aims: Alcohol dependent patients in withdrawal display a wide spectrum of neurological and neuropsychological symptoms that complicate diagnosis. We report the case of a 53-year-old male alcoholic with disorientation, ataxia and nystagmus in alcohol withdrawal probably due not to initial supposed Wernicke's encephalopathy (WE) but rather due to multiple cerebral metastases of a non-small cell cancer of the lung. Results: The findings illustrate the importance of initially maintaining a tentative attitude toward causation of symptoms and the role of brain imaging in formulating an accurate diagnosi

Benefits of short-term training with vibrotactile biofeedback of trunk sway on balance control in multiple sclerosis

Background and Aims: Patients with multiple sclerosis (MS) suffer from diminished balance control. We examined whether 4 sessions of training with vibrotactile biofeedback (VTfb) of trunk sway could improve their balance control and provide a carry-over effect. Methods: Baseline trunk sway was first measured for 15 MS patients. Then they received head mounted VTfb of trunk sway which was directionally active when trunk sway exceeded limits set using the baseline assessments. Stance and gait tasks were trained 2 times weekly for 2 weeks with VTfb. Assessments with VTfb were performed at the end of each week. Two weeks later balance was assessed without VTfb to determine if a carry-over effect was present. Results: Assessments with VTfb showed a significant decrease in trunk sway after 1 and 2 weeks of VTfb training (p<0.02). Carry-over improvements were also present (p<0.02). The greatest effects were found for tests of standing eyes closed stance on foam which resulted in a 59% decreased pitch sway angle (p=0.002) with VTfb and a 51% reduction (p=0.03) carry-over effect. Conclusions: This study indicates that balance control in MS patients improves rapidly after one week of training with VTfb and more slowly subsequently. The carry-over effect lasted at least 2 weeks. Future studies should determine, with more weeks of VTfb training, the time course of the slower balance and carry-over improvements following the first rapid improvement in balance control. We conclude that training with VTfb of trunk sway significantly improves balance control in MS patients, and could possibly reduce falls

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis, grey matter pathology occurs mostly next to or near the outer surface of the brain. Using quantitative MRI, Liu et al. reveal that white matter abnormalities are also greatest near the surface of the brain, suggesting common elements in the genesis of grey and white matter patholog

Characterization of social cognition impairment in multiple sclerosis

Multiple sclerosis (MS) has been associated with deficits in social cognition. However, little is known about which domains of social cognition are predominantly affected and what other factors are associated with it. The aim was (i) to characterize social cognition deficit in a group of MS outpatients and (ii) to relate impairment in social cognition to overall cognitive status, depression and fatigue.Methods: Thirty-five MS patients (mean disease duration 12.9 years, median Expanded Disability Status Scale (EDSS) 3 and 34 healthy controls (HCs) were examined using the German version of the Geneva Social Cognition Scale to measure different domains of social cognition. Standard neuropsychological testing was applied to all patients and to 20 HCs. Patient-reported outcomes included questionnaires for fatigue, depression, anxiety and executive-behavioural disturbances.Results: The mean social cognition raw score was lower in the MS patients compared to the HCs (86.5 ± 8.7 vs. 91.2 ± 5.9, P = 0.005; d = 0.6) and did not correlate with EDSS or disease duration. The difference was driven by facial affect recognition and the understanding of complex social situations (14% and 23% of patients respectively under the cut-off). The impairment in these two tasks did not correlate with general cognitive performance or depression but with fatigue.Conclusions: The impairment in our group was restricted to high order and affective social cognition tasks and independent of general cognitive performance, EDSS, disease duration and depression. Fatigue correlated with social cognition performance, which might be due to common underlying neuronal networks

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

OBJECTIVE: To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). METHODS: 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm(3)) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. RESULTS: Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. CONCLUSIONS: In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation

Magnetisation transfer ratio measures in normal appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis (MS), there is increasing evidence that demyelination, and neuronal damage within and beyond lesions, occurs preferentially in cortical grey matter (GM) next to the outer surface of the brain. It has been suggested that this may be due to the effects of pathology outside the brain parenchyma, in particular meningeal inflammation or through cerebrospinal fluid (CSF) mediated factors. White matter (WM) lesions are often located adjacent to the ventricles of the brain, suggesting the possibility of a similar outside-in pathogenesis, but an investigation of the relationship of periventricular normal-appearing (NA) WM abnormalities with distance from the ventricles has not previously been undertaken. The present study investigates this relationship in vivo using quantitative MR imaging and compares the abnormalities between SPMS and relapsing remitting (RR) MS. Forty-three people with RRMS and 28 with SPMS, and 38 healthy controls, were included in this study. T1-weighted volumetric, magnetisation transfer (MT) and PD/T2-weighted scans were acquired for all subjects. From the MT data, MT ratio (MTR) maps were prepared. WM tissue masks were derived from SPM8 segmentations of the T1-weighted images. NAWM masks were generated by subtracting WM lesions identified on the PD/T2 scan, and a 2 voxel perilesional ring, from the SPM8 derived WM masks. WM was divided in concentric bands, each about 1 mm thick, radiating from the ventricles toward the cortex. The first periventricular band was excluded from analysis to mitigate partial volume effects, and NAWM and lesion MTR values were then computed for the ten bands nearest to the ventricles. Compared with controls, MTR in the NAWM bands was significantly lower in MS. In controls, MTR was highest in the band adjacent to the ventricles and declined with increasing distance from the ventricles. In the MS groups, relative to controls, reductions in MTR were greater in the SPMS compared with RRMS group, and these reductions were greatest next to the ventricles and became smaller with distance from them. WM lesion MTR reductions were also more apparent adjacent to the ventricle and decreased with distance from the ventricles in both the RR and SPMS groups. These findings suggest that in people with MS, and more so in SPMS than RRMS, tissue structural abnormalities in NAWM and WM lesions are greatest near the ventricles. This would be consistent with a CSF or ependymal mediated pathogenesis

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis, there is increasing evidence that demyelination, and neuronal damage occurs preferentially in cortical grey matter next to the outer surface of the brain. It has been suggested that this may be due to the effects of pathology outside the brain parenchyma, in particular meningeal inflammation or through cerebrospinal fluid mediated factors. White matter lesions are often located adjacent to the ventricles of the brain, suggesting the possibility of a similar outside-in pathogenesis, but an investigation of the relationship of periventricular normal-appearing white matter abnormalities with distance from the ventricles has not previously been undertaken. The present study investigates this relationship in vivo using quantitative magnetic resonance imaging and compares the abnormalities between secondary progressive and relapsing remitting multiple sclerosis. Forty-three patients with relapsing remitting and 28 with secondary progressive multiple sclerosis, and 38 healthy control subjects were included in this study. T1-weighted volumetric, magnetization transfer and proton density/T2-weighted scans were acquired for all subjects. From the magnetization transfer data, magnetization transfer ratio maps were prepared. White matter tissue masks were derived from SPM8 segmentations of the T1-weighted images. Normal-appearing white matter masks were generated by subtracting white matter lesions identified on the proton density/T2 scan, and a two-voxel perilesional ring, from the SPM8 derived white matter masks. White matter was divided in concentric bands, each ∼1-mm thick, radiating from the ventricles toward the cortex. The first periventricular band was excluded from analysis to mitigate partial volume effects, and normal-appearing white matter and lesion magnetization transfer ratio values were then computed for the 10 bands nearest to the ventricles. Compared with controls, magnetization transfer ratio in the normal-appearing white matter bands was significantly lower in patients with multiple sclerosis. In controls, magnetization transfer ratio was highest in the band adjacent to the ventricles and declined with increasing distance from the ventricles. In the multiple sclerosis groups, relative to controls, reductions in magnetization transfer ratio were greater in the secondary progressive multiple sclerosis compared with relapsing remitting multiple sclerosis group, and these reductions were greatest next to the ventricles and became smaller with distance from them. White matter lesion magnetization transfer ratio reductions were also more apparent adjacent to the ventricle and decreased with distance from the ventricles in both the relapsing remitting and secondary progressive multiple sclerosis groups. These findings suggest that in people with multiple sclerosis, and more so in secondary progressive than relapsing remitting multiple sclerosis, tissue structural abnormalities in normal-appearing white matter and white matter lesions are greatest near the ventricles. This would be consistent with a cerebrospinal fluid or ependymal mediated pathogenesis

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study

BACKGROUND: In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. OBJECTIVE: To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. METHODS: Seventy-two people with MS (46 relapsing–remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. RESULTS: Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. CONCLUSION: Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability