Vm Anderson

Gray matter atrophy is related to long‐term disability in multiple sclerosis

To determine the relation of gray matter (GM) and white matter (WM) brain volumes, and WM lesion load, with clinical outcomes 20 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS).

The clinical profile of right temporal lobe atrophy

Frontotemporal lobar degeneration is currently associated with three syndromic variants. Disorders of speech and language figure prominently in two of the three variants, and are associated with left-sided frontotemporal atrophy. The detailed characterization of these syndromes contrasts with the relative paucity of information relating to frontotemporal lobar degeneration primarily affecting the right cerebral hemisphere. The objective of this study was to identify the clinical profile associated with asymmetrical, predominantly right-sided, temporal lobe atrophy. Twenty patients with predominant right temporal lobe atrophy were identified on the basis of blinded visual assessment of the MRI scans. The severity of right temporal lobe atrophy was quantified using volumetric analysis of the whole temporal lobes, the amygdala and the hippocampus. Profiles of cognitive function, behavioural and personality changes were obtained on each patient. The pattern of atrophy and the clinical features were compared with those observed in a group of patients with semantic dementia and predominant left-sided temporal lobe atrophy. The mean right temporal lobe volume in the right temporal lobe atrophy group was reduced by 37%, with the mean left temporal lobe volume reduced by 19%. There was marked atrophy of the right hippocampus and right amygdala, with mean volumes reduced by 41 and 51%, respectively (left hippocampus and amygdala volumes were reduced by 18 and 33%, respectively). The most prominent cognitive deficits were impairment of episodic memory and getting lost. Prosopagnosia was a symptom in right temporal lobe atrophy patients. These patients also exhibited a variety of behavioural symptoms including social disinhibition, depression and aggressive behaviour. Nearly all behavioural disorders were more prevalent in the right temporal lobe atrophy patient group than the semantic dementia group. Symptoms particular to the right temporal lobe atrophy patient group included hyper-religiosity, visual hallucinations and cross-modal sensory experiences. The combination of clinical features associated with predominant right temporal lobe atrophy differs significantly from those associated with the other syndromes associated with focal degeneration of the frontal and temporal lobes and it is, therefore, proposed that this right temporal variant should be considered a separate syndromic variant of frontotemporal lobar degeneration.

Volumetric MRI and cognitive measures in Alzheimer disease : comparison of markers of progression.

BackgroundBoth cognitive tests and MRI-based measures have been suggested as outcomes in trials assessing disease-modifying therapies in Alzheimers disease (AD).ObjectiveTo compare changes in longitudinal MRI measures with changes in performance on cognitive tests routinely used in AD clinical trials.MethodFifty-two subjects from the placebo-arm of a clinical trial in mild-to-moderate AD had volumetric T1-weighted scans and cognitive tests including the Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale, Disability Assessment for Dementia, AD Cooperative Study-Clinical Global Impression of Change and Clinical Dementia Rating at baseline and one-year later. Rates of brain atrophy and ventricular enlargement were measured using the boundary shift integral. Hippocampal (Hc) atrophy was calculated from manual volume measurements. The relationships between MRI and cognitive measures were investigated.ResultsRates of brain atrophy and/or ventricular enlargement were correlated with declining performance on cognitive scales. The strongest association was between brain atrophy rate and MMSE decline (r = 0.59, p < 0.0001). Hc atrophy rate was not significantly correlated with any of the cognitive scales.ConclusionThe lack of correlation between Hc atrophy and cognitive scales may reflect a combination of: the extensive functional damage to the Hc by the time AD is clinically established, the greater influence of ongoing cortical degeneration, and errors in Hc outlining. The strong correlations between brain atrophy and ventricular enlargement, and cognitive scales probably reflect the correspondence between these measures of overall cerebral loss and global cognitive measures in the moderate stages of AD.

Magnetic resonance imaging measures of brain atrophy in multiple sclerosis

Magnetic resonance imaging (MRI) has been widely used to diagnose and monitor multiple sclerosis (MS). Although MRI‐visible lesions are a key feature of MS, they are thought to correlate poorly with clinical progression. Neurodegeneration is increasingly being recognized as an important factor in the pathogenesis of MS, and MRI measures of brain atrophy have been suggested as surrogate markers of neuroaxonal loss and disease progression. This pathology may be more relevant to the progression of disability than focal inflammation. A number of MRI‐based methods have been developed for the measurement of global and regional brain atrophy. Natural‐history studies of MS and clinically isolated syndromes suggestive of MS have observed atrophy in these subjects above that seen in controls, over periods ranging from three months to years. Brain atrophy has also been incorporated as an outcome measure in therapeutic trials of disease‐modifying treatments. This paper considers neuroaxonal loss and the pathological basis of brain atrophy, methods developed to quantify brain atrophy, the findings of natural‐history and therapeutic studies, the relationship of brain atrophy to disability and cognition, and the future research directions and clinical applications of brain atrophy measurements. J. Magn. Reson. Imaging 2006.

Cognitive impairment in relapsing—remitting multiple sclerosis can be predicted by imaging performed several years earlier

Cognitive deficits in multiple sclerosis (MS) are common and correlate with contemporary MRI brain abnormalities, particularly atrophy, but the ability of imaging early in the disease to predict later cognitive impairment remains to be determined. Thirty relapsing—remitting MS patients recruited within three years of the onset of the disease, and in whom MRI had been performed at baseline and a year later, were assessed neuropsychologically five years later. Imaging parameters accounting for significant variance in cognitive performance were identified using multiple regressions, once confounding variables were controlled. Patients performed significantly worse than expected on tests of attention/speed of information processing and half of them had experienced some decline in IQ in relation to premorbid estimates. The rate of global brain atrophy in the first year of the study accounted for significant variance in the overall cognitive performance, and in memory and attention/speed of information processing. Poor performance on attention tests was associated with high T1-weighted lesion volume and reduced magnetization transfer ratio (MTR) in normal-appearing white matter (NAWM). These results suggest that neuroaxonal loss was identified early in the disease, and its rate of progression, predicted cognitive impairment later in the disease. Neuroaxonal loss is likely to affect commissural and association fibres that subserve the cognitive processes impaired in MS. Multiple Sclerosis 2008; 14: 197—204. http://msj.sagepub.com

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes

Background Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. Objective To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). Methods 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Results Mean annual brain atrophy rates were −0.38% for all patients, −0.50% in patients who had developed MS at 6 years and −0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. Conclusions The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

Longitudinal Patterns of Regional Change on Volumetric MRI in Frontotemporal Lobar Degeneration

The aim of this study was to assess the longitudinal patterns of regional change in the different syndromic variants of frontotemporal lobar degeneration (FTLD). Ten patients with semantic dementia, 7 with progressive non-fluent aphasia and 29 with frontotemporal dementia had two serial volumetric MR scans. Fluid registration was used to match serial scans from each individual. Voxel-level analysis of change across subject groups was performed using statistical parametric mapping. The analysis showed patterns of increased rates of volume loss (atrophy) in frontal, temporal and parietal regions in the whole FTLD group compared with controls. The different FTLD syndromes displayed different patterns of change. This technique gives an insight into disease evolution over time in these disorders and may be useful as a method of tracking change in clinical trials.

Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis

Background Neuroaxonal loss is a pathological substrate of disability in progressive multiple sclerosis (MS) and can be estimated in vivo by measuring tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence that brain atrophy correlates better with disability than T2 lesion load in secondary progressive MS, the clinical relevance of atrophy within specific regions of the central nervous system requires further evaluation. Methods Clinical and MRI examinations were performed in 117 subjects with secondary progressive MS. MRI analysis included measures of normalized brain volume (NBV), normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion volume. Clinical assessments included the expanded disability status scale (EDSS) and MS functional composite (MSFC). Results All MRI measures correlated significantly with the MSFC score, with the strongest correlation being for the NBV (r = 0.47; P < 0.001). NBV and SCCA were the only significant independent predictors of the MSFC score in a stepwise regression model containing all the MRI measures, and SCCA was the only MRI measure to show a significant association with the EDSS. While NGMV had stronger correlations with the clinical variables than NWMV, NBV was more correlated with clinical impairment than either measure. Conclusions This data suggests that measures of atrophy, particularly of the whole brain and spinal cord, are relevant and useful disease markers in secondary progressive MS.

MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction

Background Regional atrophy measures may offer useful information about the causes of specific clinical deficits in multiple sclerosis (MS). Objective To determine the magnitude of cerebellar gray and white matter (GM and WM) atrophy in patients with clinically isolated syndromes (CIS) and MS, and their role in clinical manifestations of cerebellar damage. Methods T1-weighted volumetric magnetic resonance imaging (MRI) of 73 patients [29 CIS, 33 relapsing–remitting MS (RRMS), 11 secondary progressive MS (SPMS)] was compared with 25 controls. GM and WM regions were generated using SPM5 and cerebellar regions delineated. Linear regression was used to investigate differences in tissue-specific cerebellar volumes between groups and the association with clinical measures. Results Mean cerebellar GM volume (CGMV) was 100.1 cm3 in controls, 96.4 cm3 in CIS patients, 91.8 cm3 in RRMS patients, and 88.8 cm3 in SPMS patients. Mean cerebellar WM volumes (CWMV) were 21.3 cm3, 20.4 cm3, 19.9 cm3, and 18.8 cm3, respectively. CGMV was reduced by 4.8 cm3 (P = 0.054) in RRMS patients, and 8.5 cm3 (P = 0.012) in SPMS patients, relative to controls. Only patients with SPMS showed a borderline significant reduction in CWMV compared with controls (mean 2.1 cm3, P = 0.053). CGMV was significantly smaller in patients assessed as having cerebellar dysfunction compared with patients who had normal cerebellar function. Significant associations of CGMV and CWMV with performance on the nine-hole peg test were also observed. Conclusion Clinically relevant GM atrophy occurs in the cerebellum of MS patients and is more prominent than WM atrophy. As such, it may provide complementary data to other regional atrophy and intrinsic tissue measures.

Cerebral Atrophy Measurement in Clinically Isolated Syndromes and Relapsing Remitting Multiple Sclerosis: A Comparison of Registration‐Based Methods

Background and Purpose. Brain atrophy is a proposed marker of disease progression in multiple sclerosis (MS). Many magnetic resonance imaging‐based methods of atrophy quantification exist, but their relative sensitivity and precision is unclear. Our aim was to compare atrophy rates from the brain boundary shift integral (BBSI), structural image evaluation, using normalization of atrophy (SIENA) (both registration‐based methods) and segmented brain volume difference, in patients with clinically isolated syndromes (CIS), relapsing remitting MS (RRMS), and controls. Methods. Thirty‐seven CIS patients, 30 with early RRMS and 16 controls had T1‐weighted volumetric imaging at baseline and 1 year. Brain atrophy rates were determined using segmented brain volume difference, BBSI, and SIENA. Results. BBSI and SIENA were more precise than subtraction of segmented brain volumes and were more sensitive distinguishing RRMS subjects from controls. A strong correlation was observed between BBSI and SIENA. Atrophy rates were greater in CIS and RRMS subjects than controls (RRMS P < .001). With all methods, significantly greater atrophy rates were observed in CIS patients who developed clinically definite MS relative to subjects who did not. Conclusion. Registration‐based techniques are more precise and sensitive than segmentation‐based methods in measuring brain atrophy, with BBSI and SIENA providing comparable results.