Biomedical subjects

Robert A Bermel

Publications and source records attributed to Robert A Bermel.

7 recordsLinked to original sources

PubMed2006

The measurement and clinical relevance of brain atrophy in multiple sclerosis.

Brain atrophy has emerged as a clinically relevant component of disease progression in multiple sclerosis. Progressive loss of brain tissue bulk can be detected in vivo in a sensitive and reproducible manner by MRI. Clinical studies have shown that brain atrophy begins early in the disease course. The increasing amount of data linking brain atrophy to clinical impairments suggest that irreversible tissue destruction is an important determinant of disease progression to a greater extent than can be explained by conventional lesion assessments. In this review, we will summarise the proposed mechanisms contributing to brain atrophy in patients with multiple sclerosis. We will critically discuss the wide range of MRI-based methods used to quantify regional and whole-brain-volume loss. Based on a review of current information, we will summarise the rate of atrophy among phenotypes for multiple sclerosis, the clinical relevance of brain atrophy, and the effect of disease-modifying treatments on its progression.

Atrophy↗

PubMed2005

Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity.

BACKGROUND: Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment. OBJECTIVE: To test whether T2 hypointensity predicts brain atrophy and whether interferon affects this relationship. DESIGN: Post hoc analysis. SETTING: A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers. Patients Patients with multiple sclerosis who took part in a 2-year clinical trial in which they received intramuscular interferon beta-1a (30 mug/wk) or placebo. MAIN OUTCOME MEASURES: Deep gray matter T2 hypointensity, brain parenchymal fraction (BPF), and total T2, gadolinium-enhancing, and T1 lesion volumes. RESULTS: T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change. CONCLUSIONS: Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.

Adult↗

PubMed2005

Measurement of brain and spinal cord atrophy by magnetic resonance imaging as a tool to monitor multiple sclerosis.

Evaluation of brain and spinal cord atrophy by magnetic resonance imaging (MRI) has become an increasingly important component of understanding the multiple sclerosis (MS) disease process. These destructive aspects of the disease develop early in the disease course. A growing body of data links brain and spinal cord atrophy to clinical impairment more closely than can be linked with conventional measures of overt lesions. Thus, irreversible tissue damage may be a key factor leading to disease progression. In this review, the authors present the proposed mechanisms leading to central nervous system (CNS) atrophy. They describe the available MRI-based techniques to measure regional and global atrophy of the brain and spinal cord. They compare the rate of atrophy among MS phenotypes and summarize the emerging data linking atrophy to neurological and neuropsychological impairment. Finally, they discuss the effect of disease-modifying immunotherapies on the rate of CNS atrophy in patients with MS. Future research to clarify the etiology and pathophysiology of brain and spinal cord atrophy should provide new targets for therapeutic development.

Atrophy↗

PubMed2003

A semiautomated measure of whole-brain atrophy in multiple sclerosis.

Brain atrophy is a proposed MRI marker of irreversible pathologic damage in multiple sclerosis (MS). The brain parenchymal fraction (BPF) is the ratio of brain parenchymal volume to the total volume within the surface contour. We developed a semiautomated measure of BPF using commercially available edge-finding and thresholding software (30-min analysis time per patient). We measured BPF in 78 patients with MS and 17 healthy controls. BPF was lower in a cohort of patients with MS (n=50) (0.843+/-0.042, range 0.743-0.906) age-matched to controls (0.877+/-0.020, range 0.835-0.901) (p<0.001). BPF correlated inversely with third ventricular width (r=-0.785, p<0.001), and total T1 hypointense lesion volume (r=-0.347, p=0.011), but not with total T2 hyperintense lesion volume (r=-0.213, p=0.13). BPF correlated negatively with expanded disability status scale (EDSS) score (r=-0.391, p=0.0006) and disease duration (r=-0.281, p=0.01). Stepwise regression compared the relative abilities of MRI variables to predict clinical data. By regression of age, BPF, third ventricular width, T2 lesions, and T1 lesions, BPF was the best predictor of disability score (R(2)=0.204, p<0.001). Third ventricular width was the best predictor of disease duration (R(2)=0.316, p<0.001). None of the MRI variables differed between relapsing-remitting (RR) (n=60) and secondary progressive (SP) (n=18) disease course (p>0.05). The intrarater, interrater, and scan-rescan BPF variability (COV) was 0.31%, 0.34%, and 0.41% and the accuracy against a phantom was 99.1%. We conclude that whole-brain atrophy in MS can be reliably and readily quantified by a semiautomated approach. Longitudinal studies are warranted to determine if this method provides a sensitive biologic marker of the MS disease process.

Adult↗

PubMed2003

Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study.

Deep gray matter damage may be an important component of the multiple sclerosis (MS) disease process. We tested whether caudate atrophy occurs in MS, and whether it correlates with conventional MRI or clinical markers of disease progression. Caudate nuclei of 24 MS patients and 10 age-matched healthy controls were traced, normalized, reconstructed and visualized from MRI scans. Normalized bicaudate volume was 19% lower in MS controls ( p< 0.001), an effect that persisted after adjusting for whole-brain atrophy ( p< 0.008). Caudate volume did not correlate with disease duration, physical disability score, whole-brain atrophy, or total T2 hyperintense or T1 hypointense lesion load (all p > 0.05). We conclude that selective caudate atrophy is associated with MS and may occur through direct mechanisms.

Adult↗

PubMed2002

T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study.

CONTEXT: While gray matter T2 hypointensity in multiple sclerosis (MS) has been associated with physical disability and clinical course, previous studies have relied on visual magnetic resonance imaging (MRI) assessments. OBJECTIVE: To quantitatively determine if T2 hypointensity is associated with conventional MRI and clinical findings in MS. DESIGN: Case-control study. SETTING: University-affiliated community-based hospital. SUBJECTS: Sixty patients with MS and 50 controls. MAIN OUTCOME MEASURES: T2 intensities of the substantia nigra, red nucleus, thalamus, putamen, globus pallidus, and caudate; third ventricular width; total brain T1 (hypointense) and T2 (hyperintense) lesion volumes; Expanded Disability Status Scale (physical disability) score; and disease course. RESULTS: Deep gray matter T2 hypointensity was present in patients with MS in all structures (P<.005) except for the substantia nigra. T2 hypointensity was associated with third ventricle enlargement and higher T2 but not T1 plaque load. The regression model predicting third ventricle width included caudate T2 hypointensity (P =.006). The model predicting T2 lesion load included globus pallidus T2 hypointensity (P =.001). Caudate T2 hypointensity was the only variable associated with disability score in regression modeling (P =.03). All T2 hypointensities differentiated the secondary progressive from the relapsing-remitting clinical courses. The final model (P<.001) predicting clinical course retained T2 hypointensity of the thalamus, caudate, and putamen but not MRI plaques or atrophy. CONCLUSIONS: Gray matter T2 hypointensity in MS is associated with brain atrophy and is a stronger predictor of disability and clinical course than are conventional MRI findings. While longitudinal studies are warranted, these results suggest that pathologic iron deposition is a surrogate marker of the destructive disease process.

Adult↗

PubMed2002

Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis.

CONTEXT: Brain atrophy has emerged as a useful surrogate marker of disease involvement in multiple sclerosis (MS). The relationship between whole-brain or regional atrophy and cognitive dysfunction is poorly understood. OBJECTIVES: To determine whether the bicaudate ratio (BCR)-the minimum intercaudate distance divided by brain width along the same line-is increased in MS and to compare the ability of the BCR, whole-brain atrophy, and other magnetic resonance imaging markers to predict cognitive dysfunction. DESIGN: Case-control study. SETTING: University-affiliated clinic. PARTICIPANTS: Sixty patients with MS and 50 age- and sex-matched control subjects. MAIN OUTCOME MEASURES: Bicaudate ratio, whole-brain atrophy, T2 lesion load, T1 ("black hole") lesion load, and caudate volume were measured quantitatively using fluid-attenuated inversion recovery, T1-weighted, and gradient-echo magnetic resonance imaging scans. Symbol Digit Modalities Test was used to assess cognitive function. RESULTS: The BCR (mean [SD]) was higher in patients with MS (0.11 [0.03]) than in controls (0.09 [0.02]) (P<.001), suggesting subcortical atrophy in MS. The BCR was related to total T2 (r = 0.56, P<.001) and T1 (r = 0.40, P<.002) lesion volumes, but not caudate volume in patients with MS. Regression modeling selected BCR (P<.05), but not whole-brain atrophy, T1 or T2 lesion volume, or caudate volume as predictive of Symbol Digit Modalities Test score in patients with MS. CONCLUSIONS: The BCR is increased in MS and is more closely associated with cognitive dysfunction than are other magnetic resonance imaging surrogate markers including whole-brain atrophy. Increased BCR is best explained by frontal horn ventricular enlargement due to atrophy of deep frontal subcortical white matter. This highlights the close relationship between subcortical atrophy and cognitive impairment in patients with MS.

Adult↗