[Show abstract][Hide abstract] ABSTRACT: The pathological differences underlying the clinical disease phases in multiple sclerosis (MS) are poorly characterized. We sought to explore the relationship between the distribution of white matter (WM) lesions in relapsing-remitting (RR) and secondary progressive (SP) MS and the normal regional variability of cerebral perfusion.
WM lesions were identified and quantified on a single magnetic resonance imaging scan from 1,249 patients with MS. The spatial distribution of lesions was compared between early RR, late RR, and SP MS in the context of normal cerebral perfusion patterns provided by a single-photon emission-computed tomography atlas of healthy individuals.
Patients with SP MS had more distinct and larger lesions than patients with RR MS. Across all subjects, lesions were present in regions of relatively lower normal perfusion than normal appearing WM. Further, lesions in SP MS were more common in areas of lower perfusion as compared to the lesion distribution in early and late RR MS.
Chronic plaques were more prevalent in WM regions with lower relative perfusion. Lesions in more highly perfused regions were more commonly observed in early RR MS and therefore, may be more likely to successfully remyelinate and resolve.
Journal of neuroimaging: official journal of the American Society of Neuroimaging 03/2011; 22(2):129-36. DOI:10.1111/j.1552-6569.2011.00585.x · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the rate of treatment failure in patients outside of a controlled treatment trial and to ascertain the factors physicians used to make this decision.
One hundred and thirty four patients with the diagnosis of relapsing-remitting (RR) multiple sclerosis (MS) or clinically isolated symptom (CIS) enrolled in the CLIMB study (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital) were treated with either interferon beta or glatiramer acetate as their initial treatment for MS.
The probability of failing initial treatment within 3 years was 30%. Clinical activity, defined as relapses and/or progression in disability, determined treatment failure in 35.7% (n=10) of nonresponders. New T2 hyperintense or gadolinium-enhancing lesions on MRI was used to define treatment failure in 28.6% (n=8) and new MRI lesions were used in combination with clinical activity in 35.7% (n=10). Treatment failures had a higher T2 hyperintense lesion volume (p=0.015) and number of gadolinium-enhancing lesions (p=0.0001) on the enrollment MRI than responders.
These observations demonstrate that treating physicians use both clinical and MRI parameters to define a response to treatment and initiation of a treatment change and that baseline MRI identified those with increased risk of treatment failure.
Journal of the neurological sciences 06/2009; 284(1-2):116-9. DOI:10.1016/j.jns.2009.04.020 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benign multiple sclerosis (MS) is defined by minimal or no disability after many years of observation, therefore a less degenerative disease process is suspected to be present in this subset of patients.
To compare brain atrophy rates in patients with long-standing benign MS vs typical early MS.
A longitudinal prospective cohort study and a retrospective database review.
An academic MS center.
Thirty-nine patients with clinically defined benign MS and an age-matched group of 40 patients with early relapsing-remitting MS.
Baseline demographic, treatment, brain magnetic resonance imaging measures, and annualized atrophy rates, derived from serial brain parenchymal fraction measurements across 2 years, were compared.
In the baseline analysis, patients with benign MS were matched to the early MS group on age, sex, treatment with immunomodulatory therapy, T2 lesion volume, and brain parenchymal fraction. The mean (SD) annualized brain atrophy rate in patients with benign MS (-0.16% [0.51%]) was lower than that in patients with early MS (-0.46% [0.72%]) (P = .02). The difference remained significant after controlling for age, sex, and treatment (P = .04).
Serial magnetic resonance imaging revealed a low 2-year rate of brain atrophy in patients with clinically benign MS, suggesting a less prominent degenerative component in its pathogenesis than in patients with typical early MS. Identification of patients with a low rate of brain atrophy may indicate a benign course.
Archives of neurology 03/2009; 66(2):234-7. DOI:10.1001/archneurol.2008.567 · 7.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Individual magnetic resonance imaging (MRI) disease severity measures, such as atrophy or lesions, show weak relationships to clinical status in patients with multiple sclerosis (MS).
To combine MS-MRI measures of disease severity into a composite score.
Retrospective analysis of prospectively collected data.
Community-based and referral subspecialty clinic in an academic hospital.
A total of 103 patients with MS, with a mean (SD) Expanded Disability Status Scale (EDSS) score of 3.3 (2.2), of whom 62 (60.2%) had the relapsing-remitting, 33 (32.0%) the secondary progressive, and 8 (7.8%) the primary progressive form.
Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV (T1:T2) assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1:T2.
The MRDSS score averaged 5.1 (SD, 2.6). Baseline MRI and EDSS correlations were moderate for BPF, T1:T2, and MRDSS and weak for T2LV. The MRDSS showed a larger effect size than the individual MRI components in distinguishing patients with the relapsing-remitting form from those with the secondary progressive form. Models containing either T2LV or MRDSS were significantly associated with disability progression during the mean (SD) 3.2 (0.3)-year observation period, when adjusting for baseline EDSS score.
Combining brain MRI lesion and atrophy measures can predict MS clinical progression and provides the basis for developing an MRI-based continuous scale as a marker of MS disease severity.
Archives of neurology 12/2008; 65(11):1449-53. DOI:10.1001/archneur.65.11.1449 · 7.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While brain MR imaging is routinely performed, the MR imaging assessment of spinal cord pathology in multiple sclerosis (MS) is less frequent in clinical practice. The purpose of this study was to determine whether measurements of medulla oblongata volume (MOV) on routine brain MR imaging could serve as a biomarker of spinal cord damage and disability in MS.
We identified 45 patients with MS with both head and cervical spinal cord MR imaging and 29 age-matched and sex-matched healthy control subjects with head MR imaging. Disability was assessed by the expanded disability status scale (EDSS) and ambulation index (AI). MOV and upper cervical cord volume (UCCV) were manually segmented; semiautomated segmentation was used for brain parenchymal fraction (BPF). These measures were compared between groups, and linear regression models were built to predict disability.
In the patients, MOV correlated significantly with UCCV (r = 0.67), BPF (r = 0.45), disease duration (r = -0.64), age (r = -0.47), EDSS score (r = -0.49) and AI (r = -0.52). Volume loss of the medulla oblongata was -0.008 cm(3)/year of age in patients with MS, but no significant linear relationship with age was found for healthy control subjects. The patients had a smaller MOV (mean +/- SD, 1.02 +/- 0.17 cm(3)) than healthy control subjects (1.15 +/- 0.15 cm(3)), though BPF was unable to distinguish between these 2 groups. MOV was smaller in patients with progressive MS (secondary- progressive MS, 0.88 +/- 0.19 cm(3) and primary-progressive MS, 0.95 +/- 0.30 cm(3)) than in patients with relapsing-remitting MS (1.08 +/- 0.15 cm(3)). A model including both MOV and BPF better predicted AI than BPF alone (P = .04). Good reproducibility in MOV measurements was demonstrated for intrarater (intraclass correlation coefficient, 0.97), interrater (0.79), and scan rescan data (0.81).
MOV is associated with disability in MS and can serve as a biomarker of spinal cord damage.
American Journal of Neuroradiology 07/2008; 29(8):1465-70. DOI:10.3174/ajnr.A1162 · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Combine MRI measures of disease severity into a composite score in patients with multiple sclerosis (MS).
Brain MRI lesion and atrophy measures assessed individually have fairly weak ability to predict clinical progression in MS.
In the Comprehensive Longitudinal Investigation of MS at Brigham, we studied 103 patients [age (mean ± SD) 42.7 ± 9.1 years, disease duration 14.1 ± 9.2 years, Expanded Disability Status Scale (EDSS) score 3.3 ± 2.2, 60% (n = 62) relapsing–remitting (RR), 32% (n = 33) secondary progressive (SP), and 8% (n = 8) primary progressive]. Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume, and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1/T2 ratio.
MRDSS score averaged 5.1 ± 2.6. Baseline MRI and EDSS correlations were moderate for BPF, T1/T2, and MRDSS and weak for T2LV. MRDSS showed a larger effect size than any of the individual MRI components in distinguishing RR from SP patients. Models containing either T2LV or MRDSS were significantly associated with EDSS disability progression during the 3.2 ± 0.3 year observation period, when adjusting for baseline EDSS score.
These results show that combining brain MRI lesion and atrophy measures can predict clinical progression in patients with MS and provide the basis to develop an MRI-based continuous scale as a marker of MS disease severity.
[Show abstract][Hide abstract] ABSTRACT: Cognitive dysfunction is common in patients with multiple sclerosis (MS), and has been associated with MRI measures of lesion burden and atrophy. Little is known about the prevalence of cognitive impairment in patients with early MS. The associations between cognitive impairment and MRI measures of disease severity early in the disease course are also unclear. This study used a brief battery of cognitive tests to determine the prevalence and pattern of cognitive impairment in patients with clinically isolated syndromes or newly diagnosed MS. The associations between cognitive impairment and MRI measures of disease severity early in the disease course were also examined. Ninety-two patients with clinically isolated syndromes or the diagnosis of MS within the last 3 years participating in the CLIMB study underwent a neurologic examination, neuropsychological evaluation and MRI at 1.5 T. Forty-nine percent of patients were impaired on one or more cognitive measures. There were no significant correlations between cognitive scores and MRI measures of disease severity including total T2 lesion volume, normal appearing white matter volume, grey matter volume, and brain parenchymal fraction. These findings suggest that cognitive impairment may predate the appearance of gross structural abnormalities on MRI and serve as an early marker of disease activity in MS.