The Relationships among MRI-Defined Spinal Cord Involvement, Brain Involvement, and Disability in Multiple Sclerosis

Departments of Neurology and Radiology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
Journal of neuroimaging: official journal of the American Society of Neuroimaging (Impact Factor: 1.73). 03/2011; 22(2):122-8. DOI: 10.1111/j.1552-6569.2011.00589.x
Source: PubMed


To determine the interrelationships between MRI-defined lesion and atrophy measures of spinal cord involvement and brain involvement and their relationships to disability in a small cohort of patients with multiple sclerosis (MS).
Although it is known that cervical spinal cord atrophy correlates with disability in MS, it is unknown whether it is the most important determinant when compared to other regions of the central nervous system (CNS). Furthermore, it is not clear to what extent brain and cord lesions and atrophy are related.
3T MRI of the whole brain and whole spinal cord was obtained in 21 patients with MS, including 18 with relapsing-remitting, one with secondary progressive, one with primary progressive, and one with a clinically isolated syndrome. Brain global gray and white matter volumes were segmented with Statistical Parametric Mapping 8. Spinal cord contour volume was segmented in whole by a semi-automated method with bins assigned to either the cervical or thoracic regions. All CNS volumes were normalized by the intracranial volume. Brain and cord T2 hyperintense lesions were segmented using a semi-automated edge finding tool.
Among all MRI measures, only upper cervical spinal cord volume significantly correlated with Expanded Disability Status Scale score (r =-.515, P = .020). The brain cord relationships between whole or regional spinal cord volume or lesions and gray matter, white matter, or whole brain volume or whole brain lesions were generally weak and all nonsignificant.
In this preliminary study of mildly disabled, treated MS patients, cervical spinal cord atrophy most strongly correlates with physical disability in MS when accounting for a wide range of other CNS measures of lesions and atrophy, including thoracic or whole spinal cord volume, and cerebral gray, white or whole brain volume. The weak relationship between spinal cord and brain lesions and atrophy may suggest that they progress rather independently in patients with MS.

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    • "In people with multiple sclerosis (MS), combined clinical and MRI studies have shown that neurological disability cannot be explained by brain white matter (WM) lesions alone, and that brain and cervical cord atrophy both independently correlate with clinical impairments (Bonati et al., 2011; Cohen et al., 2012; Kearney et al., 2014a; Lukas et al., 2013). Further, throughout the clinical course of relapsing remitting (RR) and secondary progressive (SP) MS, cervical cord cross-sectional area at the C2/3 level appears to be more consistently and strongly associated with disability than either brain WM lesion load or brain atrophy (Bonati et al., 2011; Cohen et al., 2012; Kearney et al., 2014a; Lukas et al., 2013). Measurement of spinal cord cross-sectional area has developed using dedicated volumetric spinal cord MRI. "
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    ABSTRACT: Background: In multiple sclerosis (MS), recent work suggests that cervical cord atrophy is more consistently correlated with physical disability than brain white matter lesion load and atrophy. Although spinal cord imaging has not been routinely obtained in many clinical trial and research studies, brain volumetric imaging usually has and includes the upper cervical cord. Objectives: Using volumetric T1-weighted brain images, we investigated cross-sectional area measures in the uppermost cervical cord and compared them with areas at the standard C2/3 level. Methods: Using T1-weighted brain scans from 13 controls and 37 people with MS, and an active surface technique, cross-sectional area was measured over 5 mm and 1 mm cord segments at C2/3, below the level of odontoid peg, and 2 cm and 2.5 cm below the pons. Brain volume was also measured. Results: Cord area measurements were most reliable in a 5 mm segment 2.5 cm below the pons (inter-rater coefficient of variation 1.5%, intraclass correlation coefficient 0.99). Cord area at this level correlated more with that at C2/3 area than with brain volume (r=0.811 with C2/3, r=0.502 with brain volume). Conclusion: Whereas the standard C2/3 level is often not within the field of view on brain images, the level 2.5 cm below the pons usually is, and measurement at this level may be a good way to investigate upper cervical cord atrophy when only brain images are available.
    Multiple Sclerosis and Related Disorders 01/2015; 4(1-1):52-57. DOI:10.1016/j.msard.2014.11.004 · 0.88 Impact Factor
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    • "Consistent with the concept of disease heterogeneity, clinical progression and treatment response are difficult to predict in individual patients. Furthermore, there is a topographic uncoupling of structural changes such as the lack of a relationship between brain and spinal cord involvement [5]. Taken together, these data suggest that the pathogenesis of tissue injury may differ among patients with MS. "
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    ABSTRACT: Background While disease categories (i.e. clinical phenotypes) of multiple sclerosis (MS) are established, there remains MRI heterogeneity among patients within those definitions. MRI-defined lesions and atrophy show only moderate inter-correlations, suggesting that they represent partly different processes in MS. We assessed the ability of MRI-based categorization of cerebral lesions and atrophy in individual patients to identify distinct phenotypes. Methods We studied 175 patients with MS [age (mean ± SD) 42.7 ± 9.1 years, 124 (71%) women, Expanded Disability Status (EDSS) score 2.5 ± 2.3, n = 18 (10%) clinically isolated demyelinating syndrome (CIS), n = 115 (66%) relapsing-remitting (RR), and n = 42 (24%) secondary progressive (SP)]. Brain MRI measures included T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (to assess whole brain atrophy). Medians were used to create bins for each parameter, with patients assigned a low or high severity score. Results Four MRI phenotype categories emerged: Type I = low T2LV/mild atrophy [n = 67 (38%); CIS = 14, RR = 47, SP = 6]. Type II = high T2LV/mild atrophy [n = 21 (12%); RR = 19, SP = 2]; Type III = low T2LV/high atrophy [n = 21 (12%); CIS = 4, RR = 16, SP = 1]; Type IV = high T2LV/high atrophy [n = 66 (38%); RR = 33, SP = 33]. Type IV was the most disabled and was the only group showing a correlation between T2LV vs. BPF and MRI vs. EDSS score (all p < 0.05). Conclusions : We described MRI-categorization based on the relationship between lesions and atrophy in individual patients to identify four phenotypes in MS. Most patients have congruent extremes related to the degree of lesions and atrophy. However, many have a dissociation. Longitudinal studies will help define the stability of these patterns and their role in risk stratification.
    Journal of the Neurological Sciences 11/2014; 346(1-2). DOI:10.1016/j.jns.2014.08.047 · 2.47 Impact Factor
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    • "MRI analysts were unaware of clinical information. Our techniques are semi-automated, and we have established their operational procedures and high reliability 12,18,20–23. "
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    ABSTRACT: The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.6±1.7 (mean±SD). The cerebral normalized GM fraction (GMF), the T2 lesion volume (T2LV), and the ratio of T1 hypointense LV to T2LV (T1/T2) were derived from brain images. Upper cervical spinal cord area (UCCA) was obtained from spinal cord images. A within-subject d-score (difference of MS from normal control) for each MRI component was calculated, equally weighted, and summed to form MRDSS2. With regard to the relationship between physical disability and MRDSS2 or its individual components, MRI-Expanded Disability Status Scale correlations were significant for MRDSS2 (r=0.33, P=0.013) and UCCA (r=-0.33, P=0.015), but not for GMF (P=0.198), T2LV (P=0.707), and T1/T2 (P=0.240). The inclusion of UCCA appeared to drive this MRI-disability relationship in MRDSS2. With regard to cognition, MRDSS2 showed a larger effect size (P=0.035) than its individual components [GMF (P=0.081), T2LV (P=0. 179), T1/T2 (P=0.043), and UCCA (P=0.818)] in comparing cognitively impaired with cognitively preserved patients (defined by the Minimal Assessment of Cognitive Function in MS). Both cerebral lesions (T1/T2) and atrophy (GMF) appeared to drive this relationship. We describe a new version of the MRDSS, which has been expanded to include cerebral GM and spinal cord involvement. MRDSS2 has concurrent validity with clinical status.
    Neuroreport 08/2014; 25(14). DOI:10.1097/WNR.0000000000000244 · 1.52 Impact Factor
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