Association Between Thoracic Spinal Cord Gray Matter Atrophy and Disability in Multiple Sclerosis

Abstract

IMPORTANCE In multiple sclerosis (MS), upper cervical cord gray matter (GM) atrophy correlates more strongly with disability than does brain or cord white matter (WM) atrophy. The corresponding relationships in the thoracic cord are unknown owing to technical difficulties in assessing GM and WM compartments by conventional magnetic resonance imaging techniques.OBJECTIVES To investigate the associations between MS disability and disease type with lower thoracic cord GM and WM areas using phase-sensitive inversion recovery magnetic resonance imaging at 3T, as well as to compare these relationships with those obtained at upper cervical levels. DESIGN, SETTING, AND PARTICIPANTSBetween July 2013 and March 2014, a total of 142 patients with MS (aged 25-75 years; 86 women) and 20 healthy control individuals were included in this cross-sectional observational study conducted at an academic university hospital. MAIN OUTCOMES AND MEASURESTotal cord areas (TCAs), GM areas, and WM areas at the disc levels C2/C3, C3/C4, T8/9, and T9/10. Area differences between groups were assessed, with age and sex as covariates.RESULTS Patients with relapsing MS (RMS) had smaller thoracic cord GM areas than did ageand sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm 2 [9.2%]; P = .003 at T8/T9 and 0.93 mm 2 [8.0%]; P = .01 at T9/T10); however, there were no significant differences in either the WM area or TCA. Patients with progressive MS showed smaller GM areas (mean differences [COV]: 1.02 mm 2 [10.6%]; P < .001 at T8/T9 and 1.37 mm 2 [13.2%]; P < .001 at T9/T10) and TCAs (mean differences [COV]: 3.66 mm 2 [9.0%]; P < .001 at T8/T9 and 3.04 mm 2 [7.2%]; P = .004 at T9/T10) compared with patients with RMS. All measurements (GM, WM, and TCA) were inversely correlated with Expanded Disability Status Scale score. Thoracic cord GM areas were correlated with lower limb function. In multivariable models (which also included cord WM areas and T2 lesion number, brain WM volumes, brain T1 and fluid-attenuated inversion recovery lesion loads, age, sex, and disease duration), cervical cord GM areas had the strongest correlation with Expanded Disability Status Scale score followed by thoracic cord GM area and brain GM volume.CONCLUSIONS AND RELEVANCE Thoracic cord GM atrophy can be detected in vivo in the absence of WM atrophy in RMS. This atrophy is more pronounced in progressive MS than RMS and correlates with disability and lower limb function. Our results indicate that remarkable cord GM atrophy is present at multiple cervical and lower thoracic levels and, therefore, may reflect widespread cord GM degeneration.

Long‐term evolution of multiple sclerosis disability in the treatment era

“…For example, cross-sectional data demonstrated that EDSS is highly correlated with grey matter volume in the cervical and thoracic cord, independent of brain volume. 53,54 …”

Association of HLA Genetic Risk Burden With Disease Phenotypes in Multiple Sclerosis

“…14,15 The white matter area was obtained by subtracting the spinal cord gray matter area from the upper cervical cord area, and the ratio of spinal cord gray matter to the upper cervical cord area was also included in the analysis.…”

Fully automated grey and white matter spinal cord segmentation

“…In particular, the loss of axons in the spinal cord is thought to represent one of the main contributing factors to clinical disability. In vivo , axonal loss can be assessed indirectly by estimating the reduction in cervical cord cross-sectional area (CSA) over time (i.e., spinal cord atrophy) from magnetic resonance imaging (MRI) through the use of image segmentation methods; the reduction in CSA over time has been shown to correlate with clinical scores of physical disability234. It must be noted that the measure of cord CSA alone cannot differentiate between the individual rates of GM and WM atrophy, which may have different clinical relevance, and should be best studied independently5.…”

“…However, in pathologies such as multiple sclerosis (MS) where the presence of focal and diffuse lesions may obscure the boundary between tissue-types6, tissue-specific segmentation can be challenging, and may potentially lead to biased morphometric estimates. Spinal cord GM area was the strongest correlate of disability in MS using multivariate models that include brain GM and WM volumes, fluid-attenuated inversion recovery lesion load, T1 lesion load, spinal cord CSA, number of spinal cord T2 lesions, age, sex, and disease duration34.…”