Association between thoracic spinal cord gray matter atrophy and disability in multiple sclerosis

Regina Schlaeger*, Nico Papinutto, Alyssa H. Zhu, Iryna V. Lobach, Carolyn J. Bevan, Monica Bucci, Antonella Castellano, Jeffrey M. Gelfand, Jennifer S. Graves, Ari J. Green, Kesshi M. Jordan, Anisha Keshavan, Valentina Panara, William A. Stern, H. Christian Von Büdingen, Emmanuelle Waubant, Douglas S. Goodin, Bruce A.C. Cree, Stephen L. Hauser, Roland G. Henry

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


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 GMandWMcompartments by conventional magnetic resonance imaging techniques. Objectives To investigate the associations between MS disability and disease type with lower thoracic cord GM andWMareas using phase-sensitive inversion recovery magnetic resonance imaging at 3 T, as well as to compare these relationships with those obtained at upper cervical levels. Design, Setting, and Participants Between 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 Measures Total cord areas (TCAs), GM areas, andWMareas 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 relapsingMS (RMS) had smaller thoracic cord GM areas than did ageand sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm2 [9.2%]; P =.003 at T8/T9 and 0.93mm2 [8.0%]; P =.01 at T9/T10); however, there were no significant differences in either theWMarea or TCA. Patients with progressiveMS showed smaller GM areas (mean differences [COV]: 1.02mm2 [10.6%]; P <.001 at T8/T9 and 1.37mm2 [13.2%]; P <.001 at T9/T10) and TCAs (mean differences [COV]: 3.66mm2 [9.0%]; P <.001 at T8/T9 and 3.04mm2 [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 cordWMareas and T2 lesion number, brainWMvolumes, 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 ofWMatrophy in RMS. This atrophy is more pronounced in progressiveMS 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.

Original languageEnglish (US)
Pages (from-to)897-904
Number of pages8
JournalJAMA Neurology
Issue number8
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Clinical Neurology


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