RESEARCH HIGHLIGHTS Nature Reviews Neurology 10, 425 (2014); published online 22 July 2014; doi:10.1038/nrneurol.2014.127

MULTIPLE SCLEROSIS

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ultiple sclerosis (MS) is associated with spinal cord degeneration, but little is known about how this aspect of CNS pathology relates to disease progression. In two recently published studies, MRI of the cervical spinal cord has revealed how abnormalities associated with MS manifest and change over time. In the first study, Hugh Kearney and colleagues investigated whether MS-related damage to the spinal meninges could be measured in vivo. “A number of postmortem papers have demonstrated meningeal inflammation in the brains of patients with MS, with colocalization of subpial demyelination,” says Kearney. “More recently, meningeal inflammation has been demonstrated in the spinal cord, and this process is reported to be associated with axonal loss.” Axonal loss in the spinal cord is a key source of irreversible disability in patients with MS. Elucidation of the potential involvement of meningeal inflammation in spinal degeneration might reveal new biomarkers for monitoring patients with MS, and could inform treatment development. The researchers recruited participants from across the MS disease spectrum— including patients with clinically isolated syndrome, relapsing–remitting MS, secondary progressive MS and primary progressive MS—as well as healthy controls. A total of 133 participants underwent MRI scans focusing on the brain and cervical spinal cord. To measure inflammation in the spinal pia mater, the authors used magnetization transfer imaging, which can reveal tissue integrity by measuring the ratio of proteinbound water molecules (like those in the meninges) to free water molecules (such as in cerebrospinal fluid). “Magnetization transfer imaging has been shown in ex vivo studies to reflect both inflammation and demyelination,” explains Kearney. Compared with healthy controls, all of the patient groups had reduced magnetization transfer ratios (MTRs)

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Spinal cord MRI reveals progression-related MS pathology

in the voxels thought to contain the pia mater and subpial tissue, suggesting meningeal inflammation. Furthermore, inflammation was significantly worse in relapsing–remitting patients than in those with clinically isolated syndrome, and was worse still in patients with progressive forms of MS. Kearney and colleagues also report a significant reduction in cross-sectional spinal cord area in patients with progressive forms of MS compared with healthy controls. Moreover, in all participants, MTRs in the outer spinal cord correlated independently with spinal cord area. “This finding is in line with postmortem studies that have demonstrated an association between meningeal inflammation and axonal loss in the spinal cord,” explains Kearney. The authors are currently planning to confirm their results by combining ex vivo imaging with histopathological analyses. They also hope that future experiments will examine whether MRI can be used to measure meningeal inflammation in the brain. In the second study, Carsten Lukas and co-workers further explored how spinal cord atrophy develops in patients with MS. Between two centres,

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the authors recruited 352 patients with relapsing–remitting, secondary progressive or primary progressive MS, and conducted longitudinal clinical and MRI examinations. At baseline, cross-sectional spinal cord area was lower in patients with progressive forms of MS than in those with relapsing– remitting MS. In follow-up examinations 12 and 24 months later, patients in all three groups demonstrated reductions in spinal cord area, with the annualized rates of atrophy ranging from 1–2% reductions in volume per year. Higher annualized spinal cord atrophy rates correlated with greater reductions in total brain volume and grey matter volume, as well as with increases in the volume of T1-hypointense brain lesions. The researchers also compared MRI changes between patients who did and did not experience disease progression, regardless of prior diagnosis. “Patients suffering disease progression during the follow-up period had significantly higher rates of cervical cord atrophy than patients with a stable disease course,” says Lukas. Importantly, brain and lesion volume changes did not differ between these patient groups. This result implies that clinical progression is more related to spinal cord pathology than to brain changes, Lukas explains. Further investigations are needed to address the predictive validity of this relationship. Brain MRI is frequently included as an outcome measure in clinical trials for MS, but the spinal cord is rarely assessed. Future trials might benefit from including measurements of inflammation and atrophy in the spinal cord. Alex Chase Original articles Kearney, H. et al. Investigation of magnetization transfer ratio-derived pial and subpial abnormalities in the multiple sclerosis spinal cord. Brain doi:10.1093/brain/awu171 | Lukas, C. et al. Cervical spinal cord volume loss is related to clinical disability progression in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry doi:10.1136/jnnp-2014-308021

VOLUME 10  |  AUGUST 2014 © 2014 Macmillan Publishers Limited. All rights reserved

Multiple sclerosis: Spinal cord MRI reveals progression-related MS pathology.

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