Spinal Cord, Retinal Measures Independently Relate to MS Disability
New research found statistically significant correlations between MRI measures of the spinal cord, optical coherence tomography measures of the retina, and clinical disability
Two common categories of multiple sclerosis symptoms, visual and sensorimotor, are associated with lesions in the spinal cord (SC) and optic nerve. The symptoms also co-occur frequently in specific classes of demyelinating diseases such as neuromyelitis optica. Researchers from Johns Hopkins University recently tested for a relationship between the two central nervous system structures (Oh et al., 2015).
The team conducted MRI scans of the spinal cord and optical coherence tomography scans of the retinas of 11 healthy controls and 102 patients with MS: 66 relapsing-remitting and 36 progressive. They assessed the participants for visual acuity and sensorimotor dysfunction, and then looked for statistical associations between scans and clinical phenotype.
In a univariate analysis the investigators found that several SC-related measures were associated with the peripapillary retinal nerve fiber layer (pRNFL). Incorporating those factors into a multivariate statistical model that controlled for age, sex, and prior optic neuritis, the team then analyzed SC cross-sectional area (SC-CSA), pRNFL, and brain parenchymal fraction . They found that SC-CSA and pRNFL independently correlated with multiple clinical measures. Specifically, both measures had statistically significant associations with low-contrast visual acuity (CSA: p = 0.04; pRNFL: p = 0.002), high-contrast visual acuity (CSA: p = 0.06, pRNFL: p = 0.008) and vibration sensation threshold (CSA: p = 0.01; pRNFL: p = 0.05). Additionally, SC-CSA had a significant association with Expanded Disability Status Scale (p = 0.001), but pRNFL did not associate with EDSS.
The study adds credence to the intuitive notion that MS has global effects on the central nervous system (CNS). Rather than causing damage in the brain alone, the disease affects all areas of the CNS and, as these data suggest, damage in the SC and optic nerve may be more closely associated with specific clinical symptoms of MS than with brain damage and atrophy.
But the study also had its limitations. The control group was rather small, and though 102 MS patients is a reasonable cohort size, the statistical power dwindles when they are examined by relapsing and progressive subgroups.
In the article, the authors suggest that in the future, SC and retinal scans may supplement brain scans to illuminate causes for specific variations in clinical disability. If their findings are validated, they went on to write, the approach would also better researchers’ understanding of the disease course and progression.
Key open questions
- What is the specific clinical utility of this approach?
- How might these findings affect areas of treatment such as physical therapy?
Disclosures and sources of funding
This work was funded by the Multiple Sclerosis Society of Canada Transitional Career Development Award, NIH R01NS08234 R01 NS082347, NIH K01 HDO49476, and the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. Some of the authors reported relationships with various companies, including Abbott, Acorda, Bayer, Biogen Idec, Diagnosoft, EMD Serono, Genzyme, Medical Logix, MedImmune, Novartis, Teva Neurosciences, Vaccinex, and Vertex.
This is important because it compares retinal and cord volumes directly, though I know there are some people who will disagree with the conclusions. They conclude that their data show the global nature of the disease, which is a very attractive thing to say, but it’s not 100% clear to me they’ve proved that. However, this notion of global disease is further supported by the recent report from our group and others showing strong relationships between upper cervical cord GM areas and metrics and EDSS; one way to interpret these results is that the cervical cord pathology reflects global changes and thereby correlates with the EDSS. I think that it gives you a nice hypothesis to work from, but these results need to be validated in a larger cohort. I’m surprised by the results that do not show differences in retinal layer thickness between relapsing and progressive patients, which seems to contradict earlier studies; the spinal cord shows significant differences between these groups from this study and previous ones.
Reference: Ann Neurol. 2014 Oct;76(4):568-80. doi: 10.1002/ana.24241. Epub 2014 Aug 21.
Spinal cord gray matter atrophy correlates with multiple sclerosis disability.
Schlaeger R, Papinutto N, Panara V, Bevan C, Lobach IV, Bucci M, Caverzasi E, Gelfand JM, Green AJ, Jordan KM, Stern WA, von Büdingen HC, Waubant E, Zhu AH, Goodin DS, Cree BA, Hauser SL, Henry RG.