Monday, 11 August 2014

Spinal cord grey matter shrinkage correlates with disability

How big is your spinal cord? Spinal cord shrinkage is bad. #MSBlog #MSResearch

"Two studies below demonstrate that the cross-sectional surface area of spinal cord gray matter is as a predictor of disability in MS. This is not surprising; as you lose neurons and their axons the spinal cord gray matter will shrink. Measuring by how much it has shrunk tells you how many neurons and axons are lost and is a very good indicator of disability at the group level. I say group level as there is a lot of overlap in spinal cord. and spinal cord gray matter, size between normal subjects and MSers. What is therefore important is serial changes over time; i.e. MSers whose spinal cords don't shrink will do better than MSers whose spinal do. The nice thing about the spinal cord is that it relates directly to well-defined functions, for example upper and lower limb power, walking, sensory function in the limbs and bladder, bowel and sexual function. In comparison the brain is much more complex with many functions that are difficult to measure in every day practice."

"Can these spinal cord MRI measured be used clinically? Yes, in clinical trials or controlled academic settings. The problem with using the measures described below in routine clinical practice is that they require special sequences (programmes to run the MRI scanner) and image analysis software that analyses the MRI data off-line. The latter tends to be propriety and done in specialist academic centres. What would we do if we showed your spinal cord was shrinking faster than normal? Would we switch your treatment? I suspect we would if there was other evidence to suggest your disease was active. However, to switch or escalate treatment based on spinal cord metrics alone would be difficult at present as it has not been shown to be modifiable by DMTs in clinical trials."

STUDY 1 (Epub): Schlaeger et al. Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Ann Neurol. 2014. doi: 10.1002/ana.24241.

Objective: In MS cerebral gray matter (GM) atrophy correlates more strongly than white matter (WM) atrophy with disability. The corresponding relationships in the spinal cord (SC) are unknown due to technical limitations in assessing SCGM atrophy. Using phase sensitive inversion recovery (PSIR) MRI, we determined the association of the SCGM and SCWM areas with MS disability and disease type.

Methods: 113 MSers and 20 healthy controls were examined at 3T with a PSIR sequence acquired at the C2/C3 disc level. Two independent, clinically-masked readers measured the cord WM and GM areas. Correlations between cord areas and Expanded Disability Status Score (EDSS) were determined. Differences in areas between groups were assessed with age and sex as covariates. 

Results: RRMSers showed smaller SCGM areas than age and sex matched controls (p=0.008) without significant differences in SCWM areas. Progressive MSers showed smaller SCGM and SCWM areas compared to RRMSers (all p≤0.004). SCGM, SCWM, and whole cord areas inversely correlated with EDSS (rho: -0.60, -0.32, -0.42, respectively; all p≤0.001). SCGM area was the strongest correlate of disability in models including brain GM and WM volumes, FLAIR lesion load, T1-lesion load, SCWM area, number of spinal cord T2 lesions, age, sex, disease duration. Brain and spinal GM independently contributed to EDSS.

Interpretation: SCGM atrophy is detectable in-vivo in absence of WM atrophy in RMS. It is more pronounced in progressive than RMS and contributes more to patient disability than spinal cord WM or brain GM atrophy.

STUDY 2: Kearney et al. Spinal cord grey matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014 Aug. pii: jnnp-2014-308241.

BACKGROUND: In MS, pathological studies have identified substantial demyelination and neuronal loss in the spinal cord grey matter (GM). However, there has been limited in vivo investigation of cord GM abnormalities and their possible functional effects using MRI combined with clinical evaluation.

METHODS: We recruited healthy controls (HC) and people with a clinically isolated syndrome (CIS), relapsing remitting (RR) and secondary progressive (SP) MS. All subjects had 3 T spinal cord MRI with measurement of cord cross-sectional area and diffusion tensor imaging metrics in the GM and posterior and lateral column white matter tracts using region of interest analysis. Physical disability was assessed using the expanded disability status scale (EDSS) and motor components of the MS functional composite scale. We calculated differences between MS and HC using a ANOVA and associations with disability using linear regression.

RESULTS: 113 MSers were included in this study: 30 controls, 21 CIS, 33 RR and 29 SPMS. Spinal cord radial diffusivity (RD), fractional anisotropy and mean diffusivity in the GM and posterior columns were significantly more abnormal in SPMS than in RRMS. Spinal cord GM RD (β=0.33, p<0.01) and cord area (β=-0.45, p<0.01) were independently associated with EDSS (R2=0.77); spinal cord GM RD was also independently associated with a 9-hole peg test (β=-0.33, p<0.01) and timed walk (β=-0.20, p=0.04).

CONCLUSIONS: The study findings suggest that pathological involvement of the spinal cord GM contributes significantly to physical disability in relapse-onset MS and SPMS in particular.

P.S. MouseDoc says " Remember the shrinkage seen on MRI is a balance between nerve loss are real shrinkage verses scarring and swelling filling up the space of lost nerves, so the situation may be worse and this is the case pathicularly in the white mater"


  1. Why is this finding not used as a biomarker in clinical trials?

    Where is the point at looking a the brain while it seems to be the spinal cord which holds all the answers?

    1. It is used in clinical trials, e.g. INFORMS. Fingolimod in PPMS. Cervical spinal cord volume on MRI is measured. First results are expected end of the year.

  2. Good point, some of these MRI readings are not standard MR outcomes

    1. I'm going for a MRT of my spinal cord next week (the upper part).

      Is it true that the lesions (the ones which matter for walking) appear in the upper part of the cord?

    2. yes. that is where mine are. good luck with mri.

    3. Thank you very much :-)

  3. You mention that studies have not shown spinal chord atrophy is impacted by DMT. Is this because we haven't measured this, or are even the DMT's that reduce brain atrophy not protecting against spinal atrophy? Or is this more of a relative point (i.e. nothing differentially impacts spinal chord atrophy vs overall atrophy)?

  4. Do you docs know if it's possible to have a normal looking spinal cord despite symptoms?

    I've just come back from MRI and the doc found nothing at all - perhaps the problem is the machine at 1.5 T?

    I am very surprised cos I've got balance problems and had L'hermitte.


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