Progressive Model of MS

Gilli F, Chen X, Pachner AR, Gimi B. High-Resolution Diffusion Tensor Spinal Cord MRI Measures as Biomarkers of Disability Progression in a Rodent Model of Progressive Multiple Sclerosis.PLoS One. 2016;11(7):e0160071

Disease in the spinal cord is a major component of disability in multiple sclerosis, yet current techniques of imaging spinal cord injury are insensitive and non-specific. This study seeks to remove this major impediment to research in multiple sclerosis and other spinal cord diseases by identifying reliable biomarkers of disability progression using diffusion tensor imaging (DTI), a magnetic resonance imaging technique, to evaluate the spinal cord in a model of multiple sclerosis, i.e. the Theiler’s Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD). Mice with TMEV-IDD with varying levels of clinical disease were imaged using a 9.4T small animal MRI scanner. Axial diffusivity, radial diffusivity, and fractional anisotropy were calculated. Disability was assessed periodically using Rotarod assay and data were expressed as a neurological function index. Correlation was performed between DTI measurements and disability scores. TMEV-IDD mice displayed significant increased neurological deficits over time when compared with controls (p<0.0001). Concurrently, the values of fractional anisotropy and axial diffusivity were both decreased compared to controls (both p<0.0001), while radial diffusivity was increased (p<0.0001). Overall, fractional anisotropy changes were larger in white matter than in grey matter and differences were more pronounced in the ventral region. Lower disability scores were associated with decreased fractional anisotropy values measured in the ventral (r = 0.68; p<0.0001) and ventral-lateral (r = 0.70; p<0.0001) regions of the white matter. These data demonstrate that DTI measures of the spinal cord contribute to strengthening the association between neuroradiological markers and clinical disability, and support the use of DTI measures in spinal cord imaging in MS patients.

A model of progressive MS?. I was interested, but then when I saw the model it was a viral model of MS, which was reported to be a demyelinating model of MS. This polio-like virus infects mice and causes myelin damage and animals show limb mobility issues. Other people claim that this model is a model of virus induced autoimmunity where damage to myelin producing cells triggers an autoimmune disease. These authors claim it is a progressive model. 

This study looks at Fractional anisotropy (FA) is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. 

FA is a measure often used in diffusion imaging where it is thought to reflect fibere density, axonal diameter, and myelination in white matter.  

So this paper says that as animals get more disabled they show less fractional anisotrophy so less evidence of diffusion in one direction (i.e. normal myelinated nerves) so more damage. So this would be expected because disability is related to nerve content, but the resolution of images in a mouse spinal cord is quite low. 

Is this going to tell us about progressive MS, I’m not yet sure. Let’s see how it responses to immunotherapy and neuroprotection. 

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