Thursday, 19 March 2015

Spinal cord pathology

Gass A, Rocca MA, Agosta F, Ciccarelli O, Chard D, Valsasina P, Brooks JC, Bischof A, Eisele P, Kappos L, Barkhof F, Filippi M; for the MAGNIMS Study Group. MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis.Lancet Neurol. 2015 Mar 3. pii: S1474-4422(14)70294-7. doi: 10.1016/S1474-4422(14)70294-7. [Epub ahead of print]

The spinal cord is a clinically important site that is affected by pathological changes in most patients with multiple sclerosis; however, imaging of the spinal cord with conventional MRI can be difficult. Improvements in MRI provide a major advantage for spinal cord imaging, with better signal-to-noise ratio and improved spatial resolution. Through the use of multiplanar MRI, identification of diffuse and focal changes in the whole spinal cord is now routinely possible. Corroborated by related histopathological analyses, several new techniques, such as magnetisation transfer, diffusion tension imaging, functional MRI, and proton magnetic resonance spectroscopy, can detect non-focal, spinal cord pathological changes in patients with multiple sclerosis. Additionally, functional MRI can reveal changes in the response pattern to sensory stimulation in patients with multiple sclerosis. Through use of these techniques, findings of cord atrophy, intrinsic cord damage, and adaptation are shown to occur largely independently of focal spinal cord lesion load, which emphasises their relevance in depiction of the true burden of disease. Combinations of magnetisation transfer ratio or diffusion tension imaging indices with cord atrophy markers seem to be the most robust and meaningful biomarkers to monitor disease evolution in early multiple sclerosis.


The spinal cord in MS has been under MRI scrutiny for well over 20 years (http://www.ncbi.nlm.nih.gov/pubmed/8255468) and yet spinal cord MRI plays a far lesser role in MS than imaging of the brain.  This seems surprising given the bias of the EDSS towards limb function and walking, functions frequently associated with spinal cord damage.  However, neither lesion detection (indicating focal demyelination) nor measuring spinal cord diameter (as tentative correlate of axonal preservation & loss) have fulfilled the promise of being reliable measures of spinal cord function.  Careful study reveals that removing some "cables" (= loss of axons) does not directly translate into loss of spinal cord volume.  This may due to compensatory mechanisms, such as gliosis (scar tissue formation) "filling in the gaps" thereby counteracting the expected volume loss.  The conclusion of this review is that several MRI techniques need to be combined to comprehensively characterise the spinal cord in MS.  We will discuss one of these techniques at the Research Day.

7 comments:

  1. And spinal cord imaging is not routine in the UK under the NHS.........
    Thankfully I don't live in the UK so at least I know about my personal collection of unwanted intruders in my spinal cord! I wish they'd sod off though and let my legs do what I try to tell them to do - fat chance unfortunately.

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  2. Dr. K how does imaging using MRI compare to histology of post mortem spinal cords in MS? I would believe that MRI would provide a more sensitive measure of cord pathology in early stages of the disease. Also, in brain MRI, the clincal-radiological paradox shows the disconnect between lesion load and disability levels in some patients. I imagine the damage in the cord would not show a clinical-radiological disparity due its physical limitations, if a lesion is present then there will be a deficit depending on the location. Spinal cord lesions would seem to be a bigger challenge to therapy than brain lesions?

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    1. There are a number of MRI indices out there to assess the spinal cord, summarized in the review discussed. These MRI indices allow inferences about the underlying pathology. Just as we had to learn that lesions in the brain, and certainly the "images of lesions" we obtain using MRI, are not explaining the entire clinical syndrome of MS, imaging the spinal cord has been somewhat underwhelming in terms of predicting future disability. I agree lesions in the spinal cord are generally more often symptomatic than lesions in the brain. However, about 25% of spinal cord lesions are asymptomatic. Despite (hopefully) full recovery from symptoms caused by a spinal cord lesion it is uncommon for them to vanish completely on MRI. Why? The dynamics of MS lesions evolution means that once a lesion has formed, there are two pathways: either remyelination of axons not destroyed during the acute attack ensues (repair), or gliosis (scar tissue) forms. A difference in the water content/dynamics of both outcomes (remyelination and gliosis), however, means the affected area (the "lesion" deteced on MRI) remain visible, and often indistinguishable from a new lesion, unless there is contrast-enhancement, which is less commonly seen in spinal cord compared to brain lesions. So, in conclusion, the clinico-radiological paradox also applies to the spinal cord. We - among other teams around the globe - are working on techniques to better characterise what is happening inside (and outside) of spinal cord lesions depicted by conventional MRI, and correlate so called “quantitative” MRI techniques with histological markers. In fact, we've done it before (see below), but there's more to do...

      http://download.springer.com/static/pdf/153/art%253A10.1007%252Fs00415-003-0192-3.pdf?auth66=1426847183_dc95120d8adc8199755457e6eb1b7e92&ext=.pdf

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  3. I was just recently diagnosed with MS. All lesions were in my brain according the radiologist's report. However, it was noted that the spinal cord images were motion degraded. Is it possible to miss a lesion(s) due to motion degradation of the images? The reason I ask is because some sx that I am experiencing that seem to be consistent with spinal cord lesions. Just curious.... thanks

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    1. Yes it is possible to miss lesions in the spinal cord due to motion as you breathe.

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    2. Agree MD2, and it's not only breathing. Sometimes people can become quite uncomfortable in the scanner, claustrophobia being one reason, but in pwMS pain, spasticity, and problems with bladder control more common.

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    3. Sedation for pwMS who are uncomfortable with MRI

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