Spinal Cord Demyelination Flashcards
Why is spinal cord pathology clinically relevant?
Up to 99% of multiple sclerosis (MS) cases have spinal cord (SC) affected at post-mortem studies
What does 75% of MS cases have?
Spinal cord abnormalities on MRI in vivo
What may cord lesions be?
asymptomatic in up to 50% of patients with clinically isolated syndrome (CIS) and early MS
What are the challenges of the spinal cord?
- Small size of the structure
- Cardiac pulsation and breathing motion artefacts
- Magnetic susceptibility at tissue/air/bone interface image distortions
What are the diagnosis of spinal cord demyelination?
- Demyelination in the spinal cord
- Typical features are hyperintensity on spinal cord on T2w scan
- High signal intensity at the level of the upper cervical cord
- Differentiate on routine clinical scans
- Different demyelination as focal lesions or diffuse lesions
- Focal lesions are easy to spot – well pronounced on image
- Diffuse lesions are those who are less evident in image – skill and expertise to spot them
What are discrete lesions?
- Similar MRI features to brain lesions
2. Dorsal and lateral columns of the cervical cord
What are diffuse abnormalities?
Mainly progressive MS
What can dissemination in space be demonstrated by?
one or more T2-hyperintense lesions that are characteristic of multiple sclerosis in two or more of four areas of the CNS: periventricular, cortical or juxtacortical and infratentorial brain regions, and the spinal cord
What can dissemination in time be demonstrated by?
simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time or by a new T2-hyperintense or gadolinium-enhancing lesion on follow up MRI, with reference to a baseline scan, irrespective of timing of baseline MRI
What is McDonald criteria 2017 based on?
Clinically isolated syndrome
Where are juxtacortical lesions located?
Higher up in the brain
Where are periventricular lesions located?
Lower down near the ventricles
Where are infratentorial lesions located?
Toward the base of the brain
What will patients with spinal cord lesions experience?
A second relapse much faster
What will 85% of people with CIS develop?
Multiple Sclerosis
Why is advanced spinal cord MRI used to understand?
Damage and repair
What are examples of advanced spinal cord MRI?
- Functional MRI (fMRI)
- Metabolic imaging (MRS)
- Structural Imaging (DWI)
- Volumetric imaging
Spinal cord fMRI in MS
- Extract from images the information about local blood flow in the spinal cord
- Apply a stimulus, the signal will be transferred back to the cord
What do MS patients show?
20% higher activation than healthy control
What was the average signal change of all the activated voxels within the cervical cord?
was 3.2% for healthy controls and 3.9% for MS patients
Where was there no difference found in fMRI cord activity between?
Patients with and without cervical cord T2 visible lesions
What is found in more disabled patients?
Greater fMRI activity
What suggests an adaptive response?
The correlation between greater spinal cord (and brain) damage and higher fMRI in patients
What is not a consequence of brain injury?
Spinal cord functional changes
In MRS, what does metabolites reflect?
pathological processes and metabolic cellular functions
What will each metabolite give?
Specific information about the metabolic cellular functions or pathological processes in spinal cord
What are the main metabolites found in concentrated amount?
- NAA
- Creatine
- Myo-inositol
How can you optimise the acquisition of MRS?
Using a press sequence recently in the healthy controls
In literature, what are the NAA findings in MS?
- In the study they used different magnetic field strength and different disease groups to study NAA
- In all cases there was a reduction in the NAA this can be used as a marker of the pathology that happens in spinal cord
What is the significance of reduced NAA?
Explain neuronal/axonal loss
Gives information about mitochondrial function or dysfunction
Neuronal metabolic dysfunction
You can observe how the NAA peak changes depending on the tissue damage
What did patients who recovered show?
Sustained increase in NAA after 1 month
Associated with greater recovery
How was a worse recovery predicted?
A longer disease duration at study entry
What can Myo-inostiol be used to differentiate?
Between diseases e.g. MS and NMO
What is there a huge difference between?
NAA concentration which can help diagnosis
What are the main messages in regards to the MRS?
- Cervical cord NAA and myo-inositol reflect the underlying metabolic state of the tissue which contributes to disability
- Longitudinal studies suggest that NAA reflects dynamic changes occurring in the tissue
- Partial recovery of NAA is associated with clinical recovery (enhanced mitochondrial activity)
What is DWI used to study?
The various tracts in SC and the the various sensory and motor columns
What was the main matrix identified?
- RD
- FA
Give enhanced information about the mircostructural damage
What are the main messages of DWI + Tractography?
- Reduced FA and connectivity in tracts suggest reduced fibre integrity (mainly demyelination) that contributes to disability in the acute phase
- FA is relevant to disability status in patients with high lesion load
- The predictive role of RD and FA and their dynamic changes over time suggest that they reflect important processes
Where is the spinal cord atrophy typically measured in?
Upper cervical cord
What does spinal cord atrophy acquire?
A higher resolution scan and measure area of the cord over time
What is an indication of demyelination/
Measuring the atrophy of the cord over time
What is a biomarker for clinical trials?
When the axons die and cord shrinks
This is an irreversible process
What is not present for progressive form of MS?
Many treatments
What is the strongest biomarker for explaining disability in MS?
Measuring upper cervical area
It correlates with main clinical tools for testing disability:EDDS
What is lesion load?
- looking at lesion volume
- measure volume of lesions
- optimised acquisition that can show very high-resolution images of SC
- differentiate between grey and white matter
- see exactly where the lesion is situated
- spinal cord lesion load measured quantitatively on axial 3D-PSIR independently associated with EDSS
What did Relapsing MS patients show?
smaller SC GM areas than age- and sex-matched controls (p = 0.008) without significant differences in SC WM areas
What independently contributed to EDSS?
Brain and spinal Grey matter
GM vs. WM columns abnormalities:
- Studied the various diffusion matrix in grey matter similar to atrophy measures
- Demonstrated that there are indeed changes in the GM that can independently associated with disability scores
- Diffusion to study GM is that detect changes in GM before there is shrinkage
- See diffusion matrix changing before atrophy then it means picking up changes much quicker
What do people with MS often have?
- Bladder problems
- Sexual dysfunction
- Controlled by neural supply for these organs are in lower cord
Why should methods be developed to study?
Lower cord to measure grey matter and white matter atrophy in the lower cord
Adapt the quantitative MRI used in upper cord to lower cord to understand more about the pathology
What are new metabolites that should be investigated?
- GABA
- Aspartate
- Glutathione
