Clinical forms of MS Flashcards
What are the Multiple Sclerosis Epidemiology?
- About 1 in 800 people in the UK have MS
- About 100,000 people in UK have MS
- It goes on for decades
What are the clinical features of MS?
- Weakness
- Altered sensation
- Numbness
- Pain
- Band-like sensation around torso (cord lesions)
- Lhermitte’s (cervical cord lesions)
- Sensation of water running down the back of their neck
- Sensory disturbance/visual problems
What is the Expanded Disability Status Scale?
- 10 point scale
- Biggest critique: it mostly affects patient’s ability to walk
- 0 = no disability, 10= death due to MS
- Cognition only contributes to scores below 4
- Mostly based on ability to walk
What is not strongly correlated with physical disability?
Cognitive impairment
What do 40-70% of people with MS have?
Cognitive impairment
Occurs early:
- Detectable following a clinically isolated syndrome
What are the cognitive deficit of Multiple Sclerosis?
- More marked in people with progressive disease
2. Not closely linked with neurological impairments
What are the clinically forms of MS?
- Relapsing remitting MS
- Secondary progressive MS
- Primary progressive MS
What is Relapsing remitting MS?
- Clearly defined relapses with full or partial recovery
2. No progression between relapses
What is secondary progressive MS?
- Follows RR MS
2. Progression with or without occassional relapses
What is primary progressive MS?
- Progression from onset
2. Occasional plateaus or minor improvements
What is relapsing remitting MS characterised initially by?
Episodes of neurological dysfunction
Last for at least 24 hours
People should not have change in their neurologcal function
What do people with secondary progressive MS note?
Neurological dysfunction increasing over time
What are the problems with clinical features of MS?
- Bias in research
- Relapses and remissions
- About 85% initially - Progressive:
- About 15%
What is the percentage of people with relapsing remitting MS will develop the secondary progression?
Eventually about 80%
What is benign MS?
Someone who has had multiple sclerosis for 10-15 years with low level of disability
What is the pathology of the multiple sclerosis?
- Inflammatory demyelination condition of white matter
- Evolves over time and so it is not a static process
- Multiple pathological processes that have different relevance at different stages of the disease
- Not just white matter
- Not just demyelination
- Dynamic
- Different processes may be more or less clinically relevant with time
What is classified as Multiple sclerosis?
White Matter Lesions
Why do we not observe grey matter lesions?
Contrast between demyelinate cortex and normal cortex is low
What is the pathology of multiple sclerosis (simplified)?
- Inflammation
- Demyelination
- Axonal transection
- Neuronal loss
- Gliosis
What is the role of myelin?
It doesn’t just enhance neuronal signal transmission but provides support to underlying axons
Where is neuronal loss observed?
Grey matter
What is Gliosis?
Scarring of the tissue where there has been inflammation which limits capacity for repair
What do lesions go through?
Dynamic processes
When does the lesion load increase?
As people transit from CIS to RRMS
When does the lesion load decrease in their rate of formation?
As they enter the progressive phase
When does the brain atrophy accelerate?
As people enter the progressive phase
Where are the more neurodegenerative features observed?
Grey matter
How do you look at white matter lesions?
T2 sequence of MRI
What is the clinico-radiological paradox?
Looking at correlation between number of T2 lesions and disability on the EDDS scale
What is the radiological paradox?
A lot of lesions are observed on the scan but in terms of explaining what is going on is a poor measure
What is the genetic aetiology of multiple sclerosis?
- About 25% concordance between identical twins
- About 3% concordance between non-identical twins
- HLA DRB1*1501
- IL7 and IL2
Where is multiple sclerosis more common in?
Northern-hemisphere countries
What is the environmental aetiology of multiple sclerosis?
- About 3% concordance between non-identical twins
- About 1.5% or less between non-twin siblings
- Sun exposure
- Vitamin D
- EBV
- Smoking
What is good at picking up white matter lesions?
PD
When will you see enhancing lesions?
When the BBB is disrupted and it will leak out
What will not all MS lesions do?
Enhance
Where does MS lesions tend to occur?
Around veins
Used to identify relatively characteristic features of WML
What is the evidence when you look at lesions?
There is both demyelination and remyelination potentially in the same lesions over time
What are the measures of detecting multiple sclerosis pathology (proton MRI)
- Magnetisation transfer
- Quantitative magnetisation transfer
- Myelin water fraction
- Diffusion Tensor Imaging
- Proton spectroscopy
What is the pathology of 1. Magnetisation transfer
- Quantitative magnetisation transfer
- Myelin water fraction and NAWM?
- Pathology: Demyelination and axonal loss
2. NAWM: Reduction in MTR
What is the pathology and NAWM of Diffusion Tensor Imaging?
- Pathology: Reductions in tissue integrity
2. NAWM: Decreased FA and Increased MD
What is the pathology and NAWM of Proton spectroscopy?
- Pathology: Neuroaxonal damage (N acetyl aspartate)
- Astroglial pathology (myo-inositol)
- NAWM: Decreased NAA and increased mins
What is the problem of non-proton MRI: Sodium (23NA)?
Less quality
What are non-proton MRI: Sodium (23Na) compared to proton MRI?
- 22,000 times less abundant
- Different resonance frequency
- Much faster T2 relaxation
What does a non-proton MRI: Sodium (23Na) require?
- Sodium coil
- Ultra short echo time sequence
- Optimised signal to noise
- Large voxels 4mm x 4mm x 4mm
- Scan time 23 minutes
Where do the lesions in MS occur?
Outer surface of the brain
What is cortical MTR?
- Gradient of demyelination in the cortex using MTR
- Lesions in the outer cortex
- Measure the MTR in outer cortex
- Shows more abnormalities in the outer cortex than inner cortex
- Tissue abnormalities within the cortex is not even pool of abnormalities
What is the difficulty with PET imaging?
- PET is very specific
- Traces very specific for cell lines e.g. astrocytic activation [myelin]
- Cannot keep injecting people with radiotracers
What happens during MRI:?
Exciting protons
What is more prone to atrophy than the brain?
Spinal cord
- More vulnerable
- Aggregating damage through tract degeneration
What are the agents for MS progressive treatment trials?
- Simvastatin
- Ocrelizumab
- Siponimod
- Lipoic acid
