Clinical Research in MS

Question 1

Epidemiology of MS

Answer 1

2:1 female to male
Mean onset between 29-39
More than 130000 people in UK
Figures increasing as MS can be diagnosed with MRI

Question 2

Relapsing Remitting MS

Answer 2

Clear relapses with full or partial recovery
No progression between relapses
About 85% of patients

Question 3

Secondary Progressive MS

Answer 3

Follows RR MS
Progression with or without relapses

Question 4

Primary progressive MS

Answer 4

Progression from onset
Occasional plateaus/minor improvement
About 15% of patients

Question 5

Clinical features of MS

Answer 5

Weakness
Altered sensation -> numbness, pain, band-like sensation around torso, Lhermitte’s
Visual dysfunction -> optic nerve damage, eye movement abnormalities
Cerebellar dysfunction
Bowel and bladder dysfunction
Fatigue
Cognitive impairment

Question 6

Expanded Disability Status Scale

Answer 6

Scaled from 0 (no disability) to 10 (death from MS)
Mostly based on ability to walk
Does not take into account cognition
Does not match progression of MS

Question 7

Pathology of MS

Answer 7

Inflammatory demyelinating
WM, GM and spinal cord lesions
Inflammation, ionic imbalance, demyelination, excitotoxicity, energy failure, microglia/astrocyte activation, neuroaxonal degeneration

Question 8

WML

Answer 8

Can form and repair as some remyelination occurs
Do not explain majority of disability (neurodegeneration does)

Question 9

Aetiology of MS

Answer 9

Some genetic components -> IL7, IL2, HLA DRB1*1501
Some environmental components -> lack of sun exposure, vitamin D deficiency, EBV, smoking

Question 10

Gadolinium lesion contrast enhancement

Answer 10

Enhances lesions to allow older and newer lesions to be seen
Those with inflammation are newer
Allows for dissemination in time

Question 11

Perivenous location

Answer 11

Lesions form along veins -> distinguishes them from lesions in other disorders such as ischaemia and migraine

Question 12

Remyelination

Answer 12

Molecule incorporated into radiotracer to identify demyelinating and remyelinating voxels

Question 13

Proton MRI

Answer 13

Magnetisation transfer, QMT and myelin water fraction -> reductions in MTR detect demyelination and axonal loss

Diffusion tensor imaging -> increased MD and decreased FA detect reductions in tissue integrity

Proton spectroscopy -> decreased NAA detects neuroaxonal damage and increases mIns detects astroglial pathology

Question 14

Sodium MRI

Answer 14

Sodium accumulates in dysfunctioning neurons
Create tissue sodium concentration maps

Question 15

Double Inversion Recovery

Answer 15

FLAIR -> knocks out signal from CSF
DIR -> knocks out signal from CSF and WM
Helps to visualise GML which are on the outer layer of cortex

Question 16

Cortical MTR

Answer 16

Has a higher field strength which produces a higher resolution to detect cortical changes
But has an issue with anything magnetic (tattoos warm up)

Question 17

Structural Networks

Answer 17

Considering networks helps to improve correlation between lesions and disability
e.g., reduction in volume and integrity of thalamus, but increase in connectivity

Question 18

Licensed Disease Modifying Treatments

Answer 18

All target inflammation and most for RR MS

Question 19

MRI Lesions as a Surrogate for relapses

Answer 19

Visible MRI lesions correlate well with relapses so can be used as a surrogate in early phase clinical trials
Reduces the number of patients required

Question 20

Treatments to slow progression

Answer 20

Phase II -> simvastatin, lipoic acid, biotin

Phase III -> ocrelizumab, siponimod

Question 21

Remyelinating trials

Answer 21

RXR agonist
Anti-LINGO-1
Olexosine
Histamine receptor antagonists
Mesenchymal stem cells

• Outcome measures are MRI and PET
• Magnetisation transfer ratio can be used as a marker of remyelination