MS Flashcards
What is MS? What is the pathology?
A chronic autoimmune T-cell mediated inflammatory disorder of the CNS
Leads to inflammatory processes within the white matter of brain and spinal cord
Leads to plaques of demyelination affecting white matter and tracts within CNS
Where is MS common?
Europe and North America, more common away from the equator, even within the UK it is more common up north
UK prevalence of MS
Approx 80,000 people have it which is 1.2 in 1000
M:F for MS
F:M 2:1 and is becoming wider - females becoming more affected
Age of onset of MS
20-40 years
Environmental risk factors for MS x4
Migrating from low risk area to high risk area
Viral infections can precipitate MS relapses and development of MS in susceptible individuals
Evidence of MS and EBV relationship
Exposure to infectious agents in children may reduce risk of developing MS and other autoimmune disorders
Genetic susceptibility for MS
MZ = 30% concordance, DZ = 5% concordance
Over 60 genes found to be involved - polygenic disorder
80% of these related to immune system function and regulation
Pathology of MS - what part of CNS is affected?
Plaques of demyelination 2-10mm in size in white matter (sometimes grey matter)
Axons relatively intact
Pathology of MS - What causes the damage?
Evidence suggests a role of cytokines and inflammatory infiltrate - lymphocytes etc
Can get interstitial oedema in acute lesions
Pathology of MS - Where in CNS in most commonly affected? x6
Optic nerves, periventricular region, corpus callosum, brainstem, cerebellar connections and cervical cord
What causes MS relapse?
Focal inflammation with loss of myelination and conduction block
Recovery when inflammation goes down and nerves can remyelinate
If no remyelination - progressive disease
Which is most common form of MS?
Relapsing-remitting MS (RRMS)
85-90% of cases
Relapsing attacks and okay between times
Average 1 relapse per year
Onset over days and recovery over weeks
What usually follows RRMS?
Secondary-progressive - typically after 35years of RRMS
Gradual worsening of the disease over the years
Can still sometimes get relapses = relapsing-progressive
What is 3rd least common type of MS?
Primary-progressive - 10-15%
No relapses but progressively worse disease. Usually less plaques/inflammatory changes on MRI and develops later
What is benign MS?
When years between relapses - but term used with caution
What are the 3 main types of symptoms?
Optic neuritis, brainstem lesions and spinal cord lesions
Details about optic neuritis?
1st symptom in 20% of MS patients
Inflammatory optic neuropathy associated with pain and vision problems - usually unilateral
Also get RAPD
Details about brainstem demyelination?
Diplopia, vertigo, facial weakness/numbness, dysphagia or dysarthria
Pyramidal signs if corticospinal tracts involved
Spinal cord lesions?!
Paraparesis, tetraparesis - due to plaque in thoracic or cervical cord.
Tight band around chest if thoracic
Lhermitte’s symptom on flexion of neck - electric shock type symptoms
General symptoms which accumulate over years x11
1) Vision Loss
2) Sensory symptoms
3) Clumsy/useless hand or limb
4) Unsteadiness/ataxia
5) Neuropathic pain
6) Spasticity
7) Urinary incontinence
8) Sexual dysfunction
9) Fatigue
10) Depression
11) Uhthoff’s phenomenon - worse with heat, eg. exercise, bath
Progression of MS generally
15 years walking aid and 25years wheelchair
Diagnosis of MS
2 attacks separated in time and place needed (different CNS lesions at different times - an MRI at least 1 month after the first MRI which shows development of new plaques)
One MRI is not sufficient because can have lots of incidental findings of asymptomatic plaques
Investigations in MS x5
MRI Brain and Spinal Cord shows hyperintense lesions - oval up to 2cm in diameter
- Has limited specificity in over 50 because ischeamic lesions can look like demyelination
CT not very useful
CSF will show oligoclonal IgG in around 95% but not specific for MS - will also get raised WCC and proteins in 25% of patients
Blood tests to exclude other inflammatory disorders (SLE or sarcoid)
Evoked potentials - visual, brainstem (auditory) and somatosensory
Treatment of MS
There is no cure
Disease modifying drugs =
Beta-interferon and glatiramer acetate - very expensive but can reduce relapse rate by 1/3 and serious relapses by up to 1/2 in RRMS - short term reduction of disability
SE’s = flu like symptoms and irritation at injection site (SC or IM)
Advised following 2 serious relapses in 1 year or 1 seriously debilitating relapse
Not effective in PPMS or SPMS
Stopped before pregnancy and in breastfeeding
MS generally in pregnancy
Relapses decreased in pregnancy, especially 3rd trimester but increases first 3 months after birth
Symptomatic treatment for bladder dysfunction in MS
Anticholinergics - oxybutynin - used to treat bladder dysfunction and urinary symptoms
Life expectancy of MS
Reduced by 7 years average
5% have aggressive disease and die within 5 years
Symptomatic treatment for spasticity in MS
Baclofen - GABA agonist
Diazepam - Benzodiazepine
Dantrolene - Post-synaptic muscle relaxant - decreases calcium release from ER
Tizanidine - A2 adrenergic agonist
Symptomatic treatment for cerebellar intention tremor
Treat with clonazepam - benzodiazepine
Treatment of acute MS relapses
Short treatment of steroids - methylprednisolone for 3days
Treatment of aggressive MS
Immunomodulatory treatments
Natalizumab (also used in crohns)
Alemtuzumab (also used in lymphoma and leukaemia), Fingolimod (sequesters lymphocytes in lymph nodes)
What is Behcets disease?
Relapsing remitting CNS disease
Rare immune-mediated small-vessel systemic vasculitis - often presents with mucous membrane ulceration and ocular problems
What is transverse myelitis? What could cause it other than MS?
Inflammation of the spinal cord with weakness and sensory symptoms below the lesion - also autonomic, reflex and sphincter function affected
Could be due to spinal cord compression eg. prolapsed disc or brainstem lesion (if CN involvement)
What is syringomyelia?
Cyst (syrinx) formation in spinal cord which expands
Usually gradually progressive and presents with signs of a central lesion in the spinal cord
Causes wasting and weakness of the hands, loss of arm reflexes
And pain and temp sensory loss in cervical dermatomes but not light touch or position sense (due to temp and pain decussating and light touch and position sense being in posterior columns)
DDX of MS x7
1) Behcets disease
2) CNS sarcoid
3) SLE (antinuclear factor will be present)
4) Transverse myelitis from compression
5) Brown Sequard syndrome - purely unilateral and not involving face (hemiplegia)
6) Vitamin B12 deficiency (can cause optic neuropathy and myelopathy but more slowly progressive, no remission)
7) Syringomyelia but preservation of light touch and joint position sense and gradually progressive
