What is Multiple Sclerosis (MS)?
Chronic autoimmune, T-cell mediated inflammatory disorder of the CNS in which there are multiple plaques of demyelination within the brain and spinal cord, occurring sporadically over years, characterised by progressive disability.
Is MS in the CNS or PNS?
CNS
Describe the epidemiology of MS.
- Presents between 20-40 y/o (early adulthood).
- Females > males.
- Rare in the tropics - More common the further from the equator you go.
Describe the aetiology of MS.
Exact cause: unclear
- Combination of genes + enviromental factors:
- Environment e.g. EBV infection is shown to be associated.
- Low exposure to sunlight + vitamin D
- Genetic predisposition.
- Chance.
Describe the pathophysiology of MS.
- T-lymphocytes cross BBB
- Cause inflammation in the white matter:
- Discrete plaques of demyelination at multiple CNS sites -> the oligodendrocytes
- T-cells activate B-cells
- B-cells produce auto-antibodies against myelin protein
- Repeated demyelination leads to:
- Disruption of electrical conduction along the axons
- Incomplete recovery between attacks
- Poor demyelination healing -> remyelination -> results in relapsing and remitting symptoms
Give 3 major features of an MS plaque.
- Inflammation.
- Demyelination.
- Axon loss.
Describe the remyelination process of MS pathophysiology.
Remyelination:
- Remission for a period
- Poor demyelination healing: myelin regeneration
- New myelin = less efficient + temperature-dependent
- Symptoms may reappear e.g. when exposed to high heat - axons stretched by a hot shower
= Results in relapsing + remitting symptoms
Where would MS plaques be seen histologically?
Around veins: perivenular.
Give 4 distinct CNS sites that demyelination plaques have a preference for.
- Optic nerves
- Around ventricles of the brain
- Corpus callosum (the thick bundle of fibres that connects the 2 hemispheres)
- Brainstem and cerebellar connections
- Cervical cord (corticospinal tract and dorsal columns)
Does myelin regenerate in someone with MS?
Yes, but it is much thinner - which causes inefficient nerve conduction.
What are the 3 patterns of disease course in MS?
- Relapsing-remitting
- Most common
- Partial or full recovery between
- Minimal disability - Secondary progressive
- Relapsing-remitting which becomes progressive,
- - or, gradually worsening with relapses superimposed - Primary progressive
– gradually worsens from onset
Describe the relapsing/remitting course of MS.
The patient has random attacks over a number of years.
Between attacks, there is no disease progression.
Describe the chronic progressive course of MS.
Slow decline in neurological functions from the onset.
What is key to remember about the symptoms of MS?
What key expression is there?
NOTE:
A characteristic feature of MS is that lesions vary in their location over time, meaning that different nerves are affected, and symptoms change over time.
The key expression to remember to describe the way MS lesions change location over time is that they are:
“Disseminated in time and space”.
MS symptoms can be broken down into the system that is affected based on the location of the demyelination plaques.
Give symptoms for each system:
- Phenomenon seen
- Neurologic triad
- Typical presenting symptoms
- Eye movement abnormalities
- Motor
- Sensory
- Cerebellar
- Autonomic
- Focal
2 Phenomenon:
1. Uhthoff’s phenomenon: worsening of symptoms on exercise/in warm environments (e.g. in a bath).
2. Lhermitte’s phenomenon: lightning-shock pain down the spine on flexion of the neck (when person bends neck forward), secondary to cervical cord plaque formation.
Charcot’s neurologic triad:
1. Dysarthria - difficult/unclear speech
2. Intention tremor
3. Nystagmus - involuntary rapid eye movement
Typical presenting symptoms:
1. Optic neuritis - MOST COMMON
2. Spasticity + weakness
3. Nystagmus + double vision + vertigo
Eye movement:
1. Unilateral Optic neuritis
- Pain on movement, visual field defect, loss of colour vision – particularly red
- Nystagmus
- Involuntary rapid eye movement
- Plaques in the nerves of the eye controlling eye movement - CN VI (Abducens nerve) lesions -> double vision (diplopia):
1) Internuclear ophthalmoplegia (INO)- ocular movement disorder cause by unilateral lesion
2) Conjugate lateral gaze disorder - lesion in CN VI causes disordered eye movement
- Conjugate means connected.
- Lateral gaze is where both eyes move together to look laterally to the left or right.
- When looking laterally in the direction of the affected eye, the affected eye will not be able to abduct.
Motor:
1. Loss of power
2. Spasticity
Sensory:
1. Increasing sensitivity to pain
2. Tingling
3. Burning
4. Paraesthesia
5. Sensory ataxia
Cerebellar:
1. Loss of balance
2. Diplopia
3. Dysarthria
4. Tremor
5. Cerebellar ataxia
Autonomic:
1. Bladder + sexual dysfunction.
2. ED
3. Urine retention
4. Incontinence
5. Constipation
Focal:
1. Trigeminal neuralgia
2. Numbness
3. Paraesthesia (pins and needles)
What is Lhermitte’s sign?
Sensations shooting down spine when bending neck
What is optic neuritis & why can it happen in MS?
Painful unilateral visual loss.
Demyelination of optic nerve.
Relative afferent pupillary defect: consensual but not direct constriction.
Where is the problem in a conjugate lateral gaze disorder?
CN6 - affected eye cannot abduct
What is internuclear opthalmoplegia (IPO) in MS?
Dysfunction of the fibre than connects CN 3, 4 and 6 for co-ordinated eye movement
Give 3 atypical symptoms of MS e.g. if a patient presents with these they are unlikely to have MS.
- Aphasia.
- Hemianopia.
- Muscle wasting.
What can exacerbate the symptoms of MS?
Heat - typically a warm shower.
Symptoms can be relieved by cool temperatures.
What are 2 ‘pre-MS’ syndromes?
- Radiologically isolated syndrome (RIS):
-> Changes apparent on MRI, but no symptoms - Clinically isolated syndrome (CIS):
-> 1 episode of symptoms but you need at least 2 to call it MS
What is the diagnostic criteria for MS?
- > 2 CNS lesions disseminated in time and space.
- Exclusion of conditions that may give a similar clinical presentation.
Investigations for suspected MS.
- MRI of brain and spinal cord with gadolinium contrast
- GOLD STANDARD
- CNS lesions will be apparent as T2-hyperintense white matter plaques - Lumbar puncture - CSF
- Oligoclonal IgG bands in over 90% cases - but these are not specific to MS
* CSF cell count may be raised - Electrophysiology (visual evoked potential studies)
* Delayed nerve conduction suggests demyelination - Bloods
- FBC - normal
- Metabolic panel - normal
- TSH - normal
- Vit B12 - normal
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1. Phase I Neurology353
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2. Strokes - TIA, Ischaemic + Haemorrhagic151
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3. CNS infections - Meningitis + Encephalitis69
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4. Multiple Sclerosis (MS)32
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5. Guillain-Barre Syndrome12
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6. Parkinson's Disease35
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