Define Multiple Sclerosis.
Chronic cell-mediated AI demyelinating disease characterised by the presence of episodic neurological dysfunction in at least two areas of the CNS (brain, spinal cord, and optic nerves) separated in time and space.
What are the two phenotypes of MS?
- Relapsing-remitting disease (most common - 85%)- includes clinically isolated acute attacks lasting 1-2months, followed by remission
- Progressive disease
- Primary progressive (10%)- progressive accumulation of disability from onset. More common if older.
- Secondary progressive - 65% progress to this in 15yrs from an initial relapsing course. Progressive accumulation of disability.
Who is most affected by MS?
White women (3:1, F:M)
Aged 20-40yrs (occasionally diagnosed in 60-70’s where pt have been asymptomatic for many years)
More common in higher latitudes (x5 more common than in tropics)
What are the risk factors for MS?
- Female sex
- Northern latitude
- Genetic factors
- Smoking Vit D deficiency
- AI disease
- EBV
What is the aetiology of MS?
- Environmental and genetic susceptibility (x20-40 risk in first degree relatives, 30% MZ twin concordance, 2% DZ twin concordance)
- EBV may be linked to MS but other viruses have not proved to be causative.
Infection or postnatal hormonal changes may trigger relapses. as well as surgery or stressful life events (although controversial)
Which part of the CNS is involved in MS?
CNS white matter
Demyelination of axons causes distal and retrograde degeneration over time.
What is the pathophysiology of MS?
Unknown - no specific antibody linked. Can be said to have 2 distinct but overlapping phases: inflammatory and degenerative:
- Inflammatory - lymphocytes with ecephalitogenic potential become activated and enter CNS by binding to endothelial cells, releasing MMPs and crossing the BBB. This causes a further influx of inflammatory cells which produce cytokines, attract macrophages and cause demyelination.
- Degenerative - involves axonal degeneration and loss. There is destabilisation of the axonal membrane potential which causes distal and retrograde degeneration over time.
What is the difference in pathophysiology of relapsing-remitting and progressive MS?
Relapsing-remitting MS shows the most inflammatory activity, followed by early secondary progressive MS.
Primary progressive MS is thought to be a primarily degenerative process, although some patients do have relapses and/or enhancing lesions. All currently-approved disease-modifying therapies in MS are most active against inflammation.
What are the most common presentation of MS? (2)
- Optic neuritis - usually lasting over 48hrs with no fever or other illness shows a demyelinating episode of MS
- Transverse myelitis - usually asymmetrical with patches of odd sensation like wetness/tingling
What are the signs and symptoms of MS?
- Fatigue
- Visual disturbance in one eye - like looking through petroleum jelly. May have pain moving eye and discriminating colours especially red.
- Sensory disturbance- patches of wetness, burning, hemibody sensory loss/tingling, banding pattern with spinal cord lesions
- Lhermitte’s sign
- Foot dragging/slapping after walking several miles
- Leg cramping
- Fatigue
- Urinary frequency
- Bowel dysfunction - constipation common
- Spasticity/increased tone (UMN)
- Increased reflexes (UMN) - clonus at ankles, often symmetrical
- Imbalance/incoordination
- Pale optic disc/non-correctable visual loss - optic neuritis
- Incorrect Ishihara answers
- Abnormal eye movements
What abnormal eye movements may be present in MS?
Internuclear ophthalmoplegia (nystagmus of the abducting eye with absent adduction of the other eye)
or isolated nystagmus may be present.
Which colour do people with MS have trouble seeing?
Red - seen as a ligher orange due to damage to the optic nerve
What is Lhermitte’s sign?
Electric shock-like sensations extending down the cervical spine radiating to the limbs - commonly seen in MS
Which type of neuralgia might you also get with S?
Trigeminal
What investigations would you do for MS?
Careful neurological history and examination; confirmed by MRI and CSF
- MRI- brain - sagittal FLAIR images show non-specific white matter changes but must monitor for progression to diagnose MS
- MRI spinal cord - demyelinating lesions particularly in cervical region
- FBC, metabolic panel, TSH, vit B12 - should be normal
- CSF evaluation - oligoclonal bands and elevated CSF IgG with increased IgG synthesis in 80% of MS cases
What are 3 causes of optic neuritis?
- MS
- Diabetes
- Syphilis
What are the clinical features of optic neuritis?
- Unilateral decreased visual acuity over hours/days
- Poor colour discrimination
- “Red saturation”
- RAPD
- Central scotoma
What is the management of optic neuritis?
high dose steroids
What is the prognosis with optic neuritis?
Recover within 4-6 weeks with steroids
If optic neuritis alone, but MRI shows >3 white matter lesions → 50% risk of MS in 5yrs
Which disorders are commonly seen in secondary progressive MS disease?
Gait and bladder disorders commonly seen
Which disorders are commonly seen in secondary progressive MS disease?
Gait and bladder disorders commonly seen
What are the signs of MS on MRI?
- high signal T2 lesions
- periventricular plaques
- Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
What is seen in CSF in MS?
- oligoclonal bands (and not in serum)
- increased intrathecal synthesis of IgG
What are the visual evoked potentials like in MS?
- delayed, but well preserved waveform
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Epilepsy30
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Guillain-Barre syndrome25
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Huntington's disease14
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Hydrocephalus22
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