Multiple Sclerosis Flashcards
What is MS?
The most common autoimmune, inflammatory, demyelinating disease of the CNS.
1/800 prevalence, young caucasian adults.
Relapsing remitting course early in disease, followed by secondary progressive MS later. More women than men affected.
What is the pathogenesis of MS?
A heterogenous disorder, with different presentations representing different pathways to disease.
Major mechanisms are inflammation, axonal demyelination and degeneration, with multifactoral causation including autoimmune, gentic, viral and environmental.
What pathology is seen in MS?
- Areas of demyelination in white matter in the brain and spinal cord.
- The lesions lie in close relationship with post-capillary venules, giving a predilection for certain areas.
1) periventricular areas of cerebral hemispheres
2) Corpus callosum
3) Brainstem (including medial longitudinal fasciculus), cerebellum and cerebellar peduncles.
4) Cervical cord
5) Optic nerve - inflammatory infiltrate containing lymphocytes and mononuclear cells
- remyelination is rare
What are the clinical features of MS?
Multitude:
1) relapsing-remitting
2) secondary progressive - starts as relapsing remitting but recovery from each relapse becomes less complete
3) Primary progressive - disability worsens gradually from onset
Once progression has started it continues at a steady rate.
General life-expectancy is reduce by about 6-7 years.
What are some good prognostic factors for MS?
1) Caucasian
2) Relapsing remitting
3) Monosymptomatic onset of disease (no bowel bladder involvement)
4) Complete recovery form first attack
5) Low relapse rate in first 2 years
6) Long intervals between first two attacks
7) Minimal lesion load on MRI at first presentation
What are the common presenting symptoms in MS?
Spinal cord: 50%
- Motor - weakness, clumbsiness, tonic spasms
- Sensory - numbness, tingling, burning, bandlike sensation, Lhermitte’s sign (shooting sensation down back with neck flexion), altered temp sensation
- Sphincter - Bowel and bladder disturbences, erectile dysfunction
Optic nerve: 25%
- mostly unilateral
- Visual loss, blurred vision, reduced colour vision, pain on eye movement
Brainstem/cerebellum: 20%
- Dysarthria, dysphagia, diplopia, nystagmus
- vertigo
- facial numbness weakness, trigeminal neuralgia
- deafness
- ataxia (trunk and limbs)
- pyramidal weakness due to corticospinal tract involvement
- patchy sensory loss
- tonic spasms
Cerebral Hemispheres: 5%
- hemiparesis, hemisensory loss
- visual field deficit,
- dysphasia
- seizures
- cognitive impairment
What is the most common presentation in MS?
Spinal cord lesion
Results in a spastic paraperesis (thoracic) or tetraparesis (cervical), often tonic spasms of limbs, difficulty walking
What is the association with temperature and MS?
Symptoms of MS tend to get worse in heat e.g. bath or warm weather. Uthoff’s phenomenon
What is the differential diagnosis for MS?
The relapsing remitting pattern should prompt consideration of SLE, sarcoidosis, Bechet’s disease, neurosyphilis, Lyme disease.
Progressive presentation could also include structural lesions, Vit B12 deficiency, paraneoplastic syndromes, hereditary disorders (Leucodystrophies, spiocerebellar ataxis etc.)
Each individual presentation e.g. optic, brainstem, spinal, all have multiple differentials which must be excluded.
What investigations would you perform for MS?
No diagnostic test for MS.
MRI - can pick up plaques. Important finding is that lesions can be contrast-enhancing and non-contrast enhancing suggesting some active and non-active lesions (important for diagnosis)
CSF - presence of oligoclonal bands of IgG on western blotting from CSF but not serum is suggestive of MS.
Raised leucocytes and protein in active phase.
Evoked potentials - delay of affected nerves
What is the name of the criteria for diagnosis MS and what does it state?
The McDonald criteria:
- lesions should be disseminated in time and space
- hence patients presenting for the first time may not get a clinical diagnosis until repeat later on showing new lesions.
How is MS managed?
Acute relapses - steroid therapy. Usually IV as methylprednisolone
Disease modifying treatment - Interferon-B1a / 1b and glatiramer acetate imunosuppression. These are primarily to reduce the frequency of relapses, so are not used in primary progressive disease
Other immunomodulatory agents
- Natalizumab, has shown good effects at slowing disease progression and reducing relapse, but increased risk of opportunistic infections particularly Progressive Multifocal Leucoencephalopathy.
- Mitoxantrone - significant cardiotoxicity and risk of leukaemia
- Fingolimod - latest drug, good results, prevents white cell crossing BBB. flu-like symptoms and cardiotoxicity
What is the mainstay of treatment for MS day to day?
Symptomatic treatment -
Who range of treatments for all symptoms
