age and gender prevalance
- female to male ratio 3:1
- affects young adults , onset between 20-40yrs old
viral exposure
viral exposure (Epstein Barr virus) makes you 32 times as likely to develop MS than uninfected ppl
primary vs secondary relationship
About 20% of patients with MS present with a progressive form of the disease from the start (primary progressive)
However individuals with a relapsing/remitting form of MS can go on to develop a progressive disorder (secondary progressive)
uhthoff’s phenomenon
Symptoms take a huge turn for the worse upon an increase in body temperature (e.g. upon immersion in a hot bath)
Lhermitte’s sign
Electrical sensation running down the spine upon neck flexion
6 symptoms
dysarthria, dysphagia, fatigue, diarrhea/constipation, frequency/retntion of urine, depression/anxirty, unstable moods
how can you use MRI to diagnose
to detect white matter abnormalities and spinal lesions
diagnosis
5 points on pathology
- inflammation in the brain and spial cord
- Inflammatory infiltrates mainly consist of lymphocytes and macrophages
- The initial cause of inflammation in MS is not clear, and may be multifactorial
- Loss of myelin sheaths (‘demyelination’)
- Axonal damage and neuronal loss
3 consequences of inflammation in parkinsons
- a) acute loss of function
- b) repairable damage
- c) chronic damage
primary cause and pathology of relapse
conduction block primary cause
demylenation and inflamation
primary cause and pathology of remission
restoration of conduction primary cause
remylination and deecrease inflammation
primary cause and pathology of posative phenomena
primary cause - hyperexcitability, ectopic impulses, mechanosensativity
demylination?
primary cause and pathology of progression
primary cause is persistent loss of conduction
demyelination and axonal loss
what corticosteroids used and when and why
- acute relapse episode
- reduce inflammation
- high dose of corticosteroid
- oral methylprednisolone, 500 mg daily, 3-5 days
- i.v. methylprednisolone, 1g daily, 3-5 days
Natalizumab, general how work and dose
- Monoclonal antibody which inhibits leucocyte migration into CNS
- Anti-inflammatory effects
- Natalizumab is administered by intravenous infusion; the recommended dose is 300mg every 28 days
natalizumab mechansim of action
- binds to a4 subunit of a4b1 and a4b7 integrins, expressed on the surface of activated T-cells
- Prevents binding of cells to receptors on the endothelium
4 points how fingolimod works
- Sphingosine analogue
- Sequesters lymphocytes in lymph nodes
- Prevents them crossing BBB
- Reduces rate of relapse
when use fingolimod
- Fingolimod is recommended as an option for the treatment of highly active relapsing–remitting multiple sclerosis in adults, only if:
- they have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon
how does alemtuzumab work
- Anti-CD52 antibody
- CD52: antigens expressed on B and T cells
- Reduces inflammatory response in early MS
how do steroids work and how often
- Teriflunomide inhibits DHODH
- This is required for de-novo pyrimidine synthesis pathway needed by rapidly dividing lymphocytes
- Once-daily oral immunomodulator
vit d corelation
- Lower incidence of MS in countries with more sunlight
- Some suggestion that Vitamin D may help prevent MS, leading to the idea that it could be useful in treating MS
systomatic, cognative, fatigue and emotinal liability in that order treatment
Baclofen/gabapentin, donepezil/cognative training programmes, SSRI, amirioptyline
