WEEK 3- multiple sclerosis

Question 1

what is MS and about it?

Answer 1

Chronic inflammatory autoimmune disease of the central
nervous system
• Attacks myelinated axons, destroying them in varying degrees
Significant physical disability
within 25-30 years
• Varied severity
• Periods of remission
and relapse in different
anatomical areas
-numbess, pain or tingling

Question 2

what is the epidemiology of MS?

Answer 2

• Often diagnosed between 15-45 years
• Higher incidence in women than men (3x)
• Higher incidence in northern Europe, in Caucasians,
in some populations eg Sardinians, Palestinians, Latin
America

Question 3

what is the aetiology of MS?

Answer 3

Genetics: modest effect 
– HLA DRB1 
– HLA-C*05 protective against
• Infections: EBV association
• Vitamin D: low levels increase risk
• Smoking: increases risk
• Obesity associated
• Solvents: long term exposure increases risk

Question 4

what is the pathogenesis?

Answer 4

-Autoreactive lymphocytes and Tcells cross the blood brain barrier, causing
local inflammation in the CNS
-this causes inflammatory lesions to devlop and demyelination occurs due to attacking destroing mylein sheath on nerves and plaques are produced.
• Plaques contain demyelinated neurons, reduced
oligodendrocytes, increased astrocyte
proliferation, transected axons and infiltratin of
lymphocytes and macrophages resulting in
inflammation, microglial activation and injury with
cytokine secretion
• B cells involved in lesion development antigen
presentation, cytokine production and antibidy
production

Question 5

how is myelin and axon destroyed in SLE?

Answer 5

• activated T-cells cross BBB into CNS so will neutrophiles
• they start to produce proinflammatory mediators like IL-1, THEN gamma delta T-cells start to produce TNF AND THIS AMPLIFIES THE gm-csf cells which in trun starts to prodcue IFN gamma and TNF
• the microglia is activated and they secrete cytokines and the Tcells become reactivated and are presneted with antigen from the mylein making the Tcells thing they are foreign
• B cells are switched on and theres destruction of myelin and axon due to response from INFLAMMATORY t cells and will result in destruction of oligodendrocytes

Question 6

how is MS diagnosed?

Answer 6

• Medical history and neurological exam
• Clinical symptoms
• MRI
• Lumbar puncture for detection of
autoantibodies, fragments of myelin, increase
WCC (inflammatory)
• Evoked potential tests – measures speed of
messages along nerves

Question 7

what is the symptoms for MS?

Answer 7

• NUMBNESS
• tingling
• vision problems
• speech and throat

Question 8

what is the treatment for MS?

Answer 8

• No cure, Treat symptoms – Physiotherapy, CBT, painkillers, muscle relaxants,
corticosteroids etc
• Interferon beta 1 – reduces neuronal inflammation and
reduces relapse rate
• Alemtuzumab – CD52mAb, on mature lymphocytes,
targets destruction
• Glatiramer acetate – 4aa from MBP, possibly acts as
decoy and shifts cells from Th1 to Th2 (anti—
inflammatory)
• Dimethyl fumarate – shifts from Th1 to Th2 (antiinflammatory)
• Natalizumab – targets alpha4-integrin, reducing
migration of lymphocytes into the brain, also reducing
lesioning
-• Immunosuppressants – Teriflonamide – active metabolite of leflunomide,
inhibits pyrimidine synthesis and cell proliferation,
especially T cells – Cladribine – purine analog that mimics adenosine,
accumulates in lymphocytes and prevents cell division
and activates apoptosis – Fingolimod – sphingosine-1-phosphate receptor
modulator – sequesters lymphocytes in lymph nodes – Ocrelizumab – targets CD20 on B lymphocytes,
causing cell death