7. Multiple Sclerosis

Question 1

What are the drugs used for multiple sclerosis?

3 categories

Answer 1

Acute treatment:
Methylprednisolone
Plasma exchange

Disease modifying treatments:
Immunomodulators:
Interferon-β
Glatiramer acetate
Fingolimod
Monoclonal antibodies:
Natalizumab
Alemtuzumab
Ocrelizumab
Daclizumab

Question 2

What is multiple sclerosis?

Answer 2

Autoimmune disease of the CNS
Attack myelin-oligodendrocyte
Type IV hypersensitivity reaction (cell-mediated not antibody-mediated)
Onset: 17-35yr 3 female for every male

Question 3

How many axon segments can one oligodendrocyte myelinate?

Answer 3

1 oligodendrocyte can myelinate 50 axon segments

Question 4

How does multiple sclerosis unfold?

Answer 4

Neurons normally happy inside protection of blood brain barrier
Somehow T cell becomes activated by myelin
Antibodies go into brain and attack myelin by binding to it but doesn’t destroy oligodendrocyte, produces cytokines (to dilate vessels- leaky)
Activated T cell can upregulate more receptors for circulating immune cells
Recruit B cells for antibody production and macrophages for destruction/clearance
Results in plaque (sclera) formations that can be observed on MRI scans

Slides 6-7

Question 5

What are the 4 classifications of MS?

Answer 5

1. Relapsing-remitting (RRMS-85%)
2. Primary Progressive (PPMS- 10%)
3. Progressive-relapsing (PRMS- 5%)
4. Secondary progressive (SPMS)

Slide 8

Question 6

What are the 6 symptoms of multiple sclerosis?

Answer 6

1. Charcot’s neurologic triad- nystagmus, intention tremor, unclear speech
2. Plaques in sensory pathways- numbness, pins and needles, paresthesias (tingling)
3. Lhermitte’s sign- electrical sensation that runs down the back and into the limbs
4. Plaques in ANS- bowel & bladder symptoms, sexual dysfunction
5. Higher order activities- poor concentration & critical thinking, depression & anxiety
6. Uhthoff’s phenomenon- worsening of symptoms in heat, increases in body temp can slow or block impulse conduction in demyelinated nerves

Slides 9-10

Question 7

What are the treatments; acute treatment and disease modifying therapies (DMTs)?

Answer 7

Acute treatment- aims to stop current inflammatory disease processes

Disease modifying therapies- aims to decrease risk of relapses (drive new lesions on MRI) with goal of slowing disability progression

Question 8

What do you use to treat difficulty walking in multiple sclerosis?

Answer 8

Dalfampridine- K+ channel antagonist

Thought to increase conduction in absence of myelin

Question 9

What 3 drugs do you use to treat spasticity in multiple sclerosis?

Answer 9

1. Tizanidine- muscle relaxant, more tolerable than baclofen and diazepam
2. Botulinum toxin- blocks vesicle docking
   Injected locally to affect small areas
   Specific to acetylcholine containing nerves
3. Nabiximols- cannabis sativa extract

Question 10

Read through case study slide 15

Answer 10

Ok