Multiple Sclerosis

Question 1

Multiple Sclerosis Outline

Answer 1

Immune mediated chronic CNS inflammation. Self antigens on nerves are recognised as foreign creating demethylation. Prevalence in young adults is increasing. Type 4 (CD4 mediated) hypersensitivity

Question 2

Highest Risk for MS

Answer 2

Epstein Barr Virus infection (hypothesis: MS can’t occur in people never infected). Viral mimicry: viral antigen (EBNA1) similar to neuronal antigen (GlialCAM). attacking of neuron

Question 3

Other MS Risk Factors

Answer 3

Smoking, low serum Vit D, genetics (HLA DRB) and adolescent obesity

Question 4

Observable effects of MS on brain

Answer 4

Sclerosal plaque (scarring, grey patches) on white matters, lesions form around blood vessels and perivascular inflammation

Question 5

Observable effects of MS on spinal chord

Answer 5

Damage to grey and white matter

Question 6

MS Symptoms

Answer 6

Debilitating fatigue, Uthoff’s Phenomenon (heat intolerance), Depression, neuropathic, spasms, optic neuritis (unilateral vision loss, colour blindness (rods/cones), eye pain)

Question 7

What are symtoms of damage to cerebellar and brain stem

Answer 7

Facial plasy and ataxia (loss of balance), nystagasams (eyes shake),

Question 8

What are symptoms of spinal chord damage

Answer 8

Spastic paraplegia, weakness in reflex, numbness

Question 9

MS Can Be Confused With

Answer 9

Ischemia, Lupus, inflammation due to infection (syphilis, listeria), nutritional deficiency (B12, zinc, copper), mitochondrial metabolism dysfunction and Fabry’s genetic disease

Question 10

INF Beta in MS Treatment

Answer 10

Earliest. Immunometabolic effect on T cells to reduce damage done (immune system isn’t supressed). Side effects: headache, flu like symptoms (cytokine storm). Admin: subcutaneous

Question 11

Glatiramer Acetate in MS Treatment (Not Used Anymore)

Answer 11

Myelin mimic, reduces relapse chances by bystander supression effects. Side effects: injection site reaction. Admin: subcutaneous.

Question 12

Sphingosine Phosphate Receptor Inhibitors; Fingolimod, Ponesimod

Answer 12

Reduces risk of relapse by 50%. High risk: brachycardia and reduced vaccine efficacy. Admin: oral

Question 13

Fumarates; Dimethyl fumarates, diromixel fumarates Outline

Answer 13

Reduces replaces by 40%. Side effects: lymphopenia and GI damage. Admin: oral

Question 14

Cladribine Outline

Answer 14

Immune reconstitution therapy (repurposed from cancer treatment), reduces relapses 60%. Risk: reactivation of TB or Hep B

Question 15

Natalizumab Outline

Answer 15

Relapse reduction of 60%. Risk of progressive multilukeal encephalopathy. If serum anti-JC antibodies are high treatment can’t proceed (virus is present latent). IV admin every 4 weeks

Question 16

Anti-CD20s; Rituximab, Ublituximab Outline

Answer 16

50-60% relapse remission. Risk: herpes infection. IV admin monthly

Question 17

Anti-CD52; Alemtuzumab Outline

Answer 17

55% relapse reduction, immune reconstitution therapy. Risk: headache and infusion reaction. Admin: 2 infusions 1 year apart

Question 18

Why it’s important to move to precision medicines

Answer 18

Ineffective treatment results in worsening symptoms. As it’s a progressive disorder (risk of permanent disability)

Question 19

Hit & Run EBV Hypothesis

Answer 19

EBV makes host more susceptible

Question 20

Driven EBV Hypothesis

Answer 20

EBV is the direct cause of MS symptoms. Treatment for MS can be admined at stages of EBV lifecycle. Supported by Tebeover (anti-EBV) admin

Question 21

Future MS treatment

Answer 21

Vaccination: mRNA-1195 (prevent EBV infection, not effective) and mRNA-1189 (reduces immune system response to EBV, more effective)