Multiple Sclerosis

Question 1

What type of disorder is MS?

Answer 1

Autoimmune –> inflammatory –> demyelinating

Question 2

What does the immune-mediated attack target in MS?

Answer 2

Myelin and oligodendrocytes (glial cells that produce myelin)

Question 3

How does someone get MS?

Answer 3

Immune dysregulation in someone with a genetic predisposition who is exposed to environmental triggers

Question 4

Risk factors for MS relapses (4)

Answer 4

Basically things that cause reactivation of the immune system
-Systemic infections
-Perceived stress
-Postpartum trimester
-Assisted reproductive techniques

Question 5

What happens in the brain during an MS flare? (3)

Answer 5

1. Breakdown of the BBB - due to inflammation (can see Gd-enhancing lesions on MRI)
2. Activated T cells cross the leaky BBB and target myelin and oligodendrocytes
3. Causes demyelination + axonal loss and apoptosis of oligodendrocytes

Question 6

What happens in the brain during a reparative phase of MS?

Answer 6

-Remyelination
-Repair of the BBB
-Redistribution of Na+ channels (normally concentrated at nodes of Ranvier but spread out when demyelination occurs)

Question 7

Genetic risk factors for MS

Answer 7

Having a first degree relative with MS increases the risk of getting MS

Question 8

Environmental risk factors for MS trigger in a genetically susceptible individual (3)

Answer 8

-EBV infection
-Smoking
-Vit D deficiency

Question 9

Patterns/courses of MS

Answer 9

-Relapsing-remitting
-Secondary progressive
-Primary progressive

Question 10

Relapsing-remitting MS

Answer 10

**Flares of symptoms (relapses) followed by periods of full/partial recovery (remission) ** - hallmark
No progression between attacks initially, but could progress to secondary progressive MS eventually

Question 11

Definition of a relapse

Answer 11

New episode of new or recurrent neurologic symptoms that last at least 24 hrs (can’t be associated with fever or infection)

Question 12

Secondary progressive MS

Answer 12

Gradual neurological decline with or w/o superimposed flares (relapses) - remyelination becomes less effective so at this point it’s more neurodegenerative than inflammatory
Evolves from relapsing/remitting MS after years
Need to have at least 1 year of documented progression

Question 13

Primary progressive MS

Answer 13

Progressive worsening of MS from onset

Question 14

Clinically isolated MS

Answer 14

The first episode that is suggestive of MS
Need patient-reported symptoms and objective findings of inflammatory demyelination in the CNS, lasts at least 24 hrs, no fever or infection

Question 15

Diagnosis of MS

Answer 15

Diagnosis is clinical - requires:
-Typical history
-Objective findings of inflammatory demyelination on MRI

Question 16

What does “disseminated in space” mean in the context of MS?

Answer 16

Lesions are present in multiple distinct regions of the CNS - at least 2/4 of the following:
-Periventricular
-Juxtacortical
-Infratentorial
-Spinal

Question 17

What does “disseminated in time” mean in the context of MS?

Answer 17

Lesions occur at different points in time and the disease evolves over time

Question 18

Whata re tumefacive demyelinating lesions?

Answer 18

Large demyelinating lesions (>2 cm) in the CNS that mimic brain tumors on imaging, often with mass effect or edema.

Question 19

Treatment of MS relapses

Answer 19

-Steroids (IV or oral)
-Plasmapheresis

Question 20

Goals of disease-modifying therapies in MS (3)

Answer 20

-Reduce frequency + severity of relapses
-Reduce accumulation of lesions
-Slow the progression of disability

Question 21

Examples of disease-modifying therapies in MS

Answer 21

-IFNs
-Monoclonal abs (all the “-mabs”)
More…

Question 22

Pregnancy and MS

Answer 22

During pregnancy, there is a decrease in relapses, followed by a rebound increase in relapses after birth
*Does not affect fertility