Multiple Sclerosis

Question 1

What are the 4 types of MS?

Answer 1

1. Primary progressive (PPMS)
2. Secondary progressive (SPMS)
3. Progressive-relapsing (PRMS)
4. Relapsing-remitting (RRMS)
   (lecture 13.3.18, PTS)

Question 2

Describe the pathophysiology of MS.

Answer 2

Discrete plaques of demyelination occur at multiple CNS sites, from T-cell-mediated immune response. Lymphocytes cross the BBB and cause oligodendrocyte demyelination and axonal degeneration (irreversible). (lecture). Demyelination heals poorly, causing replasing and remitting symptoms. Prolonged demyelination causes axonal loss and clinically progressive symptoms.
(OHCM)

Question 3

Give 3 risk factors for MS.

Answer 3

1. Genetics - HLA association, 1st-degree relative.
2. Ethnicity: 1. White 2. Black 3. Others
3. Location:
   a. Incidence increases with increasing distance from equator apart from aborigines and inuit communities
   b. The earlier you migrate to a high-MS country, the higher your risk.
4. Female (Autoimmune)
5. EBV - causes infectious mononucleosis, especially in teenagers in UK.

Question 4

What is Uhthoff’s phenomenon and why does it occur?

Answer 4

Increase/recurrence in symptoms in response to heat. This occurs in MS because when the myelin grows back conduction becomes temperature-dependent.

Question 5

Give 3 features of active lesions in MS.

Answer 5

1. Hypercellular plaque due to inflammatory cells
2. Perivenous inflammatory infiltrate with macrophages and T-lymphocytes.
3. Extensive BBB disruption
4. Central gliosis in older plaques.
5. Demyelination, oligodendrocyte loss
6. Lesions often in juxtacortical, periventricular, brainstem and spinal cord areas.

Question 6

Give 3 features of inactive lesions in MS.

Answer 6

1. Hypocellular plaque
2. Variable inflammatory filtrate
3. Moderate to minor BBB disruption
4. Plaques gliosed (hypertrophy of glial cells).

Question 7

Give 3 features common to all lesions in MS.

Answer 7

1. Demyelination
2. oligodendrocyte loss
3. Juxtacortical/periventricular/ brainstem/ spinal cord lesions.
4. Plaques.

Question 8

What is Brown-Sequard syndrome?

Answer 8

A rare condition in which a lesion in the spinal cord causes hemiparaplegia on one side of the body and hemianasthesia on the other side of the body. Caused by MS.

Question 9

What investigations would you do if you suspect MS?

Answer 9

LP - IgG oligoclomal bands in CSF shows inflammation is confined to the nervous system.
MRI - white spots where the contrast goes through breaks in the BBB.
Evoked potentials/ EEG - time taken for impulse to travel from optic nerve to occipital lobe.
May be diagnosed from the history and neurological examination alone.

Question 10

What are 3 initial symptoms/signs for MS?

Answer 10

1. Optic neuritis
2. Sensory and motor disturbance
3. Brainstem/cerebellar syndrome.

Question 11

Describe the management of MS.

Answer 11

Treat early and aggressively in the initial stage. Think symptomatic treatment as well as curative.

1. Analgesia - anti-epileptics can help with paroxysmal pain.
2. Prevention of immunoactivation - IFN-beta is a pro-inflamm cytokine
3. Natalizumab - modidies lymphocyte trafficking
4. Ocrelizumab - targets CD20 to deplete lymphocytes
5. Stem cell transplant to reconstitute immune system.

Question 12

How does natalizumab work and what is a side-effect?

Answer 12

modifies lymphocyte trafficking, can induce JCV infection.