Neuroimmunology

Question 1

Interferons

Use? Mechanism? Side Effects?

Answer 1

Use:
- MS DMT

Mechanism:

Side Effects:
- Flu-like symptoms
- Injection site reactions
- LFT and CBC monitoring for liver/hematotoxicity
- 1/3 w/ neutralizing ABs

Question 2

Glatiramer Acetate

Use? Mechanism? Side Effects? Metabolism?

Answer 2

Use:
- MS DMT

Mech:

Side Effects:
- Injection site reactions
- idiosyncratic chest pain
-

Question 3

Natalizumab

Use? Mechanism? Side Effects? Metabolism?

Answer 3

Use:
- MS DMT
- 60-70% relapse rate, reduced MRI activity

Mechanism:
- humanized monoclonal Ab against alpha4-integrin, a cellular adhesion molecule that binds lymphocytes and prevents adherence to the endothelium w/i the brain and gut.

Side Effects:
- PML, higher risk after 2 years or with other meds (stop drug and plasmaphereses if occurs)
- Anaphylaxis is common (don’t retry if occurs)

Question 4

Baclofen
Use? Mechanism? Side Effects? Metabolism?

Answer 4

Use:
- spasticity

Mechanism:

Side Effects:
- fatigue
- dizziness
- dose-related leg weakness
- can have withdrawal seizures

Question 5

Tizanidine
Use? Side Effects?

Answer 5

Side Effects:
- Lightheaded
- hypotension
- fatigue
- liver abnormalities

Question 6

Fingolimod
Use? Mechanism? Side Effects? Metabolism?

Answer 6

Use:
- MS DMT

Mechanism:
- modulates sphingosine-1 phosphate (S1P) receptors on thymocytes and lymphocytes, triggering receptor internalization and making cells unresponsive to signaling, which in turn traps them in the lymph nodes

Side Effects:
- macular edema
- first dose bradycardia - first dose monitoring
- bronchitis
- increased LFTs
- fatal varicella zoster

Question 7

Dalfampridine
Use? Mechanism?

Answer 7

Use:
- Improves walking in patients with MS, used in combination with DMT
- Improvement in walking speed seen in all MS subtypes

Mechanism:
- broad-spectrum inhibitor of voltage-gated K channels, improving impulse conduction in demyelinated nerve fibers

Question 8

1. Uhthoff’s Phenomenon
2. Lhermitte’s Sign
3. Useless hand of Oppenheim
4. Pulfrich’s sign

Answer 8

1. transient MS symptoms in setting of heat or exercise
2. electric sensation w/ neck flexion
3. hand can be moved but is perceived as useless by the patient
4. have trouble tracking objects visually, lateral motion perceived as having depth

Question 9

Alemtuzumab
Use? Mechanism? Side effects?

Answer 9

Use:
- relapsing MS with breakthrough of two otehr therapies
- reduces relapses and MRI burden

MoA:
- monoclonal Ab that binds CD52 in surface of B and T cells, NK cells, monocytes and macrophages, and some granulocytes -> immunomodulation

Side Effects:
- hyperthyroidism
- ITP

Question 10

Dimethyl fumarate
Use? Mechanism? Side effects?

Answer 10

Use:
- DMT

Mechanism:
- unknown

Side Effects:
- GI upset, diarrhea
- flushing
- teratogen

Question 11

Teriflunomide

Answer 11

Use:
- MS DMT

Mechanism:
- inhibits mitochondrial enzymes needed for pyrimidine synthesis

Side Effects:
- Diarrhea, nausea
- elevated LFTs
- alopecia
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