A 35-year-old woman presents with optic neuritis and sensory loss in her right arm two years after an episode of internuclear ophthalmoplegia. MRI shows periventricular T2 lesions perpendicular to the corpus callosum (Dawson fingers) and two lesions disseminated in time. This is relapsing-remitting MS. Per current NICE/EAN guidelines, the mechanism of action of natalizumab (a high-efficacy DMT) is:

• A Inhibition of sphingosine-1-phosphate (S1P) receptors, trapping lymphocytes in lymph nodes
• B Anti-CD20 monoclonal antibody causing B-cell depletion
• C Fumarate ester activating the Nrf2 antioxidant pathway
• D Monoclonal antibody against VLA-4 integrin preventing CNS lymphocyte trafficking ✓

Explanation

Natalizumab is a monoclonal antibody against alpha-4 integrin (VLA-4), which prevents lymphocyte adhesion to endothelial VCAM-1 and their transmigration into the CNS, reducing relapse rate by ~68%. Fingolimod/siponimod trap lymphocytes in lymph nodes via S1P receptor modulation. Ocrelizumab/rituximab deplete B-cells via CD20. Dimethyl fumarate activates Nrf2. Each has a distinct mechanism.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.