CNS Demyelinating Disorders

Question 1

Pathophysiology of multiple sclerosis?

Answer 1

PERIPHERAL immune cell infiltration –> immune-mediated inflammation

Immune cells infiltrate perivascular space of post-capillary venules and penetrate BBB

intrathecal synthesis of IgG –> destruction of CNS myelin AND oligodendrocytes –> demyelination

Attempts are remyelination but it is INCOMPLETE –> “shadow plaques”

Axonal injury also occurs

Question 2

How is MS defined pathologically?

Answer 2

Grossly, would see areas of gray/de-myelinated regions within white matter–feels “firm” become it is sclerotic.

Histologically, would see inflammatory infiltrate in perivascular fashion.

MS = presence of inflammatory demyelination in CNS in ABSENCE of infection

Diffuse demyelinating lesions, esp. periventricular regions

Areas of (incomplete) remyelination

Question 3

What would MRI + Gd show?

Answer 3

If MRI + Gd shows areas of flair, means that after injection of Gd BBB has been infiltrated!

Question 4

What type of molecular test would help in diagnose of MS?

Answer 4

Intrathecal synthesis of IgG –> “oligoclonal bands”

Demonstrates CLONAL expansion of B cells and establishment of ADAPTIVE immune response in CNS

Question 5

Optic neuritis in MS

Answer 5

Inflammatory demyelination of optic nerve in MS, leading to:

• Blurred vision
• Slowed conduction through CNII

Question 6

Although demyelinating lesions of MS are DISSEMINATED, the have a predilection for the:

Answer 6

Periventricular regions

Question 7

Pathophysiology for neuromyelitis optica?

What parts of the CNS does it involve?

Answer 7

Acquired autoimmune disorder where pathogenic autoantibody NMO IgG target aquaporin 4 on ASTROCYTE END FEET

Predilection for spinal cord (myelitis) and CNII (optic neuritis) with limited brain involvement

Question 8

Diagnostic criteria for neuromyelitis optica?

Answer 8

-Relapsing optic neuritis
-Relapsing myelitis
At least 2/3 following:
-Contiguous SC MRI lesions extending at least 3 vertebrae
-Brain MRI NOT meeting MS diagnostic criteria
-Anti-aquaporin 4 +

Question 9

Treatment for MS

Answer 9

Target mechanisms of immune-mediated inflammation.

Natalizumab: Target alpha4beta1 integrin (VLA-4) expressed on lymphocytes that mediate migration into CNS

Fingolimid: sphingosine-1-phosphate receptor modulator; Sphingosine-1-Phosphate targets chemotactic gradient that mediates WBC egression from LN

Ocrelizumab: anti-CD20

MS. NATALIe went to LA to play bINGO and eat OCRE.