Multiple sclerosis is caused by an immune-mediated process where activated T cells are reactivated and cross the blood-brain barrier. This leads to oligodendrocyte death and demyelination through cytokines and macrophage activity. Axonal damage can also occur through antibodies, complement activation, and oxidative stress. Symptoms are caused by disrupted conduction in partially demyelinated axons. Remyelination involves cytokine clearance and axonal rearrangement at nodes of Ranvier. Some aspects of pathogenesis remain enigmatic, such as clinically silent lesions and symptom production without demyelination.

1. Multiple Sclerosis,pathogenesis
M. MAHDY

2. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)

3. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)
• Pathophysiology of MS symptoms

4. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)
• Pathophysiology of MS symptoms
• Enigmatic aspects of pathogenesis

5. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)
• Pathophysiology of MS symptoms
• Enigmatic aspects of pathogenesis
• Remyelination

6. Senior must help
junior

7. LIFE OFT

8. T cell activation

9. Step 1
• Reactivation ofT cells
T cell
+
APC
CD 4
CD8

10. Step 2
• T cell adhesion
VLA4
Vasc.
Endoth.
M
M
P

11. Step 3
• Crossing BBB BRAINTISSUE

12. Step 4
• CNS reactivation

13. Step 5
• T cell differentiation

15. Step 6
• Oligodendrocyte death and demyelination

16. Step 5
• Oligodendrocyte death and demyelination

17. Step 5
• Oligodendrocyte death and demyelination
CD8

18. Step 5
• Oligodendrocyte death and demyelination
CD8
OLG
apoptosis

19. Step 7
• Axonal damage

20. • Axonal damage
B Cell

21. • Axonal damage
B Cell
Plasma
cell

22. • Axonal damage
B Cell
Plasma
cell
comp

23. • Axonal damage
B Cell
Plasma
cell
comp
macrophage

24. • Axonal damage
B Cell
Plasma
cell
comp
macrophage
Axonaldamage

27. Extravasation
astrocytes BRAIN
TISSUE
MY E L I N
oligodendrocyte
B cell
Rolling Adhesion
a4 Integrin
VCAM
B L O O D F L O W
LUMEN OF
VENULE
B A S A L L A M I N A
Circulation
ActivatedT cell
Proteases
Antigen presenting cell
(Astrocyte or Microglial cell)
Activated
microglia/macro
phages
T CELL
REACTIVATI
ON
Activated
Macrophage
Autoantibodies
Complement
IL-1, IL-12,
chemokines
Cytokines and
chemokines
Proteases
TNF-a
O2
•-
NO•
AXONAL
DAMAGE
MS Disease Pathology

28. Pathogenesis of remyelination
• Cytokine wash

29. Pathogenesis of remyelination
• Cytokine wash
• Resolved conduction block

30. Pathogenesis of remyelination
• Cytokine wash
• Resolved conduction block
• Rearrangement of Na channels at
nodes of ranvier &naked axons

31. Pathophysiology of symptoms
Uthoff’sL’hermitteparathesiafatigue

32. Fatigue
• Fast trains of impulses cannot be
transmitted by partially
demyelinated axons
Parathesia
• partially demyelinated axons can
discharge spontaneously

33. L’hermitte
• Increased mechanical sensitivity
Uhthoff’s
• Increased temp sensitivity,
reduction of safety factor in
partially demyelinated axons and
decreased synaptic transmission

34. Paroxysmal symptoms
• Ephaptic transmission

35. Enigmatic aspects
• Areas of demyelination can be clinically
silent.
• Areas without demyelination can produce
symptoms
• Discrepancy between :
• anatomical correlation of symptoms
and signs analysis and radiological findings