Multiple sclerosis: an immune or neurodegenerative disorder?

Question 1

What is the pathology of RRMS?

Answer 1

Inflammation, new waves of lymphocytes entering the CNS, blood-brain barrier disturbance, new active CNS lesions, and initial remyelination in active lesions.

Question 2

What is the pathology of progressive MS?

Answer 2

Incomplete remyelination, slowly expanding lesions (gliotic), diffuse white matter abnormalities, cortical demyelination, meningeal inflammation, and neurodegeneration.

Question 3

What is direct evidence of autoimmunity?

Answer 3

Requires transmissibility of the characteristic lesions of the disease from human to human, or human to animal.

Question 4

What is indirect evidence of autoimmunity?

Answer 4

Requires re-creation of the human disease in an animal model. The majority of ‘autoimmune’ disorders fit in this category.

Question 5

What are arguments in favor that MS is not a primary autoimmune disorder?

Answer 5

• Genetic variants identified thus far make only weak individual contributions to MS susceptibility.
• Histopathology studies of early lesion demonstrate mainly involvement of the innate immune system with relatively few lymphocytes.
• Immunomodulatory therapies reduce relapses but fail to halt disease progression.

Question 6

What are arguments in favor that MS is not a primary neurodegenerative disorder?

Answer 6

• Most common human ‘primary’ neurodegenerative disorders are NOT characterized by abundant demyelination.
• Research has shown that oligodendrocyte injury doesn’t induce an adaptive immune response but others have shown that it does induce an immune response.