Is Multiple Sclerosis an Inside-Out or Outside-In Disease?

Although multiple sclerosis (MS) is an autoimmune disease, controversy continues as to whether the inciting factor is the aberrant inflammatory response itself or a neurodegenerative process within the central nervous system that triggers an inflammatory response. Investigators obtained healthy-control, MS, and Alzheimer disease (AD) autopsy-tissue samples. The MS samples were classified as having normal-appearing white matter, diffusely abnormal white matter, active lesions, chronic active lesions, and inactive lesions. Swellings were classified as blisters (local myelin detachment from its axon), blebs (swelling of the axon), and axon degeneration (based on staining).

The investigators found myelin and axonal swellings in the normal-appear…