Novel findings in Balo's concentric sclerosis may shed light on pathology of MS

Researchers partly funded through the National MS Society’s “MS Lesion Project” report that a novel mechanism known as “tissue preconditioning” may explain the pattern of tissue damage that occurs in Baló’s concentric sclerosis, a rare, severe disease similar to MS, and may offer clues to a similar phenomenon in MS. Hans Lassmann, MD (Medical University of Vienna, Wien) and colleagues, including Society grantee Claudia Lucchinetti, MD (Mayo Clinic and Foundation, Rochester, MN), report their findings in Brain.

Balo's concentric sclerosis is characterized by a sudden onset of neurological symptoms and steady progression without remission, leading to major disability or death within months. Tissue damage appears in the form of large lesions (areas of damage to myelin, the substance that insulates nerve fibers) that consist of concentric rings, with alternating layers of preserved and destroyed myelin. The reason for this unique pattern of damage is unclear. Similar, smaller lesions with concentric rings have been reported to occur in MS.

Dr. Lassmann and colleagues examined tissue samples taken from 14 people diagnosed with MS who had concentric lesions indicative of Baló’s concentric sclerosis. They compared these samples with tissue taken from people with active and inactive MS who lacked this pattern.

In the Balo's lesions, but not in control samples, the group found evidence of “hypoxia-like” tissue damage involving the complete loss of the myelin protein MAG and the death of myelin-making cells. Furthermore, at the edges of the Balo's lesions, in the outermost layer of preserved myelin, the group found molecules that are involved in “tissue preconditioning.” Tissue preconditioning is a natural process by which the brain mounts protective measures to prevent further damage. The authors cite previous research suggesting that genes involved in preconditioning have been found in normal-appearing areas of the brains of persons with MS, suggesting the body mounts this protective strategy to ward off MS attacks.

Further research is needed to understand whether preconditioning is a common phenomenon in MS and whether future therapies could be developed to stimulate the body’s protective mechanisms to better ward off MS attacks.

The MS Lesion Project is an international collaborative effort to determine how clinical symptoms, imaging findings, and tissue damage correlate in people with MS. Studying the pathology of MS may offer clues to its cause. Another goal is to identify possible subtypes of MS that may respond differently to different therapies.