The implications of brain volume loss in multiple sclerosis are profound. Dr. Anton Titov, MD. Disability itself is not a measure of the amount of brain damage. Dr. Paul M. Matthews, MD. Disability in multiple sclerosis ultimately arises from brain damage. But brain damage occurs early in the multiple sclerosis. Brain damage first occurs in MS patients without causing permanent disability. Thus, the clinical state of the patient ultimately shouldn't help us to make the decision as to whether a patient needs treatment. Clinical symptoms of the patient are important for determining treatment at some level. Dr. Anton Titov, MD. Almost all patients with multiple sclerosis need some form of anti-inflammatory treatment. Dr. Paul M. Matthews, MD. We have to slow or to stop neurodegenration process in multiple sclerosis. many might ask this. Damage is ongoing in a progressive way through the multiple sclerosis. Dr. Anton Titov, MD. Why clinical symptoms and progression of neuronal and axon damage is not responsible for disability? Why isn't disability manifest at the earliest stages of multiple sclerosis? All of us know that patients with early multiple sclerosis don't show any permanent disability. Or the disability that they show is related directly to focal inflammatory processes. Disability in early multiple sclerosis shows partial resolution. Dr. Paul M. Matthews, MD. We conducted early research on this topic. Since then brain damage progression results has been repeated by many other groups. It was expanded in a variety of ways. It has been shown that the brain has a remarkable capacity for adaptive repair. This helps to preserve behavior in multiple sclerosis. Brain resilience helps to preserve the ability to perform tasks and to minimize disability. This is true even in the context of permanent change and loss of axons. Dr. Paul M. Matthews, MD. Let me tell you more precisely. In the early stages of the multiple sclerosis the following is true. Injury to large bundle of axons can be compensated for by repurposing of adjacent areas of brain. Even more distant brain areas can compensate for damaged brain areas in multiple sclerosis. That happens in some rare cases. We know that the rest of the brain is relatively intact. Dr. Paul M. Matthews, MD. Multiple sclerosis creates irreversible loss of nerve axons early. But the brain can rewire itself in important ways. As brain damage progresses, the ability of the brain to compensate for lost functions begins progressively to drop. The resilience of the brain is lost. Dr. Anton Titov, MD. That is when the irreversible damage happens first. In addition to that, we know that multiple hits to the same functional system ultimately become impossible for brain adaptive compensation to repair. Thus, patients may develop serial injury to the spinal cord along the cortical spinal tract. Then motor function recovery ultimately just doesn't occur. Patient enters the inexorable progressive stage of the multiple sclerosis. Then every further damage to the brain, every further loss of axons, gives rise to change in disability status of patients with multiple sclerosis.