You are one of several leading neurologists who discovered and studied neurodegeneration in multiple sclerosis. Dr. Anton Titov, MD. You worked with Dr. Douglas Arnold at McGill University in Montreal. You worked with Dr. Margaret Esiri, who is a neuropathologist in Oxford. Dr. Anton Titov, MD. You studied axonal loss in multiple sclerosis. Let me quote from one of your research articles on multiple sclerosis. "The main focus for treatment in multiple sclerosis must be the reduction of permanent disability. It is accepted that permanent disability results from cumulative axon loss. This axon losses occurs very early in the multiple sclerosis. Dr. Anton Titov, MD. Effective treatment may be available. Then the timing of therapeutic intervention should reflect the timing at the start of axonal damage. That would mean treating multiple sclerosis early. Treatment decisions should not being based on the severity of the clinical state of the multiple sclerosis. Therapy must focus on preventing the cumulative assaults. Cumulative damage results, eventually, in permanent disability." Dr. Paul M. Matthews, MD. This has profound implications for treatment strategy in multiple sclerosis. Dr. Anton Titov, MD. Can you assess by MRI the neuronal and axonal loss in a patient with a recent diagnosis of multiple sclerosis? How would that affect the treatment strategy choices in multiple sclerosis patients? Dr. Paul M. Matthews, MD. Well, I think we have we have learned that we can use a variety of diagnostic tests based on different imaging techniques. We can identify neuron and axon loss. We can do that even at the earliest stages of Multiple Sclerosis in the clinically isolated syndrome. Seminal work was done by Professor Nicola De Stefano, now at the University of Siena. Dr. Paul M. Matthews, MD. It showed that the rate of brain volume loss progress approximately equally through the entire course of the multiple sclerosis disease. Brain volume loss is an indirect measure of the injury to nerve cells and axons. It means that nerve cells continue to die from first symptoms of multiple sclerosis with the clinically isolated syndrome through to the late secondary progressive phase of multiple sclerosis. The rate of death of axons and nerve cells remains approximately similar. Now further data has come to demonstrate it even more directly. Dr. Elizabeth Fisher during the time that she was at the Cleveland Clinic, discovered this important finding in multiple sclerosis. Together with Dr. Rick Rudick and their colleagues, she studied cohort patients from the initial treatment groups with interferon beta over an extended period of time. They studied multiple sclerosis patients well over a decade. They demonstrated that the rates of brain volume loss over that time were approximately constant. Dr. Paul M. Matthews, MD. Moreover, in other work, she and a variety of other workers, including ourselves, show that the rate of brain volume loss in multiple sclerosis over time is a good predictor of the progression of disability.