Multiple Sclerosis: How Rate of Neuron Loss Influences Treatment and Prognosis (1)

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Exclusive interview / Dr. Anton Titov MD and Professor Dr. Paul Matthews, leading multiple sclerosis neurologist, neurodegeneration, brain imaging MRI, functional MRI, PET expert and precision medicine specialist.

Let's start with a major theme of your research: neurodegeneration in multiple sclerosis. And multiple sclerosis is generally described as a primary autoimmune disease, but you and your colleagues showed paradigm-shifting evidence that multiple sclerosis is a neurodegenerative disease. And you showed that multiple sclerosis is accompanied by significant axonal and neuronal loss. What is the significance of your discoveries about axonal and neuronal loss in multiple sclerosis? And what are the implications of loss of neurons and axons for treatment strategy and for prognosis in multiple sclerosis patients? Well, thanks! First, many people contributed to this discovery and, in fact, it was a re-discovery. So, in the pathology literature from the early 20th century, the evidence for loss of axons and even nerve cell loss is well-documented. Although what was emphasized, moving forward, was the demyelinating aspects of the inflammatory disease, which is really what entered the textbooks and became the dominant theme in the 1960s and thereafter... Until around 1990 to 95, when with Dr. Doug Arnold in Montreal we noted that there were two peculiar findings: First, we found evidence for loss of a chemical, N-acetyl-aspartate that is found largely or only in nerve cells in patients with multiple sclerosis, [there were] really substantial losses. This was unexpected, this was found both in the white matter, and in the gray matter. In addition, we recognized that associated with severe losses also was significant loss of brain volume, shrinking of the brain. Now, following on from that in very elegant neuropathological studies Dr. Bruce Trapp of Cleveland Clinic published what is really a landmark New England Journal of Medicine paper, showing how the inflammatory process within individual white matter lesions gives rise to loss of axons as they are damaged in conjunction with demyelination, and then followed on, along with us, to provide pathological evidence for more widespread damage, including damage to the gray matter. My colleagues and I, and Bruce Trapp and his colleagues, and an increasing number of other groups, particularly including also Dr. Jeroen Geurts at the Free University of Amsterdam, published a series of papers, nicely highlighting how nerve cells are lost in gray matter, particularly in subcortical structures, such as the thalamus as well as the neocortex, and, of course, there's widespread axonal loss in the white matter. Together this is creating a picture, in which inflammation is accompanied by a direct damage to nerve cells both in their axons and in the nerve cell bodies. This is associated with the progression over time, so even after a lesion is formed, the chronic inflammatory processes and possibly other factors lead to a progression of neurodegeneration. Now, why is this important to the person with Multiple Sclerosis? What we've come to recognize is that the relationship between the number and the distribution of inflammatory lesions in the brain the hyper-intense lesions that we see on the MRI T2-weighted scan is only approximately correlated with the degree of disability and the rate of its progression over time. Additional independent information is added by including in data about the degree of nerve and axon loss, and indeed we believe that it is the irreversible axon and nerve cell loss that is the proximate substrate of disability progression in the multiple sclerosis disease. Thus, what we're really doing in looking at the T2 inflammatory lesions is looking at a primary cause of the neurodegeneration. When we look at the neurodegeneration we're looking at what is the primary cause of the disability in most people as it moves forward. 1

Multiple Sclerosis: How Rate of Neuron Loss Influences Treatment and Prognosis (1) best treatment for damaged hair
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