Personal encounters with MS neuropathology over 40 years: where we were and where we have come to.

Margaret Esiri, Emeritus Professor of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, UK

This is a personal history of how the neuropathology of MS has developed over the last 40 years. I start by summarising the state of the field in the mid-1970s when I first developed an interest in it, inspired by the late David Oppenheimer from whom I learnt much of the neuropathology I knew then.

The technique of immunohistochemistry was being developed at the time and this is the technique that has informed most of my research on MS. I was curious about all aspects of MS lesions and started by studying the immunoglobulin-containing cells which were clearly present in increased numbers in acute MS lesions. It is interesting to me that interest in B cells and the plasma cells that are derived from them have become of further interest recently, given the promising use of anti-B cell therapies in the disease.

I then became interested in the work of Derek Gay who is interested in the possible involvement of bacterial antigens in MS and the manner in which they may reach the CNS.

Neurodegeneration then took my interest after we found, unexpectedly, that axonal damage is present even in the earliest lesions. I review briefly the studies undertaken with many colleagues in thalamus, optic pathways, spinal cord and cerebral cortex.

I end my talk by considering which of the questions posed in the 1970s have been answered by research in the intervening years and which still remain to be answered.