Olga Ciccarelli1, Ahmed Toosy1, Nicola De Stefano2, Claudia Angela Michela Wheeler-Kingshott3, David H. Miller3, Alan J. Thompson1
1NMR Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom; 2Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy; 3NMR Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom
Mitochondrial dysfunction is central to the pathogenesis of many neurological diseases, including MS. We propose a methodology to estimate in-vivo neuronal mitochondrial metabolism and its relatice contribution to disability. We modelled N-acetyl-aspartate (NAA), measured by spinal cord 1H-MR spectroscopy, which reflects axonal integrity and mitochondrial metabolism, together with measures of axonal integrity, such as axial diffusivity and cord area, in patients with MS studied six months after a spinal cord relapse. The residual variance in NAA concentration after accounting for the structural measures should reflect mitochondrial metabolism. A lower mitochondrial metabolism was associated with greater disability indipendent of structural damage.