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Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging
Olga Ciccarelli, Frederik Barkhof, Benedetta Bodini, Nicola De Stefano, Xavier Golay, Klaas Nicolay, Daniel Pelletier, Petra J W Pouwels, Seth A Smith, Claudia A M Wheeler-Kingshott, Bruno Stankoff, Tarek Yousry, David H Miller
The Lancet Neurology, Volume 13, Issue 8, August 2014, Pages 807–822
The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood–brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.