TY - JOUR
T1 - Pathogenesis of multiple sclerosis
T2 - Insights from molecular and metabolic imaging
AU - Ciccarelli, Olga
AU - Barkhof, Frederik
AU - Bodini, Benedetta
AU - Stefano, Nicola De
AU - Golay, Xavier
AU - Nicolay, Klaas
AU - Pelletier, Daniel
AU - Pouwels, Petra J.W.
AU - Smith, Seth A.
AU - Wheeler-Kingshott, Claudia A.M.
AU - Stankoff, Bruno
AU - Yousry, Tarek
AU - Miller, David H.
N1 - Funding Information:
We thank Paul Matthews (Imperial College London) for his helpful comments. The Nuclear Magnetic Resonance Research Unit in London is supported by the MS Society of Great Britain and Northern Ireland and University College London Hospitals (UCLH) and University College London (UCL) NIHR Biomedical Research Centre. The Amsterdam MS Centre is supported by the Dutch MS Research foundation (grant 98-531d).
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907024513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907024513&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(14)70101-2
DO - 10.1016/S1474-4422(14)70101-2
M3 - Review article
C2 - 25008549
AN - SCOPUS:84907024513
SN - 1474-4422
VL - 13
SP - 807
EP - 822
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 8
ER -