Queen Square MS Centre, University College London Institute of Neurology, London, UK; NIHR UCL/UCLH Biomedical Research Centre, London, UK.
Department of Radiology, VU University Medical Center, Amsterdam, Netherlands.
Lancet Neurol. 2014 Aug;13(8):807-22. doi: 10.1016/S1474-4422(14)70101-2. Epub 2014 Jul 6.
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.
多发性硬化症发病机制的作用导致了与复发相关的进行性残疾的基础变化。通过分子和代谢成像技术，可在临床前模型和多发性硬化症患者中研究疾病机制。此类成像研究提供了许多认识：在血脑屏障未受损的情况下持续存在炎症、病变内和病变外的活化小胶质细胞、急性病变后线粒体活性增加、脑内钠离子浓度升高、急性病变和正常外观的白质中谷氨酸增加、不同患者和病变中脱髓鞘程度不同、灰质中早期神经元损伤以及病变和白质中星形胶质细胞的早期增殖和活化。分子和代谢成像的临床转化和这些技术的扩展将能够评估针对这些疾病机制的新药，并有可能通过对患者进行分层治疗来改善健康结果。
