Brier Matthew R, Judge Bradley, Ying Chunwei, Salter Amber, An Hongyu, Patel Aakash, Wang Qing, Wang Yong, Cross Anne H, Naismith Robert T, Benzinger Tammie Ls, Goyal Manu S
Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
Ann Neurol. 2025 Apr;97(4):766-778. doi: 10.1002/ana.27165. Epub 2024 Dec 23.
Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis. We investigated cerebral metabolic changes in MS and when in the disease course they occurred, and assessed their relationship with microstructural changes.
This study used combined fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) to measure cerebral metabolic rate of glucose and oxygen, thereby quantifying glycolysis. Twelve healthy controls, 20 patients with relapsing MS, and 13 patients with non-relapsing MS were studied. Relapsing patients with MS were treatment naïve and scanned pre- and post-initiation of high efficacy disease modifying therapy.
In normal appearing white matter, we observed increased glucose utilization and reduced oxygen utilization in newly diagnosed MS, consistent with increased glycolysis. Increased glycolysis was greater in patients with a longer disease duration course and higher disability. Among newly diagnosed patients, different treatments had differential impacts on glucose utilization. Last, whereas hypermetabolism within lesions was clearly associated with inflammation, no such relationship was found within normal appearing white matter.
Increased white matter glycolysis is a prominent feature of cerebral metabolism in MS. It begins early in the disease course, increases with disease duration and is independent of microstructural evidence of inflammation in normal appearing white matter. Optimization of the metabolic environment may be an important component of therapies designed to reduce progressive disability. ANN NEUROL 2025;97:766-778.
尽管有多种治疗方法可减少多发性硬化症（MS）的复发，但仍有许多患者继续出现进行性残疾累积。MS与代谢紊乱有关，脑代谢应激易导致组织损伤，并可能影响髓鞘再生。此外，髓鞘稳态在代谢上成本高昂且依赖糖酵解。我们研究了MS患者脑代谢的变化及其在疾病进程中的发生时间，并评估了它们与微观结构变化的关系。
本研究采用氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）与磁共振成像（MRI）相结合的方法，测量脑葡萄糖代谢率和氧代谢率，从而量化糖酵解。研究对象包括12名健康对照者、20名复发型MS患者和13名非复发型MS患者。复发型MS患者未接受过治疗，在开始高效疾病修正治疗前和治疗后进行扫描。
在正常外观的白质中，我们观察到新诊断的MS患者葡萄糖利用率增加，氧利用率降低，这与糖酵解增加一致。病程较长和残疾程度较高的患者糖酵解增加更为明显。在新诊断的患者中，不同治疗方法对葡萄糖利用率有不同影响。最后，虽然病灶内的代谢亢进与炎症明显相关，但在正常外观的白质中未发现这种关系。
白质糖酵解增加是MS脑代谢的一个显著特征。它在疾病进程早期就开始出现，随病程延长而增加，且与正常外观白质中炎症的微观结构证据无关。优化代谢环境可能是旨在减少进行性残疾的治疗方法的一个重要组成部分。《神经病学年鉴》2025年；97:766 - 778。
