Zivadinov Robert, Bakshi Rohit
Buffalo Neuroimaging Analysis Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14203, USA.
Front Biosci. 2004 Jan 1;9:647-64. doi: 10.2741/1262.
A growing body of evidence indicates that irreversible tissue destruction including axonal and neuronal degeneration is a key component of the multiple sclerosis (MS) disease process. Magnetic resonance imaging (MRI) is a powerful technique that can be combined with semiautomated or automated computer assisted analysis approaches to detect progressive atrophy of the brain and spinal cord with high sensitivity and reproducibility. The pathophysiology of central nervous system (CNS) atrophy in MS is unknown but likely represents an epiphenomenon related to the effects of inflammation including chronic demyelination, axonal injury, neuronal loss and Wallerian degeneration. Other factors that may contribute to tissue atrophy include injury to the normal appearing gray and white matter by mechanisms such as loss of growth factors, altered electrical conduction and pathologic iron deposition. Prospective studies have suggested that atrophy in MS is predicted by previous inflammatory activity as measured by overt MRI lesions. Gadolinium (Gd)-enhancing lesions have shown a particularly strong predictive value in some but not all longitudinal studies of brain atrophy. Brain atrophy has also been related in cross-sectional and longitudinal studies to T2-hypointense lesions in deep grey matter, suggesting a link between tissue iron deposition and atrophy. The measurement of brain atrophy seems to be of growing clinical relevance as a biomarker of the MS disease process. Atrophy should now be included as a secondary endpoint in trials of therapies aimed at limiting disease progression. Currently available anti-inflammatory immunomodulatory agents and immunosuppressive treatments, while effective at preventing clinical deterioration, have shown at best partial effects in preventing CNS atrophy. Thus, there is a need to further validate atrophy as an outcome measure and ultimately develop treatment strategies that will protect against the destructive aspects of the disease process. This should in turn lead to better long term neurologic functioning and a better quality of life for patients with MS.
越来越多的证据表明，包括轴突和神经元变性在内的不可逆组织破坏是多发性硬化症（MS）疾病进程的关键组成部分。磁共振成像（MRI）是一种强大的技术，可与半自动或自动计算机辅助分析方法相结合，以高灵敏度和可重复性检测脑和脊髓的进行性萎缩。MS中枢神经系统（CNS）萎缩的病理生理学尚不清楚，但可能是一种与炎症影响相关的附带现象，包括慢性脱髓鞘、轴突损伤、神经元丢失和华勒氏变性。其他可能导致组织萎缩的因素包括生长因子丧失、电传导改变和病理性铁沉积等机制对正常外观的灰质和白质造成的损伤。前瞻性研究表明，MS中的萎缩可通过MRI明显病变所测量的既往炎症活动来预测。钆（Gd）增强病变在一些但并非所有脑萎缩纵向研究中显示出特别强的预测价值。在横断面和纵向研究中，脑萎缩也与深部灰质的T2低信号病变有关，提示组织铁沉积与萎缩之间存在联系。脑萎缩测量作为MS疾病进程的生物标志物，其临床相关性似乎越来越高。现在，萎缩应作为旨在限制疾病进展的治疗试验的次要终点纳入其中。目前可用的抗炎免疫调节剂和免疫抑制治疗虽然在预防临床恶化方面有效，但在预防CNS萎缩方面充其量只显示出部分效果。因此，有必要进一步验证萎缩作为一种结局指标，并最终制定能够防止疾病进程破坏性方面的治疗策略。这反过来应该会使MS患者获得更好的长期神经功能和更高的生活质量。
