Rudick Richard A, Lee Jar-Chi, Nakamura Kunio, Fisher Elizabeth
Mellen Center for MS Treatment and Research U10, Neurologic Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
J Neurol Sci. 2009 Jul 15;282(1-2):106-11. doi: 10.1016/j.jns.2008.11.018. Epub 2008 Dec 19.
Gray matter (GM) pathology is an important component of the multiple sclerosis (MS) disease process. Accelerated gray matter atrophy has been observed in MS patients, but its relationship to neurological disability is not defined. This study was done to determine the relationship between whole brain, GM, and white matter (WM) atrophy and MS disability progression.
Patients with MS and Clinically Isolated Syndromes (CIS), and age- and gender-matched healthy controls were entered into an observational protocol. Baseline brain parenchymal fraction (BPF), GM fraction, and WM fraction, and change over 4 years were correlated with sustained disability progression over the entire study duration. Disability progression was measured using the Multiple Sclerosis Functional Composite (MSFC) and the Expanded Disability Status Scale (EDSS).
Seventy MS and CIS patients and 17 HCs were studied for an average of 6.6 years (range, 3.6-7.8 years). At the final visit, 7 patients were classified as CIS, 36 as relapsing-remitting MS (RRMS), and 27 as secondary progressive MS (SPMS). Baseline whole brain, GM, and WM atrophy predicted EDSS >6.0 at the last study visit. Twenty-one (33%) patients worsened using the EDSS to define disability progression; 29 (46%) worsened using MSFC to define disability progression. Patients with MSFC progression had significantly higher GM atrophy rates compared with patients who were stable on MSFC. White matter atrophy was similar in patients with and without disability progression. Atrophy rates were not different in patients with or without disability progression defined using EDSS.
Whole brain, GM, and WM atrophy predicted MS disability progression observed over the next 6.6 years. Gray matter atrophy rates over 4 years correlated with disability progression measured with the MSFC, but not EDSS. This indicates that MSFC defined disability progression is more closely linked to brain atrophy than EDSS defined disability progression, and provides important new insight into the poor correlation between MRI and clinical disability in MS. The findings confirm the clinical relevance of gray matter atrophy in MS.
灰质（GM）病变是多发性硬化症（MS）疾病进程的重要组成部分。已观察到MS患者存在加速的灰质萎缩，但其与神经功能障碍的关系尚未明确。本研究旨在确定全脑、灰质和白质（WM）萎缩与MS残疾进展之间的关系。
将MS和临床孤立综合征（CIS）患者以及年龄和性别匹配的健康对照纳入观察方案。基线脑实质分数（BPF）、灰质分数和白质分数以及4年期间的变化与整个研究期间持续的残疾进展相关。使用多发性硬化症功能综合评分（MSFC）和扩展残疾状态量表（EDSS）测量残疾进展。
对70例MS和CIS患者以及17例健康对照进行了平均6.6年（范围3.6 - 7.8年）的研究。在最后一次随访时，7例患者被归类为CIS，36例为复发缓解型MS（RRMS），27例为继发进展型MS（SPMS）。基线全脑、灰质和白质萎缩可预测最后一次研究随访时EDSS>6.0。21例（33%）患者使用EDSS定义残疾进展时病情恶化；29例（46%）患者使用MSFC定义残疾进展时病情恶化。与MSFC稳定的患者相比，MSFC进展的患者灰质萎缩率显著更高。有或无残疾进展的患者白质萎缩相似。使用EDSS定义有或无残疾进展的患者萎缩率无差异。
全脑、灰质和白质萎缩可预测未来6.6年观察到的MS残疾进展。4年期间的灰质萎缩率与用MSFC测量的残疾进展相关，但与EDSS无关。这表明MSFC定义的残疾进展比EDSS定义的残疾进展与脑萎缩的联系更紧密，并为MS中MRI与临床残疾之间的不良相关性提供了重要的新见解。这些发现证实了MS中灰质萎缩的临床相关性。
