Monitoring brain atrophy during the course of MS

这一提议将验证这样的假设，即脑萎缩的测量将被证明是多发性硬化症患者疾病过程的实用、敏感和相关的替代标志物。对替代标志物的需求是基于新出现的证据，即MS的病理过程不可逆转地损害髓磷脂和轴突，这一过程从疾病开始就活跃，但临床症状只能松散地反映疾病复发缓解阶段的潜在病理严重程度。当MS患者进入继发性进展阶段时，组织破坏已经超过了代偿机制可以维持神经功能的程度。一种高度可重复的量化脑实质损失程度的方法，称为脑实质分数（BPF），将用于实现前三个具体目标。在目的1中，将采用一项涉及145名多发性硬化症患者和30名健康对照者的纵向研究设计来确定多发性硬化症患者发生萎缩的模式。目的2的目的是确定脑萎缩的临床相关性，并验证MS复发期脑萎缩预测后来转化为继发性进展性MS的假设。目的3将确定脑萎缩的MRI和CSF相关性。特异性MR病变的意义。类型将从它们与脑萎缩的关系中推断出来。这些特定MR病变类型的意义将在第4章中直接使用从尸检材料中得出的临床- mri相关性进行测试。该项目的长期临床目标是开发方法，以促进改善MS个体患者的疾病管理，并开发改进的实验疗法监测技术，包括神经保护因子。

This proposal will test the hypothesis that measures of brain atrophy will prove to practical, sensitive, and relevant surrogate markers of the disease process in multiple sclerosis patients. The need for a surrogate marker is based on emerging evidence that the pathologic process in MS irreversibly damages myelin and axons, that this process is active from disease onset, but that clinical symptoms only loosely reflect the severity of the underlying pathology in the relapsing remitting stage of the disease. By the time an MS patient enters the secondary progressive stage, tissue destruction has progressed beyond the point where compensatory mechanisms can sustain neurologic function. A highly reproducible method for quantifying the extent of brain parenchymal loss, termed the brain parenchymal fraction (BPF), will be used to accomplish the first three specific aims. In aim 1, the pattern with which MS patients develop atrophy will be determined using a longitudinal study design involving 145 MS patients and 30 healthy controls. The purpose of aim 2 is to determine clinical correlates of cerebral atrophy and to test the hypothesis that cerebral atrophy in the relapsing phase of MS predicts later conversion to secondary progressive MS. In aim 3, MRI and CSF correlates of cerebral atrophy will be determined. The significance of specific MR lesion. Types will be inferred from their relationship to cerebral atrophy. The significance of these specific MR lesion types will be directly tested using clinical-MRI correlation derived from autopsy material in aim 4. This project will lead to improve methods for monitoring the pathologic process during the course of MS. The long term clinical goals of this project are to develop methods to promote improved disease management for individual MS patients, and to develop improved monitoring techniques for experimental therapies, including neuroprotective factors.