Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts2Laboratory for Neuroimaging Research, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Center for Brain Research, Medical University of Vienna, Vienna, Austria.
JAMA Neurol. 2017 Jan 1;74(1):100-109. doi: 10.1001/jamaneurol.2016.4237.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system traditionally characterized by an initial relapsing-remitting clinical course and focal inflammatory lesions that have a predilection for the periventricular white matter. Recently, however, histopathologic and imaging studies have illustrated a more complex pathologic substrate involving cortical demyelination, gray matter atrophy, and meningeal inflammation. Neuroimaging advances have facilitated improved detection of cortical pathology, but our understanding of the pathogenesis of cortical disease remains incomplete. The purpose of this review is to evaluate the current status and future prospects regarding the emerging role of magnetic resonance imaging to visualize leptomeningeal enhancement in patients with MS and place these findings in the proper pathobiologic and clinical context.
Cortical atrophy and demyelination along the subpial surface appear early in the disease course in patients with MS but accelerate in progressive stages. Histopathologic studies of patients have shown the presence of inflammatory infiltrates, in some cases with features of B cell-rich tertiary lymph follicles, along the cortical meningeal surface. Recent magnetic resonance imaging data demonstrate the ability to detect such inflammation using high-resolution gadolinium-enhanced contrast scans by the presence of leptomeningeal enhancement. Clinical and magnetic resonance imaging correlation studies indicate that leptomeningeal enhancement is most common in patients with progressive forms of MS and shows a relationship to subpial cortical lesions and cortical atrophy.
A growing body of evidence suggests that gray matter demyelination, cortical atrophy, and leptomeningeal inflammation may be important components of progressive MS pathology and provide a new therapeutic target. Leptomeningeal enhancement may prove a useful surrogate marker for such pathology, perhaps improving our understanding of the natural history of progressive MS, although its ultimate effect on therapeutic development and clinical care requires further study.
多发性硬化症（MS）是一种中枢神经系统的慢性脱髓鞘疾病，传统上以初始复发缓解的临床病程和有利于脑室周围白质的局灶性炎症病变为特征。然而，最近的组织病理学和影像学研究表明，存在更复杂的病理基质，涉及皮质脱髓鞘、灰质萎缩和脑膜炎症。神经影像学的进步促进了皮质病变的更好检测，但我们对皮质疾病发病机制的理解仍然不完整。本综述的目的是评估磁共振成像（MRI）在显示 MS 患者软脑膜增强方面的新兴作用的现状和未来前景，并将这些发现置于适当的病理生物学和临床背景中。
在 MS 患者中，皮质萎缩和沿软脑膜表面的脱髓鞘在疾病早期出现，但在进行性阶段加速。对患者的组织病理学研究表明，在皮质脑膜表面存在炎症浸润，在某些情况下具有富含 B 细胞的三级淋巴滤泡的特征。最近的磁共振成像数据表明，通过软脑膜增强，可以使用高分辨率钆增强对比扫描来检测这种炎症。临床和磁共振成像相关性研究表明，软脑膜增强在进展型 MS 患者中最为常见，并与皮质下皮质病变和皮质萎缩有关。
越来越多的证据表明，灰质脱髓鞘、皮质萎缩和软脑膜炎症可能是进展型 MS 病理学的重要组成部分，并为新的治疗靶点提供了依据。软脑膜增强可能证明是这种病理学的有用替代标志物，也许可以提高我们对进展型 MS 自然史的理解，尽管其对治疗发展和临床护理的最终影响需要进一步研究。
