Sicotte N L, Kern K C, Giesser B S, Arshanapalli A, Schultz A, Montag M, Wang H, Bookheimer S Y
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Brain. 2008 Apr;131(Pt 4):1134-41. doi: 10.1093/brain/awn030.
Gray matter brain structures, including deep nuclei and the cerebral cortex, are affected significantly and early in the course of multiple sclerosis and these changes may not be directly related to demyelinating white matter lesions. The hippocampus is an archicortical structure that is critical for memory functions and is especially sensitive to multiple insults including inflammation. We used high-resolution MR imaging at 3.0 T to measure hippocampal volumes in relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients and controls. We found that both groups of MS patients had hippocampal atrophy and that this volume loss was in excess of global brain atrophy. Subregional analysis revealed selective volume loss in the cornu ammonis (CA) 1 region of the hippocampus in RRMS with further worsening of CA1 loss and extension into other CA regions in SPMS. Hippocampal atrophy was not correlated with T2-lesion volumes, and right and left hippocampi were affected equally. Volume loss in the hippocampus and subregions was correlated with worsening performance on word-list learning, a task requiring memory encoding, but not with performance on the Paced Auditory Serial Addition Task (PASAT), a test of information processing speed. Our findings provide evidence for selective and progressive hippocampal atrophy in MS localized initially to the CA1 subregion that is associated with deficits in memory encoding and retrieval. The underlying histopathological substrate for this selective, symmetric and disproportionate regional hippocampal vulnerability remains speculative at this time. Further understanding of this process could provide targets for therapeutic interventions including neuroprotective treatments.
灰质脑结构，包括深部核团和大脑皮层，在多发性硬化病程中早期就会受到显著影响，且这些变化可能与脱髓鞘白质病变并无直接关联。海马体是一种古皮质结构，对记忆功能至关重要，且对包括炎症在内的多种损伤特别敏感。我们使用3.0T高分辨率磁共振成像来测量复发缓解型多发性硬化（RRMS）和继发进展型多发性硬化（SPMS）患者及对照组的海马体体积。我们发现，两组MS患者均存在海马体萎缩，且这种体积损失超过了全脑萎缩。亚区域分析显示，RRMS患者海马体的海马角（CA）1区存在选择性体积损失，而在SPMS患者中，CA1区损失进一步恶化并扩展至其他CA区域。海马体萎缩与T2病变体积无关，左右海马体受影响程度相同。海马体及其亚区域的体积损失与单词列表学习任务（一项需要记忆编码的任务）表现变差相关，但与信息处理速度测试——听觉连续加法任务（PASAT）的表现无关。我们的研究结果为MS患者海马体选择性和进行性萎缩提供了证据，这种萎缩最初局限于CA1亚区域，与记忆编码和检索缺陷相关。目前，这种选择性、对称性和不成比例的海马体区域易损性的潜在组织病理学基础仍具有推测性。对这一过程的进一步了解可为包括神经保护治疗在内的治疗干预提供靶点。
