Liu C, Edwards S, Gong Q, Roberts N, Blumhardt L D
Department of Medicine, University Hospital, Queen's Medical Centre, Nottingham, UK.
J Neurol Neurosurg Psychiatry. 1999 Mar;66(3):323-30. doi: 10.1136/jnnp.66.3.323.
The association between brain atrophy and permanent functional deficits in multiple sclerosis and the temporal relation between atrophy and the clinical disease course have seldom been investigated. This study aims to determine the amount of infratentorial and supratentorial atrophy in patients by comparison with healthy controls, to establish the relation between atrophy and disability, and to derive the rates of volume loss in individual patients from their estimated disease durations.
Three dimensional acquired MRI was performed on 20 relapsing-remitting and 20 secondary progressive multiple sclerosis patients and 10 control subjects. Volume data on infratentorial and supratentorial structures were obtained using the Cavalieri method of modern design stereology in combination with point counting. Corpus callosal sectional area and "T2 lesion load" were also determined.
Significantly reduced infratentorial and cerebral white matter volumes and corpus callosal sectional areas occurred in all patients compared with controls (p=0.0001-0.004). Mean estimates of volume loss in the cohort were -21%, -19%, -46%, and -12% for the brain stem, cerebellum, upper cervical cord and white matter, respectively, and -21% for the corpus callosal sectional area. Analysis of the amount of atrophy (volume differences between patients and controls) showed that upper cervical cord and cerebral white matter atrophy correlated with the expanded disability status scale (r=-0.37 and -0.37, p=0.018-0.023) and the Scripps neurologic rating scale scores (r=+0.49 and +0.43, p=0.002-0.007). There was no relation between estimated volume loss in the supratentorial and infratentorial compartments. The "T2 lesion load" was associated with ventricular enlargement and corpus callosal atrophy (r=+0.50 and -0.55, p=0.0003-0.0012). Infratentorial atrophy rates correlated with baseline exacerbation rates (r=-0.50 to -0.48, p=0.0016-0.0021) and were higher in relapsing-remitting than secondary progressive patients (p=0.009-0.02).
Significant cerebral and spinal cord volume reductions occurred in both patient subgroups compared with controls. Functional correlates were found with estimated volume loss in the upper cervical cord and cerebral white matter. Particularly for infratentorial structures, estimated rates of atrophy were higher in relapsing-remitting than secondary progressive patients, suggesting that atrophy, perhaps mainly due to tract degeneration, begins early in multiple sclerosis and may relate predominantly to acute inflammatory events, with or without other gradual non-inflammatory processes later in the disease course.
脑萎缩与多发性硬化症永久性功能缺陷之间的关联以及萎缩与临床病程之间的时间关系鲜有研究。本研究旨在通过与健康对照比较，确定患者幕下和幕上萎缩的程度，建立萎缩与残疾之间的关系，并根据个体患者的估计病程得出其体积损失率。
对20例复发缓解型和20例继发进展型多发性硬化症患者以及10名对照者进行三维磁共振成像（MRI）检查。采用现代设计体视学的卡瓦列里方法结合点计数法获取幕下和幕上结构的体积数据。还测定了胼胝体截面积和“T2病变负荷”。
与对照组相比，所有患者的幕下和脑白质体积以及胼胝体截面积均显著减小（p = 0.0001 - 0.004）。该队列中脑干、小脑、颈上段脊髓和白质的体积损失平均估计值分别为 - 21%、- 19%、- 46%和 - 12%，胼胝体截面积为 - 21%。对萎缩程度（患者与对照组之间的体积差异）分析表明，颈上段脊髓和脑白质萎缩与扩展残疾状态量表（r = - 0.37和 - 0.37，p = 0.018 - 0.023）以及斯克里普斯神经学评分量表得分（r = + 0.49和 + 0.43，p = 0.002 - 0.007）相关。幕上和幕下区域的估计体积损失之间无关联。“T2病变负荷”与脑室扩大和胼胝体萎缩相关（r = + 0.50和 - 0.55，p = 0.0003 - 0.0012）。幕下萎缩率与基线加重率相关（r = - 0.50至 - 0.48，p = 0.0016 - 0.0021），复发缓解型患者的幕下萎缩率高于继发进展型患者（p = 0.009 - 0.02）。
与对照组相比，两个患者亚组均出现显著的脑和脊髓体积减小。发现颈上段脊髓和脑白质的估计体积损失与功能相关。特别是对于幕下结构，复发缓解型患者的估计萎缩率高于继发进展型患者，这表明萎缩可能主要由于神经纤维变性，在多发性硬化症早期就已开始，并且可能主要与急性炎症事件有关，无论疾病后期是否伴有其他渐进性非炎症过程。
