Department of Clinical Neurology, University of Nottingham, UK.
Mult Scler. 2010 Apr;16(4):406-11. doi: 10.1177/1352458510364992. Epub 2010 Mar 9.
Growing evidence suggests that axonal degeneration rather than demyelination is the pathological substrate underlying chronic, irreversible disability in multiple sclerosis. However, direct evidence linking clinical disability measured in vivo with corresponding post-mortem measures of axonal pathology is lacking. Our objective in this study was to investigate the relationship between motor disability accumulated by patients with multiple sclerosis during life and the degree of axonal loss observed in their descending motor tracts after death. Human spinal cord derived at autopsy from 45 patients with multiple sclerosis was investigated. The medical records of each patient were reviewed by a multiple sclerosis neurologist to determine the degree of motor disability reached before death. Spinal cord sections were stained immunohistochemically. The degree of demyelination and the number of surviving corticospinal tract axons were measured in each patient. Patients who had accumulated higher levels of motor disability prior to death demonstrated fewer surviving corticospinal axons. Motor disability did not correlate with degree of demyelination. This study provides for the first time, direct clinico-pathological evidence that axonal loss is the pathological substrate of established disability in multiple sclerosis.
越来越多的证据表明，轴突变性而非脱髓鞘是多发性硬化症慢性、不可逆残疾的病理基础。然而，直接将临床残疾与死后轴突病理的相应测量结果联系起来的证据尚缺乏。本研究的目的是探讨多发性硬化症患者在其一生中累积的运动障碍与死后观察到的下行运动束中轴突丢失程度之间的关系。本研究对 45 例多发性硬化症尸检脊髓进行了研究。由多发性硬化症神经科医生对每位患者的病历进行了回顾，以确定其死亡前的运动障碍程度。对脊髓切片进行免疫组织化学染色。在每位患者中测量脱髓鞘程度和存活的皮质脊髓束轴突数量。在死亡前累积更高运动障碍水平的患者表现出较少的存活皮质脊髓轴突。运动障碍与脱髓鞘程度无关。本研究首次提供了直接的临床病理学证据，表明轴突丢失是多发性硬化症中已确立残疾的病理基础。
