Tallantyre E C, Bø L, Al-Rawashdeh O, Owens T, Polman C H, Lowe J, Evangelou N
Department of Clinical Neurology, School of Clinical Sciences, University of Nottingham, UK.
Brain. 2009 May;132(Pt 5):1190-9. doi: 10.1093/brain/awp106.
The pathological substrate of progressive disability in multiple sclerosis is hypothesized to be axonal loss. Differences in the demographic, pathological and radiological features of patients with primary progressive compared with secondary progressive multiple sclerosis raise the question as to whether they actually represent separate clinical entities. So far, large pathological studies comparing axonal damage between primary progressive and secondary progressive multiple sclerosis have not been reported. In this clinico-pathological study we examined the cervical spinal cord in patients with primary and secondary progressive multiple sclerosis. Human cervical spinal cord was derived at autopsy from 54 patients (17 primary progressive, 30 secondary progressive and 7 controls). Tissue was stained immunohistochemically and examined to determine: (i) the number of surviving corticospinal tract axons; (ii) the extent of grey and white matter demyelination; (iii) the degree of inflammation inside and outside of lesions; and (iv) the relationship between demyelination and axonal loss. Associated clinical data was used to calculate expanded disability status scale for each patient preceding death. Motor disability in the primary progressive and secondary progressive groups was similar preceding death. Secondary progressive multiple sclerosis patients showed considerably more extensive demyelination of both the white and grey matter of the cervical spinal cord. The total number of corticospinal axons was equally low in primary progressive and secondary progressive multiple sclerosis groups versus controls. The reduction of axonal density in demyelinated regions compared to normal appearing white matter was significantly more extensive in primary progressive versus secondary progressive patients (33% reduction versus 16% reduction, P < 0.001). These findings suggest axonal loss is the pathological substrate of progressive disability in both primary progressive and secondary progressive multiple sclerosis with a common plaque-centred mechanism. More extensive axonal loss within areas of demyelination in primary progressive multiple sclerosis could explain high levels of axonal loss observed in these patients despite low levels of demyelination.
多发性硬化症中进行性残疾的病理基础被认为是轴突损失。原发性进行性多发性硬化症患者与继发性进行性多发性硬化症患者在人口统计学、病理学和放射学特征上的差异，引发了一个问题，即它们是否实际上代表不同的临床实体。到目前为止，尚未有比较原发性进行性和继发性进行性多发性硬化症之间轴突损伤的大型病理学研究报告。在这项临床病理学研究中，我们检查了原发性和继发性进行性多发性硬化症患者的颈脊髓。人类颈脊髓取自54例患者的尸检样本（17例原发性进行性、30例继发性进行性和7例对照）。组织进行免疫组织化学染色并检查，以确定：（i）存活的皮质脊髓束轴突数量；（ii）灰质和白质脱髓鞘的程度；（iii）病变内外的炎症程度；以及（iv）脱髓鞘与轴突损失之间的关系。相关临床数据用于计算每位患者死亡前的扩展残疾状态量表。原发性进行性组和继发性进行性组在死亡前的运动残疾情况相似。继发性进行性多发性硬化症患者的颈脊髓白质和灰质脱髓鞘范围明显更广。原发性进行性和继发性进行性多发性硬化症组与对照组相比，皮质脊髓轴突总数同样较低。与正常外观的白质相比，原发性进行性患者脱髓鞘区域的轴突密度降低程度明显大于继发性进行性患者（降低33%对降低16%，P<0.001）。这些发现表明，轴突损失是原发性进行性和继发性进行性多发性硬化症中进行性残疾的病理基础，存在一种以斑块为中心的共同机制。原发性进行性多发性硬化症脱髓鞘区域内更广泛的轴突损失，可以解释这些患者尽管脱髓鞘程度较低但仍观察到高水平轴突损失的现象。
