在渐进的多发性硬化症中,残疾独立于大脑白质脱髓化
Vikas Singh1, Yufan Zheng2, Daniel Ontaneda3
1Department of Neurosciences, NC30, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Acta neuropathologica
|August 31, 2024
概括
渐进性多发性硬化症 (MS) 的残疾可能并不总是源于白质 (WM) 脱髓化. 新的MRI方法揭示了周周结膜性退化,这表明MS中神经退化的替代途径.
科学领域:
- 神经科学是一个神经科学.
- 神经病理学神经病理学
- 放射学 放射学是一门学科.
背景情况:
- 进展性多发性硬化症 (PMS) 中神经障碍的致病机制尚不清楚.
- 皮质神经元损失和残疾进展独立于复发活动 (PIRA) 表明除了白质 (WM) 脱髓化之外的机制.
- 骨髓皮质性MS (MCMS) 呈现出明显的病理特征,需要进一步调查.
研究的目的:
- 在死后的MCMS大脑中研究髓化T2病变的三维分布和病理学.
- 开发和验证一个MRI分类器来区分MCMS和典型的MS (TMS).
- 评估不同多发性硬化症亚型的患病率及其与活着的PMS患者残疾的关联.
主要方法:
- 来自MCMS和TMS病例的死后大脑切片被分析并与MRI数据一起注册.
- 基于T1强度值的新型MRI分类器被开发出来,以区分MCMS和TMS.
- 该分类器在死后大脑中得到验证,并应用于SPRINT-MS研究中活着的PMS参与者的基线MRI.
主要成果:
- 尸检后的MCMS大脑显示了周周结膜髓化T2高强度,与轴突退化的表面入梯度.
- 磁力共振成像分类器准确地区分了病理确认的MCMS和TMS病例 (94%准确率).
- 在SPRINT-MS中,分类器识别了78%的TMS,10%的MCMS和12%的最小大脑WM变化;残疾指标在MCMS和TMS队列之间是相似的.
结论:
- 在活着的PMS患者中,很大一部分患者表现出有限的大脑WM脱髓化,这挑战了它在残疾进展中的普遍作用.
- 周腹筋髓化纤维退化支持MS中神经退化的表面梯度.
- 这些发现对了解多发性硬化病理和优化PMS临床试验结果有意义.
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