Abstract：
BACKGROUND: A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.0) to less-disabled (EDSS 3.0-6.5) community dwelling (CD) progressive pwMS, matched on age-, sex- and disease-duration (DDM).
OBJECTIVE: To identify neuroimaging and molecular biomarker characteristics that distinguish SD/SN from DDM-CD progressive pwMS.
METHODS: This study was carried at SN facility and at a tertiary MS center. The study collected clinical, molecular (serum neurofilament light chain, sNfL and glial acidic fibrillary protein, sGFAP) and MRI quantitative lesion-, brain volume-, and tissue integrity-derived measures. Statistical analyses were controlled for multiple comparisons.
RESULTS: 42 SD/SN and 42 DDM-CD were enrolled. SD/SN pwMS showed significantly lower cortical volume (CV) (p < 0.001, d = 1.375) and thalamic volume (p < 0.001, d = 0.972) compared to DDM-CD pwMS. In a logistic stepwise regression model, the SD/SN pwMS were best differentiated from the DDM-CD pwMS by lower CV (p < 0.001) as the only significant predictor, with the accuracy of 82.3%. No significant differences between the two groups were observed for medulla oblongata volume, a proxy for spinal cord atrophy and white matter lesion burden, while there was a statistical trend for numerically higher sGFAP in SD/SN pwMS.
CONCLUSIONS: The CASA-MS study showed significantly more gray matter atrophy in severe compared to less-severe progressive MS.
OBJECTIVE: To identify neuroimaging and molecular biomarker characteristics that distinguish SD/SN from DDM-CD progressive pwMS.
METHODS: This study was carried at SN facility and at a tertiary MS center. The study collected clinical, molecular (serum neurofilament light chain, sNfL and glial acidic fibrillary protein, sGFAP) and MRI quantitative lesion-, brain volume-, and tissue integrity-derived measures. Statistical analyses were controlled for multiple comparisons.
RESULTS: 42 SD/SN and 42 DDM-CD were enrolled. SD/SN pwMS showed significantly lower cortical volume (CV) (p < 0.001, d = 1.375) and thalamic volume (p < 0.001, d = 0.972) compared to DDM-CD pwMS. In a logistic stepwise regression model, the SD/SN pwMS were best differentiated from the DDM-CD pwMS by lower CV (p < 0.001) as the only significant predictor, with the accuracy of 82.3%. No significant differences between the two groups were observed for medulla oblongata volume, a proxy for spinal cord atrophy and white matter lesion burden, while there was a statistical trend for numerically higher sGFAP in SD/SN pwMS.
CONCLUSIONS: The CASA-MS study showed significantly more gray matter atrophy in severe compared to less-severe progressive MS.
摘要：
背景：多发性硬化症（pwMS）患者的一个亚组将发展为严重的残疾。严重MS的病理生理学尚不清楚。对严重影响的MS（CASA-MS）的综合评估是一项病例对照研究，该研究比较了熟练护理（SD/SN）（EDSS≥7.0）中的严重残疾与较少残疾（EDSS3.0-6.5）社区居住（CD）进行性pwMS，按年龄匹配-，性别和疾病持续时间（DDM）。
目的：确定区分SD/SN和DDM-CD进行性pwMS的神经影像学和分子生物学特征。
方法：本研究在SN机构和三级MS中心进行。这项研究收集了临床，分子(血清神经丝轻链，sNfL和胶质酸性原纤维蛋白，sGFAP）和MRI定量病变-，大脑容量-，和组织完整性衍生的措施。对统计分析进行多重比较。
结果：纳入42SD/SN和42DDM-CD。与DDM-CDpwMS相比，SD/SNpwMS显示出明显较低的皮质体积（CV）（p<0.001，d=1.375）和丘脑体积（p<0.001，d=0.972）。在逻辑逐步回归模型中，SD/SNpwMS与DDM-CDpwMS的最佳区别在于较低的CV(p<0.001)作为唯一显著的预测因子,准确率为82.3%。两组延髓体积无显著差异，脊髓萎缩和白质病变负担的代表，而SD/SNpwMS中sGFAP数值较高存在统计趋势。
结论：CASA-MS研究显示，与不太严重的进行性MS相比，重度患者的灰质萎缩明显更多。
目的：确定区分SD/SN和DDM-CD进行性pwMS的神经影像学和分子生物学特征。
方法：本研究在SN机构和三级MS中心进行。这项研究收集了临床，分子(血清神经丝轻链，sNfL和胶质酸性原纤维蛋白，sGFAP）和MRI定量病变-，大脑容量-，和组织完整性衍生的措施。对统计分析进行多重比较。
结果：纳入42SD/SN和42DDM-CD。与DDM-CDpwMS相比，SD/SNpwMS显示出明显较低的皮质体积（CV）（p<0.001，d=1.375）和丘脑体积（p<0.001，d=0.972）。在逻辑逐步回归模型中，SD/SNpwMS与DDM-CDpwMS的最佳区别在于较低的CV(p<0.001)作为唯一显著的预测因子,准确率为82.3%。两组延髓体积无显著差异，脊髓萎缩和白质病变负担的代表，而SD/SNpwMS中sGFAP数值较高存在统计趋势。
结论：CASA-MS研究显示，与不太严重的进行性MS相比，重度患者的灰质萎缩明显更多。
