Remyelination varies between and within lesions in multiple sclerosis following bexarotene.
Remyelination varies between and within lesions in multiple sclerosis following bexarotene.
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DOI：
10.1002/acn3.51662
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发表时间：
2022-10
影响因子：
5.3
通讯作者：
Chard, Declan
中科院分区：
文献类型：
--
作者：
Brown, J. William L.;Prados, Ferran;Altmann, Daniel R.;Kanber, Baris;Stutters, Jonathan;Cunniffe, Nick G.;Jones, Joanne L.;Georgieva, Zoya G.;Needham, Edward J.;Daruwalla, Cyrus;Wheeler-Kingshott, Claudia Gandini;Connick, Peter;Chandran, Siddharthan;Franklin, Robin;MacManus, David;Samson, Rebecca;Coles, Alasdair;Chard, Declan
在多发性硬化症中，慢性脱髓鞘与轴突丢失有关，并最终导致不可逆转的进行性残疾。增强髓鞘再生可能会减缓甚至逆转残疾。我们最近在49名多发性硬化症患者中试验了贝沙罗汀与安慰剂。虽然主要MRI结果为阴性，但有会聚的神经生理学和MRI证据表明疗效。多种因素影响损伤髓鞘再生。在本研究中，我们进行了一项系统性探索性分析，以确定治疗反应（通过磁化传递率的变化测量）是否受位置（组织类型和与CSF的接近程度）或异常程度（使用基线磁化传递率和T1值）的影响。我们检查了整个病变水平、病变成分水平（核心、边缘和病变周围组织）和单个病变体素水平的治疗效果。在整个病变水平上，在GM而不是WM病变中观察到显著的治疗效果。体素水平分析在基线MTR最低的WM病变体素中检测到显著治疗效应，并在WM和CGM病变体素中发现治疗效应梯度，表明CSF间隙附近的治疗效应较低。最后，与内核相比，在GM病变的外部和周围组件中观察到更大的治疗效果。病变内和病变间的髓鞘再形成有显著差异。GM病变中更大的髓鞘再生效应与神经病理学观察结果一致。对于未来的髓鞘再生试验，与WM病变（需要体素水平分析）相比，整个GM病变测量需要的后处理不太复杂，并且显着减少样本量。
In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response – measured by change in magnetisation transfer ratio – is influenced by location (tissue type and proximity to CSF) or the degree of abnormality (using baseline magnetisation transfer ratio and T1 values). We examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level. At the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel‐level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores. Remyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post‐processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.
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影响因子：
11.2
作者：
Kolb, Hadar;Absinta, Martina;Beck, Erin S.;Ha, Seung-Kwon;Song, Yeajin;Norato, Gina;Cortese, Irene;Sati, Pascal;Nair, Govind;Reich, Daniel S.
通讯作者：
Reich, Daniel S.
影响因子：
11.2
作者：
Chang, Ansi;Staugaitis, Susan M.;Dutta, Ranjan;Batt, Courtney E.;Easley, Kathryn E.;Chomyk, Anthony M.;Yong, V. Wee;Fox, Robert J.;Kidd, Grahame J.;Trapp, Bruce D.
通讯作者：
Trapp, Bruce D.
影响因子：
6.4
作者：
Albert, Monika;Antel, Jack;Stadelmann, Christine
通讯作者：
Stadelmann, Christine
影响因子：
9.9
作者：
Chen, Jacqueline Tien-Hsiang;Easley, Kathryn;Trapp, Bruce D.
通讯作者：
Trapp, Bruce D.
DOI：
10.1093/jnen/62.7.723
发表时间：
2003-07-01
影响因子：
3.2
作者：
Bo, L;Vedeler, CA;Mork, SJ
通讯作者：
Mork, SJ