Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis
Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis
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DOI：
10.1093/brain/awv396
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发表时间：
2016-03-01
期刊：
影响因子：
14.5
通讯作者：
Toosy, Ahmed T.
中科院分区：
文献类型：
--
作者：
Tur, Carmen;Goodkin, Olivia;Toosy, Ahmed T.
了解多发性硬化症中正常脑组织微结构损伤的机制将有助于神经保护策略的发展。Tur等人通过纵向评估急性视神经炎后视辐射扩散特性的变化，获得了顺行跨突触变性是损伤机制之一的证据。了解多发性硬化症中正常脑组织微结构损伤的潜在机制将有助于神经保护策略的制定。通过纵向评估急性视神经炎后视辐射扩散特性的变化，Tur等人获得了证据，表明顺行性跨突触变性是损伤机制之一。在多发性硬化症中，正常外观脑组织的显微结构损伤是其病理学的重要特征。了解这些机制对于帮助开发神经保护策略至关重要。视觉通路是研究脱髓鞘损伤和修复机制的重要模型。已经提出了跨外侧膝状体核的顺行跨突触变性作为组织损伤的机制，以解释与脱髓鞘疾病和视神经炎相关的视辐射异常，尽管这方面的证据仅依赖于横断面研究。因此，我们旨在评估：（i）视神经炎后视辐射扩散特性的纵向变化，提示跨突触变性;（ii）早期视神经磁共振成像测量对晚期视辐射变化的预测价值;以及（iii）视神经炎后视神经和脑变化对视觉结果的影响。在基线、3个月、6个月和12个月时，对28例连续急性视神经炎患者和8例健康对照进行了目视评估（logMAR、色觉和Sloan 1.25%、5%、25%）和磁共振成像。进行磁共振成像序列（和获得的度量）是：（i）视神经液衰减的反转恢复（视神经横截面积）;（ii）视神经质子密度快速自旋回波（视神经质子密度-病变长度）;（iii）视神经钆后T-1加权（Gd增强的病变长度）;和（iv）脑扩散加权成像（以导出光学辐射分数各向异性、径向扩散率和轴向扩散率）。进行混合效应和多变量回归模型，调整年龄，性别和视神经放射损伤负荷。这些研究确定了随时间的变化以及早期视神经测量与1年总体视辐射/临床测量之间的相关性。在视神经炎后1年内，患者的视辐射各向异性分数降低（P = 0.018），径向扩散率增加（P = 0.002），而对照组的视辐射测量值不变。此外，视神经炎后3个月受影响的视神经的横截面积较小，预测1年时视辐射的各向异性分数较低，径向扩散率较高（P = 0.007），而视神经的炎症指标均不能预测视辐射的变化。最后，基线时Gd增强病变长度和1年时视神经质子密度-病变长度越大，1年时的视功能越差（两者P = 0.034），视神经炎后受影响的视神经横截面积和视放射损伤均与1年视力结果无关。我们的纵向研究表明，视神经炎后，有进行性损害的视辐射，更大的早期残余视神经萎缩的患者，即使调整后的视辐射病变。这些发现为跨突触变性提供了证据。了解多发性硬化症中正常脑组织微结构损伤的潜在机制将有助于神经保护策略的发展。通过纵向评估急性视神经炎后视辐射扩散特性的变化，Tur等人获得了顺行跨突触变性是损伤机制之一的证据。
Understanding the mechanisms underlying microstructural damage to normal-appearing brain tissue in multiple sclerosis will aid the development of neuroprotective strategies. By longitudinally assessing changes in the diffusion properties of optic radiations after acute optic neuritis, Tur et al. obtain evidence that anterograde trans-synaptic degeneration is among the damage mechanisms.Understanding the mechanisms underlying microstructural damage to normal-appearing brain tissue in multiple sclerosis will aid the development of neuroprotective strategies. By longitudinally assessing changes in the diffusion properties of optic radiations after acute optic neuritis, Tur et al. obtain evidence that anterograde trans-synaptic degeneration is among the damage mechanisms.In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T-1-weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients' optic radiations decreased (P = 0.018) and radial diffusivity increased (P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year (P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year (P = 0.034 for both).Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration.Understanding the mechanisms underlying microstructural damage to normal-appearing brain tissue in multiple sclerosis will aid the development of neuroprotective strategies. By longitudinally assessing changes in the diffusion properties of optic radiations after acute optic neuritis, Tur et al. obtain evidence that anterograde trans-synaptic degeneration is among the damage mechanisms.