Trans-Synaptic Axonal Degeneration in the Visual Pathway in Multiple Sclerosis
Trans-Synaptic Axonal Degeneration in the Visual Pathway in Multiple Sclerosis
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DOI：
10.1002/ana.24030
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发表时间：
2014-01-01
影响因子：
11.2
通讯作者：
Villoslada, Pablo
中科院分区：
文献类型：
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作者：
Gabilondo, Inigo;Martinez-Lapiscina, Elena H.;Villoslada, Pablo
目的：探讨多发性硬化症(MS)前后视路损害作为逆行性和顺行性跨突触变性存在的相关性。方法：对100例多发性硬化症(MS)患者进行纵向研究，分别于入选时和1年后行视网膜光学相干断层扫描测量前视路损害(视乳头周围视网膜神经纤维层(RNFL)厚度和黄斑体积)，3T脑磁共振成像(MRI)测量后视路损害(视皮层体积和波谱，视神经辐射范围内病变体积)。MRI分析采用Freesurfer和SPM8软件。我们通过基于体素的形态计量学(VBM)、多元线性回归和一般线性模型来评估前后部视路损伤之间的关系。结果：VBM分析显示RNFL变薄与视皮层萎缩和视神经放射损伤之间存在特异性关联(p<；0.05)。视皮层体积(β=+0.601，95%可信区间[CI]=+0.04~+1.16)、视皮层N-乙酰天冬氨酸(β=+1.075，95%CI=+0.190~+1.961)和视神经照射内病变体积(β=-2.551，95%CI=-3.910~-1.192)显著影响纳入研究时平均视网膜神经纤维层变薄，与其他混杂因素无关，尤其是视神经炎(ON)。该模型表明，视皮层体积每减少1 cm(3)，RNFL厚度将减少0.6lm。在1年的随访期内也观察到了这种联系。有重度On(调整后差值=-3.01，95%CI=-5.08~-0.95)和轻度On(调整后差值=-1.03，95%CI=-3.02~+0.95)的患者的调整后平均视皮层体积低于未发生On的患者。
Objective: To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans-synaptic degeneration in multiple sclerosis (MS).Methods: We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple linear regressions, and general linear models.Results: VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (beta = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl aspartate in visual cortex (beta = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (beta = -2.551, 95% CI = -3.910 to -1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm(3) in visual cortex volume predicts a reduction of 0.6lm in RNFL thickness. This association was also observed after 1 year of follow-up. Patients with severe prior ON (adjusted difference = -3.01, 95% CI = -5.08 to -0.95) and mild prior ON (adjusted difference = -1.03, 95% CI = -3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON.Interpretation: Our results suggest the presence of trans-synaptic degeneration as a contributor to chronic axon damage in MS.