The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Brain. 2012 Feb;135(Pt 2):534-41. doi: 10.1093/brain/awr324. Epub 2012 Feb 1.
Following damage to the human post-geniculate visual pathway retrograde trans-synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 µm per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 µm per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5-112) and ending at a mean of 426.6 days post-stroke (range 170-917). Evidence from clinical observation (funduscopy) suggested that retrograde trans-synaptic degeneration occurred in humans only where the damage to the post-geniculate pathway occurred prenatally. The results reported herein add weight to the previous demonstration that this type of degeneration does indeed occur in the human visual system by showing that it can be monitored over time and hence may provide a model for trans-synaptic degeneration in the human central nervous system.
人类视节后通路受损后，会发生视神经纤维逆行性(trans-synaptic)变性。从灵长类动物的研究中已经知道了一段时间，枕叶切除术会导致视网膜神经节细胞数量减少。然而，这在所有研究的物种中都不是可检测到的，并且直到最近的研究表明，在枕叶损伤后，通过光学相干断层扫描测量的视网膜神经纤维层厚度会减少，并且可以通过磁共振成像显示相应的视神经束收缩，这种情况是否发生在人类中仍存在争议。然而，人类的变性时间过程尚不清楚。在本研究中，我们首次使用光学相干断层扫描术(optical coherence tomography，OCT)证明，由于中风导致的枕叶/视辐射损伤后，视网膜神经纤维层(retinal nerve fibre layer，RNFL)逐渐变薄。首先，在一组 38 名患者中，在已知的中风后时间间隔内进行了单次测量，时间范围从 6 天到 67 年。这里，发现神经纤维层厚度与受伤后对数年的时间之间呈负直线关系(线性回归 r=0.54，P<0.001)，调整年龄后，每年的下降率为 9.08 µm。这表明与同一组中随年龄增长而发现的下降率不同，这表明通过调整疾病持续时间，每年的变薄率为 0.4 µm(P=0.006)。在第二项研究中，在一组 7 名具有同视性偏盲的患者中，在急性事件后进行了连续测量；这里，在从中风后平均 36.9 天(范围 5-112)开始的一段数据采集期间，在微米级的时间和神经纤维层厚度之间发现了负直线关系，结束于中风后平均 426.6 天(范围 170-917)。临床观察(眼底检查)的证据表明，只有当视节后通路的损伤发生在产前时，人类才会发生逆行性(trans-synaptic)变性。本报告中的结果通过表明可以随时间监测到这种变性，从而为人类中枢神经系统中的突触变性提供了模型，进一步证明了这种类型的变性确实发生在人类的视觉系统中，这为以前的证明增加了份量。
