Longitudinal assessment of oxaliplatin-induced neuropathy
Longitudinal assessment of oxaliplatin-induced neuropathy
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DOI：
10.1212/wnl.0b013e31822cfc59
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发表时间：
2011-09-01
期刊：
影响因子：
9.9
通讯作者：
Polydefkis, M.
中科院分区：
文献类型：
--
作者：
Burakgazi, A. Z.;Messersmith, W.;Polydefkis, M.
目的：表征奥沙利铂相关神经病变（ON）的自然病史，并确定表皮内神经纤维密度（IENFD）是否是神经病变进展的敏感指标。此外，我们试图评估ON作为神经保护模型的潜力，并深入了解轴突丢失与神经性症状之间的关系。方法：对8例接受奥沙利铂治疗的晚期结直肠癌患者在化疗开始前以及治疗完成后30、90、180和360天（治疗完成后180天）进行前瞻性随访。在每个时间点进行电生理、穿孔活检、症状评估和计算降低的神经病变总评分（rTNS）的检查。通过IENFD的泊松回归和rTNS和电生理测量的混合效应模型来评估随时间的变化。结果：小腿远端IENFD、rTNS、腓骨和腓肠波幅均随时间显著降低，而传导速度（腓骨和腓肠）和大腿远端IENFD无明显变化。停止使用奥沙利铂后，轴突损失的测量继续恶化。8名受试者中有5名报告了与奥沙利铂治疗相关的显著症状。结论：这项研究表明奥沙利铂与轻度、感觉和运动轴突损失有关，这种损失可能是不可逆转的。通过电生理、rTNS和远端腿部IENFD检测轴突损失。一些受试者报告了与轴突丧失无关的显著感觉症状，这些症状可能代表也可能不代表神经病变。ON是神经保护研究的一个有吸引力的范例，小腿远端IENFD是一个客观的测量，需要最少的受试者参与或研究现场的专业知识。神经病学(R) 2011；77:980 - 986
Objectives: To characterize the natural history of oxaliplatin-associated neuropathy (ON) and determine whether intraepidermal nerve fiber density (IENFD) is a sensitive measure of neuropathy progression. In addition, we sought to assess the potential of ON as a neuroprotection model and gain insight into the relationship between axon loss and neuropathic symptoms.Methods: Eight subjects receiving oxaliplatin for advanced colorectal cancer were prospectively followed prior to starting chemotherapy and at 30, 90, 180, and 360 days (180 days after completing treatment). Electrophysiology, punch biopsies, symptom assessment, and examinations with calculation of a reduced total neuropathy score (rTNS) were performed at each time point. Changes over time were assessed through Poisson regression for IENFD and a mixed effects model for rTNS and electrophysiology measures.Results: The distal leg IENFD, rTNS, peroneal, and sural amplitudes were all significantly reduced over time, while conduction velocity (peroneal and sural) and distal thigh IENFD were not. Measures of axon loss continued to worsen following discontinuation of oxaliplatin. Five of 8 subjects reported prominent symptoms associated with oxaliplatin administration.Conclusions: This study demonstrates that oxaliplatin is associated with mild, sensory, and motor axon loss that may not be reversible. Axonal loss was detected by electrophysiology, rTNS, and distal leg IENFD. Several subjects reported prominent sensory symptoms that were not associated with axon loss, and that may or may not represent neuropathy. ON is an attractive paradigm for neuroprotection studies and the distal leg IENFD is an objective measure that requires minimal subject participation or study site expertise. Neurology (R) 2011;77:980-986