Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark; Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Institute of Neurology, Queen Square House, London, United Kingdom.
Clin Neurophysiol. 2018 Mar;129(3):694-706. doi: 10.1016/j.clinph.2017.11.015. Epub 2017 Nov 26.
Neurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity.
Questionnaires, quantitative sensory tests, nerve conduction studies and nerve excitability testing were undertaken in 12 patients with high-risk colorectal cancer treated with adjuvant oxaliplatin and in 16 sex- and age-matched healthy controls. Examinations were performed twice for patients: once within 3 days after oxaliplatin treatment (post-infusion examination) and once shortly before the following treatment (recovery examination).
The most frequent post-infusion symptoms were tingling paresthesias and cold allodynia. The most prominent nerve excitability change was decreased superexcitability of motor axons which correlated with the average intensity of abnormal sensations (Spearman Rho = 0.80, p < .01). The motor nerve excitability changes were well modeled by a slowing of sodium channel inactivation, and were proportional to dose/m with a half-life of about 10d.
Oxaliplatin induces reversible slowing of sodium channel inactivation in motor axons, and these changes are closely related to the reversible cold allodynia. However, further studies are required due to small sample size in this study.
Nerve excitability data provide an index of sodium channel dysfunction: an objective biomarker of acute oxaliplatin neurotoxicity.
神经毒性是抗癌药物奥沙利铂最常见的剂量限制副作用，但机制尚不清楚。本研究使用神经兴奋性测试来研究急性神经毒性的病理生理学。
对 12 例接受辅助奥沙利铂治疗的高危结直肠癌患者和 16 名性别和年龄匹配的健康对照者进行问卷调查、定量感觉测试、神经传导研究和神经兴奋性测试。患者进行了两次检查：一次是在奥沙利铂治疗后 3 天内（输注后检查），一次是在下次治疗前（恢复检查）。
最常见的输注后症状是刺痛感和冷感觉异常。最明显的神经兴奋性变化是运动轴突的超兴奋性降低，与异常感觉的平均强度相关（Spearman Rho=0.80，p<.01）。运动神经兴奋性的变化可以很好地用钠通道失活的减慢来模拟，并且与剂量/m 成正比，半衰期约为 10d。
奥沙利铂诱导运动轴突钠离子通道失活的可逆性减慢，这些变化与可逆性冷感觉异常密切相关。然而，由于本研究样本量较小，需要进一步研究。
神经兴奋性数据提供了钠通道功能障碍的指标：急性奥沙利铂神经毒性的客观生物标志物。
