Department of Neurology, Odense University Hospital, Odense C, Denmark.
Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark.
Eur J Neurol. 2020 Jan;27(1):68-76. doi: 10.1111/ene.14035. Epub 2019 Aug 2.
Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy.
Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison.
Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD.
Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.
奥沙利铂治疗期间慢性周围神经病变严重程度的评估基于症状。为了防止严重神经病变而调整奥沙利铂的总剂量,可能会因治疗后神经病变症状恶化而变得复杂。在治疗早期,对外周神经结构和功能的客观测量可能有助于确定个体患者的最佳奥沙利铂剂量。表皮内神经纤维密度(IENFD)已被提议作为周围神经病变的早期标志物。
60 例患者在治疗前、接受 25%和 50%总计划奥沙利铂剂量后以及化疗完成后和 6 个月后进行了检查。其中 55 例还在基线时和 6 周和 52 周后进行了检查,用于比较。
治疗期间 IENFD 未减少。在治疗过程中,腓肠神经的幅度和传导速度、振动检测阈值、机械检测阈值和冷觉检测阈值显著降低。与参考值和健康受试者的自发变化相比,发现振动检测阈值的患者恶化比例最大,其次是神经传导研究、机械检测阈值、冷觉检测阈值和 IENFD。
对于大纤维功能的测量,尤其是振动感觉,变化最为明显。皮肤活检似乎不能提供奥沙利铂治疗期间外周神经恶化的临床相关客观测量。