化疗诱导的周围神经病变生物标志物研究进展

Progress in Research on Biomarkers of Chemotherapy-Induced Peripheral Neuropathy

摘要: 化疗诱导的周围神经毒性(CIPN)是化疗药物常见的不良反应。CIPN可能涉及周围神经系统的多个区域，从自主神经和背根神经节(DRG)到轴突和任何周围神经纤维类型。大直径感觉髓鞘纤维(Aβ)常受累，但运动纤维、小髓鞘纤维(Aδ)、无髓鞘纤维(C)或自主神经纤维也可能受累。在此，我们回顾了目前临床和实验环境中CIPN评估技术的证据。神经传导研究(NCS)可用于亚临床和早期CIPN阶段，以评估大神经纤维损伤的程度并监测长期预后，其中腓肠或腓肠背神经是最值得研究的。定量的感觉神经学检查与NCS一起提供了有价值的数据。定量感觉测试和神经兴奋性研究增加了病理生理学方面的信息。神经MRI和高分辨率超声可提供神经肿大、神经信号强度增加和DRG或脊髓改变的信息。表皮内电刺激可以揭示NCS无法检测到的小无髓神经纤维的损伤程度。分子成像技术科应用于临床前高通量药物筛选。光体积描记术提示血管生理测试或许也是一种评估手段。因此，推荐使用多模态测试作为最佳CIPN评估策略，采用客观NCS和其他专业技术以及患者主观报告的结果测量。

Abstract: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common adverse reaction to chemotherapeutic drugs. CIPN may involve multiple regions of the peripheral nervous system, ranging from the autonomic nerves and dorsal root ganglia (DRG) to the axons and any type of peripheral nerve fibers. Large-diameter sensory myelinated fibers (Aβ) are often affected, but motor fibers, small myelinated fibers (Aδ), unmyelinated fibers (C), or autonomic nerve fibers may also be involved. Here, we review the evidence for CIPN assessment techniques in current clinical and experimental settings. Nerve conduction studies (NCS) can be utilized in the subclinical and early stages of CIPN to assess the extent of large nerve fiber damage and monitor long-term prognosis, with the sural or sural dorsal nerves being the most worthy of study. Quantitative sensory neurological examinations provide valuable data alongside NCS. Quantitative sensory testing and nerve excitability studies add information regarding pathophysiology. Neuroimaging techniques such as nerve MRI and high-resolution ultrasound can provide information on nerve enlargement, increased nerve signal intensity, and changes in the DRG or spinal cord. Intraepidermal electrical stimulation can reveal the extent of damage to small unmyelinated nerve fibers undetectable by NCS. Molecular imaging techniques can be applied in preclinical high-throughput drug screening. Photoplethysmography suggests that vascular physiological testing may also be an assessment tool. Therefore, multimodal testing is recommended as the optimal CIPN assessment strategy, using objective NCS and other specialized techniques as well as patient subjectively reported outcome measures.