Riva Nilo, Bonelli Filippo, Lasagni Vitar Romina Mayra, Barbariga Marco, Fonteyne Philippe, Lopez Ignazio Diego, Domi Teuta, Scarpa Fabio, Ruggeri Alfredo, Reni Michele, Marcatti Magda, Quattrini Angelo, Agosta Federica, Rama Paolo, Ferrari Giulio
Experimental Neuropathology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology and Neurorehabilitation Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
Front Med (Lausanne). 2022 Feb 18;9:832344. doi: 10.3389/fmed.2022.832344. eCollection 2022.
Chemotherapy-induced neurotoxicity is an increasingly recognized clinical issue in oncology. confocal microscopy (IVCM) of corneal nerves has been successfully used to diagnose peripheral neuropathies, including diabetic neuropathy. The purpose of this study was to test if the combination of corneal nerve density and morphology assessed by IVCM is useful to monitor the neurotoxic effects of chemotherapy compared to epidermal nerve quantification. Overall, 95 adult patients with different cancer types were recruited from the oncology and hematology departments of the San Raffaele Hospital. Neurological examination, including clinical Total Neuropathy Score, and corneal confocal microscopy (IVCM), were performed before and after chemotherapy. In a group of 14 patients, skin biopsy was performed at the first and last visit. In the group of 14 patients who underwent both skin biopsy and corneal nerve imaging, clinical worsening (+69%, = 0.0018) was paralleled by corneal nerve fiber (CNF) density reduction (-22%, = 0.0457). Clinical Total neuropathy score significantly worsened from the first to the last visit (+62%, < 0.0001). CNF length was not significantly reduced overall. However, CNF density/tortuosity ratio significantly decreased after therapy. Correlation analysis showed that the CNF density/tortuosity ratio was also correlated with the number of chemotherapy cycles ( = -0.04790, = 0.0009). Our data confirm that corneal confocal microscopy is a helpful, non-invasive tool which shows promise for the diagnosis of chemotherapy-induced peripheral neuropathies. IVCM could allow a rapid, reproducible and non-invasive quantification of peripheral nerve pathology in chemotherapy-associated neuropathy.
化疗引起的神经毒性是肿瘤学中一个日益受到认可的临床问题。角膜神经的共聚焦显微镜检查（IVCM）已成功用于诊断周围神经病变，包括糖尿病性神经病变。本研究的目的是测试与表皮神经定量相比，通过IVCM评估的角膜神经密度和形态的组合是否有助于监测化疗的神经毒性作用。总体而言，从圣拉斐尔医院的肿瘤学和血液学部门招募了95名患有不同癌症类型的成年患者。在化疗前后进行了神经学检查，包括临床总神经病变评分和角膜共聚焦显微镜检查（IVCM）。在一组14名患者中，在首次和末次就诊时进行了皮肤活检。在14名同时接受皮肤活检和角膜神经成像的患者组中，临床恶化（+69%，P = 0.0018）与角膜神经纤维（CNF）密度降低（-22%，P = 0.0457）平行。从首次就诊到末次就诊，临床总神经病变评分显著恶化（+62%，P < 0.0001）。总体而言，CNF长度没有显著减少。然而，治疗后CNF密度/迂曲度比值显著降低。相关性分析表明，CNF密度/迂曲度比值也与化疗周期数相关（r = -0.04790，P = 0.0009）。我们的数据证实，角膜共聚焦显微镜检查是一种有用的非侵入性工具，对化疗引起的周围神经病变的诊断具有前景。IVCM可以对化疗相关神经病变中的周围神经病理学进行快速、可重复和非侵入性的定量。
