角膜基底层涡状神经丛：转甲状腺素蛋白家族性淀粉样多发性神经病早期和随访评估的标志。

Corneal sub-basal whorl-like nerve plexus: a landmark for early and follow-up evaluation in transthyretin familial amyloid polyneuropathy.

机构信息

Department of Neurology, Peking University Third Hospital, Beijing, China.

Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China.

出版信息

Eur J Neurol. 2021 Feb;28(2):630-638. doi: 10.1111/ene.14563. Epub 2020 Oct 24.

DOI:10.1111/ene.14563

PMID:33098366

Abstract

BACKGROUND AND PURPOSE

Small-fiber nerves are the first to be involved in transthyretin familial amyloid polyneuropathy (TTR-FAP) patients. In vivo corneal confocal microscopy (CCM) is a noninvasive technique to detect small-fiber polyneuropathy (SFN) by quantifying corneal nerve morphology. The characteristic whorl-like pattern of the corneal nerve provides a static landmark for observation. We aimed to evaluate whether CCM images of the whorl-like plexus can sensitively evaluate and monitor disease progression in FAP patients.

METHODS

Fifteen FAP patients and 15 controls underwent neurological evaluation and CCM observation. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) detected by conventional method and inferior whorl length (IWL), inferior whorl fiber density (IWFD), and inferior whorl branch density (IWBD) were compared in controls and patients. The Langerhans cell (LC) density in each image was calculated.

RESULTS

All CCM parameters were significantly reduced with disease progression. Preclinical patients had significantly lower IWL (P = 0.008) than age-matched controls. IWL (P = 0.006), CNFL (P = 0.005), CNBD (P = 0.008), and CNFD (P = 0.014) were significantly lower in early-phase patients. LC density was significantly increased around the central whorl in early-phase patients and was relatively lower in progressive patients. Both IWL and CNFL correlated with the severity of neuropathy, and IWL was more significantly reduced. The area under the receiver operating characteristic (ROC) curve for FAP with CNFL and IWL was 88.0% (95% CI, 70.9%-96.9%) and 89.3% (95% CI, 72.6%-97.6%), respectively, exceeding other parameters.

CONCLUSIONS

IWL is a more sensitive surrogate to detect preclinical SFN in FAP and can best discriminate patients from controls. The clustering of immature LCs at the inferior whorl area might reflect the inflammatory response of small-fiber nerves at the early stage.

摘要

背景与目的

小纤维神经是转甲状腺素蛋白家族性淀粉样多发性神经病（TTR-FAP）患者最先受累的部位。活体角膜共焦显微镜（CCM）是一种通过量化角膜神经形态来检测小纤维神经病（SFN）的非侵入性技术。角膜神经的特征性涡旋状模式为观察提供了一个静态标记。我们旨在评估 CCM 的涡旋状神经丛图像是否能敏感地评估和监测 FAP 患者的疾病进展。

方法

15 例 FAP 患者和 15 例对照者接受了神经学评估和 CCM 观察。比较了对照组和患者的角膜神经纤维长度（CNFL）、角膜神经纤维密度（CNFD）、常规方法检测的角膜神经分支密度（CNBD）以及下涡长度（IWL）、下涡纤维密度（IWFD）和下涡分支密度（IWBD）。计算了每个图像中的郎格汉斯细胞（LC）密度。

结果

随着疾病的进展，所有 CCM 参数均显著降低。与年龄匹配的对照组相比，亚临床患者的 IWL 明显较低（P=0.008）。早期患者的 IWL（P=0.006）、CNFL（P=0.005）、CNBD（P=0.008）和 CNFD（P=0.014）明显较低。早期患者中央涡旋周围的 LC 密度显著增加，而进行性患者的 LC 密度相对较低。IWL 和 CNFL 与神经病变的严重程度均相关，且 IWL 降低更为显著。CNFL 和 IWL 对 FAP 的 ROC 曲线下面积分别为 88.0%（95%CI，70.9%-96.9%）和 89.3%（95%CI，72.6%-97.6%），均优于其他参数。