小纤维神经首先涉及转甲状腺素蛋白家族性淀粉样多发性神经病(TTR-FAP)患者。体内角膜共聚焦显微镜(CCM)是一种通过量化角膜神经形态来检测小纤维多发性神经病(SFN)的非侵入性技术。角膜神经的特征性螺纹状图案为观察提供了静态标志。我们旨在评估螺旋神经丛的CCM图像是否可以敏感地评估和监测FAP患者的疾病进展。
15例FAP患者和15例对照者接受了神经学评估和CCM观察。角膜神经纤维长度(CNFL),角膜神经纤维密度(CNFD),通过常规方法检测的角膜神经支密度(CNBD)和下螺纹长度(IWL),下螺纹纤维密度(IWFD),比较了对照组和患者的下螺纹分支密度(IWBD)。计算每个图像中的朗格汉斯细胞(LC)密度。
所有CCM参数随着疾病进展而显著降低。临床前患者的IWL明显低于年龄匹配的对照组(P=0.008)。IWL(P=0.006),CNFL(P=0.005),CNBD(P=0.008),早期患者中CNFD(P=0.014)显著降低。早期患者的中心螺纹周围的LC密度显着增加,而进行性患者的LC密度相对较低。IWL和CNFL均与神经病变的严重程度相关,和IWL更显著降低。具有CNFL和IWL的FAP的受试者工作特征(ROC)曲线下面积为88.0%(95%CI,70.9%-96.9%)和89.3%(95%CI,72.6%-97.6%),分别,超过其他参数。
IWL是检测FAP中临床前SFN的更敏感的替代方法,可以最好地区分患者和对照组。未成熟LCs在下螺纹区的聚集可能反映了早期小纤维神经的炎症反应。
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.
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.
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.
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.