Tavakoli Mitra, Marshall Andrew, Thompson Lorraine, Kenny Margaret, Waldek Stephen, Efron Nathan, Malik Rayaz A
Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester M13 9NT, UK.
Muscle Nerve. 2009 Dec;40(6):976-84. doi: 10.1002/mus.21383.
Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal aesthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS) and heat-induced pain (HIP) were only significantly increased in males on ERT (P < 0.01). However, corneal sensation assessed with NCCA was significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QST and CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.
神经病变是法布里病患者严重残疾的一个原因，但其诊断困难。在本研究中，我们将用于量化小纤维病变的新型非侵入性技术角膜共焦显微镜检查（CCM）以及用于量化角膜感觉丧失的非接触式角膜测痛法（NCCA），与法布里病患者已有的神经病变检测方法进行了比较。10名未接受酶替代疗法（ERT）的法布里病杂合子女性、6名杂合子女性、6名接受ERT的半合子男性以及14名年龄匹配的健康志愿者接受了神经病变症状、神经功能缺损、神经生理学、定量感觉测试（QST）、NCCA和CCM的详细量化。所有法布里病患者均有明显的神经病变症状且美因茨评分升高。所有患者的腓总神经振幅均降低，接受ERT的男性和女性患者的振动觉阈值均升高。接受ERT的男性和女性患者的冷觉（CS）阈值均显著降低（P < 0.02），但接受ERT的男性患者的温觉（WS）和热诱发性疼痛（HIP）仅显著升高（P < 0.01）。然而，与对照组相比，接受ERT的女性（P < 0.02）和男性（P < 0.04）患者用NCCA评估的角膜感觉显著降低。根据CCM，与对照组相比，接受ERT的女性（P < 0.03）和男性（P < 0.02）患者的角膜神经纤维和分支密度显著降低。此外，神经病变症状的严重程度和美因茨严重程度评分指数的神经学成分与QST和CCM显著相关。本研究表明，CCM和NCCA分别为检测法布里病患者早期神经纤维损伤和功能障碍提供了一种新方法。
