Neuromuscular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy.
J Peripher Nerv Syst. 2010 Sep;15(3):202-7. doi: 10.1111/j.1529-8027.2010.00271.x.
The diagnostic reliability of skin biopsy in small fiber neuropathy depends on the availability of normative reference values. We performed a multicenter study to assess the normative values of intraepidermal nerve fiber (IENF) density at distal leg stratified by age deciles. Eight skin biopsy laboratories from Europe, USA, and Asia submitted eligible data. Inclusion criteria of raw data were healthy subjects 18 years or older; known age and gender; 3-mm skin biopsy performed 10-cm above the lateral malleolus; bright-field immunohistochemistry protocol, and quantification of linear IENF density in three 50-µm sections according to published guidelines. Data on height and weight were recorded, and body mass index (BMI) was calculated in subjects with both available data. Normative IENF density reference values were calculated through quantile regression analysis; influence of height, weight, or BMI was determined by regression analyses. IENF densities from 550 participants (285 women, 265 men) were pooled. We found a significant age-dependent decrease of IENF density in both genders (women p < 0.001; men p = 0.002). Height, weight, or BMI did not influence the calculated 5th percentile IENF normative densities in both genders. Our study provides IENF density normative reference values at the distal leg to be used in clinical practice.
皮肤活检在小纤维神经病中的诊断可靠性取决于是否有规范的参考值。我们进行了一项多中心研究，以评估按年龄十分位数分层的小腿远端表皮内神经纤维（IENF）密度的规范值。来自欧洲、美国和亚洲的 8 个皮肤活检实验室提交了合格的数据。原始数据的纳入标准为年龄在 18 岁或以上的健康受试者；已知年龄和性别；在外侧踝上方 10cm 处进行 3mm 皮肤活检；采用明场免疫组织化学方案，并根据已发表的指南在三个 50µm 切片中量化线性 IENF 密度。记录了身高和体重的数据，并在有可用数据的受试者中计算了体重指数（BMI）。通过分位数回归分析计算规范 IENF 密度参考值；通过回归分析确定身高、体重或 BMI 的影响。来自 550 名参与者（285 名女性，265 名男性）的数据被汇总。我们发现两性的 IENF 密度都随年龄的增长而显著下降（女性 p<0.001；男性 p=0.002）。身高、体重或 BMI 并不影响两性计算得出的第 5 百分位数 IENF 规范密度。我们的研究提供了在临床实践中使用的小腿远端 IENF 密度规范参考值。
