Collongues Nicolas, Samama Brigitte, Schmidt-Mutter Catherine, Chamard-Witkowski Ludivine, Debouverie Marc, Chanson Jean-Baptiste, Antal Maria-Cristina, Benardais Karelle, de Seze Jérôme, Velten Michel, Boehm Nelly
Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.
Clinical Investigation Center, INSERM U1434, University Hospital of Strasbourg, Strasbourg, France.
PLoS One. 2018 Jan 25;13(1):e0191614. doi: 10.1371/journal.pone.0191614. eCollection 2018.
Skin biopsy is the most relevant tool to diagnose small-fiber neuropathy. A well-documented normal dataset for intraepidermal nerve fiber in the distal leg is required to improve its diagnostic value.
Three hundred healthy subjects were enrolled in the study, after clinical and biological screening to exclude neurological and systemic pathologies. A distal leg biopsy was taken and intraepidermal nerve fiber density after protein gene product-9.5 immunocytochemistry with brightfield microscopy was determined. Morphological variations of intraepidermal nerve fibers, previously described in small-fiber neuropathies, were analyzed. One hundred biopsies were also analyzed at the ultrastructural level.
The median number of fibers was lower in men compared to women and decreased with age. Using statistical modeling taking into account age and gender, we calculated the 5th percentile of intraepidermal nerve fiber density as follows: 7.6156-0.0769 x age (years) + 1.5506 x gender (woman = 1; man = 0). We observed a low frequency of large swellings or horizontal branchings but an increasing frequency of small swellings of intraepidermal nerve fibers and irregular distribution along the dermal-epidermal junction with age. Axonal diameter of unmyelinated fibers of the papillary dermis did not vary with age or gender. Ultrastructural analysis also showed that fiber endings in close apposition to Merkel cells should not be mistaken for small-fiber swellings.
Our dataset allows accurate calculation of the normal density of intraepidermal nerve fibers for each year of age and provides original morphological observations that improve the diagnostic value of skin biopsy in the distal leg for small-fiber neuropathy.
皮肤活检是诊断小纤维神经病变最相关的工具。需要一个记录完善的小腿远端表皮内神经纤维正常数据集来提高其诊断价值。
对300名健康受试者进行临床和生物学筛查以排除神经和系统性疾病后纳入研究。取小腿远端活检组织，通过蛋白基因产物9.5免疫细胞化学结合明场显微镜测定表皮内神经纤维密度。分析先前在小纤维神经病变中描述的表皮内神经纤维的形态学变化。还对100份活检组织进行了超微结构分析。
男性的纤维中位数低于女性，且随年龄增长而减少。通过考虑年龄和性别的统计模型，我们计算出表皮内神经纤维密度的第5百分位数如下：7.6156 - 0.0769×年龄（岁）+ 1.5506×性别（女性 = 1；男性 = 0）。我们观察到表皮内神经纤维出现大肿胀或水平分支的频率较低，但小肿胀的频率随年龄增加，且沿真皮 - 表皮交界处分布不规则。乳头层真皮无髓纤维的轴突直径不随年龄或性别变化。超微结构分析还表明，与默克尔细胞紧密相邻的纤维末梢不应被误认为是小纤维肿胀。
我们的数据集能够准确计算出各年龄段表皮内神经纤维的正常密度，并提供了原始的形态学观察结果，提高了小腿远端皮肤活检对小纤维神经病变的诊断价值。
