Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy
Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy
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DOI：
10.1212/wnl.0000000000004016
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发表时间：
2017-06-06
期刊：
影响因子：
9.9
通讯作者：
Ando, Yukio
中科院分区：
文献类型：
--
作者：
Masuda, Teruaki;Ueda, Mitsuharu;Ando, Yukio
目的：目的：探讨遗传性甲状腺素运载蛋白（TTR）淀粉样变性和医源性TTR淀粉样变性的早期皮肤失神经支配。方法：对32例遗传性TTR淀粉样变性患者、11例无症状TTR突变携带者、6例医源性TTR淀粉样变性患者和23例健康志愿者进行了表皮内神经纤维密度（IENFD）和临床表现的研究。V30 M突变患者的IENFD值降低（1.9 ± 2.1/1 mm），非V30 M突变患者（5.8 ± 3.2/1 mm），医源性TTR淀粉样变性患者（3.5 ± 1.8/1 mm）与健康志愿者（11.8 ± 3.2/1 mm）相比（p < 0.01）。皮肤去神经也发生了，即使在症状前V30 M突变携带者中也是如此（每1 mm 5.0 +/- 2.2）。IENFD与病程相关（rho =-0.533，p = 0.002）和各种周围神经病变参数，如熊本临床评分中的感觉障碍（rho =-0.575，p = 0.001）、热痛检测阈值（rho =-0.704，p < 0.001）和腓肠感觉神经动作电位（rho = 0.481，p = 0.005）。结论：遗传性TTR淀粉样变和医源性TTR淀粉样变患者在症状前期皮肤神经损伤较早。因此IENFD可能有助于早期诊断，并可作为遗传性和医源性TTR淀粉样变性临床试验中的生物标志物。
Objective: To elucidate early skin denervation in hereditary transthyretin (TTR) amyloidosis and iatrogenic TTR amyloidosis.Methods: We investigated intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients with iatrogenic TTR amyloidosis, and 23 healthy volunteers.Results: IENFD values were reduced in patients with the V30M mutation (1.9 +/- 2.1 per 1 mm), patients with non-V30M mutations (5.8 +/- 3.2 per 1 mm), and patients with iatrogenic TTR amyloidosis (3.5 +/- 1.8 per 1 mm) compared with healthy volunteers (11.8 +/- 3.2 per 1 mm) (p < 0.01). Skin denervation also occurred, even in presymptomatic V30M mutation carriers (5.0 +/- 2.2 per 1 mm). The IENFD was correlated with disease duration (rho = -0.533, p = 0.002) and various peripheral neuropathy parameters such as sensory impairment in the Kumamoto clinical score (rho = -0.575, p = 0.001), heat-pain detection threshold (rho = -0.704, p < 0.001), and sural sensory nerve action potential (rho = 0.481, p = 0.005). TTR amyloid deposits frequently occurred in connective tissues and vessels of the dermal reticular layer in patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis.Conclusions: Patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis may show early skin denervation even in the presymptomatic stage. IENFD may thus be useful for early diagnosis and may serve as a biomarker in clinical trials for hereditary and iatrogenic TTR amyloidosis.