Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", section of Neuroscience, University of Catania, 95123, Catania, Italy.
Environmental and Food Hygiene Laboratory (LIAA), Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123, Catania, Italy.
Environ Res. 2020 Sep;188:109820. doi: 10.1016/j.envres.2020.109820. Epub 2020 Jun 24.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system (CNS) that causes progressive and irreversible damage in motor neurons. Different causal hypotheses include genetic, viral, traumatic and environmental mechanisms, such as exposure to heavy metals. The aim of this study was to compare metal/metalloid levels in cerebro-spinal fluid of ALS subtypes (spinal vs bulbar clinical onset).
This observational study consecutively screened all ALS patients referring to the Neurology Clinic of the University of Catania (Italy). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify magnesium (Mg), cuprum (Cu), selenium (Se), iron (Fe), manganese (Mn), vanadium (V), zinc (Zn), alluminium (Al), arsenic (As), cobalt (Co), nickel (Ni), mercury (Hg), lead (Pb), cadmium (Cd) and palladium (Pd) levels.
Thirty-seven patients were enrolled (62.2% females), median age of 65 years (IQR: 59-71 years). Thirty-one (83.8%) patients had a spinal onset and 6 (16.2%) a bulbar onset. Se and As levels were higher compared to the reference values (RV) both in spinal and bulbar onset, while Cu was higher than RV only in bulbar onset. Moreover, Cu (129.8 μg/L vs 29.8 μg/L), Fe (54.5 μg/L vs 33.3 μg/L), Mn (3.4 μg/L vs 1.8 μg/L), Zn (46.1 μg/L vs 35.7 μg/L), Al (12.2 μg/L vs 6.7 μg/L), Ni (2.80 μg/L vs 1.40 μg/L), and Pb (0.60 μg/L vs 0.30 μg/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 μg/L vs 1.10 μg/L). Overall, Cu (129 μg/L vs 31 μg/L), Fe (92.2 μg/L vs 32.9 μg/L), Mn (3.35 μg/L vs 1.80 μg/L), Zn (56.5 μg/L vs 35.2 μg/L), Al (14.45 μg/L vs 6.70 μg/L), and Cd (0.40 μg/L vs 0.08 μg/L) levels were higher in patients with disease duration less than 19 months.
Our results supported the hypothesis that metals/metalloids with neurotoxic effects could be involved in the etiology of ALS, showing higher levels of Cu, Se and As. Relevant differences in Cu and Mn levels were found between bulbar and spinal onset patients.
肌萎缩侧索硬化症（ALS）是一种中枢神经系统（CNS）的神经退行性疾病，会导致运动神经元进行性和不可逆转的损伤。不同的病因假说包括遗传、病毒、创伤和环境机制，如接触重金属。本研究旨在比较 ALS 亚型（脊髓型 vs 延髓型临床发病）的脑脊液中金属/类金属水平。
本观察性研究连续筛查了所有到意大利卡塔尼亚大学神经病学诊所就诊的 ALS 患者。采用电感耦合等离子体质谱法（ICP-MS）定量测定镁（Mg）、铜（Cu）、硒（Se）、铁（Fe）、锰（Mn）、钒（V）、锌（Zn）、铝（Al）、砷（As）、钴（Co）、镍（Ni）、汞（Hg）、铅（Pb）、镉（Cd）和钯（Pd）水平。
共纳入 37 例患者（62.2%为女性），中位年龄为 65 岁（IQR：59-71 岁）。31 例（83.8%）患者为脊髓型发病，6 例（16.2%）为延髓型发病。脊髓型和延髓型患者的 Se 和 As 水平均高于参考值（RV），而 Cu 水平仅在延髓型发病时高于 RV。此外，Cu（129.8μg/L 比 29.8μg/L）、Fe（54.5μg/L 比 33.3μg/L）、Mn（3.4μg/L 比 1.8μg/L）、Zn（46.1μg/L 比 35.7μg/L）、Al（12.2μg/L 比 6.7μg/L）、Ni（2.80μg/L 比 1.40μg/L）和 Pb（0.60μg/L 比 0.30μg/L）水平在延髓型发病中均高于脊髓型发病，相反，As 在脊髓型发病中略高于延髓型发病（1.40μg/L 比 1.10μg/L）。总体而言，Cu（129μg/L 比 31μg/L）、Fe（92.2μg/L 比 32.9μg/L）、Mn（3.35μg/L 比 1.80μg/L）、Zn（56.5μg/L 比 35.2μg/L）、Al（14.45μg/L 比 6.70μg/L）和 Cd（0.40μg/L 比 0.08μg/L）水平在病程小于 19 个月的患者中更高。
我们的结果支持了金属/类金属具有神经毒性作用的假说，表明 Cu、Se 和 As 水平较高。在延髓型和脊髓型发病患者中，Cu 和 Mn 水平存在显著差异。
