CSF neurotoxic metals/metalloids levels in amyotrophic lateral sclerosis patients: comparison between bulbar and spinal onset

Introduction: 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). Material and methods: 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. Results: 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 mu g/L vs 29.8 mu g/L), Fe (54.5 mu g/L vs 33.3 mu g/L), Mn (3.4 mu g/L vs 1.8 Zn (46.1 mu g/L vs 35.7 mu g/L), Al (12.2 mu g/L vs 6.7 mu g/L), Ni (2.80 mu g/L vs 1.40 mu g/L), and Pb (0.60 mu g/L vs 0.30 mu g/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 mu g/L vs 1.10 mu g/L). Overall, Cu (129 mu g/L vs 31 mu g/L), Fe (92.2 mu g/L vs 32.9 mu g/L), Mn (3.35 mu g/L vs 1.80 Zn (56.5 mu g/L vs 35.2 mu g/L), Al (14.45 mu g/L vs 6.70 mu g/L), and Cd (0.40 mu g/L vs 0.08 mu g/L) levels were higher in patients with disease duration less than 19 months. Conclusion: 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.