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Metal Concentrations in Cerebrospinal Fluid, Blood, Serum, Plasma, Hair, and Nails in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis Publisher Pubmed



Kamalian A1 ; Foroughmand I2 ; Koski L3 ; Darvish M4 ; Saghazadeh A5, 6 ; Kamalian A1 ; Razavi SZE8, 9 ; Abdi S6 ; Dehgolan SR10 ; Fotouhi A11 ; Roos PM3, 12
Authors
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Authors Affiliations
  1. 1. Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, MD, United States
  2. 2. Bloomberg School of Public Health, Johns hopkins University, Baltimore, MD, United States
  3. 3. Institute of Environmental Medicine, Karolinska Institutet, Nobels vag 13, Stockholm, 171 77, Sweden
  4. 4. Clinical Research Development Center, Shahid Modarres Hospital, Tehran, Iran
  5. 5. Systematic Review and Meta Analysis Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  6. 6. Department of Neurology, School of Medicine, Tehran University of Medical Sciences, Poursina st., Enghelab-e-Eslami avenue, Tehran, Iran
  7. 7. School of Medicine, Yazd Shahid Sadoughi University of Medical Sciences, Shahid Bahonar Square, Yazd, Iran
  8. 8. Physical Medicine and Rehabilitation Department, Imam Khomeini Hospital Complex, Tohid Square, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Joint Reconstruction Research Center (JRRC), Imam Khomeini Hospital complex, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. School of Medicine, Tehran University of Medical Sciences, Poursina st., Enghelab-e-Eslami avenue, Tehran, Iran
  11. 11. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Department of Clinical Physiology, St. Goran Hospital University Unit, St. Goransplan 1, Stockholm, 112 81, Sweden

Source: Journal of Trace Elements in Medicine and Biology Published:2023


Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10–15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients. Purpose: This meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients. Methods: We searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison. Findings: Twenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88 µg/L (95 % CI: 0.83–4.93, p = 0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21 µg/L (95 % CI: 0.01 – 0.41, p = 0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26 µg/L (95% CI: 0.73 – 7.79, p = 0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups. Conclusion: Lead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS. © 2023 Elsevier GmbH
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