Patients with multiple sclerosis (MS) are more likely to have deposits of metal toxicants in their brains, and combinations of toxic metals also appear to be more present in this patient population compared with individuals without MS. These are the findings of a retrospective study published in the journal Scientific Reports.
Researchers have suggested that metal toxicants in locus ceruleus neurons weaken the blood-brain barrier, thus enabling multiple interacting toxicants to pass through blood vessels, and enter astrocytes and oligodendroglia, leading to demyelination in individuals with MS.
Recognizing that potentially toxic elements (PTEs), such as aluminum and lead, may play a role in the pathogenesis of MS, for this study, the researchers examined the distribution of several possible toxic elements in the autopsied brains of individuals with and without MS who had pre-donated their brains to the Multiple Sclerosis Research Australia Brain Bank.
They used 2 different methods of elemental bio-imaging autometallography and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI). The researchers also utilized toxicants that were detected in the locus ceruleus as indicators of prior exposures.
Brain samples were collected from 21 individuals with MS — 6 of whom were men and 15 of whom were women. The mean patient age was 61±12 years (range, 36-84 years). All of the 21 individuals had been diagnosed by a neurologist with MS, and the clinical diagnosis was confirmed based on macroscopic and microscopic examination of the brain by a neuropathologist. Of the 21 patients, 20 had multiple chronic demyelinated MS plaques, and had an average time between MS diagnosis and death of 25±11 years (range, 6-42 years). Additionally, 1 patient exhibited acute and subacute plaques, and a time between MS diagnosis and death of 0.4 years.
Among the 109 control individuals — 79 men and 34 women — without MS, the mean age was 54±16 years (range, 28-104 years). Rostral pons paraffin blocks that contained the locus ceruleus were available from these individuals, all of whom had had autopsies performed at the New South Wales Department of Forensic Medicine. The premortem diagnoses among the control individuals included no diagnosis in 44; neurodegenerative disorder in 33; psychosis in 29; and 1 each with anorexia nervosa, epilepsy, and cancer.
Autometallography of paraffin secretions from multiple regions of the brain was performed in 21 individuals with MS and 109 control individuals. The analysis detected inorganic mercury, silver, or bismuth in many locus ceruleus neurons in both of the arms, as well as in widespread blood vessels, oligodendrocytes, astrocytes, and neurons from 4 patients with MS and 1 control individual.
Based on LA-ICP-MSI of pons paraffin sections from all 21 individuals with MS and 12 control individuals, combinations of silver, iron, nickel, aluminum, mercury, lead, and bismuth were observed more often in the locus ceruleus of patients with MS. These combinations were located mainly in white matter tracts.
Several limitations of the study warrant mention. Since the researchers were unable to evaluate the presence in the brain of all of the known PTEs, other PTEs may play a role in the pathogenesis of MS as well. Further, no occupational or demographic data were available to estimate the sources of PTEs, including the presence of dental amalgams or the frequency of fish consumption. Additionally, data on cigarette smoking — a known risk factor for MS — were not available.
“[O]ur findings suggest that a precautionary approach to reducing the risk of MS would be to limit as much as possible occupational and domestic exposure to toxic metals, take steps to reduce the emissions of toxic metals into the atmosphere from burning fossil fuels, reduce intake of food containing toxic metals (such as mercury in large fish like shark or swordfish), stop smoking cigarettes, re-assess the use of toxic metals in nanoparticles, and consider options other than toxic metal-containing materials for dental restorations,” the researchers concluded.
Pamphlett R, Buckland ME, Bishop DP. Potentially toxic elements in the brains of people with multiple sclerosis. Sci Rep. Published online January 12, 2023. doi:10.1038/s41598-022-27169-9