Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

Lewis, Mechelle M.; Flynn, Michael R.; Lee, Eun Young; Buren, Scott Van; Buren, Eric Van; Du, Guangwei; Fry, Rebecca C.; Herring, Amy H.; Kong, Lan; Mailman, Richard B.; Huang, Xuemei

doi:10.1016/j.neuro.2016.08.012

Cited by 17 publications

(6 citation statements)

References 37 publications

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“…In contrast, we designed a screening tool that could be administered consistently by an ancillary staff person in a physician’s office. Nevertheless, we modeled our proposed manganism screening on their tiered-screening protocol and recommend that workers identified undergo magnetic resonance imaging (MRI) of the brain to measure T1 relaxation time(Lee et al, 2015; Lewis et al, 2016) or pallidal index. (Criswell et al, 2012; Nelson et al, 1993) We recommend that those workers identified as having parkinsonism and who have a shortened T1 relaxation time or high pallidal index, should have an evaluation by a neurologist, preferably one with movement disorders training, in order to confirm clinical status.…”

Section: Discussionmentioning

confidence: 99%

A screening tool to detect clinical manganese neurotoxicity

et al. 2018

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Manganese (Mn) over-exposure in occupational settings is associated with basal ganglia toxicity and a movement disorder characterized by parkinsonism (i.e., the signs and symptoms of Parkinson disease). A simple test to help non-neurologists identify workers with clinical Mn neurotoxicity represents an unmet need. In a cohort of Mn-exposed workers from welding worksites, with extensive clinical data, we developed a linear regression model to predict the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score. We primarily considered factors easily obtained in a primary care or occupational medicine clinic, specifically easily assessed signs of parkinsonism and factors likely to be associated with UPDRS3 such as age, timed motor task results, and selected symptoms/conditions. Secondarily we considered other demographic variables and welding exposure. We based the model on 596 examined workers age≤65years and with timed motor task data. We selected the model based on simplicity for clinical application, biologic plausibility, and statistical significance and magnitude of regression coefficients. The model contained age, timed motor task scores for each hand, and indicators of action tremor, speech difficulty, anxiety, depression, loneliness, pain and current cigarette smoking. When we examined how well the model identified workers with clinically significant parkinsonism (UPDRS3≥15) the receiver operating characteristic area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.67, 0.77). With a cut point that provided 80% sensitivity, specificity was 52%, the positive predictive value in our cohort was 29%, and the negative predictive value was 92%. Using the same cut point for predicted UPDRS3, the AUC was nearly identical for UPDRS3≥10, and was 0.83 (95% CI 0.76, 0.90) for UPDRS3≥20. Since welding exposure data was not required after including its putative effects, this model may help identify workers with clinically significant Mn neurotoxicity in a variety of settings, as a first step in a tiered occupational screening program.

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Section: Discussionmentioning

confidence: 99%

A screening tool to detect clinical manganese neurotoxicity

et al. 2018

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“…A one-year follow-up analysis was conducted on this cohort that demonstrated changes in R1 values in all ROIs correlated with changes in HrsW 90 (the short-term welding exposure metric), whereas blood Mn levels or the PI value failed to show any associations with changes in HrsW 90 (Lewis et al, 2016a). This result is consistent with a previous finding that the GP T1 relaxation time (1/R1) in Mn-exposed monkeys was lowest after 120 days of Mn-exposure, but returned to control values two months after cessation of Mn-exposure, suggesting that R1 may sensitively capture the temporal dynamics of Mn brain accumulation and clearance (Han et al, 2008).…”

Section: R1 (1/t1) Signals Capture Non-linear Short-term Mn Accumulamentioning

confidence: 95%

Welding-related brain and functional changes in welders with chronic and low-level exposure

et al. 2018

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Although an essential nutrient, manganese (Mn) can be toxic at high doses. There is, however, uncertainty regarding the effects of chronic low-level Mn-exposure. This review provides an overview of Mn-related brain and functional changes based on studies of a cohort of asymptomatic welders who had lower Mn-exposure than in most previous work. In welders with low-level Mn-exposure, we found: 1) Mn may accumulate in the brain in a non-linear fashion: MRI R1 (1/T1) signals significantly increased only after a critical level of exposure was reached (e.g., ≥300 welding hours in the past 90days prior to MRI). Moreover, R1 may be a more sensitive marker to capture short-term dynamic changes in Mn accumulation than the pallidal index [T1-weighted intensity ratio of the globus pallidus vs. frontal white matter], a traditional marker for Mn accumulation; 2) Chronic Mn-exposure may lead to microstructural changes as indicated by lower diffusion tensor fractional anisotropy values in the basal ganglia (BG), especially when welding years exceeded more than 30 years; 3) Mn-related subtle motor dysfunctions can be captured sensitively by synergy metrics (indices for movement stability), whereas traditional fine motor tasks failed to detect any significant differences; and 4) Iron (Fe) also may play a role in welding-related neurotoxicity, especially at low-level Mn-exposure, evidenced by higher R2* values (an estimate for brain Fe accumulation) in the BG. Moreover, higher R2* values were associated with lower phonemic fluency performance. These findings may guide future studies and the development of occupation- and public health-related polices involving Mn-exposure.

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“…Indeed, X-ray fluorescence imaging has shown accumulation of Mn in the globus pallidus (GP), thalamus and substantia nigra pars compacta (Robison et al, 2012;Robison et al, 2015). Chronic Mn exposure affects the GP via the production of a large number of free radicals that interfere with neurotransmitter metabolism and ultimately lead to neuronal damage (Avila et al, 2008;Lewis et al, 2016). Mn also accumulates in the hippocampal formation, as revealed by magnetic resonance imaging (Robison et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats

Zhang

et al. 2021

Toxicol Ind Health

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Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.

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Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

Cited by 17 publications

References 37 publications

A screening tool to detect clinical manganese neurotoxicity

A screening tool to detect clinical manganese neurotoxicity

Welding-related brain and functional changes in welders with chronic and low-level exposure

Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats

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