The "disease of the crazy hatman" and the effects of human exposure to mercury: A case report / A "doença do homem do chapéu maluco" e os efeitos da exposição humana ao mercúrio: Um relato de caso

INTRODUCTION: Mercury, in addition to being a heavy metal, is considered a neurotoxin, that is, a substance capable of negatively affecting the neurological functions of the human body. Nowadays, ““Mad Hatter's Disease”” is the name used to characterize these neurological disorders caused by mercury. PURPOSE: to report a clinical case of the manifestation of “Mad Hatter's Disease”, as well as to discuss about the effects of human exposure to mercury. METHODOLOGY: this is a clinical case report, in which the patient is essential. CASE REPORT: A 45-year-old male patient, gold miner, from a riverside community in the Amazon, was referred to the hospital with complaints of headache, extremities tremor, diarrhea, tiredness, discouragement, irritability, depression, unusual shyness and hallucinations. On physical examination, the patient was anxious, irritable, symmetrical small-amplitude tremors in the extremities, hyperreflexia ++/4+ in the upper limbs, +/4+ in the lower limbs, normal muscle strength, mild ataxia of the right hand, stained skin and mucous membranes, and acyanotic, with erythematous-scaly lesions, confluent on the trunk, palms and soles of the feet. Screening for mercury poisoning was performed, where it was found, both in blood and urine, the presence of mercury 20 times above the biological tolerance limit. A battery of specific neuropsychological tests was carried out in neurotoxicological assessments and these demonstrated impairment of the cognitive domains (deficit of memory, attention, concentration, reasoning and abstraction) and alterations in motor functions, showing reduced coordination and motor speed. The diagnosis of hydrargyrism or occupational chronic metallic mercuralism (MMCO) was given. DISCUSSION: Chronic occupational exposure to inorganic mercury can cause subclinical abnormalities, as well as long-term psychomotor and neuromuscular behavioral impairment. Neuropsychiatric abnormalities (inattention, memory, interpretation, and motor performance) appear to be dose-related. FINAL CONSIDERATIONS: chronic exposure to metallic mercury vapor characteristically compromises the nervous system, initially with nonspecific symptoms and, later, with characteristic motor disorders - small amplitude tremor, paresis, dysreflexia and difficulty in motor coordination, which gives rise to the "Disease of the Mad Hatter”, and inhaling large amounts of mercury vapor can be lethal.

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.

Efficacy of Hair Total Mercury Content as a Biomarker of Methylmercury Exposure to Communities in the Area of Artisanal and Small-Scale Gold Mining in Madre de Dios, Peru

Total mercury content (THg) in hair is an accepted biomarker for chronic dietary methylmercury (MeHg) exposure. In artisanal and small-scale gold mining (ASGM) communities, the validity of this biomarker is questioned because of the potential for contamination from inorganic mercury. As mining communities may have both inorganic and organic mercury exposures, the efficacy of the hair-THg biomarker needs to be evaluated, particularly as nations begin population exposure assessments under their commitments to the Minamata Convention. We sought to validate the efficacy of hair THg for public health monitoring of MeHg exposures for populations living in ASGM communities. We quantified both THg and MeHg contents in hair from a representative subset of participants (N = 287) in a large, population-level mercury exposure assessment in the ASGM region in Madre de Dios (MDD), Peru. We compared population MeHg-THg correlations and %MeHg values with demographic variables including community location, sex, occupation, and nativity. We observed that hair MeHg-THg correlations were high (r > 0.7) for all communities, regardless of location or nativity. Specifically, for individuals within ASGM communities, 81% (121 of 150 total) had hair THg predominantly in the form of MeHg (i.e., >66% of THg) and reflective of dietary exposure to mercury. Furthermore, for individuals with hair THg exceeding the U.S. EPA threshold (1.0 μg/g), 88 out of 106 (83%) had MeHg as the predominant form. As a result, had urine THg solely been used for mercury exposure monitoring, approximately 59% of the ASGM population would have been misclassified as having low mercury exposure. Our results support the use of hair THg for monitoring of MeHg exposure of populations in ASGM settings where alternative biomarkers of MeHg exposure are not feasible.