Neuropsychological Effects of Mercury Exposure in Children and Adolescents of the Amazon Region, Brazil.

BACKGROUND: Studies with children exposed to methylmercury (MeHg) through fish consumption in the Brazilian Amazon region report that the high levels of hair Hg are associated with significant decreases in intelligence, memory, attention, and visuospatial processing. OBJECTIVE: To investigate the relationship between mercury exposure and neuropsychological functions in riverside communities of the Brazilian Amazon. METHOD: 263 participants aged 6 to 14 years old were assessed, from resettlement regions, near the Madeira river, Rondônia, Brazil. To assess the neuropsychological functions we used the following instruments: intelligence (WASI), working memory (Corsi Block-Tapping Task and Digit Span), verbal fluency (Word Generation - NEPSY II), inhibitory control (Inhibition Errors - NEPSY II), shifting (Trail Making Test) and manual motor dexterity (Grooved PegBoard Test). Socioeconomic status was obtained through household surveys. Total Hg levels were quantified hair samples (Total HgH) collected from the occipital region of the scalp and analyzed by Cold Vapor Atomic Absorption Spectrometry. RESULTS: The group in the upper quartile of Total HgH levels presented lower scores on the tasks that assessed estimated IQ, visuospatial working memory, semantic knowledge and phonological verbal fluency, when compared to the group in the lower quartile level. A regression analysis controlled for age, sex, and maternal education showed that for each increase of 10 µg/g of Total HgH, there was a decrease around half standard deviation in Verbal IQ, estimated IQ scores, semantic knowledge, phonological verbal fluency and for verbal and visuospatial working memory. CONCLUSIONS: High concentrations of Total Hg in hair were associated with a lower performance in neuropsychological functions tests. The results show that environmental exposure to Hg is associated to children and adolescents' lower neuropsychological performance in the riverine and resettled areas of the Brazilian Amazon region.

Another umbrella murder? - A rare case of Minamata disease.

We report a rare case of fatal intoxication in a 40-year-old man caused by injection of a fluid containing organic mercury, allegedly in an attack with a syringe fixed to the tip of an umbrella. The man suffered from severe neurological symptoms and progressive multiorgan failure and died 10 months later in refractory status epilepticus. Autopsy revealed severe brain atrophy and non-specific kidney damage. Neuropathological examination showed neuronal loss especially in the occipital lobe, distinct granule cell necrosis in the cerebellum and Wallerian degeneration in the brainstem. Postmortem toxicological analysis revealed extremely increased levels of mercury in liver and kidney tissue as well as methylmercury levels in peripheral blood.

Metales pesados en el ambiente: síndrome de Guillain-Barré / likeHeavy metals in the enviroment: Guillain-Barré like syndrome

El síndrome de Guillain-Barré constituye una entidad de etiología diversa, que se caracteriza por debilidad muscular aguda, simétrica, ascendente y progresiva, y es una de las polineuropatías adquiridas más frecuentes en la infancia. Entre los diagnósticos diferenciales, deben considerarse las neuropatías producidas por metales pesados, mercurio y plomo, y metaloides, como el arsénico, plaguicidas organofosforados y el tetracloruro de carbono.Se presenta a un paciente de 14 años con diagnóstico de síndrome de Guillain-Barré sin respuesta al tratamiento convencional con gammaglobulina. Considerando otras etiologías, se sospechó neuropatía producida por metales pesados, y se confirmó intoxicación por mercurio.El objetivo de esta presentación es concientizar a los pediatras acerca del impacto de los tóxicos ambientales en la salud infantil para realizar un diagnóstico precoz pesquisando datos clave a través de la historia clínica ambiental

Guillain-Barré syndrome is an entity of diverse etiology, characterized by acute, symmetric, ascending and progressive muscle weakness, being one of the most frequent acquired polyneuropathies in childhood. Neuropathies produced by heavy metals, mercury and lead, and metalloids, such as arsenic, organophosphorus pesticides and carbon tetrachloride, should be considered among the differential diagnoses.We present a 14-year-old patient with a presumptive diagnosis of Guillain-Barré syndrome without response to conventional treatment with gamma globulin. Considering other etiologies, heavy metal neuropathy was suspected, and mercury poisoning was confirmed.The aim of this presentation is to make pediatricians aware about the impact of environmental toxic agents on children's health in order to make an early diagnosis by researching key data through the environmental clinical history.

[Heavy metals in the enviroment: Guillain-Barre like syndrome]. / Metales pesados en el ambiente: smdrome de Gmllam-Barre like.

Guillain-Barré syndrome is an entity of diverse etiology, characterized by acute, symmetric, ascending and progressive muscle weakness, being one of the most frequent acquired polyneuropathies in childhood. Neuropathies produced by heavy metals, mercury and lead, and metalloids, such as arsenic, organophosphorus pesticides and carbon tetrachloride, should be considered among the differential diagnoses. We present a 14-year-old patient with a presumptive diagnosis of Guillain-Barré syndrome without response to conventional treatment with gamma globulin. Considering other etiologies, heavy metal neuropathy was suspected, and mercury poisoning was confirmed. The aim of this presentation is to make pediatricians aware about the impact of environmental toxic agents on children's health in order to make an early diagnosis by researching key data through the environmental clinical history.

El síndrome de Guillain-Barré constituye una entidad de etiología diversa, que se caracteriza por debilidad muscular aguda, simétrica, ascendente y progresiva, y es una de las polineuropatías adquiridas más frecuentes en la infancia. Entre los diagnósticos diferenciales, deben considerarse las neuropatías producidas por metales pesados, mercurio y plomo, y metaloides, como el arsénico, plaguicidas organofosforados y el tetracloruro de carbono. Se presenta a un paciente de 14 años con diagnóstico de síndrome de Guillain-Barré sin respuesta al tratamiento convencional con gammaglobulina. Considerando otras etiologías, se sospechó neuropatía producida por metales pesados, y se confirmó intoxicación por mercurio. El objetivo de esta presentación es concientizar a los pediatras acerca del impacto de los tóxicos ambientales en la salud infantil para realizar un diagnóstico precoz pesquisando datos clave a través de la historia clínica ambiental.

Principles of studying low-level neurotoxic exposures in children: using the Seychelles Child Development Study of methyl mercury as a prototype.

Epidemiological studies to determine the impact of low level toxic exposure on child development are important in guiding clinical and public health action. However, carrying out such studies and interpreting their findings presents a number of significant challenges to the investigators. First, they must find a cohort with suitable exposure, select a biomarker that will accurately determine the level of exposure and determine the endpoints that are most likely to detect subtle differences in neurodevelopment. Following that, the logistics of the study must be organised and collaboration established with the local population and health authorities. To accurately interpret the data, they must also accurately determine covariates that impact child development. After the data are collected, interpreting the findings presents a further challenge. Throughout this process, the study must adhere to fundamental epidemiological principles and clearly defined statistical approaches. This paper discusses those principles and uses the Seychelles Child Development Study to show how one epidemiological study addressed them.

Congenital Minamata disease: a description of two cases in Niigata.

Minamata disease or methyl mercury poisoning from industrial pollution was first described from Minamata, Japan in the 1950s. Subsequently, a similar poisoning episode occurred at Niigata, Japan in the 1960s. This paper describes the Minamata event and then presents two case reports believed to be prenatal poisoning from consumption of contaminated fish at Niigata. Case number one is of special interest because it is the only subject with congenital Minamata disease for whom exposure was actually measured near the time of birth.

Prenatal and postnatal methyl mercury exposure in Niigata, Japan: adult outcomes.

Methyl mercury (MeHg) poisoning or Minamata disease (MD) from fish consumption is a public health concern throughout the world because all fish contain small amounts. The lowest exposure level needed to impair children's development is controversial. Actual poisoning with MeHg from fish consumption has been reliably reported only two times. It occurred in Minamata, Japan in the 1950s and then in Niigata, Japan in the 1960s. On each occasion, massive industrial pollution led to local fish having mercury levels as high as 40ppm. In Niigata the pollution was on the Agano River and there were over 2000 commercial fishermen active at that time. We studied adult subjects who had been exposed perinatally to MeHg from fish consumption during the Niigata poisoning to determine the long-term impact of exposure. We identified mothers with elevated levels of exposure during the epidemic and those diagnosed with MeHg poisoning. The subjects of the study were their adult children, born during the epidemic. The evaluation consisted of a questionnaire (administered by interview) focusing on development, symptoms, and current function and a standard medical and neurological examination. The subjects were divided into four groups based upon prenatal levels of mercury in maternal hair or the presence of MD. For Group A the hair mercury levels were 50ppm or more, for Group B the mercury levels were 25-49ppm, and for Group C 10-24ppm. The subjects in Group D were born to mothers diagnosed with MD, but their mercury levels were not measured. Exposure was predominantly prenatal, but some mothers also breast fed their infants. Group A included 13 subjects among whom two were diagnosed with congenital MeHg poisoning and in two others it was suspected. Group B included 10 subjects, of whom three had symptoms compatible with MeHg poisoning. Group C had nine subjects including one with intellectual deficit and another with hearing loss. Group D had eight subjects of whom four had symptoms compatible with MeHg exposure, but only one had abnormal neurological findings. Among the subjects thought to have congenital or childhood MeHg poisoning, intelligence did not appear to have declined over time. More children were affected by prenatal and postnatal MeHg exposure at Niigata than was previously reported.

Relatório de Avaliação Rápida da Situação de Saúde -Moçambique: Implementação piloto do novo quadro da OMS para apoiar o Desenvolvimento de Estratégias de Saúde Pública na Mineração Artesanal e de Pequena Escala de Ouro no Contexto da Convenção de Minamata sobre Mercúrio / Rapid Health Situation Assessment Report -Mozambique: Pilot Implementation of the New WHO Framework to Support the Development of Public Health Strategies in Artisanal and Small-Scale Gold Mining in the Context of the Minamata Convention on Mercury

A Mineração Artesanal e de Pequena Escala de Ouro (MAPEO) é, em termos gerais, a exploração de pequenos depósitos de ouro por indivíduos, pequenos grupos ou pequenas cooperativas (1). A MAPEO é, geralmente, um trabalho intensivo com nenhuma ou limitada mecanização, e pode ter baixos índices de recuperação. O sector é geralmente caracterizado por baixos níveis de capital, produtividade, segurança ocupacional e acesso limitado aos mercados de terra e comércio. A MAPEO é praticada em mais de 70 países em todo o mundo. Estima-se que 10-15 milhões de pessoas estejam envolvidas na MAPEO, incluindo 4-5 milhões de mulheres e 1 milhão de crianças, enquanto outros 80 a 100 milhões de meios de subsistência de pessoas estão afectados pela MAPEO (2, 3). A MAPEO é uma actividade importante em muitos países em desenvolvimento, uma vez que representa uma fonte primária e adicional de renda, particularmente em regiões rurais onde as alternativas económicas à agricultura são limitadas. Estima-se que o sector de MAPEO contribua com cerca de 25% da produção global de ouro (2)

Determination of mercury in hair of children.

Although high or repeated exposure to different forms of Hg can have serious health consequences, the most important toxicity risk for humans is as methylmercury (MeHg) which exposure is mainly through consumption of fish. Generally, more than the 80% of Hg in hair is as MeHg, which is taken up by hair follicles as MeHg-cysteine complexes. In this context, hair samples were collected from 200 children (7 years) living in a coastal site in the North-East (A) of Italy and from 299 children (6-11 years) living in a urban area of South of Italy (B) to determine the levels of MeHg. Considering the neurotoxicity of MeHg, children were subjected to cognitive and neuropsychological tests. The hair values of Hg in the children population groups were comparable with data reported in other international surveys. On the other hand, combining results of the neurological tests with Hg levels, a possible relationship between Hg and an increase of the errors average reported in some neurological tests has been noted. Although the Hg levels were not elevated, a possible neurological influence in children, a population more susceptible than adults, might not be excluded, but the influence on neurological performances of the children could be also due to the family environment (socio economic status, educational level, etc.).

Saint Ioannis Lampadistis, the first possible case of blindness due to organic mercury poisoning in history.

Saint Ioannis Lampadistis is a Cypriot saint of the Greek Orthodox Church, widely venerated in his island of origin. He lived during the 11th century and was blinded by ingesting contaminated fish in the mountainous area of Galata, withdrew from civil life when he was 18, and died at the age of 22. The reason for his blindness remains unknown, though it is widely attributed to an unknown poison related to the copper mines of the region. As fish is the end reservoir of organic mercury, it is quite possible that his blindness was the result of heavy metal toxicity. Organic mercury is associated with CNS atrophy and hypoplasia, and blindness is a frequent presenting symptom. While not much is known about the saint's clinical symptoms (as his ecclestiastical biography focuses on his example and miracles), organic mercury poisoning could explain his sudden loss of vision, thus possibly making him the first-recorded case of organic mercury poisoning in history.

The blood of my veins - mercury, Minamata and the soul of Japan.

The methylmercury contamination of Minamata Bay during the WWII postwar period resulted in thousands of Japanese citizens suffering horrific neurological injury. Fear and miscommunication destroyed and changed family and social structure. In addition, the Minamata poisoning caused momentous changes in the civic discourse in Japan and was an instrumental event in the democratization of the country. This manuscript describes the effects that the environmental contamination and human poising had in the transition of Japan from a feudal society to a democratic one.

[Mechanisms underlying changes in state of central nervous system pathways under exposure to metallic mercury].

The authors revealed mercury role in pathologic changes of central mechanisms underlying cerebral circulation in metabolic circle, associated with changes in central afferent pathways in thalamic region. Relationship was established between intensity of the diagnosed affect and changes in levels of antibodies to proteins S-100, general myeline protein, myeline-associated glycoprotein - that can indicate general neurodegeneration process. Antibodies level can serve as a marker of demyelination intensity in central pathways under exposure to neurotoxicants.

Is mercury in Tibetan Medicine toxic? Clinical, neurocognitive and biochemical results of an initial cross-sectional study.

Mercury an important therapeutic substance in Tibetan Medicine undergoes complex "detoxification" prior to inclusion in multi-ingredient formulas. In an initial cross-sectional study, patients taking Tibetan Medicine for various conditions were evaluated for mercury toxicity. Two groups were identified: Group 1, patients taking " Tsothel" the most important detoxified mercury preparation and Group 2, patients taking other mercury preparations or mercury free Tibetan Medicine. Atomic fluorescence spectrometry of Tibetan Medicine showed mercury consumption 130 µg/kg/day (Group 1) and 30 µg/kg/day (Group 2) ( P ≤ 0.001), levels above EPA (RfDs) suggested threshold (0.3 µg/kg /day) for oral chronic exposure. Mean duration of Tibetan Medicine treatment was 9 ± 17 months (range 3-116) (Group 1) and 5 ± 1.96 months (range 1-114) (Group 2) (NS) with cumulative days of mercury containing Tibetan Medicine, 764 days ± 1214 (range 135-7330) vs. 103 days ± 111 (range 0-426), respectively ( P ≤ 0.001). Comparison of treatment groups with healthy referents (Group 3) not taking Tibetan Medicine showed no significant differences in prevalence of 23 non-specific symptoms of mercury toxicity, abnormal neurological, cardiovascular and dental findings and no correlation with mercury exposure variables; consumption, cumulative treatment days, blood/ urine Hg. Liver and renal function tests in treatment groups were not significantly increased compared to referents, with mean urine Beta2 Microglobulin within the normal range and not significantly associated with Hg exposure variables after correcting for confounding variables. Neurocognitive testing showed no significant intergroup differences for Wechsler Memory Scale, Grooved Pegboard, Visual Retention, but Group1 scores were better for Mini-Mental, Brief Word Learning, Verbal Fluency after correcting for confounding variables. These results suggest mercury containing Tibetan Medicine does not have appreciable adverse effects and may exert a possible beneficial effect on neurocognitive function. Since evidence of mercury as a toxic heavy metal, however, is well known, further analysis of literature on mercury use in other Asian traditional systems is highly suggested prior to further studies.

Characteristics of hand tremor and postural sway in patients with fetal-type Minamata disease.

About forty certified patients aged around 50 years old existed as living witnesses to fetal-type Minamata disease (methylmercury poisoning due to in utero exposure) in Minamata, Japan in 2006. Computerized hand tremor and postural sway tests with spectral analysis were conducted for 24 of them and in matched control subjects to examine the pathophysiological feature of neuromotor function. The tremor intensities of the patients with fetal-type Minamata disease were significantly larger than those of the 67 controls at every frequency band for both hands. In the patients, proportions for intensity at 1-6 Hz of both hands were larger, but those of the intensity at 6-10 Hz were smaller compared with the controls. The center frequency of a tremor was significantly lower in the patients than in the controls. Only eight males of the 24 patients were examined to evaluate postural sway because of extremely low scores in activities of daily living in the remaining. Most of the postural sway parameters obtained with eyes open and closed were significantly larger in the patients than in the male controls. Likewise, Romberg quotients of postural sway in anterior-posterior direction were significantly higher in the patients. In conclusion, the patients with fetal-type Minamata disease of our study showed a larger tremor of low frequency at less than 6 Hz and postural instability. Spectral analyses of computerized hand tremor and postural sway are suggested to be useful for assessing the pathophysiological change, related to a lesion of the cerebellum, resulting from prenatal methylmercury exposure.

[The evaluation of immunoregulatory markers in the course of neurointoxication by mercury over the post-exposure period].

There was executed the examination of patients with occupational chronic mercury intoxication in the post-exposure period after the exposure to metallic mercury vapor. 47 persons with an established diagnosis of chronic mercury intoxication (HMI) passed the laboratory and immunological examination in the period of exposure to metallic mercury vapor in a production environment. The average age of men accounted for 49.2±1.2 years. The experience of work in hazardous working conditions amounted of 21.65±1.61 years (1 observation). All these same cases were observed in the institute clinic again after 5 years (2 observation) and 10 years (3 observation). A control group of healthy men consisted of 47 cases included persons of representative both age and general work experience, without a professional route of contact with hazardous substances. The level of such cytokines as IL-1ß, IL-2, IL-4, IL-6, TNF-a, INF-y and neurotropic IgG class antibodies directed to proteins of the nervous tissue (NF-200, GFAP, MBP, B-dependent Ca-channel, Glu-R, DA-R, R-GABA, Ser-R, R-Chol, DNA, B2GP) in serum were determined by enzyme linked immunosorbent assay. There was established the gain in the imbalance of inflammatory mediators and production ofneural antibodies in dynamics after the termination of the production in conditions of metallic mercury vapors. Revealed features of the regulatory relationship between the level of cytokines and the severity of the autoimmune process were shown to contribute to the maintenance and progression of neurodegenerative processes. There was recommended the identification of immunoregulatory markers (IL-1ß, IL-4, TNF-a, NF-AT to 200, GFAP, S-100) as an additional criteria for the diagnosis of health disorders in operating and monitoring the course of the progredient professional mercury intoxication.

Neuropsychological Effects of Mercury Exposure Among Dentists in Monastir City.

AIMS: The aim of this study is to assess the neuropsychological manifestations of mercury exposure in dentists. METHODS: A cross-sectional study was carried out including 64 dentists matched to a control group according to age and gender. This study protocol included a neurological evaluation, a questionnaire assessing the study groups' general characteristics and personal factors that may affect mercury urinary excretion in both groups. EUROQUEST questionnaire and Hospital Anxiety and Depression scale (HADS) were used to evaluate the neuropsychological symptoms reported during the last 12 months. In both groups, mercury impregnation was assessed by monitoring urinary mercury. RESULTS: In the exposed group, scores of neurological symptoms, memory disturbances and anxiety were found to be significantly higher than those in controls (p < 0.01). Mean scores of HAD Depression's scale were higher in the exposed group than in controls. Most of the neurotoxic manifestations were correlated to the levels of urinary mercury excretion in the exposed group. Mean levels of urinary mercury were significantly higher in the dentists group than in controls, with respective values of 21.1 ± 19.6 µg/g of creatinine and 0.05 ± 0.9 µg/g of creatinine. In nine dentists having urinary mercury levels higher than 35 µg/g of creatinine, neurological examination showed a bilateral and symmetric intentional tremor in both upper limbs. In the exposed group, the neuropsychological manifestations and levels of urinary mercury were found to be significantly correlated. CONCLUSION: Increased levels of urinary mercury observed in dentists suggest that exposure to mercury vapour emissions adversely affects dental professionals, therefore prevention measures should be strengthened, with a special medical supervision program of dentists exposed to mercury vapours should be implemented. We have also outlined some relevant patents in this article.

[Epidemiology of Minamata Disease--Focus on the Clinical Features Related to the 1977 Diagnostic Criteria].

Large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s (Minamata Disease). Although the diagnostic criteria for the disease was controversial and difficult during that time, we, the Kumamoto University Study Group, carried out a large-scale study to assess the clinical features in 1972-1973. The author tried to reassess the results of that study to appraise the diagnostic criteria established in 1977 on the basis of those results. A substantial number of residents in the exposed area exhibited neurologic signs, especially paresthesia of only the extremities, namely, the male residents of Minamata City showed a positive predictive value of 0.73 and a negative predictive value of 0.23. The relative risks of paresthesia only were 2.6 (2.0-3.3) and 1.2 (0.9-1.5), in Minamata and Goshonoura related to Ariake (control), respectively. At least until 1977, the diagnostic criteria remained valid, although it was inadequate. Nevertheless, presently, a follow-up study of the certified patients may lead to the development of efficient new diagnostic criteria.