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We had an opportunity to perform a general autopsy of a case with chronic organic mercury toxicosis in 2017. He had been engaged in synthesizing a variety of organic mercury compounds throughout the four years from 1966 and developed chronic organic mercury poisoning in 1969. Almost forty years on, he still remained to complain of persistent paresthesia at finger tips and tongue, and of narrowed visual field. Neurological examinations clarified a rise of two-point discrimination thresholds, a systemic increase of touch thresholds, constriction of the visual field caused by general visual depression, and sensorineural hearing loss while primary modalities of his somatic, visual, and auditory sensations were preserved. These symptoms and signs are characteristic of human organic mercury poisoning. Furthermore, he had difficulty in processing a lot of visual and auditory information at a time. His two-point discrimination thresholds and systemic elevation of touch thresholds were comparable to those of mild organic mercury poisoning cases. He had slight sensory ataxia, but not cerebellar ataxia. Brain [ 18 F]-2-fluorodeoxyglucose positron emission tomography analysis exhibited marked hypometabolism at bilateral postcentral gyrus, striate cortex, and superior temporal gyrus, but not the cerebellum. Histopathological studies revealed considerable decrease of granular neurons and neuronal networks in bilateral primary somatosensory, visual, and auditory cortices. Those characteristic brain lesions fairly explain increase of thresholds of somatic, visual, and auditory sensations, and degradation of integrating sensory information. It is noted that damages to the peripheral nervous system and the cerebellum were not detected and that his intellectual faculties were preserved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Minamata disease, which happened during the 1950s and 1960s in Minamata, Japan, is a well-known case of food poisoning caused by methylmercury-contaminated fish. Although many children were born, in the affected areas, with severe neurological signs after birth (known as congenital Minamata disease (CMD)), few studies have explored the possible effects of low-to-moderate methylmercury exposure in utero, probably at lower levels than in CMD patients, in Minamata. We, therefore, recruited 52 participants in 2020: 10 patients with known CMD; 15 moderately exposed residents; and 27 non-exposed controls. The average umbilical cord methylmercury concentrations were 1.67 parts per million (ppm) for CMD patients and 0.77 ppm for moderately exposed participants. After conducting four neuropsychological tests, we compared the functions among the groups. Compared with the non-exposed controls, both the CMD patients and moderately exposed residents had worse scores in the neuropsychological tests, although the score decline was more severe in the CMD patients. For example, even after adjusting for age and sex, the CMD patients and moderately exposed residents had 16.77 (95% CI: 13.46 to 20.08) and 4.11 (95% CI: 1.43 to 6.78) lower scores in the Montreal Cognitive Assessment, respectively, than the non-exposed controls. The present study indicates that residents of Minamata who experienced low-to-moderate prenatal methylmercury exposure also have neurological or neurocognitive impairments.

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.

Introduction: Autism spectrum disorders are neurodevelopmental dysfunctions that are characterised by deficits in social integration and communication, associated with restricted interests and stereotypic behaviour. A high percentage are related to language disorders, sensory dysfunctions, attention deficit disorder, bipolarity, intellectual disability or epilepsy, among other comorbidities. It is estimated that around 30% of children with autism, with typical early development, may present regression in the first years of life, which was already reported by Kanner in one of his original cases. The term regression refers to the loss of social, communicative or motor skills. It is essential to be alert to any symptoms of autistic regression, since it is not always an unspecific usual manifestation of the clinical spectrum of autism. Although little is known about the pathogenesis of regression, it needs to be organised hierarchically, as it can be part of different conditions with a variety of causes., Aims: The aim of this study is to analyse distinct conditions that need to be addressed in the case of a child with autistic regression, including genetic and toxic causations, autoimmune and nutritional phenomena, and epilepsies., Conclusion: When faced with a case of autistic regression it is essential to try to identify the possible aetiology, as this can allow specific treatment and adequate genetic counselling to be established.

Fetal-type Minamata disease is caused by the exposure to high concentrations of methylmercury in the fetal period and shows cerebral palsy-like clinical features. Relief of spasticity is a major task of rehabilitation to improve their activities of daily living. Here we report the effect of long-term vibration therapy on bilateral lower-limb spasticity in 3 patients with fetal-type Minamata disease. We used a simple, inexpensive, and noninvasive approach with hand-held vibration massagers, which were applied to the plantar fascia at 90 Hz for 15 minutes. The effect was observed soon after the first treatment and resulted in better performance of the repetitive facilitation. Vibration therapy for 1 year improved Modified Ashworth Scale for the ankle flexors in 2 cases. The labored gait improved and gait speed increased in another case. Continued vibration therapy for another 1 year further improved Modified Ashworth Scale score and range of motion of ankle dorsiflexion in 1 case. This case showed the decreased amplitude of soleus H-reflex after the 15-minute vibration therapy, suggesting that α-motor neuron excitability was suppressed. Vibration therapy using a hand-held vibration massager may offer safe and effective treatment for lower-limb spasticity in patients with chronic neurological disorders.

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.

To differentiate cognitive disorders in toxic (mercurial) and alcohol encephalopathy, the authors determined peculiarity of mental disorders in patients with toxic encephalopathie of various origins. Discriminant analysis helped to evaluate totality of informative neurophysiologic and psychologic parameters to assign patients to a group with cognitive disorders due to mercurial toxic encephalopathy or to a group with that due to alcohol encephalopathy.

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.

Objective: To identify features of cognitive impairment in patients with toxic (mercury or alcohol) encephalopathy., Material and Methods: The study involved 36 patients with chronic mercury intoxication and 30 people with chronic alcoholism. A control group included 30 age-matched healthy men who were not exposed to toxic substances and alcohol abuse. All patients underwent neuropsychological examination, which involved a set of neuropsychological Luria rated memory status, praxis, gnosis and speeches. MMSE and FAB were used for the diagnosis of moderate cognitive impairment. Computer electroencephalography and cognitive evoked potentials method were used as well., Results and Conclusion: The diffuse brain injury in toxic encephalopathy (alcohol and mercury) on EEG, and according to the results of neuropsychological testing was identified. Changes in analytical and synthetic thinking, audio-verbal, long-term, visual memory, reciprocal coordination, finger gnosis, impressive speech were observed in mercury encephalopathy. Functional failure of the frontal lobe and the premotor area of the left hemisphere were revealed in alcoholic encephalopathy.

The extent to which postnatal methylmercury exposure contributes to neurobehavioral delays is uncertain. Confounding may occur because the child's dietary exposure likely correlates with the mother's. This conundrum was examined in the Faroese birth cohort 1 born in 1986-1987. Exposure parameters included mercury concentrations in maternal hair at parturition, cord blood, and child blood and hair at the age-7 clinical examination (N=923). In regression analyses, the child's current blood-mercury at age 7 (N=694) showed only weak associations with the neuropsychological test variables, but visuospatial memory revealed a significant negative association. Mutual adjustment caused decreases of the apparent effect of the prenatal exposure. However, such adjustment may lead to underestimations due to the presence of correlated, error-prone exposure variables. In structural equation models, all methylmercury exposure parameters were instead entered into a latent exposure variable that reflected the total methylmercury load. This latent exposure showed significant associations with neurodevelopmental deficits, with prenatal exposure providing the main information. However, postnatal methylmercury exposure appeared to contribute to neurotoxic effects, in particular in regard to visuospatial processing and memory. Thus, addition in the regression analysis of exposure information obtained at a different point in time was not informative and should be avoided. Further studies with better information on exposure profiles are needed to characterize the effects of postnatal methylmercury exposure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To assess severity of cognitive disorders in chronic mercury intoxication, the authors performed claster and discrimination analysis of neuropsychologic and neurophysiologic research data from workers exposed to mercury during long length of service, from patients with early and marked stages of chronic mercurial intoxication. Cognitive disorders in chronic mercurial intoxication have three severity degrees, in the light degree disorders patients demonstrate lower amplitude of cognitive evoked potentials, poor long-term memory and associative thinking. Moderate cognitive disorders are characterized by decreased visual, long-term memory, concentration of attention, poor optic and spatial gnosis. Marked cognitive disorders with chronic mercurial intoxication present with more decreased long-term, short-term, picturesque memory, poor intellect, optic and spatial gnosis and associative thinking.

Objectives: To clarify the prevalence of lower urinary tract symptoms and overactive bladder in patients with chronic methyl mercury poisoning., Methods: A total of 151 patients (61 men and 90 women; mean age 72.1 years) with Niigata Minamata disease were enrolled. An age- and sex-matched group of 150 participants was used as control. Patients reported their International Prostate Symptom Score and overactive bladder symptom score., Results: In men, the total, storage and voiding International Prostate Symptom Score scores were higher in the Niigata Minamata disease group than in the control group (10.6 ± 7.8 vs 5.0 ± 5.0, 4.5 ± 3.3 vs 2.4 ± 2.4 and 6.1 ± 5.1 vs 2.7 ± 3.1, respectively, P < 0.001 in all). In women, these scores were also higher in the Niigata Minamata disease group than in the control group (8.9 ± 7.3 vs 4.0 ± 4.0, 4.4 ± 3.2 vs 2.8 ± 2.4 and 4.5 ± 5.0 vs 1.3 ± 2.0, respectively, P < 0.001 in all). The prevalence of overactive bladder was more frequent in the Niigata Minamata disease group compared with that in the control group (51.7% vs 26.7%, P < 0.001). In both men and women, the overactive bladder symptom score was higher in the Niigata Minamata disease group than in the control group (4.1 ± 3.0 vs 2.4 ± 2.9, P = 0.002 and 4.6 ± 3.6 vs 2.7 ± 2.9, P < 0.001, respectively). The International Prostate Symptom Score and overactive bladder symptom score in the Niigata Minamata disease group were highest in patients aged 60-69 years (P < 0.001 in both), whereas these increased in an age-dependent manner in the control group., Conclusions: Lower urinary tract symptoms and overactive bladder are severe and highly prevalent conditions among patients with methyl mercury poisoning. The higher prevalence of lower urinary tract symptoms among patients aged 60-69 years might be related to the fact that they were exposed to methyl mercury during their childhood/development., (© 2012 The Japanese Urological Association.)

The authors present a novel treatment for spasticity using a hand-held vibration massager. A fetal-type Minamata disease patient showing spasticity of lower limbs had direct application of vibratory stimuli to the right plantar fascia and to the left hamstring. After the treatment for 1 year, the Modified Ashworth Scale (MAS) of the lower limbs was improved from three (right > left) to two (right < left). After then, direct application of the same method with the left plantar fascia improved the MAS of the left lower limb to two (right = left). The increased deep tendon reflexes had diminished and markedly positive Babinski's sign had also decreased to slightly positive on both sides. This method is so simple that patients can treat themselves at home. The authors think that direct application of vibratory stimuli to the plantar fascia is valuable to patients with neurologic disorders, particularly those who cannot receive more invasive treatments.

Since 1995, the Caruso Project used an Ecosystem Approach to Human Health to examine mercury (Hg) exposure in fish-eating communities in the Brazilian Amazon and develop interventions to maximise nutrition from traditional diet and minimise toxic risk. In 1995, 2000 and 2006, this study followed fish consumption, Hg levels, and visual and motor functions in 31 villagers. Questionnaires gathered information on socio-demographics and diet. Hair Hg (H-Hg) levels were measured. Visual acuity, colour vision, manual dexterity and grip strength were assessed. Data was analysed using general linear models of repeated measures. Total fish consumption, similar in 1995 and 2000, decreased in 2006. Carnivorous fish consumption initially decreased and then remained stable, whereas non-carnivorous fish consumption first increased and then decreased. H-Hg declined from 17.6 to 7.8 μg/g. Visual functions showed a significant decrease over time, with those with H-Hg ≥ 20 μg/g in 1995 showing greater loss. Motor functions showed initial improvement and then returned to the 1995 performance level. Decrease in Hg exposure is attributed to the intervention and socio-economic changes in the village. While there may be a certain reversibility of motor deficits, visual capacities may decrease progressively with respect to exposure prior to the intervention.

Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn 1 week before randomization and 1 week after treatment began when succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 microg/L and 0.52 microg/L and post-treatment concentrations were 0.51 microg/L and 0.48 microg/L for placebo and succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable., (2009 Elsevier Inc. All rights reserved.)

Evaluation of neuromotor function has been used in several epidemiological studies of workers with long-term exposure to mercury vapor (Hg 0). Some recent studies indicate adverse effects at relatively low exposure levels. In the present study, we used sensitive quantitative methods, developed specifically to detect subtle effects of exposure to toxins on motor function. After exclusion of individuals with neurological diseases or other conditions that may affect performance, 43 chloralkali workers with current low exposure to Hg 0, and 22 age-matched referents remained for further analysis. The median urinary mercury concentration in exposed workers was 5.9 microg/g (range 1.3-25) creatinine (microg/gC), while that in referents was 0.7 microg/gC (range 0.2-4.1). The mean exposure time was 15 years, and the median cumulative mercury index was 161 years x microg/gC in exposed workers. A eurythmokinesimeter (EKM) was used to quantify eye-hand coordination, and a diadochokinesimeter, to measure rapid alternating rotation of the forearms. In general, the differences in performance between the exposed workers and the referents were small. Age was associated with a decrease in speed, more tremor, and longer contact duration between the stylus and the metal targets in performance of rapid pointing movements. Smokers had significantly more tremor, and more contacts per event in the EKM test, than nonsmokers. Taking age, shift work, and smoking habits into account, no significant associations with current or cumulative mercury exposure were found for the majority of the outcome variables from the quantitative tests. In general, this study indicates no significant adverse effects of Hg 0 on neuromotor function at the exposure levels studied.

Objectives: Minamata disease (MD), first discovered in 1956, is a neurological disorder caused by mercury poisoning due to daily intake of fish and shellfish that have been contaminated by methylmercury discharged from chemical factories. However, reports of ill health increased sharply following the 2004 Supreme Court ruling instructing the Japanese government to pay damages to MD patients. We examined the distribution of disability in activities of daily living (ADL), and the association between MD status in terms of compensation system and ADL disability among the general population of previously methylmercury-polluted areas., Methods: Data were collected by two-stage stratified sampling of residents 40-79 years old in 172 postal-code areas on the Shiranui Sea coast, the endemic area of MD. Questionnaires were distributed to eligible subjects (n = 2100) and collected at a later visit or by mail. Information on demographic factors, basic ADL (BADL), and instrumental ADL (IADL) was obtained using questionnaires. We performed logistic regression analysis to assess the relationship between MD status in terms of compensation system and ADL disability., Results: We classified the 1422 residents who completed the questionnaire in accordance with their MD status in terms of compensation system: Early (those who received MD compensation before the Supreme Court decision), Recent (those who applied for compensation after the Supreme Court decision), Not Yet (those who have not yet applied for compensation, but have health-related anxieties about MD effects), and Normal (those who have not applied for compensation, and do not have health-related anxieties about MD effects). Adjusting for confounding factors, MD status was significantly associated with the disability grades of BADL and IADL with an increasing trend in the order of Normal, Not Yet, Recent, and Early. The odds ratios (95% CI) based on Normal were 2.08 (1.08-4.01), 3.87 (2.14-7.01), and 4.50 (2.66-7.61) for BADL and 2.41 (1.62-3.61), 3.20 (2.12-4.85) and 3.68 (2.52-5.38) in Not Yet, Recent, and Early for IADL, respectively., Conclusion: Early, Recent, and Not Yet had lower ADL grades than Normal. Moreover, the population with a low ADL grade and health-related anxieties had increased throughout the previously methylmercury-polluted areas. The issue of ill health among populations living in previously methylmercury-polluted areas should be addressed in the wider context of public and community health.

Serra Pelada is a village in the Amazon region of Brazil where most of the inhabitants are former gold miners. Of 235 individuals evaluated, 219 were males (93.19%), 16 were females (6.80%), and the mean age was 52.07 years (standard deviation = 11.57). Most were heavy drinkers (62.44%) and smokers (70.30%), and 85.53% had previously suffered from malaria. Reported symptoms included fatigue (30.60%), irritability (35.62%), excitability (14.16%), insomnia (34.48%), memory loss (61.80%), visual field constriction (4.18%), paresthesia (64.93%), partial hearing loss (16.35%), and gingivitis (18.01%). After an examination of the residents, the authors observed several neurological symptoms: tremors (22.80%), involuntary ocular movement (2.20%), visual field constriction (4.18%), Romberg syndrome (2.33%), involuntary tongue movement (2.19%), dysdiadochokinesia (0.43%), failure of a finger-nose test (10.96%), failure of a knee-heel test (4.84%), inability to complete a tandem march (6.25%), muscular weakness (2.27%), and damage to sensory organs (24.66%). The authors concluded that these neurological changes possibly resulted from mercury toxicity; however, they could not determine a significant correlation with the mercury levels detected in participants' urine.

Objectives: The main purposes of this study are to compare the current statuses and activities of daily living (ADL) scores with the same parameters 15 years ago in fetal-type Minamata disease patients and to identify the communication disorders in these patients., Methods: An interview survey was conducted on 31 fetal-type Minamata disease patients mainly in 2002 concerning family structure, present status of care, their demand for care, communication status, and ADLs. Changes in ADLs during the past 15 years were also studied in 22 of the patients., Results: Their mean ages were 45.5+/-3.5 (n=20) for males, and 46.1+/-1.9 (n=ll) for females. The average numbers of family of the patients was 2, and 15 patients lived alone. An analysis of ADLs showed that about 50% of the patients could not walk or take a bath, and 30 to 40% of the patients could not eat, excrete, change their clothes, or wash their face alone. Approximately 80% of the patients could understand daily conversation to some degree. However, their ability to express their demands and thoughts, put an idea into action, remember events, and live like ordinary people were significantly worse than their ability to understand daily conversation. The changes in the ADLs of the 22 patients were not significant for the past 15 years. However, two patients showed a rapid decrease for ADL of movement and 2 other patients died after an interview before 50 years of age., Conclusions: Appropriate care in daily living is an important issue for fetal-type Minamata disease patients. Further, the individual health care of such patients is an urgent issue and can prevent their health from rapidly deteriorating.

The association between environmentally released mercury, special education and autism rates in Texas was investigated using data from the Texas Education Department and the United States Environmental Protection Agency. A Poisson regression analysis adjusted for school district population size, economic and demographic factors was used. There was a significant increase in the rates of special education students and autism rates associated with increases in environmentally released mercury. On average, for each 1,000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism. The association between environmentally released mercury and special education rates were fully mediated by increased autism rates. This ecological study suggests the need for further research regarding the association between environmentally released mercury and developmental disorders such as autism. These results have implications for policy planning and cost analysis.

A study of 47 firemen exposed to a complex of toxic substances while putting out fire and 46 subjects with chronic mercury intoxications was carried out 5-10 years after the exposure to toxic substances. Along with clinical psychiatric examination, neuropsychological testing was conducted. Non-specificity of mental disorders, polymorphism and progressive development were found. Psychoorganic syndrome with secondary neurotic disturbances proved to be a core feature of mental disorders. It is emphasized that neuropsychological examination or usage of neuropsychological methods during a psychiatric examination are important for practical diagnosis of exogenous organic mental disorders, especially for outpatient examination of corresponding occupational groups.

Background: The neurotoxic effects of methylmercury (MeHg) have been demonstrated in both human and animal studies. Both adult and fetal brains are susceptible to the effects of MeHg toxicity. However, the specific effects of adult exposures have been less well-documented than those of children with prenatal exposures. This is largely because few studies of MeHg exposures in adults have used sensitive neurological endpoints. The present study reports on the results of neuropsychological testing and hair mercury concentrations in adults (>17 yrs) living in fishing communities of Baixada Cuiabana (Mato Grosso) in the Pantanal region of Brazil., Methods: A cross-sectional study was conducted in six villages on the Cuiaba River. Participants included 129 men and women older than 17 years of age. They were randomly selected in proportion to the age range and number of inhabitants in each village. Questionnaire information was collected on demographic variables, including education, occupation, and residence history. Mercury exposure was determined by analysis of hair using flameless atomic absorption spectrophotometry. The neurocognitive screening battery included tests from the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale, Concentrated Attention Test of the Toulouse-Pierron Factorial Battery, the Manual Ability Subtests of the Tests of Mechanical Ability, and the Profile of Mood States., Results: Mercury exposures in this population were associated with fish consumption. The hair mercury concentration in the 129 subjects ranged from 0.56 to 13.6 microg/g; the mean concentration was 4.2 +/- 2.4 micrograms/g and the median was 3.7 microg/g. Hair mercury levels were associated with detectable alterations in performance on tests of fine motor speed and dexterity, and concentration. Some aspects of verbal learning and memory were also disrupted by mercury exposure. The magnitude of the effects increased with hair mercury concentration, consistent with a dose-dependent effect., Conclusions: This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures.

Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon4 groups was found in the patients p<0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.

Pregnant C57BL/6 mice were chronically treated with 0, 4, 6, or 8 ppm of methylmercury chloride (MeHg) in drinking water during fetal and early postnatal development. Four behavioral functions were analyzed in female and male offspring between the age of 6 and 12 weeks: motor coordination learning on the rotarod; training to spatial alternation in the standard T maze followed by a working memory test with delays; spontaneous locomotion and rearings in the open field; reference and working memory assessment in the modified T maze [Behav. Neurosci. 102 (1988) 635]. Chronic perinatal treatment with MeHg resulted in moderate brain levels of mercury near birth which rapidly decreased during nursing. MeHg exerted an effect on the performance of females, but not of males, on two of the four measurements. All treated females exhibited less locomotion than control mice when the open field was new, but not in the following four sessions when the environment was becoming increasingly familiar. Working memory was impaired in females treated with 6 and 8 ppm of MeHg in the modified T maze, but not on the test with delays in the standard T maze. Taken together, these results show that chronic exposure to MeHg during fetal and postnatal development had sex-dependent effects on horizontal exploration and on working memory in the modified T maze, and no effects on motor coordination learning and reference memory.

Parkinson syndrome occurs in the course of chemical intoxication, especially Mn, CS2, CO. It is rarely caused by chronic mercury intoxication. We present the case of 55 year old man who was exposed to metallic mercury vapor during 33 years of working in the chemical plant at the production of chlorine. On several occassions patient was removed from contact with Hg because of the symptoms of increased Hg absorption. At the age of 52 he developed hand tremor, balance and gait disturbance with bradykinesia, paresthesias of the upper extremities, neurobehavioral abnormalities, slight memory loss, and spatial disorientation. Psychoneurological examination revealed dementia, Parkinson's syndrome and ataxia of the lower limbs. Mercury excretion in the urine, which equaled 18.3 mu\g creatinine, confirmed exposure to Hg. MRI of the head revealed cortical and cerebellar atrophy. Electroneurography examination found features of subclinical peripheral sensory axonopathy of the upper limbs. Despite atypical clinical course (parkinsonismus) chronic mercury encephalopathy was diagnosed based on documented occupational exposure and diagnostic test results.

In order to assess the cardiovascular autonomic nervous functions in patients with fetal type Minamata disease (FMD), we investigated blood pressure (BP), and conducted time and frequency domain analysis of heart rate variability (HRV). Subjects were 9 patients in Meisuien recognized as FMD, and 13 healthy age matched control subjects. HRV and BP were assessed after subjects rested in a supine position for 10 minutes. Electrocardiographic (ECG) data were collected for 3 minutes during natural breathing. Time domain analysis (the average of R-R intervals [Mean RR], standard deviation of R-R intervals [SD RR], coefficient of variation [CV]), and frequency domain analysis by fast Fourier transformation (FFT) (power of low frequency [LF] and high frequency [HF] component, expressed in normalized units[nu]) were then conducted. In the time domain analysis, the mean RR of the FMD group was significantly lower than that of the control group. Neither SD RR nor CV showed significant differences between the two groups, but both tended to be lower in the FMD group. In the frequency domain analysis, the HF component of the FMD group was significantly lower than that of the control group. Pulse pressure (PP) was significantly lower in the FMD subjects. These findings suggest that parasympathetic nervous dysfunction might exist in FMD patients, who were exposed to high doses of methylmercury (MeHg) during the prenatal period. Decrease of PP might be due to degenerative changes of blood vessels driven by exposure to high doses of MeHg.

Background: Observational studies in epidemiology always involve concerns regarding validity, especially measurement error, confounding, missing data, and other problems that may affect the study outcomes. Widely used standard statistical techniques, such as multiple regression analysis, may to some extent adjust for these shortcomings. However, structural equations may incorporate most of these considerations, thereby providing overall adjusted estimations of associations. This approach was used in a large epidemiological data set from a prospective study of developmental methyl-mercury toxicity., Results: Structural equation models were developed for assessment of the association between biomarkers of prenatal mercury exposure and neuropsychological test scores in 7 year old children. Eleven neurobehavioral outcomes were grouped into motor function and verbally mediated function. Adjustment for local dependence and item bias was necessary for a satisfactory fit of the model, but had little impact on the estimated mercury effects. The mercury effect on the two latent neurobehavioral functions was similar to the strongest effects seen for individual test scores of motor function and verbal skills. Adjustment for contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates only marginally, but the mercury effect could be reduced to non-significance by assuming a large measurement error for the PCB biomarker., Conclusions: The structural equation analysis allows correction for measurement error in exposure variables, incorporation of multiple outcomes and incomplete cases. This approach therefore deserves to be applied more frequently in the analysis of complex epidemiological data sets.

Autism is a developmental disease characterized by a spectrum of symptoms ranging from decreased verbal skills and social withdrawal, to repetitive behavior and violent outbursts. Genetic analysis has yielded a few potentially interesting genes, however no clear linkage has been established. For this reason, it has been suggested that the etiology of autism may involve multiple loci. This, in large part, explains why so many different theories abound. One such theory is that of mercury poisoning. Environmentally acquired mercury, either through some causal contact or through vaccination, has been postulated as the culprit. Mercury is thought to be exerting its neurological effect on the brain. The standard treatment has been to apply chelating agents in an attempt to extricate the mercury. One missing component in the treatment is the utilization of the body's own detoxification mechanisms. Arguably the largest detoxification component of the body, the endogenous enteric bacteria are an enormous reservoir, which can be constantly and safely replenished. This paper discusses the use of high-dose probiotics as an adjuvant for detoxification protocols with an emphasis on use in autistics., (Copyright 2002 Published by Elsevier Science Ltd.)

Introduction: The department of Antioquia in Columbia is the main producer of gold in Columbia. In the gold-producing regions the population is exposed to high levels of mercury used in the processes of extraction and purification. Studies done in Columbia on neurotoxicity underline the hazards of mercury from the environmental and occupational-health point of view, but the effect of long-term exposure on cognitive function has not been studied., Objective: To determine whether the miners of El Bagre (Antioquia, Columbia) have neuropsychological and/or behavior disorders as a result of occupational exposure to toxic mercury vapor., Patients and Methods: The sample was made up of 22 right-handed men, residents of El Bagre, aged between 20 and 45 years old who had been exposed to mercury vapor for at least three years. The control group consisted of 22 men who lived in the non-mining regions of the department and had not been exposed to mercury, paired with the cases considered for age and educational status. Neuropsychological assessment, a medical examination and behavioral performance tests were applied to all the men (in both groups)., Results: In the study group alterations were seen and classified as: intellectual damage (mainly alteration of executive function and constructional praxis); emotional changes (symptoms of depression and anxiety) and neurological changes (amnesia, insomnia and tremor of the tongue). No changes were found in the control group., Conclusion: Exposure to mercury causes specific neuropsychological and behavior disorders in the absence of clinically detectable physical or physiological damage.

Background: Mercury poisoning presents a variety of clinical pictures depending on chemical structure, amount absorbed, total mercury burden, and individual factors. Distant skin lesions, after subcutaneous injection of metallic mercury, have not been previously described., Case Report: We present a homicidal, subcutaneous injection of mercury resulting in widespread skin lesions, remote from the radiologically visible mercury. The lesions appeared at 40 days and began to clear at 6 months after the injection.