Environmental exposure to manganese in air: Tremor, motor and cognitive symptom profiles.

BACKGROUND: Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD. METHODS: Residents of East Liverpool (n=83) and Marietta, OH (n=99) exposed to chronic (>10years) environmental Mn through industrial pollution were administered neuropsychological measures and a physician-rated scale of movement-disorder symptoms. Two-step cluster analysis was used to group residents based on tremor symptoms, bradykinesia/rigidity symptoms, gait disturbance, and executive function. Cluster membership was validated using modeled air-Mn exposure and a computerized tremor measure. RESULTS: Elevated tremor and motor symptoms and executive dysfunction were observed, and TD and NTD symptom clusters were identified. Two additional clusters were also identified: Executive Dysfunction and Normal Functioning. The NTD residents, with elevated levels of gait disturbance and other movement disorder symptoms, did not evidence EF impairment, as predicted. Instead, residents with EF impairment formed their own cluster, and were relatively free of movement disorder symptoms. CONCLUSIONS: Results resemble reports in the PD literature with TD and NTD clusters identified, but executive dysfunction did not cluster with NTD symptoms. PD and Mn exposure likely have differing pathophysiology and developmental courses, and therefore different symptom patterns, even when similar symptoms are present.

Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age.

Neuropsychological dysfunction, mood disturbance, and emotional status of munitions workers.

The objective of this study was to compare the neuropsychological function, emotional status, visual function, and illness prevalence of 265 former munitions plant workers (M age = 56.7 years, M years of education = 12.07; 201 African American, 64 White) exposed to organic solvents for an average of 17.03 years with that of a group of 77 unexposed controls (M age = 51.3 years, M years of education = 13.07; 30 African American, 47 White). Neuropsychological tests were selected from the World Health Organization Neurobehavioral Core Test Battery, Wechsler Adult Intelligence Scale-III (WAIS-III), and Wechsler Memory Scale-III (WMS-III) and also included the Brief Symptom Inventory, Profile of Mood States, Beck Anxiety Inventory, and Beck Depression Inventory. Vision tests included the Lanthony d-15 color vision, the Vistech Contrast Sensitivity, and the Snellen. The exposed group showed greater deficits than the controls in verbal learning (WMS-III Logical Memory I Learning Slope and Word Lists I Recall), visuomotor tracking speed (Cancellation H, WAIS-III Digit Symbol-Coding) and psychomotor function (Dynamometer and Grooved Pegboard), and dysfunction in emotional status, illness prevalence, and visual function. African American workers reported higher levels of exposure than Whites. Exposure relations demonstrated increased neuropsychological dysfunction with increased exposure.

Neuropsychiatric effects of manganese on mood.

Adverse mood effects of overexposure to Manganese (Mn) have been described in 15 studies which frequently report an association of Mn exposure with adverse effects in six dimensions of mood: 1) anxiety, nervousness, irritability; 2) psychotic experiences; 3) emotional disturbance; 4) fatigue, lack of vigor, sleep disturbance; 5) impulsive/compulsive behavior; 6) aggression hostility. Only 1:15 studies used a standardized psychological measure of mood, while the current study of environmental Mn exposure used two standardized mood scales in evaluating low levels of Mn exposure and mood sequelae. The Profile of Moods State (POMS) and Brief Symptom Inventory (BSI) were used, and results indicate that men who are older and have higher Mn levels show significant disturbances on four of the six mood dimensions. Increased scores were seen in the anxiety, nervousness, irritability; emotional disturbance; and aggression, hostility dimensions relative to those who had lower levels of Mn. The BSI and POMS are useful adjuncts in the assessment of mood/Mn effects.

Amnestic disturbance and posttraumatic stress disorder in the aftermath of a chemical release.

Neuropsychological assessments were performed on 70 patients referred after a Catacarb chemical release in a Northern California town. After appropriate exclusions, the 59 patients used in the final analysis were mostly White (66%), with 56% having some college level education. They were administered the: Wechsler Adult Intelligence Scale-Revised (WAIS-R), Memory Assessment Scale (MAS), Trails A and B, Stroop, Controlled Oral Word Association Test (COWAT), Fingertapping Test, Purdue Pegboard, Dynamometer, Rey 15-Item Test, Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Brief Symptom Inventory (BSI), Beck Depression Index (BDI), Profile of Mood States (POMS), and Impact of Events Scale (IES) scales in addition to a health questionnaire and symptom checklist. Results indicate impaired scores on mnestic function and information processing when compared to Heaton's (1992) normative data, and the MAS norms (Williams, 1991). MMPI-2, BSI, BDI, POMS, and IES results indicate significant elevations on scales of depression, anxiety, anger, and posttraumatic stress disorder (PTSD) symptoms. The more brief tests of affect and mood appear sufficiently sensitive in measuring the dysphoric mood in group research studies. Clinical diagnoses using criteria from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV; American Psychiatric Association, 1994) criteria indicate a prevalence of 54% PTSD and 64% Amnestic or Cognitive disturbance. New onset of dermatological, respiratory, visual, and gastrointestinal symptoms and illnesses are consistent with the chemical exposure, the PTSD may be in reaction to it, and Amnestic/Cognitive disturbance, from both an organic and functional etiology.

Epidemiological health study of a town exposed to chemicals.

The purpose of this survey was to assess the health status of community residents exposed to a 16-day release of Catacarb from a nearby refinery and to document the prevalence rates of symptoms and illnesses of this town. The health status of the exposed residents was compared to that of unexposed residents of a demographically similar control town. An epidemiologic study design was used and questionnaires were mailed to all households in both towns. Response rate was 43%. Household cluster effects, gender, education, and race were controlled in the analysis. Questionnaire health data reveal increased reporting of symptoms in the exposed, specifically headaches, respiratory, visual, gastrointestinal, and dermatologic with odds ratios ranging between 1.3 and 3. Exposure relationships with increased symptoms and worsening of illnesses was found.

Symptom base rates after chemical exposure for white, Hispanic and African-Americans.

The results of a symptom checklist of three matched-pair studies (N = 460) of the following exposed groups are presented: Study 1, a primarily white community (N = 220) environmentally exposed to the pesticide metam sodium; Study 2, a Hispanic group (N = 180) who worked in a microelectronics plant and had extensive past exposure (M = 6.7 yrs) to multiple organic hydrocarbon solvents; and Study 3, an African-American group (N = 168) environmentally exposed to sulfuric acid. Each exposed group was compared to a matched (race, age +/- 3 years, gender, education +/- 2 years and number of children) unexposed reference group, resulting in 90 pairs for the white metam sodium group, 62 pairs for the Hispanic organic solvent group, and 78 pairs for the African-American sulfuric acid group. Symptom prevalence rates and relative risk ratios show very strong associations: in Study 1, the relative risk for all 33 symptoms ranged from 1.5 to 37; in Study 2, the relative risk for 31 of the symptoms ranged from 1.5 to 11.1; and in Study 3, the relative risk for 16 of the symptoms ranged from 1.5 to 6. Mann Whitney U results of each symptom indicate significantly greater symptomatology in the exposed vs. the reference groups in all three studies: in Study 1, at p < .01 for all 33 symptoms; in Study 2, at p < .01 for 31 symptoms, and p < .05 for one additional symptom; and in Study 3, at p < .01 for 24 symptoms and p < .05 for another three symptoms. These results suggest a robust symptom complex following chemical exposure regardless of specific chemical.

Surveillance of early neurotoxic dysfunction.

Surveillance of early neurotoxic alterations was undertaken in 3 reinforced plastics plants, with a view to preventive intervention. Using a longitudinal study design, exposure parameters (environmental styrene in the respiratory zone of each worker and end-shift mandelic acid (MA)) and neurobehavioral performance (Neurobehavioral Core Test Battery and Field Assessment: Sensory Tests), were assessed at time zero (T0); recommendations were made to reduce exposure at jobsites with the highest risk. Reassessment was made two years later (T2). Complete exposure data was available for 118 workers at T0; 75 were still employed at T2; of these, 57 (76%) returned for testing. Those who returned had more seniority (p < 0.001) and higher MA (p < 0.01) and styrene (p < 0.05) levels at T0 than the others. Analyses, performed on the T0-T2 differences, showed improvement in exposure parameters in Plant 3, where lower levels were observed at T2 for styrene (p < 0.05) and MA (p < 0.001). workers in Plant 3 (n = 29) performed better (p < 0.05) at T2 for short term memory, perceptuo-motor speed, motor precision and manual dexterity; they reported more vigor (p < 0.05) and less anger (p = 0.07). This was not the case for the workers from the other plants. Generally, the T0-T2 difference in MA was associated (Spearman's Rho) with differences in color vision (p < 0.001), simple reaction time (mean and standard deviation), digit span forward, tension, fatigue and the number of symptoms (p < 0.05); aiming precision showed a similar tendency (p < 0.10). These findings suggest that group surveillance of early nervous system changes for jobs with exposure to neurotoxins, using a sensitive neurofunctional test battery, may be useful for preventive intervention.

Psychological, psychosocial, and psychophysiological sequelae in a community affected by a railroad chemical disaster.

Psychological, psychosocial, and psychophysiological sequelae were studied in a community which had experienced a railroad chemical spill of 19,000 gallons of the toxic pesticide metam sodium. Two hundred twenty exposed residents were compared to 114 controls and paired on age, education, gender, race, and number of children. A clinical interview and physiological measurements (blood pressure, pulse, and cortisol level) were taken, the MMPI-2, IES Scale, Mood Scale, Environmental Worry, Perceived Social Support, and Perceived Control Scale and a questionnaire were administered. Results indicated greater levels of depression, anxiety, and somatic symptoms in the spill residents in addition to greater environmental worry and lower perceived social support. Spill residents had higher blood pressure and less fluctuation of cortisol levels than controls. No difference on litigation status was obtained except on the IES, Intrusion and the POMS scales. Chemical disasters are associated with a wide variety of psychological, psychosocial, and physiological distress.

Aftermath of a chemical spill: psychological and physiological sequelae.

Psychological, and psychophysiological sequelae were studied in a community which had experienced a railroad chemical spill of 19,000 gallons of the toxic pesticide metam sodium. Information was collected on 350 persons living in the area of the spill (spill residents) and 114 nonexposed controls, recruited using a randomized sampling strategy, from a nearby similar, but unexposed control town. Psychological measures used were the MMPI-2, POMS, IES Scale, Environmental Worry, Perceived Social Support and Perceived Control Scale. Physiological measurements were two measurements of blood pressure, pulse, and salivary cortisol level, taken both at the beginning and the conclusion of the study. Demographic and medical information was asked in a Questionnaire. Results indicate greater levels of depression, anxiety, and somatic symptoms in the spill residents in addition to greater environmental worry and lower perceived social support. Spill odor perception was related to increased psychological and physiological sequelae. The spill residents had higher blood pressure and less fluctuation of cortisol levels than the controls. Comparison of spill residents who were litigants and those who were not, indicates no differences for blood pressure, pulse, and cortisol, MMPI-2, Environmental Worry and the Control Scale. Litigants scored slightly higher on the IES, Intrusion and the POMS scales. No dose/response relationship between distance to the river and evacuation status was obtained. The chemical spills was associated with a wide variety of psychological and physiological reactions.

Stability of psychological impairment: two year follow-up of former microelectronics workers' affective and personality disturbance.

For the past twenty years women's complaints in the microelectronics industry have often been diagnosed as mass psychogenic illness, despite evidence of potential exposure to organic solvents, which have been associated with affect and mood changes. In the present study, the standard version of the Minnesota Multiphasic Personality Inventory (MMPI) was used to evaluate affective and personality disturbance among 63 former microelectronics workers (56 women and 7 men) over a two-year period of time. In both 1986 and 1988, the former workers obtained mean scale score elevations beyond two standard deviations above the normative sample (T = greater than 70) on the MMPI clinical scales of schizophrenia, hypochondriasis, psychasthenia, depression and hysteria. For most scales, 86-88 mean score differences did not attain the 0.05 significance level (two-tailed paired t-test) and no significant differences were observed for 86-88 comparison scale scores = greater than 70 (McNemar paired statistic). Although there were too few men to perform gender comparisons, men scored higher than women on 5 scales and all of the men had scores = greater than 70 on hypochondriasis, depression, hysteria, psychasthenia and schizophrenia. These findings reveal that these former microelectronics workers manifested affective and personality disturbances, consistent with organic solvent toxicity, which persisted over a two year period, indicating that they were not reactive, transient hysterical neurosis.

Pesticide exposure and neuropsychological impairment in migrant farm workers.

The chronic, long-term effects from exposure to many frequently used pesticides have yet to be fully documented. Migrant Hispanic farm workers who are the frequent victims of such exposures are rarely studied. A neuropsychological test battery was administered to 21 migrant farm workers acutely exposed to Phosdrin, Lannate and Maneb on two occasions, and to 11 controls matched for age, sex, education, socioeconomic status, and ethnicity. Results revealed that two years after the pesticide exposures, the exposed group was significantly more impaired than controls on tests of psychomotor speed, dexterity, and visuospatial memory. Disturbing emotional symptoms were reported with significantly greater frequency by the exposed group in comparison to controls. Results are consistent with the previously reported constellation of symptoms and neuropsychological deficits associated with pesticide exposure.

Neuropsychological impairment among former microelectronics workers.

Although chemicals posing potential neurotoxic hazards are commonly used in the microelectronics industry, there has been no systematic study of possible chronic nervous system effects in microelectronics workers. The objective of the present study was to assess neuropsychological functions of a group of former microelectronics plant assembly workers and a group of referents, using a matched pair design. During employment, the former microelectronics workers had been exposed to multiple organic solvents, including trichloroethylene, xylene, chlorofluorocarbons and trichloroethane. Referents were recruited from the same geographic region. From a pool of 180 former workers and 157 referents, 67 pairs were matched on the basis of age, sex, ethnicity, educational level, sex and number of children. Comparison of results on the subtests of the California Neuropsychological Screening Battery-Revised (CNS-R) revealed significantly lower performance by the former microelectronics workers on tests of attention/concentration, verbal ability, memory functions, visuospatial functions, visuomotor speed, cognitive flexibility, psychomotor speed, and reaction time (t-test for pairs or Wilcoxon Signed Rank p less than 0.05). No significant differences were observed for performance on tests assessing mental status, visual recall, tactile function and learning. This overall pattern of impairment is consistent with organic solvent-related chronic toxic encephalopathy, and possible early stages of dementia. These findings underline the need for more studies among workers currently or previously employed in microelectronics industries.

Affective and personality disturbances among female former microelectronics workers.

The production and manufacture of microelectronic components, carried out primarily by women workers, require extensive use of organic solvents. Affective and personality disturbances frequently have been associated with organic solvent toxicity. A group of women, former microelectronics workers (N = 70), primarily of Hispanic origin (77.1%) but raised in the United States, were evaluated for affective and personality disturbance with the MMPI. Profiles were analyzed, and diagnostic classification was performed blind. Results showed that (1) 85.7% of the profiles indicated abnormally high clinical elevations; and (2) MMPI profile classification revealed four clinical diagnostic groups: somatoform (24.3%), depression (15.7%), anxiety (28.6%), and psychotic (14.3%). These findings indicate significant psychopathology among these women, who formerly had worked in a microelectronics plant. The patterns of impairment present similarities to previous reports of organic solvent toxicity.

Comparison of the NES and CNS/B neuropsychological screening batteries.

Computer and hand administered neuropsychological tests are utilized in the evaluation of central nervous system changes associated with environmental or occupational exposure to neurotoxicants. This study compares the computerized Neurobehavioral Evaluation System (NES) developed by Baker et al., 1985, with the hand administered California Neuropsychological Screening Battery (CNS/B) developed by Bowler et al., 1986. Both batteries were designed for screening of the effects of neurotoxicants on the central nervous system and require less than one hr to administer. Both screening batteries consist of tests of: mood, word knowledge, attention, concentration, learning and memory and psychomotor and visuomotor and visuospatial abilities. They were administered in a standardized fashion to 106 subjects. Results indicate strong positive correlations for tests of word knowledge, moderate correlations for attention and concentration, while weaker correlations were obtained for tests of memory, psychomotor and visuomotor and visuospatial ability. The NES may be more useful for large epidemiological studies while the CNS/B appears more useful for individual screening and clinical studies.

Neurotoxicological evaluation of hospital sterilizer workers exposed to ethylene oxide.

Ethylene oxide is now frequently used to chemically sterilize heat-sensitive materials in the hospital setting. Previous reports of neurotoxic effects of ethylene oxide have been described in animals and humans. Recent reports suggest that cognitive deficits may be associated with chronic low-level ethylene oxide exposure. We undertook this study of hospital workers with chronic ethylene oxide exposure and compared them with a non-exposed control group in an attempt to detect neurological and neuropsychological abnormalities. Ethylene oxide breathing zone levels of up to 250 ppm in exposed subjects were reported. All evaluations were done without examiners' knowledge of exposure status of the subjects. The exposed group was found to have a statistically significant lower P300 amplitude, bilaterally hypoactive distal deep tendon reflexes and poorer performance on neuropsychological tests involving psychomotor speed. Exposed subjects acknowledged more symptoms and higher levels of depression and anxiety. Nerve conduction velocities and EEG spectral analysis were similar in both exposed and control groups as were scores on most psychological tests. Based upon this information and prior reports, ethylene oxide should be considered in a differential diagnosis of neuropsychological, peripheral and central nervous system dysfunction in workplace settings associated with ethylene oxide exposure.

Neuropsychologic "impairment" in a cohort of hospital workers chronically exposed to ethylene oxide.

Ethylene Oxide is widely used to sterilize heat-sensitive materials. Acute and chronic neurogenic effects to the central and peripheral nervous system in man and animals have been described. To assess the chronic, subtle neuropsychologic effects of ethylene oxide, we performed a cross-sectional study of 25 hospital central supply workers exposed to low levels of ethylene oxide and 24 unexposed control workers. Subjects were tested using a neuropsychological screening battery by examiners blinded to exposure status. Testing results were reviewed independently by two neuropsychologists without knowledge of exposure. Subject status was categorized as normal, "impaired," or disagreement (between the two neuropsychologists). There were significantly more subjects concordantly judged as impaired in the exposed group versus the control group (chi 2 (2) = 6.0861, p less than 0.05). Although limited by the cross-sectional study design and the global categorization, these findings suggest that CNS dysfunction and cognitive impairment may result from chronic ethylene oxide exposure in hospital central supply units.

An evaluation of the effects of lithium in the treatment of chronic alcoholism. I. Clinical results.

To evaluate the efficacy of lithium in chronic alcoholism, we enrolled 47 male alcoholics in a prospective double-blind two-period crossover study. Nineteen subjects completed the 6-mo study during which they received lithium and placebo each for a 3-mo period. Self-reported alcohol intake and social and psychological factors were monitored. Three subjects claimed that they did not drink during the study. Mean self-reported alcohol intake of the remaining 16 was less during lithium therapy but was also less during the first treatment period. Neither of these differences reached statistical significance. The nine depressed patients, diagnosed from their profiles of the Minnesota Multiphasic Personality Inventory did not consume significantly less alcohol and did not change scores for depression significantly during lithium therapy. We could not demonstrate the lithium therapy was of benefit in our group of alcoholic patients.