Elsevier

NeuroToxicology

Volume 27, Issue 3, May 2006, Pages 315-326
NeuroToxicology

Manganese exposure: Neuropsychological and neurological symptoms and effects in welders

https://doi.org/10.1016/j.neuro.2005.10.007Get rights and content

Abstract

Manganese exposure reportedly may have an adverse effect on CNS function and mood. Sixty-two welders with clinical histories of exposure to manganese were compared to 46 matched regional controls chosen at random from a telephone directory. The following tests were given: Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III), Boston Naming, WRAT-3, Cancellation H, Trail Making Tests A and B, Auditory Consonant Trigrams, Stroop, Rey-Osterreith, Animal Naming, Controlled Oral Word Association (COWAT), Test of Memory Malingering, Rey 15-item, Fingertapping, Grooved Pegboard, Dynamometer, Visual Attention Test, Lanthony d-15 Color Vision, Vistech Contrast Sensitivity, and Schirmer strips. The controls were administered a shorter battery of tests and the Rey-Osterreith, Animal Naming and some of the subtests of the WAIS-III, WMS-III were not administered. Mood tests, given to both groups, included the Symptom Checklist-40, Symptom Checklist-90-R, Profile of Mood Scale, Beck Depression Inventory II, and Beck Anxiety Inventory.

Forty-seven welders and 42 controls were retained for statistical analysis after appropriate exclusions. Results showed a high rate of symptom prevalence and pronounced deficits in motor skills, visuomotor tracking speed and information processing, working memory, verbal skills (COWAT), delayed memory, and visuospatial skills. Neurological examinations compared to neuropsychological test results suggest that neuropsychologists obtain significantly more mood symptoms overall. Odds ratios indicate highly elevated risk for neuropsychological and neurological symptomatology of manganism. Mood disturbances including anxiety, depression, confusion, and impaired vision showed very high odds ratios. Neurological exams and neuropsychological tests exhibit complementarity and differences, though neuropsychological methods may be more sensitive in detecting early signs of manganism. The present study corroborates the findings of our previous study in another group of welders.

Introduction

Manganese (Mn) has been known as a neurotoxicant for more than 150 years (ATSDR, 2000). Manganese intoxication, sometimes referred to as manganism, is a condition whose symptoms may be indistinguishable from idiopathic Parkinsons disease (Racette et al., 2001). Symptomatic therapy is limited, with highly variable results, which may depend on the area of the brain damaged (Huang et al., 1998). Results of the reports of levodopa treatment, hoped to be of benefit (Chu et al., 1995) have been shown to be of no or transient benefit at best (Cook et al., 1974, Koller et al., 2004, Spencer, 2000, Lu et al., 1994). Other anti-Parkinsonian drugs such as amantadine and trihexyl phenidyl have been also shown to be ineffective (Cook et al., 1974, Spencer, 2000). Exposure to manganese from mining, working in manganese metal and alloy smelters, dry-cell battery production, working with fertilizers and fungicides containing manganese, and welding are examples of industrial work which may cause damage to the central and peripheral nervous systems which can be irreversible and progressive. In the United States, the health of between 68,000 and 185,000 workers is potentially adversely affected by manganese and its compounds (Tanaka, 1994). OSHA archives indicate that more than 500,000 persons are identified as having welding as their primary occupation, which includes carbon steel, mild steel, stainless steel, aluminum, and multitude metal alloys, among them manganese-based alloys (Racette et al., 2005a, Racette et al., 2005b).

Manganese is essential for the production of steel, which utilizes more than 90% of the world's mined manganese. Currently, steel alloy welding is likely to be the source of most cases of manganism, and is one of the leading causes of manganism. Enclosed space welding, common in the building of ships, bridges and train boxcars increase welder's exposure to manganese and other toxic fumes. In a current study of enclosed space welding, air monitoring in and around the vicinity of the welder showed that the welders and welder's helpers were consistently exposed to manganese levels above the 2003 proposed TLV of 0.03 mg/m3 and often above the current TLV of 0.2 mg/m3. In addition, respirable manganese was consistently higher for welder's helpers (Harris, 2002). Current reports on health effects are increasing rapidly. Manganese is contained in the welding fluxes (or coating on welding rods or welding wire). Though there are approximately 80 different types of welding processes used in manufacturing, manganese is present in most welding fumes. The fume comprises vaporized metal that oxidizes on contact with oxygen. The toxicity of the fume is related to the toxicity of the vaporized metal and other materials and or gases present. In addition to manganese, silica and various other metals are often found in welding fumes among which are lead, chromium, nickel, iron, cadmium, zinc, and copper. Welding also produces several toxic gases among which are ozone, carbon monoxide, nitrogen oxides, phosgene, and fluoropolymer pyrolysis products (Behrman, 1997). The possible additive/synergistic adverse effects of the toxic compounds in welding fumes are not well understood; however, some of the symptoms and signs seen in welders are similar to those in workers in other occupations who have over-exposure to manganese.

The signs and symptoms of manganese intoxication were first described by Couper (1837), who observed that workers inhaling manganese oxides in the process of grinding pyrolusite ore (MnO2) had developed changes in speech and gait. In the 1940s and 1950s, Chilean manganese miners with symptoms of the disease were said to have “manganese madness” characterized by emotional liability, postural instability, and frequent hallucinations (Schuler et al., 1957, Mena et al., 1967, Penalver, 1955). The exact mechanisms underlying the mood deregulation are not fully understood, however, depression is common. A recent neurophysiological study of manganese exposed welders which included EEG found that welders had increased abnormal theta and delta wave activity as opposed to controls, and is likely indicative of depression or fatigue (He and Niu, 2004).

The earliest signs of intoxication can be subtle, and include behavioral changes, fatigue, poor sleep, mood changes, and changes in appetite. The onset can be insidious or gradual and similarly, the illness can develop after weeks, months, or years of exposure. Manganism has been known to manifest years after exposure to the metal or manganese compounds has stopped (Cook et al., 1974, Bernheimer et al., 1973, Cotzias et al., 1968). There is some evidence that in the early stages of intoxication, symptoms may be reversible (Roels et al., 1999). Intensity of exposure as well as individual susceptibility are factors in the onset of the disease. Even at its earliest stages, neuropsychological testing may detect deficits (Roels et al., 1987, Roels et al., 1992, Tanner, 1992, Feldman, 1999, Bowler et al., 2003b). It has been found that psychomotor testing of workers exposed to inorganic manganese is of greater sensitivity than a standardized neurological examination for the early detection of central nervous system deficits. Decreased visual reaction time, audio-verbal short-term memory, and hand–eye coordination were measurable on testing (Roels et al., 1987, Roels et al., 1992, Mergler et al., 1994). It has also been found that early stage neuropsychological testing can detect significant increases in tremor, mood disturbance, sexual dysfunction, and possible memory and intellectual loss (Roels et al., 1987, Iregren, 1990, Wennberg et al., 1991, Mergler et al., 1994, Bowler et al., 2003b, Hochberg et al., 1996).

More noticeable and overt signs and symptoms of manganese toxicity can include aberrant, sometimes compulsive behavior and emotional deregulation, in particular clinically significant levels of tension, hostility, and hallucinations. These symptoms can either precede or accompany the typical Parkinsonian signs of tremor, masked face, gait disturbance, increases in muscle tone (rigidity), slowed body movements (bradykinesia), loss of postural balance, and difficulty initiating movements (Barceloux, 1999, Huang et al., 1998). At this stage, a clinical case series of 76 welders showed significantly lower scores than controls on tests of verbal learning, working memory, cognitive flexibility, visuomotor and visuospatial information processing, and motor efficiency (Bowler et al., 2003b) similar to an earlier report on workers by Hua and Huang (1991).

Despite some overlap in clinical presentation, some important distinctions between idiopathic Parkinson's disease and manganism have been found. Manganism has an earlier age of onset, with younger workers developing signs and symptoms sometimes soon after their over-exposure began (Sadek et al., 2003, Bowler et al., 2005). In manganism, intellectual loss has been noted in relatively early stages of the disease (Sadek et al., 2003, Bowler et al., 2005). With respect to the Taiwanese workers (Hua and Huang, 1991) an earlier report found neuropsychological deficits with impaired general intelligence, visuoperceptive impairment and defective manual dexterity in addition to slowed response speed. A more recent 10-year follow-up of these workers indicates that their symptoms worsened and they had “continuing deterioration of neurologic features … 10 years after cessation of exposure” (Huang et al., 1998). The dementing process in Parkinson's generally occurs late in the course of the disease. Early signs of dementing and intellectual loss are atypical in Parkinson's disease and may indicate the presence of another condition (Facca and Koller, 2003).

Manganese toxicity causes damage to cells in the basal ganglia, showing an affinity for the globus pallidus in particular, and to a lesser extent the caudate nucleus, putamen, subthalamus, midbrain tegmentum, and substantia nigra. There may be greater sparing of the substantia nigra than is seen in Parkinson's disease (Nelson et al., 1993, Shinotoh et al., 1997, Feldman, 1999). There are reports of substantial damage to the substantia nigra in Mn patients (Wolters et al., 1989, Bernheimer et al., 1973). This was also found in non-human primates experimentally exposed to manganese (Newland et al., 1989, Shinotoh et al., 1995, Olanow, 2004, Gupta et al., 1980).

For the present study, the opportunity arose to clinically assess a number of welders exposed to Mn-containing fumes, who reported adverse health effects, which they feared were related to their work. The primary objective of this study was to evaluate the welders’ health symptoms by a neuropsychological and neurological examination, and to determine if the findings in this group corroborate those obtained previously in a different group of welders by using a shorter neuropsychological screening battery (Bowler et al., 2003b). A second goal was to determine if an association could be established between the lengths of time of the workers’ exposure to manganese and various neuropsychological and neurological variables.

Section snippets

Materials and methods

All of the welders (n = 62) had mental, medical, and neurological complaints that prompted physician/neurologist referrals to the principal investigator (RMB) for a comprehensive clinical neuropsychological and neurological evaluation. All but four welders are no longer actively welding.

Demographic characteristics

Demographic characteristics of the final group of 47 Mn-exposed welders and 42 regional controls are shown in Table 2. All were men and there was no significant age difference between the exposed and control participants. All but four of the exposed welders are no longer actively welding. Mean of education years in the exposed group was significantly lower than that in the controls. With regard to ethnicity, the exposed group also had a significantly higher percentage of non-whites than the

Discussion

In this report of a clinical case series, it is important to note that the group of welders that participated in the study constituted a sample of welders who had been adversely affected as assessed by their referring physicians. The welders had very lengthy, primarily unprotected exposure to manganese fumes, which has been shown in other studies to cause a neurologic/neuropsychiatric syndrome (Racette et al., 2001, Bowler et al., 2003b). None of the welders had other significant chemical

Note added in proof

Although funding for the clinical assessments of participants was provided by the attorneys representing these plaintiffs, no funding was provided for the computerization and analysis of the data or the writing of this manuscript. Rosemarie Bowler discloses having been a consultant and providing expert consultation to the plaintiffs. Part of this work was presented at the International Conference of the International Neuropsychological Society 2004 (Baltimore, MD) and was totally independent of

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    This work was presented at the conference entitled Health Effects, Clinical Research and Industrial Hygiene Issues in Occupational Exposure to Manganese held April 17 & 18, 2004 in New Orleans, LA.

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