Mercury (Hg) exists in the environment as inorganic (metallic Hg vapor, mercurous and mercuric salts) or organic (bonded to a structure containing carbon atoms) forms. Neurotoxic effect of Hg is known for years. While the organic form (methylmercury (meHg)) led to the Minamata incidence in Japan and “wonder-wheat” disaster in Iraq, the “mad hatters” and “Danbury shakes” were related to the inorganic elemental form (Hg vapor). Human exposure to toxic Hg continues in the modern world to a large extent by artisanal gold mining, biomass combustion, chloralkali production, and indigenous medicine use to name a few. Heavy industrial use of Hg contaminates air and landfills, affecting the aquatic ecosystem and marine food chain. A detailed social and occupational history with a high index of clinical suspicion is required to not miss this toxic etiology for movement disorders like ataxia, tremor, or myoclonus. In this review, we have discussed the past and present global health impact of Hg from a movement disorder perspective. The connection of Hg with neurodegeneration and autoimmunity has been highlighted. We have also discussed the role of chelating agents and the preventive strategies to combat the neurotoxic effects of Hg in the modern world.

Organic mercury, especially methylmercury, poisoning causes chronic neurological disease predominantly affecting the brain. There have been documented exposures from eating fish from contaminated waters in Japan and in northwestern Ontario and in Iraq from eating bread made from seed wheat treated with methylmercuric fungicide. The neurological disease is called Minamata disease in Japan. Visual field constriction due to involvement of the calcarine cortex, sensory disturbance due to involvement of the somatosensory cortex, and cerebellar ataxia due to involvement of granule cell neurons of the cerebellum are common and characteristic features due to methylmercury poisoning. Other neurological features include dysarthria, postural and action tremor, cognitive impairment, and hearing loss and dysequilibrium. In contrast, peripheral nerve disease is more characteristic of inorganic mercury intoxication. Similarly, psychosis is more typical of exposure to inorganic mercury, which has been documented in the felt hat industry (“mad hatter”). Laboratory tests (e.g., on blood and hair and toenail samples) are of limited value in the assessment of chronic neurological disease due to mercury poisoning because they may not reflect remote neuronal injury due to mercury. Methylmercury also causes injury to fetal brains during development. There is no effective treatment.

Patients with damage to the cerebellum make reaching movements that are uncoordinated or “ataxic.” One prevailing hypothesis is that the cerebellum functions as an internal model for planning movements, and that damage to the cerebellum results in movements that do not properly account for arm dynamics. An exoskeleton robot was used to record multi-joint reaching movements. Subsequently, joint-torque trajectories were calculated and a gradient descent algorithm found optimal, patient-specific perturbations to actual limb dynamics predicted to reduce directional reaching errors by an average of 41%, elucidating a promising form of robotic intervention and adding support to the internal model hypothesis.

This study examined phonemic (letters), semantic (animals) and action verbal fluency cues in twenty-four patients with FRDA, and twenty matched healthy control subjects. The Action Fluency Test (AFT) is a newly-developed verbal fluency cue that consists in asking the subject to rapidly generate verbs. Given the high presence of dysarthria and cognitive slowness in FRDA patients, control tasks were administered in order to dissociate motor/articulatory impairment and cognitive slowness from verbal fluency deficit. Results showed that patients and control subjects performed similarly on the semantic fluency task. In contrast, patients performed significantly poorer on phonemic and action fluency tests. Correlational analyses showed that the deficits cannot be attributed to dysarthria or cognitive slowness. Although executive processes are necessary for initiating and monitoring all verbal fluency tasks, phonemic and action fluency may place a greater burden on strategic processes, given that they require a more unusual type of lexicon search. Thus, the deficits found occur in tasks that require greater executive/prefrontal control. This impairment might be the result of an affectation of cerebellum-prefrontal cortex connections, although the possibility of a primary prefrontal dysfunction remains to be investigated. (JINS, 2007, 13, 944–952.)