Manganese poisoning results from the chronic inhalation and ingestion of manganese particles and occurs in miners of manganese ore and in workers who separate manganese from other ore. Several clinical syndromes have been observed. The initial stages of intoxication may be marked by a prolonged confusional-hallucinatory state. Later, the symptoms are predominantly extrapyramidal. They are often described as parkinsonian in type, but in the patients seen by the authors, the resemblance was not close: an odd gait (“cock” walk), dystonia and rigidity of the trunk, postural instability, and falling backward were features seen in two South American miners. Others, however, have reported stiffness and awkwardness of the limbs, often with tremor of the hands, “cogwheel” phenomenon, gross rhythmic movements of the trunk and head, and retropulsive and propulsive gait. Corticospinal and corticobulbar signs may be added. Progressive weakness, fatigability, and sleepiness as well as psychiatric symptoms (manganese madness) are other clinical features. Rarely, severe axial rigidity and dystonia, like those of Wilson disease, are said to have been the outstanding manifestations. The emergence of an extrapyramidal syndrome from the use of illicit drugs that are synthesized with potassium permanganate has already been mentioned in relation to the cathionine stimulants. The differences between manganism and conventional parkinsonism have been reviewed by Calne et al.
Neuronal loss and gliosis, affecting mainly the pallidum and striatum but also the frontoparietal and cerebellar cortex and hypothalamus, have been described, but the pathologic changes have not been carefully studied.
The neurologic abnormalities have not responded to treatment with chelating agents. In the chronic dystonic form of manganese intoxication, dramatic and sustained improvement has been reported with the administration of l-dopa; patients with the more common parkinsonian type of manganese intoxication have shown only slight, if any, improvement with l-dopa.
Mercury poisoning arises in two forms, one caused by inorganic compounds (elemental or mercury salt) and the other, more dangerous, caused by organic mercury. The sources of potential exposure are reviewed by Clarkson. Among the organic compounds, methylmercury gives rise to a wide array of serious neurologic symptoms that may be delayed for days or weeks after exposure, including tremor of the extremities, tongue, and lips; mental confusion; and a progressive cerebellar syndrome, with ataxia of gait and arms, intention tremor, and dysarthria. Choreoathetosis and parkinsonian facies have also been described. Changes in mood and behavior are prominent, consisting at first of subjective weakness and fatigability and later of extreme depression and lethargy alternating with irritability. This delayed form of subacute mercury poisoning has been reported in chemical laboratory workers after exposure to methyl mercury compounds. These agents, particularly dimethylmercury, are extremely hazardous because they are absorbed transdermally and by inhalation, allowing severe toxicity to occur with even brief contact. In a fatal case of a chemist reported by
Nierenberg and colleagues, a rapidly progressive ataxia and stupor progressing to coma developed 154 days after exposure. Cerebellar function was most severely impaired, and visual function was affected.
The pathologic changes are characterized by a striking degeneration of the granular layer of the cerebellar cortex, with relative sparing of the Purkinje cells and neuronal loss and gliosis of the calcarine cortex and to a lesser extent of other parts of the cerebral cortex, similar to the Minamata disease cases described later.