Elsevier

Neurologic Clinics

Volume 38, Issue 4, November 2020, Pages 853-865
Neurologic Clinics

Toxin-Induced Parkinsonism

https://doi.org/10.1016/j.ncl.2020.08.003Get rights and content

Section snippets

Key points

  • •

    Toxin-induced parkinsonism is a clinical syndrome of resting tremors, bradykinesia, and rigidity with postural instability resembling Parkinson disease but caused by toxins or drugs.

  • •

    Mercury has been implicated as having an association with Parkinson disease risk.

  • •

    The effects of Agent Orange on the development of parkinsonism are still being investigated, although more evidence seems to show a possible connection between the two.

There are several toxins that have been identified as causing

Manganese

Manganese exposure may occur in certain occupations, including miners, welders, steel work, battery manufacturing, intravenous (IV) drug use, long-term parenteral nutrition (IV sources of manganese are almost entirely retained),2,3 and the manufacture/use of Maneb (fungicide and polymeric complex that includes manganese).4,5 Ingestion of foods with manganese is the primary nonoccupational exposure source. These food sources include grains, dried fruit, vegetables, nuts, and tea.6, 7, 8

Mercury

Per a 2013 report, there were 1300 mercury exposures in the United States during that year with only 24 being classified as having moderate to major effects.17 Internationally, these rates are higher. There have been two large-scale exposures over the course of the last century, including incidents in Minamata Bay, Japan (1956) and in Iraq (1971).18 During the incident in Minamata Bay, mercury was dumped into the water and any ingested fish during that time contained methylmercury. In total,

History and Exposure

MPTP is the chemical that has been the most researched in regard to parkinsonism.1 The first reported exposures leading to parkinsonism were described in users of “synthetic heroin,” specifically 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP).13 MPTP was found to be a by-product of the synthesis of MPPP and some of the MPPP in use at the time was contaminated with it. Historically, study of MPTP suggested for the first time that environmental factors may play a role in the development of

History and Exposure

Organochlorines and organophosphates make up a significant portion of historical and current pesticides. Organochlorides were used regularly from the 1940s to the 1970s, although most of these have since been banned in the United States secondary to their neurotoxic effects. There are a few of these compounds still registered for use in the United States. One of the most well-known organochlorines is dichlorodiphenyltrichloroethane (DDT), which has not been consistently linked with PD risk. Of

History and Exposure

Paraquat is a bipyridyl herbicide that has been associated with idiopathic PD through several case-control studies.13,29 The chemical structure of paraquat is quite similar to MPTP. The chemical is widely used primarily for weed and grass control. The Environmental Protection Agency classifies this chemical as “restricted use,” making it only available to those that are licensed. In the United States, there are several safeguards in place with this chemical, including a blue dye, an added

History and Exposure

Rotenone is a naturally occurring pesticide that is regularly used as an insecticide and as an agent to kill fish.13 The compound is found is several plant species, including barbasco, cub, haiari, nekoe, and timbo.35 This compound was the first used as an insecticide in the 1840s.36 Rat models have shown that rotenone may cause elements of PD, including bradykinesia, postural instability, and rigidity. The effect is reproducible to the extent that rotenone-exposed animals have become the

History and Exposure

The effects of Agent Orange on the development of parkinsonism are still being investigated, although more evidence seems to show a possible connection between the two. Agent Orange was an herbicide and defoliant chemical that was most notably used by the US military as an herbicidal warfare tactic in the Vietnam War. Agent Orange was a mixture of two compounds, 2,4-D and 2,4,5-T. These compounds are both chlorinated phenoxy acids. The potentially dangerous compound in Agent Orange is actually

Clinics care points

  • 1.

    Acute-onset tremors, bradykinesia (slowing of movements), and rigidity should always be investigated as a toxin exposure.

  • 2.

    Isolate and stop the offending toxin.

  • 3.

    Hospitalize until a cause is known or the person is medically stable.

  • 4.

    Parkinsonism secondary to toxin exposure does not usually progress once the agent is stopped.

  • 5.

    Parkinsonism may not improve after stopping the agent; however, 10% to 20% may have improvement.

Disclosure

The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government.

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