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Manuscript Title: Pesticide Exposure & Parkinson Disease: Unanticipated Sequela of An Attempted Suicide

Authors: Jonathan T. Grossman, D.O. ²; Asia Filatov, M.D. ²; Thomas C. Hammond, M.D. ^{1, 2}

Institutional Affiliations:

1. The Marcus Neuroscience Institute, Boca Raton Regional Hospital; Boca Raton, Florida
2. The Florida Atlantic University, Charles E. Schmidt College of Medicine; Boca Raton, Florida

Funding & Conflict of Interest: None

Corresponding Author: Thomas C. Hammond, M.D.

Pesticide Exposure & Parkinson Disease: Unanticipated Sequelae of An Attempted Suicide

Parkinson disease (PD) is a neurodegenerative disease with core features of tremor, bradykinesia, rigidity, and postural instability. Additional motor features include decreased facial expression (hypomimia), decreased blink rate, small handwriting (micrographia), stooped posture, shuffling gait with reduced arm swing, festination (increasingly rapid small steps), difficulty turning when walking, and difficulty turning over in bed [1]. PD is thought to evolve secondary to progressive loss of dopaminergic neurons within the substantia nigra pars compacta. Parkinsonism can be described as the sum of any of the aforementioned core motor features of PD irrespective of cause. While genetic predisposition appears to be the most significant risk factor for developing PD during one’s lifetime, the contribution of environmental exposures is an ongoing area of speculation and study. At present, it is presumed that environmental factors such as pesticide exposure could serve as a trigger for manifestation of disease in those with genetic susceptibility to PD. Specifically, an association with two commercial agrochemicals, paraquat and maneb, has been described. Paraquat is typically used during the growing process and maneb is applied following harvesting to prevent spoiling. Because the contribution of pesticides to the evolution of PD has been presumed to be dependent on both dose and frequency of exposure, a focus on farming/rural communities has emerged. Further, there is an absence of literature regarding ingestion of pesticide (intentional or otherwise) and its influence on conferred risk of developing PD. With the advent of modern farming practices, ingestion of commercially farmed produce is certainly a potential source of exposure for populations outside of farming/rural communities. Unfortunately, the mechanisms underlying neurodegeneration in PD are yet to be fully understood. The specific physiologic changes that occur with pesticide exposure/ingestion and their contribution to developing PD in genetically susceptible populations remains to be elucidated. In this case report, we describe the evolution of PD following an attempted suicide via intentional ingestion of pesticide.

Case 1

A 65-year-old male with past medical history significant for major depressive disorder and generalized anxiety disorder who presented to our clinic April 2019 for follow-up evaluation of resting tremor, postural imbalance that began November 2018. These symptoms began to evolve following an attempted suicide via intentional ingestion of 4 ounces of a liquid pesticide in January 2016. The specific agrochemical is unknown. He was hospitalized at that time following abrupt onset of ataxia, confusion, and seizures. Thereafter, he spent some time in a behavioral health facility. He was subsequently hospitalized February 2016 for evaluation of “jerking movements” of the upper and lower extremities. Notably, he endorsed noticeable tremor of the left hand prior to this intentional ingestion. Subsequently, in the years that followed, he developed slowness of movements, diminished facial expression, softened speech, and small handwriting.

Prior to ingestion, he endorsed taking alprazolam for many years to manage his generalized anxiety which he says eventually lost efficacy. In 2015, a year prior to ingestion, he attended a detoxification program in hopes of weaning himself from alprazolam. He was apparently successfully transitioned from alprazolam to a combination of olanzapine, bupropion, and clonazepam at the discretion of his psychiatrist. Still, his depression and anxiety persisted without improvement.

Almost 3 years following ingestion, his resting left-handed tremor progressed in intensity with eventual involvement of the right hand; albeit, the tremor remained most pronounced in the left hand. The bradykinesia, hypomimia, hypophonia, and micrographic handwriting all evolved following the evolution of bilateral tremor. He mentioned that he had taken ropinirole prior to November 2018 without clear benefit. Aside from the aforementioned Parkinsonian symptoms, he also reported persistent debilitating anxiety and sleep difficulties. He had been taking one teaspoon of “Kratom,” dissolved in water, approximately four times per day which reported did not provide resolution of, but at least enabled him to tolerate, both his anxiety and sleep difficulties. He had also tried sertraline for his depression and buspirone for his anxiety which he found largely ineffective. Upon his first evaluation at our clinic back in November 2018, he was prescribed combination carbidopa/levodopa and reports improvement in tremor, bradykinesia, and hypophonia since initiation.

The association between exposure to agrochemicals and their influence upon the development of PD in populations with known genetic predisposition continues to be explored. This case report presents a unique exposure history considering that this was a solitary, intentional ingestion. Most of the literature currently published describes a population with known frequency or dose-dependent exposure e.g. farmers, agricultural workers, or more simply those residing in rural settings. Notably, this individual endorsed history of resting tremor of the left hand which he appreciated years prior to ingestion. This piece of history could suggest that his PD was in its early evolution prior to pesticide exposure and that this exposure served as a potentiating factor, thereby accelerating the manifestation of inevitable disease. Although he had no known predisposing genetic profile, he did endorse a family history of PD in a paternal aunt.

Discussion:

Parkinson’s disease is a progressive nervous system disease that affects the movement of individuals. The symptoms of the condition start progressively. In some cases, it starts with a barely notable tremor in just one hand. According to the study conducted by Ahmed et al. (2017), tremors are common, but the disease usually causes slowing movement or stiffness. While the causes of PD are linked to the genes of an individual and environment factor, the use of pesticides has been highly linked as one of the major causes of the disease. Based on the symptoms and the history provided by this patient, it is apparent that the cause of PD in this case is the liquid pesticide that was intentionally taken by the patient. It is important to note that before the attempted suicide using the unknown pesticide, the client was only suffering from other diseases such as depression that do not present with symptoms such as ataxia, confusion, and seizures, and jerking movements that are particularly the symptoms of Parkinson’s disease. According to the study conducted by Wan and Lin (2016), low-levels exposure to pesticides interrupts the functions of the cells in a manner that impersonates the impacts of mutations that are known to cause Parkinson’s disease. On the same note, a study conducted by Elbaz et al. (2016) reveals that individuals that are exposed to chemicals, especially pesticides, are at about 250 percent at higher risk of getting the disease than the rest of the population. Additionally, higher exposure to such chemicals as observed in this patient can have a long term effect whose symptoms can be observed even after several years. It is in this context that it is concluded that although the patient’s case can be caused by certain factors on the environment, it is apparent that the symptoms started to show immediately the patient took the pesticide, one of the major cause of Parkinson’s disease