Environmental Contamination Linked to Neurologic Disorders

Daniel M. Keller, PhD

November 12, 2019

DUBAI, United Arab Emirates — Airborne chemical contamination is a major environmental risk factor worldwide and contributes significantly to many diseases, including neurologic diseases.

Here at the XXIV World Congress of Neurology (WCN), a session on the environment and neurology explored the link between environmental contamination and neurologic disorders.

Environmental pollution is considered the third greatest contributor to disability-adjusted life years (DALYs) due to stroke, as supported by observations of seasonal, diurnal, and geographic variations in stroke incidence. Strokes track very closely with and soon after increases in conjunction with levels of carbon monoxide, sulfur dioxide, nitrogen dioxide, and fine particulate matter (≤2.5 μm).

The World Health Organization (WHO) has estimated that 90% of the world's population breathes air that exceeds WHO contamination limits. The Global Burden of Diseases study 2015 estimated that 898,100 cerebrovascular disease deaths and 19.2 million DALYs were attributable to ambient particulate matter air pollution.

Air pollution accounts for nearly 30% of global stroke burden, with the greatest effects in low- and middle-income countries. In these countries, much of the pollution is within households as a result of incomplete combustion of fuels for cooking and heating.

Long-term exposure to airborne contaminants results in accelerated carotid atherosclerosis, damage to vascular endothelium, increased sympathetic nervous system activity, vasoconstriction, increased blood pressure, and thrombosis. Acute exposures affect cerebrovascular hemodynamics and vascular resistance, with reduced blood flow and atrial arrhythmia. Not only are these exposures important risk factors for neurodegenerative diseases, but they also play a role in neurodevelopmental disorders.

Even solid particles in the environment can affect the nervous system. It has been documented that solid plastic nanoparticles work their way up the food chain; they are ingested by algae, which are eaten by daphnia, then spread to fish, disrupting the function of ecosystems all along the way. Eventually these particles end up at the top of the food chain, including humans. They are small enough to cross the blood-brain barrier.

Contaminant concentration occurs up the food chain. The now banned insecticide DDT (dichlorodiphenyltrichloroethane) could be found in water at 3 parts/trillion in past years. It spread from zooplankton to small fish to larger fish and ended up in the tissue of fish-eating birds at 25 parts/million ― a more than 8 million–fold increase. DDT and other endocrine disrupting chemicals  affected birds in various physical and behavioral ways, culminating in reduced reproductive success.

Endocrine Disruptors

Endocrine disrupting chemicals (EDCs) may be pesticides, solvents, pharmaceuticals, metals, ingredients in household products, or industrial ingredients. Gustavo Román, MD, professor of neurology at Houston Methodist Hospital, Texas, told delegates that EDCs are ubiquitous in the environment.

Some organophosphate pesticides and polychlorinated biphenyls used in plastics, electrical transformers, and adhesives have been banned. But bisphenol A is still used in plastic coatings in some food containers and other products. Phthalates are in soft plastics, including squeeze toys that toddlers chew on, as well as in cosmetics, body washes, and more items that people apply to their skin and in containers that people drink from.

Phthalate concentrations may be particularly high in young children because of their teething behavior as well as dermal absorption from lotions, powders, and shampoo. These chemicals have also been linked in the general population with asthma, breast cancer, obesity, diabetes, male infertility, delayed cognitive development, attention deficit disorder, and autism, Román said.

Autism Rates

For children born after 1987, rates of autism have increased eightfold; by comparison, there has been a 1.8-fold increase in rates of all other childhood developmental, neurologic, or psychiatric disorders. The neuropathology of brain development in autism involves altered neuronal migration that affects the cerebral cortex and cerebellum, and thyroid hormone is critical for proper development of the cortex.

Thyroid hormone deficiency in utero and in the early postpartum period may lead to mental retardation, psychomotor delay, and deafness. Iodine intake is essential for thyroid hormone production, and iodine deficiency has been increasing in women of childbearing age in the United States and Europe.

Besides iodine deficiency, several EDCs can affect thyroid function. These antithyroid agents, which include polychlorinated or polybrominated biphenyls, perchlorate, mercury, and coal derivatives, contaminate water supplies and foodstuffs.

Many herbicides, plant isoflavonoids, and constituents of soy and many other plants interfere with enzymes involved in thyroid hormone production; they also interfere with thyroid function itself or act on the hypothalamic-pituitary-thyroid axis. Severe maternal hypothyroxinemia during a critical period of fetal development has been associated with an almost fourfold risk of giving birth to an autistic child.

Lack of dietary iodine is probably a factor for a minority of women. "Most likely what we are dealing with is the so-called neuroendocrine disruptors, plastics, a number of things," Román said. "So a number of factors in the environment could be responsible for some of...these cases of autism that you never found a real reason for."

Wide-Ranging Effects of Climate Change

The health effects of climate change and its causes go far beyond acute and chronic diseases. The effects are pervasive, long lasting, and act at the "planetary level," Jacques Reis, MD, of the University of Strasbourg, France, who is chair of the Environmental Neurology Group of the World Federation of Neurology (WFN), said during the session.

On a global level, interaction occurs among the atmosphere, the geosphere (natural components of the planet), the biosphere, which consists of all living things, and the hydrosphere, which consists of all the waters of the earth above and below ground and as vapor in the air. Changes in these components are persistent and are often irreversible. It requires a great amount of time to assess their effects and their global impact, he said.

Commenting to Medscape Medical News, Reis gave an example of plastic nanoparticles taken up by algae, which are eaten by tiny crustaceans and eventually move up the food chain to fish, where "they damage the blood-brain barrier, and they produce changes in the behavior of the fish."

Another troubling example with more direct medical implications is the finding of metal particles in the brains of children who died in Mexico City from unrelated causes.

"So how it gets there, through the nose or following the pathway, is not very clear, but that may be the path that is followed by manganese particles in miners who end up having Parkinson's disease," he said. "So the brain is no longer the sacred, isolated organ. It can be affected by the migration of these smaller and smaller particles that get into the brain and induce inflammation...that then are accompanied by deposits of beta amyloid and tau proteins and inflammatory changes certainly."

He said the particles are so small that they are not stopped by the blood-brain barrier.

Overall, he painted a very concerning picture of a physical landscape affected by agricultural practices, industry, urbanization, transportation, deforestation, and the burning of fossil fuels. The threats to humanity are manifold: air pollution, climate change, dispersion of chemicals, infectious disease risks, antimicrobial resistance, and the spread of vectors, invasive species, and germs.

For many of these factors, the common link is human behavior. "Is there a breaking limit for recovery mechanisms, which has been crossed?" Reis asked.

Health Consequences of Environmental Changes

Direct consequences of environmental changes include injuries during severe weather events, heatstroke, psychological stress from weather events, release of chemicals and poisoning after weather events and industrial accidents, and infectious diseases after natural disasters. Although not solely attributable to air pollution, stroke is demonstrably linked to it.

Delayed and long-term consequences include outbreaks of bacterial, viral, and parasitic diseases related to climate change and to expanding ranges of vectors and reservoirs of disease agents. Similarly, some pathogens are reemerging in areas where they once were gone.

Among the neurologic consequences of environmental changes, epidemiology shows an increase in morbidity and mortality from neurovascular disease such as stroke and dementia; neurodegenerative disease such as Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis; neurodevelopmental conditions such as autism spectrum disorder and attention-deficit/hyperactivity disorder; and brain cancer related to ionizing radiation in childhood, nanoparticle air pollution; and acoustic neuroma related to mobile phones.

In addition, because so many drugs are based on natural products, loss of biodiversity may affect future drug discovery.

Reis said it is difficult to pinpoint in most cases any one culprit chemical in the environment. "When you put in the air particles, when you put germs, when you put the different compounds, and you add some...energy [from sunlight], you may produce new gases," he explained. "We have to face all this mixture of compounds, mineral, biological ones, chemicals produced by man."

In their talks, Román and Reis highlighted a multitude of environmental factors that can affect health and disease in general as well as neurologic conditions specifically, most of which do not have simple solutions.

Mitigating Health Consequences

"I think that there are many questions which are still unanswered. That's why we have a growing burden of diseases, neurodevelopmental diseases, and neurological diseases," session co-chair Mohammad Wasay, MD, professor of neurology at Aga Khan University in Karachi, Pakistan, who is secretary of the Environmental Neurology Specialty Group of the WFN, commented to Medscape Medical News. "Hopefully in the next 5, 10 years, we'd have very specific, precise mechanistic information, and then we'll be able to intervene."

Air and water contamination are particularly problematic for developing countries. Local, regional, and national governments can promulgate regulations to, for example, lower industrial or auto emissions or prohibit the burning of trash, but ultimately, advances will depend on public support for these efforts.

Wasay said that if "we are able to get to populations and we are able to get to media and politicians, things will change, like they have changed in developed countries." But he noted that even in those cases, it has taken a lot of advocacy efforts over decades to make significant advances. "But you know, where they have regulations, they have decreased mortality, they have better outcomes, they have longevity," he said.

There is also an economic argument to be made. "In my opinion, the cost of care is much, much higher as compared to changing the environment and preventing the burden," he said. "It's going to cost much less as compared to what...you end up spending on the healthcare and any rehabilitation of a stroke and cardiovascular patient, so it's better to prevent than just start spending money on treatment."

Positive economic factors include increased worker productivity and fewer days of work lost, as well as other societal gains.

Personal lifestyle factors also need to change for improving health, and Wasay said attitudes need to change early. "We have to educate our children about hygiene and health. So I think a lot of things are tying to the lifestyle and education at a very basic level."

The neurology profession is on the forefront of efforts to raise awareness of the connection between the environment in all its aspects to specific diseases and developmental abnormalities, as exemplified by the WFN having established a specialty group within it to focus on the environment, he said. So the question remains whether other medical specialties will also get on board.

"We [in neurology] are more interested because we are the hardest hit at this point," Wasay said. "But I think we have to work together with the whole World Health Organization...[the] United Nations, all the politicians and everyone."

There is still work to be done within their own specialty. The Environmental Neurology section of the WFN has new leadership, and Wasay said there are ambitious plans for awareness, advocacy, education, and research. One aspect of that research will focus on the role of nanoparticles in neurodegenerative diseases.

"One of our main targets is to just increase awareness among the neurology community and then reach out to all other health communities and then reach out to all other environmental activists, even human rights activists, media, and politicians, everyone," he said.

Román, Wasay, and Reis have reported no relevant financial relationships. Reis is a member of the Environmental Neurology Specialty Group.

XXIV World Congress of Neurology (WCN): Presented October 30, 2019.

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