Neurotoxicity

What is neurotoxicity?

Neurotoxicity happens when exposure to natural or manufactured toxic substances (neurotoxicants) changes the function of any part of your nervous system. This could include your brain, spinal cord and/or nerves.

These changes can range from mild to severe. They may be treatable or long-lasting. In severe cases, neurotoxicity can lead to death.

Neurotoxicity may result from exposure to excess amounts of normally nontoxic substances, like certain medications. Or it can result from substances that are neurotoxic at all doses, like lead.

Neurotoxicity can happen during fetal development, child development or in adulthood. The severity is typically greater when neurotoxicant exposure happens during fetal development and early childhood. In addition, certain conditions increase your vulnerability to neurotoxicity, like hyperbilirubinemia (jaundice) in newborns and Charcot-Marie-Tooth Disease (CMT).

What are neurotoxicants?

There are hundreds of neurotoxicants. They can come in gas, liquid and/or solid form. For some neurotoxicants, trace amounts of them or a single exposure can cause symptoms. For others, only large amounts and/or repeated exposure cause noticeable symptoms.

Some examples of neurotoxicants include:

• Heavy metals, like lead and mercury
• Other naturally occurring substances, like carbon monoxide, arsenic and trichothecene mycotoxins from certain molds
• Pesticides, like organophosphates and chlorpyrifos
• Industrial and/or cleaning solvents, like tetrachloroethylene
• Manufacturing materials, like vinyl chloride, toluene, formaldehyde and polybrominated diphenyl ethers (PBDEs)
• Substances, like alcohol, amphetamines, opioids, inhalants and cocaine

Endocrine-disrupting chemicals (EDCs), like bisphenol A (BPA), phthalates and polychlorinated biphenyl compounds (PCBs), can also indirectly cause neurotoxicity.

Medications and neurotoxicity

Medications, like antibiotics and antipsychotics, for example, can also lead to neurotoxicity for a variety of reasons. But in many cases, their benefit far outweighs the risk of neurotoxic effects.

Cancer-related therapies often have neurotoxic effects, like these chemotherapy medications:

• Platinum-based agents (oxaliplatin, cisplatin, carboplatin)
• Taxanes (paclitaxel, docetaxel)
• Vinca alkaloids (vincristine, vinblastine)
• Proteasome inhibitors
• Thalidomide analogs

Radiation therapy may also lead to neurotoxicity by damaging your central nervous system.

How common is neurotoxicity?

There are so many neurotoxicants, and the symptoms of neurotoxicity vary considerably. So, it’s difficult for researchers to estimate how common neurotoxicity is. But researchers do consider neurotoxicant exposure to be widespread.

To highlight just two examples of toxins that cause neurotoxicity:

• One study estimated that 385 million cases of unintentional, acute (sudden and severe) pesticide poisoning happen every year worldwide, resulting in about 11,000 deaths.
• Each year, an estimated 1 million people die from lead poisoning. About 1 in 3 children — up to 800 million globally — have elevated blood lead levels.

What are the symptoms of neurotoxicity?

The symptoms of neurotoxicity vary widely depending on the type of neurotoxicant exposure. Symptoms can range from mild to severe. They may appear immediately after exposure or develop over time — over weeks, months or even years.

Examples of physical symptoms include:

• Coordination and balance problems
• Diarrhea
• Fatigue
• Headache
• Loss of appetite
• Pain disorders, like neuropathic pain
• Muscle issues, like weakness, spasms and twitching
• Nausea and/or vomiting
• Numbness
• Sleep changes, like insomnia
• Slurred speech (dysarthria)
• Vision issues or loss of vision

Examples of cognitive (mental) symptoms include:

• Behavioral changes or issues
• Cognitive decline, like mild cognitive impairment
• Dizziness or disorientation
• Executive dysfunction, like difficulty regulating your emotions and issues with attention and focus
• Increased aggression
• Memory loss
• Mood changes

If you notice changes in or issues with your or your child’s thinking, behavior, mood or physical health, it’s always a good idea to see a healthcare provider. While neurotoxicants may be the culprit, there are several other possible causes.

Emergency symptoms of neurotoxicity

There are many possible symptoms of acute (sudden and severe) neurotoxicity. They typically come on suddenly. If you have the following symptoms, you should seek emergency medical care. Call 911 or go to the nearest hospital.

Acute neurotoxicity symptoms can include:

• Changes in heart rate
• Confusion or delirium
• Loss of consciousness
• Psychosis, including experiencing hallucinations
• Seizures
• Significant changes in body temperature (hyperthermia or hypothermia)
• Sudden and extreme muscle weakness
• Sudden vision issues or vision loss
• Trouble breathing

What causes neurotoxicity?

Neurotoxicity happens when exposure to neurotoxicants damages, changes or kills cells in your peripheral or central nervous system. This often affects neurons (nerve cells). Neurons are essential for transmitting and processing signals in your brain, spinal cord and peripheral nerves. Other parts of your central or peripheral nervous system can also be damaged, like myelin.

Because your nervous system is a very intricate body system, neurotoxicity damage can present in many ways. A few examples include:

• Changes in neurotransmitter (like dopamine) levels and signaling
• Inflammation in your brain or spinal cord (neuroinflammation)
• Structural brain changes, like differences in grey matter and white matter volume
• Damage to the myelin sheath of peripheral nerves

Neurotoxicant exposure

Neurotoxicants may enter your body by or through:

• Breathing them in
• Consuming (eating or drinking) them
• Skin absorption

Neurotoxicants can also affect a fetus. If neurotoxicants enter a pregnant person’s body, they can transfer from the pregnant person’s blood to the fetus through the umbilical cord. Some medications are unsafe in pregnancy due to potential neurotoxic effects on the fetus.

Once neurotoxicants are in your bloodstream, they may cross your blood-brain barrier (BBB) and directly affect aspects of your central nervous system. Or they may indirectly affect your brain by altering other body systems, like in the case of endocrine-disrupting chemicals (EDCs).

Exposure to neurotoxicants can happen in multiple places because the sources of these toxins are widespread. You can experience exposure from:

• Broad environmental pollution from traffic, agriculture and industrial activities
• Local pollution in areas like parks and schools or from local chemical incidents
• Home pollution, like from household items or foods

What are the complications of neurotoxicity?

Some cases of neurotoxicity can result in chronic (long-term) neurological issues, and severe cases can lead to death.

Exposure to certain neurotoxicants during fetal development and early childhood has been associated with several conditions. Examples include:

• Attention-deficit/hyperactivity disorder (ADHD)
• Learning disabilities
• Depression
• Anxiety
• Schizophrenia
• Autism spectrum disorder (ASD)

It’s important to note that there’s a link between neurotoxicant exposure and these conditions. Researchers don’t know yet if neurotoxicity directly causes them. They’re actively studying all the possible effects and complications of neurotoxicants.

How is neurotoxicity diagnosed?

Because there are hundreds of neurotoxicants and the symptoms of neurotoxicity are wide-ranging, diagnosis may involve many tests and exams. Your healthcare provider will start by asking about your symptoms and medical history. They’ll then do physical and neurological exams.

They may recommend any of the following tests or exams:

• Behavioral assessment
• Blood tests
• Cognitive tests
• Electroencephalogram (EEG)
• Eye exam
• Imaging tests, like a brain MRI
• Nerve conduction study and electromyography (EMG)
• Neuropsychological testing and assessment
• Spinal tap for cerebral spinal fluid (CSF) analysis

In some cases, healthcare providers may be unable to find the exact cause of neurotoxicity symptoms.

How is neurotoxicity treated?

Treatments vary widely based on your symptoms and which neurotoxicant is the cause. In general, treatment involves eliminating or reducing exposure to the neurotoxicant, followed by treating or managing symptoms.

Can I prevent neurotoxicity?

It’s practically impossible to prevent all exposure to neurotoxicants due to how prevalent they are in everyday life. But there are some steps you can take to try to reduce your risk of exposure, like:

• Install a carbon monoxide detector in your home and change the batteries yearly.
• Never mix cleaning products or household chemicals. The results can be deadly.
• Have your house tested for lead and other harmful toxins.
• Keep your windows closed on days with bad air quality to prevent air pollution from getting into your house.
• Avoid using substances.
• If you’re pregnant, talk to your healthcare provider about neurotoxicant exposure and how it might affect fetal development.

It’s important to remember that preventing neurotoxicant exposure to you and your family isn’t just your responsibility — it’s the collective responsibility of federal and local governments, corporations and citizens. Groups like the NIEHS (National Institute of Environmental Health Services) are actively researching how the environment and neurotoxicants can affect human health.

What is the prognosis for someone with neurotoxicity?

The prognosis (outlook) for someone with neurotoxicity varies greatly depending on several factors, including:

• The type of neurotoxicant(s)
• The amount of exposure
• The length of exposure
• The extent of nervous system damage
• Your age and overall health

Exposure to certain neurotoxins can be fatal. In some cases, you may survive the exposure, but you may not recover all of your neurological functions. In other cases, you may completely recover after receiving treatment.