Chemicals and the Nervous System — The Dana Guide

by Herbert H. Schaumburg

March, 2007

sections include: the many types of neurotoxic diseasesspecific chemicals and their effectsdiagnosis and treatment 

Neurotoxicology is the medical specialty that deals with the unwanted effects of chemicals on the nervous system. In the United States and Canada, most adults with serious neurotoxic disease are showing the side effects of either prescribed drugs, substance abuse, or suicide attempts involving neurotoxic chemicals. People can also contract neurotoxic disease from biological poisons (venoms, fish toxins, toxic plants) and from occupational and environmental chemicals, but such illnesses are uncommon in North America. For children, most neurotoxic problems arise from unknowingly ingesting hazardous household substances. (Neurotoxicology is also a specialty of veterinary medicine, and in that field the most common toxins are plants.)

The Many Types of Neurotoxic Diseases

A substance’s potential damage to our nervous system depends on its chemical makeup. Toxins that are fat soluble or have certain ionic structures readily penetrate our brains and nerves. Others, especially large complex molecules, cannot easily pierce the blood-brain barrier. Some neurotoxic chemicals, once they have entered the nervous system in large amounts, spread widely and produce generalized effects; for example, strychnine causes epileptic seizures, and many organic solvents cause coma. Other neurotoxic agents attack only specific groups of cells or fibers and produce local effects; the designer drug MPTP destroys the pigmented nerve cells of the midbrain and causes a form of Parkinson’s disease, while vincristine and other anticancer drugs primarily affect nerve ends and cause numbness of the hands and feet (peripheral neuropathy). Stated simply, there is no single type of neurotoxic disease.

Many toxins disrupt the chemical balance and functioning of nerve cells without actually destroying their architecture. Some of these substances cause problems primarily in the central nervous system (CNS): people may become confused and delusional (as with phencyclidine, better known as PCP), turn drowsy or even comatose (heroin), display cognitive impairment (bromine), or have seizures (tetanus). Other toxins of this sort act primarily on the peripheral nervous system and produce paralysis (botulism) or abnormal sensations (ciguatera fish toxin).

Another class of neurotoxins actually degenerates the structure of nerve cells. This damage can occur in the CNS (as with mercury) or peripheral nerves (acrylamide monomer). However, neurotoxins rarely destroy large focal areas of the nervous system. Most chemicals that trigger structural damage to the nervous system produce a consistent pattern of disease that closely matches the dose and duration of exposure.

A person may develop different neurotoxic illnesses from exposure to the same chemicals at different levels. Short-term inhalation of large amounts of the solvent n-hexane may end in a fatal coma, while exposure to lower levels for weeks can cause severe peripheral neuropathy with no CNS symptoms. A few substances produce multiple illnesses following one exposure; for example, exposure to some organophosphates may produce a sudden (sometimes fatal) paralysis by inhibiting the action of acetylcholinesterase and, two weeks later, peripheral neuropathy.

We cannot reliably predict a substance’s neurotoxic potential from its chemical formula. Substances with similar chemical structures may have very different effects on our nervous system. Physicians familiar with the side effects of acrylamide monomer, a potent neurotoxin, have needlessly alarmed workers who handle acrylamide polymer, an innocuous substance. Each new chemical created for the workplace or environment must therefore undergo rigorous laboratory testing in tissue culture or experimental animals before it is marketed. Sometimes this screening does not detect neurotoxicity, however, and there are unexpected outbreaks of disease. Failure to detect toxicity in the laboratory usually happens because the experiments were not conducted at the appropriate dose and duration or because of biological differences between humans and animals.

To further complicate matters, a chemical with no known neurotoxic effects may either enhance or depress the toxicity of a neurotoxic agent. This phenomenon was exemplified by a mini-epidemic of peripheral neuropathy among paint sniffers in Berlin. The solvent these people inhaled originally contained the potent neurotoxin n-hexane, but at a harmless level. The manufacturer reformulated the solvent, introducing another nonneurotoxic chemical, methyl ethyl ketone, and lowering the amount of n-hexane further. Several sniffers then developed severe neuropathy. Subsequent animal studies disclosed that while methyl ethyl ketone did not itself cause neuropathy, it made n-hexane more toxic. Such chemical interactions have become an emotional issue, as many fear the mixtures at hazardous waste sites. However, any modulation of a neurotoxin’s effect by another chemical should be reproducible in a laboratory.

Specific Chemicals and Their Effects

Many people worry about the effects of substances they encounter at work or in their other environments. Some of these chemicals can indeed be toxic to our nervous systems, but only after unusually high-level or prolonged exposures. Casual contact with solvents, pesticides, and heavy metals is not associated with nervous system dysfunction.

Some medications can cause neurotoxic effects at customary doses (anticancer and psychiatric drugs), while others can do so only after being administered at unusually high levels (antiepilepsy, antibiotic, and anti-HIV agents). Megadoses of vitamins can also be neurotoxic. In contrast, minute doses of some venoms and potent microbiological agents, such as a form of botulinum, can cause severe, sometimes fatal, nervous system dysfunction.

The list of proven or presumed neurotoxins numbers more than 440 chemicals, and we will doubtless identify more. The table on page 621 includes some of the most common. In looking at these substances, you must remember that in most cases a person must take in a high dose to suffer damage. And all the artificial chemicals listed have their uses, often important ones.

Diagnosis and Treatment

When a person seeks help for a neurological problem, the physician’s first task is to minimize any acute symptoms or immediate danger. The second step is to determine the reason for the problem. In diagnosing a neurotoxic disorder, doctors must rule out other conditions that can cause the same symptoms. The signs and symptoms of neurotoxic diseases may mimic naturally occurring diseases, such as uremia from kidney failure, Parkinson’svitamin deficiency, and diffuse demyelinating diseases (leukodystrophy).

The key to diagnosis is a complete and accurate history of the person’s symptoms—when they appeared, how strongly, and with what connection, if any, to neurotoxins. Doctors who have prescribed medications that can affect the nervous system are usually on the alert for their side effects. Similarly, physicians are reasonably familiar with the syndromes of exposure to well-known industrial chemicals.

A more trenchant problem is posed when a person’s history of chemical exposure is unclear. For example, cognitive impairment and jerking movements are characteristic of Creutzfeldt-Jakob disease, a naturally occurring prion disorder. The same symptoms may also result from taking long-term doses of antacid preparations containing bismuth. A person suffering these symptoms may not mention a common over-the-counter antacid to his or her doctor. Special toxicology tests are helpful in confirming some diagnoses, especially those involving heavy metals (mercury, lead, arsenic) and overdoses from substance abuse (alcohol, cocaine, heroin). For many pharmacological and industrial agents, however, there are no tests. Also, relatively few neurotoxins stay in the body for weeks, so by the time a person sees a doctor the exposure may be long over. Because most neurotoxins do not cause large areas of destruction, brain imaging techniques usually show nothing amiss; these tests are most useful for ruling out other conditions. 

Neurotoxic illness generally improves after a person stops being exposed. Improvement can be rapid (in hours or days) if the toxin caused only biochemical or pharmacological changes, as in snakebites and illegal-drug overdoses. If structural alterations have occurred only in the peripheral nervous system, as with many anticancer drugs, recovery may be slow and incomplete because nerves regenerate at the rate of only eight hundredths to one tenth of an inch each day. If CNS cells have been damaged or destroyed, the recovery will be poor and incomplete. 

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