Neurotoxin Exposure in the Workplace

Acute Encephalopathy

An acute encephalopathy is a common but nonspecific manifestation that may consist solely of headache and malaise that settle shortly after exposure is discontinued. With more severe involvement, symptoms may come to include confusion, irritability, poor concentration, impaired judgment, drowsiness, vertigo, tinnitus, sensory complaints, ataxia, weakness or fatigue, and nausea and vomiting. Neurologic examination is usually normal. Neuropsychologic examination may be abnormal but, because recovery is rapid and complete (usually within 24 hours), is rarely performed. With continued exposure, level of consciousness becomes depressed, sometimes leading to coma; seizures may also occur. Recovery is then likely to be more protracted and may be incomplete. The cause of this acute syndrome usually is easy to determine because of the history of exposure, because many workers are affected, and because a variety of other manifestations are common, such as conjunctival, mucosal, and cutaneous irritation, and respiratory difficulties.

Chronic Encephalopathy

The occurrence of a chronic encephalopathy relating to long-term low-level neurotoxin exposure is widely reported but of uncertain validity. Its symptoms include headache, “dizziness,” poor concentration, memory impairment, irritability, affective disorders, various sleep disturbances, loss of libido, numbness and paresthesias, and “weakness.” Such symptoms are nonspecific in nature, usually mild in degree, but may lead to surprising disability. Examination is typically normal, but ataxia and nystagmus are sometimes found; the results of laboratory and electrophysiologic studies are generally unhelpful or of questionable significance or relevance. Neurobehavioral studies may be abnormal, but often the findings are inconsistent, difficult to interpret in the absence of premorbid baseline studies, and of uncertain relevance. At present, then, whether such an entity truly exists—and its pathophysiologic basis—remains unclear.

Peripheral Neuropathy

Peripheral neuropathy is a better understood consequence of toxin exposure in the workplace. It may occur as a delayed effect of single high-dose exposure or after short-term repeated exposure to certain organophosphates, arsenic, or thallium. Chronic exposure to these and other neurotoxins, such as acrylamide and many organic solvents, also leads to neuropathy, causing that portion of the axon farthest from the cell body to degenerate, a phenomenon described as a distal axonal neuropathy or axonopathy , or a dying-back neuropathy. Its clinical features are similar to those of neuropathies of other etiologies. Symptoms and signs begin distally in the legs and then progress proximally depending on the severity of exposure. Sensory axons pass both peripherally to the limbs and centrally into the spinal cord; both degenerate toward the cell body. Some of the central sensory fibers ascend in the posterior columns to the cuneate and gracile nuclei in the medulla and, because of their length, are often among the first to degenerate. As regeneration does not occur in the CNS, recovery after axonal degeneration will be incomplete despite effective regeneration of the peripheral nerves.

The presence of abnormalities on general examination may help to suggest a toxic cause of the neuropathy. For example, sweating and bullous dermatitis of the hands is found in acrylamide toxicity, and scalp alopecia occurs with thallium poisoning.

In subjects who are chronically exposed to other neurotoxins in the workplace but who have no clinical deficit, minor electrodiagnostic abnormalities are sometimes found. Although these will not necessarily progress to clinical neuropathy, such subjects need careful monitoring to limit exposure and minimize any risk of progression.

Clinical Evaluation

An occupational history is an important part of the medical record, especially when patients with obscure neurologic disorders are encountered. Job titles may need clarification for the nature of an occupation to be appreciated. If exposure to toxins is suspected, a detailed list of chemicals used in the workplace—and at previous places of employment, if symptoms are longstanding—should be obtained. Details of the work environment are also important, such as whether it is well ventilated, the nature of any protective measures (such as a requirement to wear special clothing and gloves, and the use of other devices including masks and goggles), and the provisions made for washing after exposure and for storage of food. The most common routes of occupational exposure are inhalation and through the skin.

It may be necessary to question co-workers to determine whether they have similar symptoms to those of a subject with a suspected neurotoxic disorder, and even to examine those working in a similar environment. When asymptomatic but exposed co-workers are screened, questioning may be focused, based on the clinical features in recognized cases; self-administered, standardized symptom questionnaires may be especially helpful.

Neurotoxin exposure may also relate to environmental factors (such as a subject’s residence or its location close to, for example, an industrial plant) and to social and personal factors (such as hobbies, other recreational activities, or dietary peculiarities) rather than to the workplace. The history must therefore exclude these possibilities.

Routine neurologic examination is of limited utility for screening purposes, its principal role being to exclude other conditions that might underlie the patient’s symptoms. Generalized rather than focal neurologic abnormalities are the expected finding in many neurotoxic disorders. In some instances, however, focal findings—such as parkinsonism from manganese exposure—may be conspicuous. Techniques have been developed for quantifying aspects of the neurologic—especially the sensory—examination for screening purposes and for following changes over time. These include quantitative tests of muscle strength, coordination, body sway, balance, vibration and discriminative tactile sensibility, cold and warm thermal thresholds, and heat pain thresholds.

Electrodiagnostic Testing and Neuroimaging

Electroencephalography (EEG) and evoked potential studies can be used to assess CNS function. The EEG is commonly slowed diffusely—but occasionally more focally—in patients with acute toxic or metabolic encephalopathies, but may be normal in chronic encephalopathies. It is therefore of little use in screening patients for neurotoxic injury. Changes are nonspecific and do not distinguish between toxic and other encephalopathies or between different toxic disorders. Evoked potentials provide some measure of the functional integrity of certain afferent CNS pathways, but normal responses may show marked amplitude variation between subjects and on the two sides of the same subject. Because most neurotoxins produce axonal degeneration, which causes changes in amplitude rather than latency of responses, evoked potentials are of limited utility in evaluating patients with suspected neurotoxicity.

Electromyography (EMG) and nerve conduction studies evaluate the function of the PNS, neuromuscular junctions, and muscle. The findings help to identify subclinical disease, follow disease progression, and characterize the pathophysiologic basis of symptoms. Nerve conduction studies are useful in studying both axonal and demyelinating neuropathies. Needle EMG can indicate the cause of weakness and localize pathologic processes to different regions of the motor units (spinal cord, nerve root, plexus, peripheral nerve, neuromuscular junction, or muscle). When evaluating exposed workers, comparison with appropriate control subjects is important. For example, sedentary office workers should not be used as controls for manual workers, who frequently develop minor abnormalities of nerve conduction as a result of occupationally related, repeated minor trauma or subclinical entrapment neuropathies.

Neuroimaging of the CNS, when normal, does not exclude a neurotoxic disorder. In some instances, however, the findings may show characteristic abnormalities, such as in manganese poisoning, discussed later.

Neuropsychologic Evaluation

Advances in neuropsychologic test procedures have improved their utility as a screening device. Such test procedures may reveal subtle cognitive dysfunction but the findings are not diagnostic of toxic encephalopathy. Moreover, testing is time-consuming even when self-administered questionnaires and computerized test procedures are used, and thus costly and impractical for screening large numbers of subjects. Careful matching for age, gender, ethnicity, and social, cultural, and educational background is necessary when making comparisons between groups.

Other Laboratory Testing

Workers with possible occupationally related neurotoxic disorders commonly come to medical attention when exposure has already ceased and laboratory testing is of limited utility. With the exception of screening for heavy metal excretion in the urine or their presence in other tissues, laboratory studies are generally unhelpful in screening for neurotoxic disorders.