Clinical Applications
The diagnosis of a TxPN should be considered upon the following circumstances:
There is a suggestive history and the physical examination indicates a generalized, relatively symmetric PN;
There is no alternative medical explanation for the PN;
The onset timing, progression and improvement are consistent with the aforementioned tenets of neurotoxic disease;
The electrodiagnostic studies indicate a relatively symmetric distal axonopathy;
Appropriate testing demonstrates elevated body burdens, or clinical improvement clearly ensues after cessation of potential exposure.
The initial step in determining if a PN has a toxic etiology is to obtain a thorough occupational history. Determining the type, method and duration of neurotoxin exposure is critical. Patients may not be able to accurately determine the timing of their potential neurotoxin exposure in insidiously progressive TxPN. As such, the clinician should question the patient on any potential chronic, low-level, toxin intoxication, focusing on occupational, environmental and iatrogenic exposures. Consideration should be given to the individual habits of the patient regarding if and what protective devices are worn, and whether potentially contaminated work clothes are discarded before returning home. Other potential indicators or risk factors for intoxication include: eating in the workplace, especially if there is poor hand washing hygiene; the presence of other workers who are also manifesting similar symptoms; improvement of neuropathic symptoms when the patient is removed from the suspected toxin, including vacations and weekends; and inadequate workplace protection against intoxication, such as faulty ventilation and drainage, which may increase occupation exposure to a potential neurotoxin. An accurate determination of neurotoxicity may necessitate a visit to the home or workplace. Domestic exposure to neurotoxins or recreational substance abuse may go unreported unless a home visit is performed to examine food and water sources, home workshops and the contents of medicine cabinets. Inquiry should address recent potential pesticide exposure. The finding of concomitant similar symptoms among neighbors, family members or fellow workers should suggest the possibility of neurotoxic exposure. In rare cases, the presence of a neurotoxin is suggested by an unexplained illness in the household pet. Since neurotoxic and naturally occurring PN are often clinically similar, the investigator should not immediately jump to the diagnosis of TxPN. It is far more common for a PN from nutritional, metabolic, endocrine or hereditary degenerative conditions to be misdiagnosed as neurotoxic in etiology, than the reverse. Traumatic nerve and spine injury may mimic a toxic distal axonopathy if symptoms and signs are bilateral and symmetric. A detailed review of all recent medications, including alternative herbal treatments is critical in uncovering potential neurotoxin exposure. Unfortunately, there is no shortcut to diligently reviewing the potential adverse effects of a patient's medications, except to thoroughly examine the relevant PDR and related toxicology reports.
The physical examination can occasionally provide a clue to the underlying neurotoxin by nature of the clinical deficits. For example, PN plus a tremor and mild cerebellar dysfunction should suggest mercury intoxication, especially in the proper occupation setting. In general, a suspicion of a TxPN should be supported by a clinical exam that demonstrates a PN with relatively symmetric deficits, and with a severity commensurate with the degree and duration of toxin exposure. Neuropathies that are multifocal, or affect predominantly small fibers rather than large sensory fibers are unlikely to be neurotoxic.