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Diseases of the nervous system are known for their diverse clinical manifestations. When the central nervous system (CNS) is affected, symptoms may include headache, cognitive and psychiatric disturbances, visual changes, seizures, ataxia, tremors, rigidity, weakness, and sensory manifestations. In peripheral nervous system diseases, pain, weakness, paresthesias, and numbness are common, and in some instances there may be additional autonomic disturbances.
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The pattern of neurologic symptoms depends on the nature of the insult. For instance, excessive exposure to many industrial or environmental chemicals causes a generalized disorder of peripheral nerves, that is, peripheral neuropathy. This presents usually as a diffuse and symmetric clinical syndrome. In contrast, some occupations may predispose workers to physical injuries to peripheral nerves. Common examples are carpal tunnel syndrome from median nerve entrapment and lumbar radiculopathy from compression of the spinal roots. Single nerves or spinal roots are affected in these instances, leading to a localized pattern of neurologic symptoms and signs.
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Neurologic evaluation of patients largely depends on history and physical examination, supplemented by traditional diagnostic tests such as computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or spine, electroencephalography (EEG), nerve conduction study, electromyography (EMG), lumbar puncture, neuropsychologic testing, and specialized sensory testing (eg, audiology, color vision discrimination, olfactory perception). Toxicologic tests of blood or urine may provide evidence of recent exposures for some toxicants, whereas tests of hair or nail can sometimes clarify distant or chronic exposures. However, the increasingly common use of blood or urine testing to screen for low levels of metals and other toxicants without a clear toxicologic basis is of questionable value due to the lack of meaningful reference ranges and often unvalidated testing methods.
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With few exceptions, the pathophysiology of most neurotoxic injuries is not well understood. Animal models of toxin exposure provide at best a rough guide to human disease. Moreover, it is nearly impossible to study the effects of toxins under controlled conditions in humans. Much of our current knowledge is gained from clinical observations of intense exposures during accidents or chronic heavy occupational exposures. Extrapolation of these classic observations to other situations is problematic. For instance, for many compounds, there is considerable uncertainty concerning the exposure level and duration necessary to cause neurologic injury. It has been especially difficult to ascertain the sequelae of chronic low-level exposure, a situation particularly likely to be encountered by today’s physicians.
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Despite our incomplete understanding in many of these diseases, several generalizations have been useful in the clinical approach to these disorders.
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A dose-toxicity relationship exists in the majority of neurotoxic exposures. In general, neurologic symptoms appear only after an exposure reaches a time-dependent threshold level. Although dose-toxicity relationships may be multiphasic on a population level (eg, due to variation in genes encoding metabolic enzymes), individual susceptibility to most neurotoxicants varies over a limited range and ...