Triorthocresyl phosphate and acrylamide are potent peripheral nerve toxins. Both of these drugs cause a dying-back polyneuropathy with axonal degeneration and have been used experimentally to produce this effect. Vacor, a phenylnitrosourea rodenticide, taken as a suicidal agent, gives rise to a profound sensory and autonomic neuropathy with abdominal pain and hyperglycemia caused by acute pancreatitis.
Detailed accounts of the clinical and experimental neurotoxicology of these agents can be found in the monograph by Spencer and colleagues.
A large number of medications are potential sources of polyneuropathy of predominantly sensory type. Most are dose-dependent and are therefore more or less predictable after large cumulative doses of the drug have been given (e.g., in cancer chemotherapy) or after prolonged administration for other reasons. A more complete list than can be compiled here can be found in the review by England and Asbury.
Antineoplastic drugs (See also Chap. 41.) Among chemotherapeutic agents in current use, particularly cisplatin, carboplatin, and bortezomib, are known to evoke a dose-dependent, predominantly sensory polyneuropathy, which begins several weeks after completion of therapy in at least half of the patients. Proprioception and vibratory sensation are most severely impaired. Some patients develop acrodynia and episodic color changes in the fingertips and toes suggesting that autonomic nerves are also involved; in severe cases there is sensory ataxia and pseudoathetosis. The severity of histopathologic changes in the peripheral nervous system corresponds to the concentration of platinum in these tissues, the highest being found in dorsal root ganglia. Secondary degeneration in the posterior columns is the basis for a Lhermitte symptom reported by some patients.
The taxanes paclitaxel and the more potent docetaxel, both cited as inhibitors of the depolymerization of neurotubules, are used mainly in the treatment of ovarian cancer. They produce a sensory polyneuropathy similar to that of cisplatin. The nerve lesion regresses slowly with a reduction in dosage. Pathologic studies have shown a neuronopathy and distal axonopathy affecting mainly large fibers.
For decades it has been known that peripheral neuropathy commonly complicates the use of vincristine, an antineoplastic agent most widely used in treatment of the lymphomas and leukemia. Paresthesias are the most common early symptom, and loss of ankle jerks is an early sign. Some degree of weakness usually precedes objective sensory loss; the extensor muscles of the fingers and wrists are affected; later the dorsiflexors of the toes and feet causing foot-drop become involved either early or late in the clinical course. With the dose regimens currently used, the weakness is usually mild, but in the past, some patients became quadriparetic and bedbound. Adults are more severely affected than are children, as are persons with preexisting polyneuropathies. The neuropathy is strictly dose-related and reduction in dosage is followed by improvement of neuropathic symptoms although this may take several months. Many patients are then able to tolerate vincristine in low dosage, such as 1 mg every 2 weeks, for many months. Thalidomide produces a similar sensory neuropathy. It is finding use in the treatment of inflammatory conditions such as Behçhet disease, graft versus host reactions, erythema nodosum, lepromatous eruptions, aphthous stomatitis in HIV patients and highly vascular tumors and certain tumors such as renal cell cancer.