Neuropathy: Answers Emerging?

Neuropathy has become a problem for many people with HIV infection, and can develop for a variety of reasons. Fortunately, it might be controllable with a number of promising treatments, many already available for other purposes.

The progression of HIV alone can apparently lead to two different disorders of the peripheral nervous system. One kind is a painful sensory dysfunction resulting from the degeneration of the axon, the component of nerve cells responsible for conducting impulses. The other, less frequent, neuropathy results in a motor weakness caused by an inflammatory process which damages the myelin covering the nerve fibers. This kind may resemble "myopathy," a discomfort or fatigue of muscle fibers, which is also identified with HIV or with long-term use of AZT.

Other possible causes of neuropathy include some opportunistic infections and tumors, as well as some of the drugs used in HIV/AIDS therapies (such as ddI, ddC, interferon and certain chemotherapies). Distinguishing the cause or type of neuropathy is important for deciding which treatment approach to take. Discontinuing a medication from which neuropathy has been known to result may resolve the symptoms completely, especially if done in a timely manner. But if an infection or medication is determined not to be the cause, nerve conduction tests may help with a diagnosis.

Much of the previous medical literature discussing neuropathy came from experimental approaches for the often painful neuropathy experienced by people with diabetes. Research into diabetic neuropathy has suggested a number of possibilities, and achieved some limited successes.

Among these are a number of treatments already licensed for other indications: piroxicam, plasmapheresis, calcitonin (nasal spray), capsaicin, antiarrhythmia drugs like mexiletine and lidocaine (intravenous), antidepressants such as nimodipine, imipramine, desipramine or fluoxetine, anticonvulsants like phenytoin, and narcotics for very painful neuropathy.

Some others, regarded generally as investigational agents, are coenzyme Q-10, gamma-linolenic acid, prostaglandin E1, and tolrestat.

We interviewed two physicians familiar with aspects of HIV-related neuropathy: Ari Ganer, M. D., of the Santa Clara Valley Medical Center, and Harry Hollander, M. D., at the University of California San Francisco.

Dr. Hollander told us that, although the rationales for trying some of these drugs theoretically would apply to HIV as well as to diabetic neuropathy, their side effects are not dependably uniform: a treatment reported to be safe in one situation might not be so in the other. He told us that antidepressants are usually tried first for symptomatic relief; if they fail, he follows with an anticonvulsant, noting that the course of neuropathy and the sequence of drug choices are variable for every patient.

Dr. Ganer and Dr. Stanley Deresinski are studying mexiletine to treat HIV-related neuropathy in a controlled clinical trial sponsored by a community-based research organization, the AIDS Community Research Consortium (ACRC). This trial is funded by the American Foundation for AIDS Research (AmFAR), and has two sites south of San Francisco, both of which are open to more participants. This study employs the "crossover" design, so that for the first half of the study, some patients will be given mexiletine, the others a placebo. After a short "washout" period, the placebo and active drugs are switched. Neither the investigators nor participants know when active drug was given until the study is finished.

Nevertheless, patterns are often apparent in crossover trials if the treatment is making a difference. Dr. Ganer said that he is encouraged by preliminary impressions of the study: some people have obviously experienced significant relief from the symptoms of neuropathy during part of the trial. The only measures of response in the study are the patients' reports of pain or pain relief.

Brian Camp, RN, the clinical coordinator of the Redwood City site, shared similar impressions, and hopes to see neuropathy studies expanded in scope and number.

Of the other agents discussed as potential treatments for HIV-associated neuropathy, Dr. Ganer thinks capsaicin is a good candidate for clinical trials, alone or in combination with mexiletine. Two pharmaceutical preparations containing capsaicin are already marketed for treating the discomfort of herpes zoster (shingles) lesions. Both are supplied as creams; one of them, Axsain, contains a 0.075% concentration of capsaicin, and the other, Zostrix, contains 0.025%. [Note: capsaicin is the component of hot peppers which makes them hot.]

If the mexiletine trial proves useful, Dr. Ganer hopes to expand HIV neuropathy trials to test capsaicin, or other agents. He remarked that surprisingly little attention has been paid to this common problem. The current trial is recruiting people with neuropathy resulting from HIV, but future studies will probably accept people with drug-induced symptoms as well. Persons interested in this study can contact the Santa Clara Valley Medical Center site at 408/299-5588, or the Redwood City site at 415/364-6563.

AmFAR has granted the ACRC funding for expanded trials. Of course, since mexiletine, capsaicin and some of the other possibilities mentioned above are already available by prescription, physicians and patients have access to those drugs now, without enrolling in a trial. Meanwhile, AIDS TREATMENT NEWS welcomes anecdotal reports of experience with treating neuropathy from our readers.

References

Parry, GJ, Kozu H. Piroxicam may reduce the rate of progression of experimental diabetic neuropathy. Neurology, volume 40, number 9, pages 1446-1449, September 1990.

Zieleniewski W. Calcitonin nasal spray for painful diabetic neuropathy. (letter) The Lancet, volume 336, number 8712, page 449, August 18, 1990.

Boulton AJ, Levin S, Comstock J. A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia, volume 33, number 7, pages 431-437, July 1990.

Nakamura Y, Takahashi M. Clinical application of prostaglandin on peripheral neuropathy. Nippon Rinsho, volume 48, number 6, pages 1224-1228, June 1990.

Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabetic Medicine, volume 7, number 4, pages 319-323, May 1990.

Kastrup J, Petersen P, Dejgard A. Intravenous lidocaine and cerebral blood flow: impaired microvascular reactivity in diabetic patients. Journal of Clinical Pharmacology, volume 30, number 4, pages 318-323, April, 1990.

Egbunike IG, Chaffee BJ. Antidepressants in the management of chronic pain syndromes. Pharmacotherapy, volume 10, number 4, pages 262-270, 1990.

Masson EA, Boulton AJ. Aldose reductase inhibitors in the treatment of diabetic neuropathy. A review of the rational and clinical evidence. Drugs, volume 39, number 2, pages 190-202, February, 1990.

Hollander, H. Peripheral neuropathy and HIV infection. AIDSFILE, volume 3, number 2, page 1, June 1988.

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