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Neuropathies in HIV Patients


GMHC Treatment Issues 1991 Jun 20; 5(5): 2

Peripheral neuropathy is usually characterized by a sensation of pins and needles, burning, stiffness, or numbness in the feet and toes. It is a common, sometimes painful, condition in HIV-positive patients, affecting up to 30% of people with AIDS. It is perhaps most common in people with a history of multiple opportunistic infections (OIs) and low T4 cell counts. The range of severity among patients with neuropathy is dramatic, from a minor nuisance to a disabling weakness. Additionally, the kinds of neuropathies occurring in people with AIDS are numerous and must be identified before appropriate treatment can be prescribed. The underlying cause of the most common type of peripheral neuropathy remains elusive and possibly attributable to a number of factors.

Most definitely, neuropathy has been a continuous problem for patients throughout the AIDS epidemic. The course of this elusive nerve damage has had its twists and turns. What was a common complaint early in HIV infection of severe neuropathy -- usually, burning feet, causing patients to walk on their heels -- has greatly diminished, according to practicing physicians. The decrease in such complaints may be attributable to the antiviral effects of AZT. On the other hand, new varieties of drug-induced nerve damage have been recognized in the use of antivirals like ddI and ddC. Underlying some of these changes are the commonly reported, sometimes overlooked neuropathies whose origins remain mysterious and are generally believed to be caused by HIV itself or by immunosuppression. Researchers have also identified cytomegalovirus (CMV) as a contributing factor in some kinds of neuropathy. This article overviews the different kinds of neuropathies in HIV disease and some of the treatment options available.

SENSORY NEUROPATHIES The most common type of neuropathy associated with AIDS is called distal symmetrical polyneuropathy (DSPN). This syndrome is a result of the degeneration of the nerves responsible for conducting impulses, and is characterized by numbness and a sensation of pins and needles. DSPN causes few serious abnormalities and mostly results in numbness or tingling of the feet and slowed reflexes at the ankles. It generally occurs with more severe immunosuppression and is steadily progressive. Treatment with tricyclic antidepressants, such as Elavil, relieves symptoms but does not affect the underlying nerve damage. Side effects to note when using Elavil include dry mouth, difficulty urinating, sweating, and drowsiness. Taking Elavil at night may offer relief and is a way for patients to sleep through these effects.

MORE SERIOUS NERVE DAMAGE A less frequent, but more severe type of neuropathy is known as acute or chronic inflammatory demyelinating polyneuropathy (AIDP/CIDP). In AIDP/CIDP there is damage to the fatty membrane covering the nerve impulses. This kind of neuropathy involves inflammation and resembles the muscle deterioration often identified with long-term use of AZT. It is sometimes the first manifestation of HIV infection, where the patient may not complain of pain, but fails to respond to standard reflex tests, such as vibrations or pin pricks on the toepads. This kind of neuropathy may be associated with seroconversion, in which case it can sometimes resolve spontaneously. It can serve as a sign of HIV infection and indicate that it might be time to consider antiviral therapy. AIDP/CIDP may be an auto-immune phenomenon, which means the body launches a kind of misguided attack on itself with disease-fighting antibodies.

AIDP/CIDP responds to treatment with steroids or plasmapheresis, a procedure in which blood is removed from a patient's body and returned again without antibodies. Physicians are often reluctant, however, to subject patients to plasmapheresis, which is time-consuming, potentially hazardous, and expensive. Additionally, the chronic use of steroids in immunosuppressed patients has well-known hazards, including aggravation of thrush and Kaposi's sarcoma (KS).

DRUG-INDUCED NEUROPATHIES Drug-induced, or toxic, neuropathies can be very painful. Antiviral drugs like ddI and ddC commonly cause peripheral neuropathy, as do vincristine (a drug frequently used to treat KS), Dilantin (an anti-seizure medication), high-dose vitamins, isoniazid (INH), and folic acid antagonists. Peripheral neuropathy is often used in clinical trials for ddI and ddC as a dose-limiting side effect, which means that more drugs should not be administered. Additionally, the use of ddI, ddC, and vincristine can exacerbate otherwise minor neuropathies. Usually, these drug-induced neuropathies are reversible with the discontinuation of the drug.

CMV-RELATED NEUROPATHIES CMV causes several neurological syndromes in AIDS, including encephalitis, myelitis, and polyradiculopathy. Polyradiculopathy, a rapidly developing, ascending paralysis that affects both hands and feet, is difficult to treat. Fuller et al have hypothesized that recognition of painful peripheral neuropathy (PPN) may help in the diagnosis of CMV infection, and allow for earlier initiation of treatment.

TREATMENT NOTES Neuropathy-related symptoms are very difficult to treat, since often the underlying cause of the neuropathy is not known. Two physicians with considerable experience in treating neuropathy spoke with Treatment Issues about practical approaches to treatment. General practitioner Dr. Dan Williams finds that Tylenol or Tylenol with codeine is clinically helpful for minor complaints. For neuropathies which are not controllable by mild pain relievers, he prescribes tricyclic antidepressants, and has had the most success with low-dose Elavil in gradually increasing doses. He has also tried anti-seizure drugs, such as Dilantin, but has had mixed results.

A neurologist, Dr. Josh Torgovnick prescribes treatment according to specific complaints. For burning he prescribes tricyclics, and for shooting pain, anticonvulsants, like Tegretol. For stiffness or pain in the calves, he uses Lioresal. He has tried topical preparations such as Zostrix, without success. Sometimes he prescribes opiates. Unlike Dr. Williams, Dr. Torgovnick does not hesitate to prescribe steroids for more sever neuropathy, specifically, AIDP/CIDP. He is also in favor of plasmapheresis. Torgovnick points out that sometimes what appears to be neuropathy may turn out to be standard tension- related muscular pain, which responds to antidepressants, massage, and sleep.

Essential to treating neuropathies is eliminating the possibility of other causes such as syphilis, vitamin B-12 deficiency, myelopathy, and neuropathies caused by drugs or drug interactions. Many patients with severe neuropathy require narcotics, such as codeine, Percocet, Dilaudid or morphine to relieve the pain. Physicians should not be reluctant to prescribe narcotics to these patients, since in most cases it is the only treatment that will relieve the pain. Problems to watch out for in these patients are narcotic dependence and the development of tolerance.

RESEARCH Research and treatment studies of neuropathy have traditionally taken a back seat to more pressing, life- threatening AIDS infections. Recently, however, that has begun to change. Researchers have looked to the medical literature concerning experimental treatments of painful neuropathy experienced by diabetes. Among the medications already licensed to treat neuropathy in diabetics are: piroxicam (Feldene), calcitonin (nasal spray), capsaicin (which is, by the way, the ingredient in hot peppers which makes them hot), the anticonvulsant phenytoin (Dilantin), antidepressants such as imipramine, desipramine, and fluoxetine (Prozac). Also drugs for cardiac patients, such as intravenous lidocaine and mexiletine seem to have some effect.

Mexiletine is the focus of a controlled clinical trial sponsored by the AIDS Community Research Consortium (ACRC) in Northern California, funded by American Foundation for AIDS Research (AmFAR). A derivative of lidocaine, originally an anticonvulsant and now used to treat an irregular heartbeat, mexiletine caught the attention of medical researchers when it appeared to resolve neuropathies occurring in cardiac patients. Among diabetics, mexiletine significantly relieved the symptoms of chronic, painful neuropathy.

In addition to conducting basic research on the interaction of mexiletine and AZT, ACRC is running a phase I, 13-week, placebo-controlled crossover study of HIV-related neuropathy. Patients in one arm of the trial will take drug for six weeks and then, after a one-week washout period (time off of the drug), will switch to placebo. The other group of participants will first take placebo and then switch over to drug. This study, conducted by Dr. Ari Ganer and Dr. Stanley Deresinski, is still seeking to enroll participants. Fifteen to 17 patients with moderate to severe neuropathy have been enrolled so far. Brian Camp is the coordinator of the study for ACRC and can be reached at (415) 364-6563.

Community Research Initiative (CRI), New England, meanwhile, is conducting a study of acupuncture as a treatment for HIV- related neuropathy. Also funded by AmFAR, the protocol excludes patients with ddI-or ddC-related neuropathy, unless they have been off the drug for more than two months. Those suffering from chemotherapy-related neuropathies are eligible. All participants will receive free acupuncture treatments twice weekly for up to six months. A neurologist will screen all participants upon entry, at six weeks, and again at six months. More than 25 people have been enrolled so far, and the maximum enrollment will be 40. Preliminary reports on the first ten to 12 people who have completed six weeks of therapy describe patients as having a subjective sense of improvement. One of the goals of this study is to convince doctors to consider acupuncture for treatment of chronic pain and to persuade insurance companies to reimburse patients for acupuncture. The coordinator is Dr. Cal Cohen who can be contacted at (617) 424- 1524.

CONCLUSION There is no question that neuropathy is one of the major problems in treating AIDS. It is an undeniable contributor to physical weakness, difficulty standing and walking, and overall disability. Long overshadowed by more serious and acute medical problems, neuropathy continues to assert a nagging need for attention to its elusive cause and a sure-fire treatment.

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Copyright © 1991 -Gay Men's Health Crisis, Publisher. All rights reserved to Gay Men's Health Crisis (GMHC) Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, INC. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011 Email GMHC. Visit GMHC

Information in this article was accurate in June 20, 1991. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.