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.
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, 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 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.
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 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-
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.
Copyright (c) 1991 - Gay Men's Health Crisis, Inc. All rights
reserved. Non-commercial reproduction is encouraged.
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