Neurological treatment of HIV patients can be tricky
Neurological treatment of HIV patients can be tricky
Experts offer guidelines to treating neuropathy
Antiretroviral therapy has reduced the incidence of AIDS dementia in recent years to about one-quarter of its previous level. But other HIV-related neurological problems are on the rise, due in part to the very same drugs that are keeping patients healthy longer.
HIV affects the entire nervous system, and peripheral nerve disorders have become the most common neurologic complication of HIV. The disorders greatly impact patients’ quality of life.1
"There are a myriad of peripheral nerve manifestations from AIDS, and added to these are the side effects of antiretroviral therapy," says Gordon Smith, MD, assistant professor of neurology at the University of Utah in Salt Lake City.
The greatest challenge for clinicians is to appropriately diagnose the neurological condition and to determine whether it’s caused by the disease or the treatment, says David Simpson, MD, an associate professor of neurology and director of the clinical neurophysiology laboratories, as well as director of the Neuro-AIDS Research Program at Mt. Sinai Medical Center in New York.
"There is a fair amount of neurological side effects of the antiretroviral drugs, and it can be particularly confusing because HIV itself is associated with a whole range of neurological complications," Simpson says.
Clinicians could begin by evaluating the symptoms and determining whether a patient has a history of alcoholism, hereditary neuropathies, and other problems. Also, they should treat the patient’s pain immediately.
Peripheral neuropathy typically causes patients a great deal of discomfort and pain, particularly as it progresses, so opiate medications often are necessary, Smith says.
"Most of these patients complain of pain in the feet, which starts off insidiously as burning, tingling pain and gradually becomes very severe," Smith says. "It tends not to cause weakness or motor dysfunction, but the pain can be debilitating enough that in the worst cases patients have a hard time walking."
"It’s very clear that most clinicians are not treating pain adequately," Simpson says. "Research shows that 85% of patients with AIDS are being undertreated for pain, according to World Health Organization guidelines."
Clinicians need to be aware of how painful and psychologically devastating the condition is to patients who experience it, says John Senneff, JD, a retired attorney who has peripheral neuropathy and has written a book offering guidance on treating and coping with the condition. The book, titled Numb Toes and Aching Soles: Coping With Peripheral Neuropathy, was published in 1999 by MedPress of San Antonio. Although Senneff doesn’t have HIV, he included a chapter in the book related to HIV patients who experience the condition.
Senneff’s condition began as a numbness in his toes. Since he was an avid jogger, he first attributed the pain to the aches and pains of his physical exercise. Then the pain progressed to the point that he had difficulty standing on concrete floors, and the pain would sometimes awaken him in the middle of the night.
"I’d get stabbing pains, particularly at night," Senneff says. "It was like a bolt of lightning hit my foot, and then 30 to 40 seconds later the bolt would hit again."
After years of misdiagnoses and ineffective treatments, Senneff reached the point that he thought he could have his feet chopped off and not miss them. Finally, he found an internist who suspected peripheral neuropathy as the problem and referred him to a neurologist who made the diagnosis. Now, thanks to medications, vitamins, and exercise, his pain has lessened and his quality of life has greatly improved.
Once clinicians help patients manage the pain, they can pursue other treatments, including antidepressants, anticonvulsants, and topical agents. One treatment for severe cases of neuropathy is plasmapheresis, a procedure in which the blood plasma, which contains the antibodies that attack the myelin sheath, is removed from blood cells by a cell separator and then the white and red blood cells are returned to the body. Clinicians also sometimes prescribe immunosuppressive therapy, such as azathioprine or prednisone or a chemotherapy medication called cyclophosphamide.
An expensive and less widely available therapy is IVIg, which is a high dose of gamma globulins containing antibodies that have immunity against disease. Nerve blocks also are used by injecting a local anesthetic or neurolytic into a peripheral nerve to decrease its activity. And some clinicians help patients alleviate pain through transcutaneous electrical nerve stimulation.
Some of the newer treatments under study include nerve growth factor, which promotes nerve cell growth, and Lidoderm, a topical anesthetic that can be applied in gel or patch form.
There are a variety of alternative therapies available, such as psychotherapy, biofeedback, physical therapy, acupuncture, reflexology, magnets for pain, and others. But Smith says he typically doesn’t prescribe a particular alternative therapy unless a patient expresses an interest in it.
Standard treatments work for HIV patients
HIV patients often respond to the same treatments for peripheral neuropathy as patients who don’t have HIV. And HIV patients have the same types of symptoms and pain as people who have the condition without a known cause. The only difference is HIV patients often are diagnosed with peripheral neuropathy much faster because clinicians are more aware that it could be a problem, Senneff says.
Plus, HIV patients are well-educated about their potential medical problems. "When their symptoms first appear, bells ring for them a little louder and they get to the doctor or neurologist faster than most people, who just sit back and think they have no reason to suspect they have a serious medical condition," Senneff says.
When HIV patients tell their doctors they have shooting pains or numbness in their limbs, it should signal a potential neurological condition, Simpson says.
"Clinicians need to know how to take the right history and ask the right questions," he says. "They need to assess the patient’s reflexes in the knees and ankles, use a vibration tuning fork, and use a pin to determine how the patient feels a pin prick."
Simpson says that clinicians often misdiagnose neuropathies, mistaking one type of problem for another. For example, they might call carpal tunnel syndrome an HIV neuropathy, when it’s an entirely different problem. "Just because a person has HIV doesn’t mean all their problems are because of HIV," he notes.
Here are guidelines to some of the neuropathies associated with HIV/AIDS:
• Distal symmetrical polyneuropathy. This is the most common and important condition, and it’s usually seen in the late stage of the disease when the CD4 cell count is below 200 cells/mm3, Simpson says. It may be caused by the infection itself; neurotoxic drugs, such as didanosine, zalcitabine, and stavudine; or a vitamin B12 deficiency.
"Patients will complain of numbness, tingling, pins-and-needles types of sensation, and they often have severe pain that begins in their toes and feet and moves up the legs, later effecting the fingertips and hands," Simpson says. "It feels like the sensation when the feet fall asleep, an uncomfortable numbness and burning sensation."
Patients might have these symptoms continually, and they sometimes will reach the point of not being able to walk or put on shoes and socks.
Drug-related neuropathy easily resolved
If the patient’s neuropathy is caused by a drug, there typically will be an acute onset and immediate pain, with symptoms beginning from eight to 20 weeks after initiation of drug therapy. Also, the condition usually will go away when the medications are stopped.
Clinicians may treat HIV-related distal symmetrical polyneuropathy with nonsteroidal anti-inflammatory agents, acetaminophen, or salicylates. Common pain treatments include tricyclic antidepressants, including desipramine or amitriptyline. Simpson also has found anticonvulsants, such as carbamazepine, phenytoin, or lamotrigine, can provide relief to some neuropathy patients.
Patients also should be instructed to correct vitamin deficiencies, abstain from abusing alcohol, and control diabetes mellitus, if any of these problems are present.
If a clinician believes a patient’s condition is due to medications, then the first line of treatment might be to try alternative drug therapies. If the drugs are the culprit, the neuropathy symptoms should be resolved after a coasting period of up to 19 weeks.
• Mononeuropathy multiplex. Sometimes occurring early in HIV infection, this is a limited sensory or motor deficit in one or more nerves.2 Patients may have asymmetric neurologic signs, facial weakness, and symptoms of a foot dropping or wrist dropping. They sometimes have cranial neuropathy.
When the condition is more extensive, it may be a result of cytomegalovirus (CMV) infection in immunocompromised patients. This condition has been associated with Horner’s syndrome, which is when the patient’s eyeball sinks in and there’s a narrowing of the palpebral fissure due to a paralysis of the cervical sympathetic nerve supply.3
Mononeuritis can be treated with ganciclovir
Mononeuritis multiplex can occur late in HIV disease when the CD4 cell counts are less than 50 cells/mm3. When it occurs later in the disease, it typically is more severe, affecting three or more nerves and several limbs.
Clinicians may treat mononeuritis multiplex with ganciclovir therapy, particularly when the patient has a CMV infection.
• Inflammatory demyelinating polyneuropathy. Characterized by chronic or acute muscle weakness and paresthesia, this condition occurs early in asymptomatic HIV patients.4 Patients may have symptoms of areflexia, variable sensory loss, and symptoms similar to those of Guillain-Barre syndrome.5,6
The condition may even be the first clinical sign of seroconversion. Intravenous immunoglobulin may be effective, and demyelinating polyneuropathy responds to plasmapheresis or steroids. Like mononeuritis multiplex, demyelinating polyneuropathy is thought to be caused by CMV, so clinicians also could treat it with ganciclovir.
• Progressive lumbosacral polyradiculopathy. This condition typically occurs late in the disease, when CD4 cell count levels are very low and opportunistic infections have set in.
Patients will show signs of rapidly progressive lower extremity and sacral paresthesia, sensory loss, urinary retention, flaccid paraparesis, and decreased reflexes.
For example, a patient may become so debilitated that he or she can no longer walk or move the legs to either side, except for flexing the ankles.
CMV repeatedly crops up as cause
The condition has multiple causes, but the most common culprit is CMV; Mycobacterium tuberculosis also is often a causative agent.7 Other causes include neurosyphilis and leptomenin geal lymphoma.
When clinicians examine the patient’s spinal fluid, they’ll typically see significant pleocytosis with hundreds or thousands of polymorphonuclear leukocytes.8
Treatment includes anti-tuberculous drugs in cases where that infection is evident, plus ganciclovir or foscarnet. It’s important to treat patients early in the course of the syndrome or they may suffer from irreversible nerve root necrosis.9
References
1. Simpson D, Tagliati M. Neuromuscular syndromes in human immunodeficiency virus disease. AIDS and the Nervous System. 2nd ed. Philadelphia: Lippincott-Raven Publishers; 1997, pp. 189-221.
2. Simpson DM, Olney RK. Peripheral neuropathies associated with human immunodeficiency virus infection. Neurol Clin 1992; 10:685-711.
3. Harada H, Tamaoka A, Yoshida H, et al. Horner’s syndrome associated with mononeuritis multiplex due to cytomegalovirus as the initial manifestations in a patient with AIDS. J Neurol Sci 1998; 154:91-93.
4. Gilmer WS. Neurologic problems of the lower extremity associated with HIV and AIDS. Clin Podiatr Med Surg 1998; 15:281-303.
5. Cornblath DR, McArthur JC, Kennedy PGE, et al. Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 1987; 21:32-40.
6. So YT, McGuire D. "Neuromuscular Disorders." In: The AIDS Knowledge Base: A Textbook on HIV Disease from the University of California, San Francisco and San Francisco General Hospital. 2nd ed. Boston: Little, Brown and Co.; 1994, 5.9.
7. Corral I, Quereda C, Casado JL, et al. Acute polyradiculopathies in HIV-infected patients. J Neurol 1997; 244:499-504.
8. de Gans J, Tiessens G, Portegies P, et al. Predominance of polymorphonuclear leukocytes in cerebrospinal fluid of AIDS patients with cytomegalovirus polyradiculomyelitis. J Acquir Immune Defic Syndr 1990; 3:1,155-1,158.
9. Simpson DM, Tagliati M. Neurologic manifestations of HIV infection. Ann Intern Med 1994; 121:769-785.
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