Head and Nerve Problems

The nervous system has two parts: the central nervous system and the peripheral nervous system. The central nervous system is made up of the brain, where thinking takes place, and the spinal cord, which is a bun­dle of nerves that carries directions from and to the brain.

The central nervous system—primarily the brain—is somewhat more likely to be affected than the peripheral nervous system, either by HIV itself or by a medical complication. The most common symptoms of central nervous system involvement are (1) mental slowing, with memory loss, personality changes, and impaired concentration; (2) sei­zures; (3) weakness or paralysis; (4) poor coordination; and (5) head­ache that is often severe or different from the usual headache. All of these symptoms suggest infection in the brain or meninges (the membrane sur­rounding the brain) and require medical treatment. In many instances, the person with these symptoms will be referred to a neurologist, a spe­cialist in diseases of the nervous system.

The most frequent and serious diseases of the central nervous system in the era of HAART are complications associated with a weakened im­mune system, and an infection caused by HIV itself, called HIV-associ­ated dementia. The most common of the complications are toxoplasma encephalitis and cryptococcal meningitis; less common are lymphomas of the brain, Kaposi’s sarcoma, cytomegalovirus, progressive multifocal leukoencephalopathy, Mycobacterium avium complex, tuberculosis, and the herpes viruses.

All these diseases cause similar symptoms and most occur when the CD4 cell count is less than 200.

Other major laboratory tests are computerized tomography (CT scan) and magnetic resonance imaging (MRI) of the brain. Both tests are methods of viewing the brain in three dimensions to look for specific changes. These changes indicate the location of the problem and its probable cause. Diagnosis of central nervous system problems, then, is based on the symptoms, the results of a neurologic examination, the re­sults of examination of the cerebrospinal fluid, and any changes in the images of the brain.

Many diseases of the central nervous system can be treated success­fully, especially early in the course of the disease. Many of the symptoms suggesting central nervous system infections, however, occur even when there is no problem in the central nervous system at all. Weakness, seizures, and mental changes, for instance, can be caused by medica­tions, changes in the balance of electrolytes in the blood, and fever caused by some other infection. Particularly difficult to sort out are headaches: 90 percent of all people, with or without HIV infection, have periodic headaches.

The final part of this section on head and nerve problems will dis­cuss the problems HIV infection causes with the peripheral nervous system.

Headaches

Headaches are extremely common. In most cases, headaches bother the person who has them far more than they bother the physician who treats them. This is because headaches rarely indicate severe or progressive dis­ease.

Certain headaches, however, require a doctor’s attention. Like other focal neurologic symptoms and like fever and stiff neck (see below), headaches can be a symptom of an infection of the brain or the meninges. Headaches associated with infections of the brain or meninges have one or more of the following characteristics:

1. They are unusually severe or last unusually long.

2. Either the character of the pain or the location of pain makes the headache different from headaches the person usually has.

3. They occur along with problems with vision.

4. They occur along with weakness of an arm or leg, with dizziness, or with impaired coordination.

5. They occur along with stiff neck, nausea and vomiting, or ex­treme lethargy or sleepiness.

6. They are severe and occur along with an unexplained fever.

The major infections that cause such headaches in people with ad­vanced HIV infection are toxoplasma encephalitis and cryptococcal meningitis. Both of these infections, as well as a multitude of other in­fections of the brain and meninges, occur only in the late stages of HIV infection and are relatively easy to diagnose. They are also treatable. A less common cause of headaches in people with HIV infection is lym­phoma.

Toxoplasma encephalitis. The symptoms of toxoplasma encephalitis include headache, fever, confusion, personality changes, and what physi­cians call focal neurologic symptoms that occur generally with a prob­lem in a specific part of the brain: paralysis or weakness on one side of the body, loss of speech, loss of coordination, and certain kinds of seizures.

Toxoplasma encephalitis is caused by a parasite, Toxoplasma gondii, which is commonly found in cat stool and in inadequately cooked meat. After infection, the parasite remains—generally dormant—in the hu­man body for life. In fact, 10 to 30 percent of all adults in the United States have blood tests positive for antibodies to Toxoplasma gondii. The parasite causes severe disease primarily in people with a CD4 count less than 100.

Toxoplasma encephalitis can be diagnosed with a blood test that de­tects antibodies to Toxoplasma gondii, combined with a CT scan or MRI scan for imaging the brain. Either scan will show a characteristic pattern of inflammation in the brain.

The standard treatment for toxoplasma encephalitis is an antibiotic, pyrimethamine, taken in combination with other antibiotics, either sul­fonamides or clindamycin. These drugs are given initially by vein and then by mouth in relatively high doses. Most people improve within one week; brain scans two weeks after treatment generally show reduction in the size of the area of inflammation. People usually respond to treatment impres­sively, but toxoplasmosis is likely to recur when treatment is discontinued, so treatment is continued until the CD4 count comes back up.

To prevent toxoplasma encephalitis in people whose CD4 counts are below 100, the common recommendations are to take Bactrim, or a combination of dapsone and pyrimethamine, to prevent toxoplasmosis. Lymphoma. Another common cause of focal neurologic problems in people with HIV infection is lymphoma, a tumor of lymph cells. Almost any part of the body can be affected by lymphoma, but the brain is one of the parts most commonly affected. Lymphoma is often suspected if treatment for suspected toxoplasma encephalitis is ineffective. Treat­ment is with radiation and the chemotherapy drugs used to treat can­cers. Most people improve, but the improvement is temporary. (See also below, under “Problems Affecting the Whole Body.”)

Cryptococcal meningitis.

Cryptococcal meningitis is caused by a fungus called Cryptococcus neoformans, which is found throughout the world and is transmitted when the fungus is inhaled. The infection itself cannot be transmitted from one person to another.

Cryptococcus usually causes either a trivial disease or no disease at all until the CD4 cell count is less than 100 and the immune system is weakened. Cryptococcus neoformans is the most common cause of meningitis in people with AIDS. The infection may develop in several different places in the body; it is most damaging and most common in the brain. Cryptococcal meningitis is both serious and treatable, so it is important to make the diagnosis. The test for cryptococcal meningitis is a blood test and a spinal tap. A spinal tap is done so that a sample of the cerebrospinal fluid can be examined for evidence of inflammation and for Cryptococcus. For people with a severe headache, a spinal tap will often reduce the pressure and immediately relieve the pain. This is one of the rare cases in which people will beg for a spinal tap.

Treatment usually consists of the antibiotic amphotericin B (given by vein), followed by fluconazole (given by mouth). Treatment is usually successful, but the infection tends to recur when treatment is discontin­ued. Fluconazole by mouth is continued until the CD4 count rebounds from HAART.

Slowed Mental Processes or Dementia

Slowed mental processes, including forgetfulness, loss of recent memory (that is, the person can remember childhood experiences, but not the morning’s events), and difficulty concentrating, can be symptoms of HIV-associated dementia (HAD). HAD, which used to be called AIDS dementia complex, is a mental deterioration that accompanies HIV in­fection.

The progress of HAD often follows a certain pattern. At first, men­tal slowing is noticed, either by caregivers or people with HIV infection themselves: a comment might be that they are less sharp, or they are not as quick, or their thinking is cloudier. They take longer to organize their thoughts, to respond to questions. This doesn’t happen all at once: some days they are slower, and other days they’re clear and sharp. Later, men­tal slowing progresses and can be accompanied by apathy and with­drawal. Most people with HAD eventually have problems controlling their muscles. They walk unsteadily, and they trip or fall easily; their legs are often weak. Their coordination is reduced, and they have problems with eating and writing. Eventually, they may become totally with­drawn. HAD is different for different people. Some people with demen­tia experience a mild mental slowing that never becomes more serious; for these people, dementia has only a small impact on their lives. For others, dementia progresses rapidly and mental impairment is severe.

During the pre-HAART era, HAD occurred in 20 to 30 percent of people with HIV infection. With HAART, that percentage is lower, though it hasn’t decreased as much as the other HIV-related complica­tions have. The reason for this difference is not clear, but it could possi­bly be that to HIV, the brain and the rest of the body are two separate things. That is, in the body apart from the brain, HAART kills off HIV and reconstitutes the immune system; but in the brain, HAART has less effect on HIV and immune function. Part of the problem in sorting this puzzle out is that no one understands the cause of HAD. Evidence sug­gests that the cause might be HIV in the brain: the cerebrospinal fluid that bathes the brain often shows evidence of HIV early in the course of the infection, before the person shows any symptoms.

A person with the symptoms of HAD should be examined and tested to exclude the possibility that the symptoms are caused by depression or by an infection of the central nervous system. Diagnosis of dementia will often be made by specialists: neurologists or AIDS physicians. The tests for dementia include a series of tests of mental abilities, a neurological examination, a spinal tap, and a brain scan. The purpose of the tests is to find out what the person can and cannot do mentally, to determine the severity of the dementia, and to exclude other causes—like crypto- coccal meningitis, toxoplasmosis, or lymphoma of the brain—that could be causing the same symptoms.

So far, we have little in the way of treatment for HAD. Some med­ical researchers think what’s most important is a drug’s ability to get into the brain: drugs often cannot get into the brain, and the brain may serve as a sort of isolated harbor for HIV. In any case, the most important part of treating HAD is to select the HAART drugs that get into the brain es­pecially well. AZT, abacavir (Ziagen), indinavir (Crixivan), nevirapine (Viramune), and efavirenz (Sustiva) get into the brain better than most other drugs.

A note of caution: For reasons medical scientists do not yet under­stand, most drugs that act on the central nervous system, including drugs for sleep, antidepressant drugs, and anti-anxiety drugs, have a greater- than-usual effect on people with dementia. These include alcohol and all benzodiazepines: Valium, Librium, Xanax, and Ativan. Physicians must be made aware of the diagnosis of HAD so they can prescribe and mon­itor drugs carefully.

People with a confirmed diagnosis of HAD need appropriate med­ical care for this and other aspects of HIV infection, need support in their living arrangements, and need to do some long-term planning. They need to start considering some difficult decisions. Some of these deci­sions include signing a durable power of attorney, writing a will, and writing a living will and a medical order not to resuscitate (see chapter 9). Another decision is when to stop driving a car. Clues that it may be time to stop include these: they feel that their motor abilities or reaction times are impaired, they notice people blowing horns, they start getting traffic tickets, they sometimes forget where they are, or they are worried about hurting others when they’re behind the wheel. They must also de­cide when to stop work, especially if they think they are doing sloppy work or can’t work as well as they used to or can’t remember what they need to. Quitting work or not driving does not automatically mean that a person is dependent and useless, or that life can’t be enjoyable.

One of the biggest questions that people with HIV infection and their caregivers need to answer is how long HAART will be useful. HAART can clearly delay or prevent the onset of HAD, and the drugs can sometimes reverse the changes, especially when the regimen is started in the early stages of HAD. But when HAD becomes advanced and the person is no longer responding, then it is appropriate to consider discontinuing HAART, which is, after all, difficult to administer and substantially toxic. In this case, HAART may reduce the quality of life without providing any perceived benefit. The decision to stop HAART in such cases is complex.

Numbness, Tingling, or Pain in the Feet

The symptoms listed so far in this section on head and nerve problems have dealt with problems in the central nervous system. People with HIV infection also have symptoms of problems in the peripheral nervous system, the network of nerves throughout the body that bring sensory messages to the brain and deliver commands to the muscles. The most common symptoms are numbness, tingling, or pain in the feet. The symptoms may worsen to the point where wearing shoes becomes in­tolerable and walking becomes impossible.

These symptoms are called painful sensory neuropathy, that is, painful sensations due to damaged nerves (neuropathy). Painful sensory neuropathy in people with HIV infection is usually caused either by HIV itself or by one of two anti-HIV drugs, ddI (didanosine, Videx) or d4T (stavudine, Zerit). These drugs must be stopped promptly when these symptoms occur, since continued use will cause progression of the symp­toms to the point of irreversibility. Report the symptoms of painful sen­sory neuropathy to your physician to determine the cause and to begin treatment. Other drugs that produce the same or similar symptoms are metronidazole (Flagyl), cisplatin, disulfiram, INH, phenytoin (Dilantin), and vincristine. The symptoms can also be caused by diabetes and alco­holism.

Treatment is mainly to relieve pain. If the symptoms are severe, you may have to stop wearing shoes or wear only soft slippers. If blankets and sheets cause pain, build a sort of bridge at the foot of the bed that lifts up the blankets and sheets. Nonprescription drugs that may help include aspirin, acetaminophen, and ibuprofen. In some cases, a physi­cian will prescribe narcotics or drugs called tricyclic antidepressants, such as amitriptyline (Elavil) or nortriptyline (Pamelor). Side effects of the drugs include drowsiness, so these drugs are best taken at night. Some creams, like HEET or those like Zostrix that contain capsaicin, also relieve the symptoms, though some people complain that they also cause burning pain. HEET requires no prescription.