Systemic lupus erythematosus (SLE, or “lupus” for short) is a chronic autoimmune disease that can inflame any and all organs of the body””hence the term systemic. Lupus can produce a wide range of symptoms, the most common of which include arthritis, rashes (particularly on the cheeks), fever, a low number of white blood cells, or platelets, and kidney and brain disease. Few people with lupus have all the possible symptoms, but up to half have neurological symptoms or complications, which this section will concentrate on. Please refer to Appendix C, “Resource Groups,” at the back of this book for contacts that can provide you with information on the disease in its full range of manifestations.
We do not know why, but lupus and related diseases spontaneously wax and wane (“flare” and “remit”), so their symptoms vary considerably over time. Lupus can be very mild, or it can be lethal. Because its symptoms are so varied, we are really not sure how many people suffer from it. Its onset is difficult to pin down, and we do not know its cause. We do know that lupus mostly affects young women, particularly those who are non-Caucasian. It has been estimated that up to 1 in 250 black women between 15 and 45 develop the disease, compared with 1 in 800 white women of the same age. The fact that lupus tends to run in families suggests that there is a genetic component to the disease, but no specific gene has been identified.
Lupus is an autoimmune disorder, which means that the immune system, which normally controls a person”s defenses against infection, turns against the body and produces antibodies against its own cells. This leads to direct damage and to inflammation, which often blocks small blood vessels (a condition called vasculitis). Because many lupus symptoms reflect loss of blood flow to a specific part of the body, those symptoms can be as varied as our organs and tissues are.
It is common for people with lupus to develop some neurological symptoms, but rare for these to be the first symptoms to show up. Most often people are diagnosed with the disease because of symptoms affecting other parts of the body. Neurological symptoms can be caused by lupus antibodies, which directly inflame the brain; by blocked blood vessels; and by such lupus complications as high blood pressure, spontaneous hemorrhage, and kidney failure. Furthermore, many of the drugs used to combat the disease can also cause brain symptoms.
Symptoms Due to Lupus Antibodies
Some individuals with lupus make antibodies to various brain, spine, and nerve cells. We do not know precisely how these antibodies injure the brain, but when they do the injury is widespread. Often people with lupus antibodies to their brain cells complain that it is difficult to focus their thoughts or to remember things. Some show bizarre behavior (lupus psychosis). Sometimes a magnetic resonance imaging (MRI) or computed tomography (CT) scan will show that parts of the brain have atrophied, but usually they show nothing. In rare cases, people with severe brain disease will develop seizures or coma.
When antibodies attack the spinal cord, the result is either a disease like multiple sclerosis or meningitis or a localized inflammation of the cord, called transverse myelitis, that causes paralysis from the site of the injury downward. A few individuals will develop antibodies against their peripheral nerves, which can cause numbness and weakness in the feet and hands (polyneuropathy).
Lupus antibodies can also block the chemical message passed between a nerve and a muscle, causing quick fatigue and weakness. This is similar to the disease process found in myasthenia gravis. Still other people develop muscle inflammation (myositis), usually in the muscles nearest the torso, which weakens their shoulders and thighs but leaves their hands and feet strong. Lupus can also produce depression and hallucinations, usually paranoia; these episodes almost always remit completely.
Fortunately, in most cases brain cells recover from the injury they suffer from lupus antibodies, so the neurological impairment is not permanent. Most people return to their usual lives.
Symptoms Due to Blood Vessel Blockage
About one third of people with lupus have an unusual antibody, called antiphospholipid antibody, that can cause clotting and blockage in blood vessels. Lupus can also inflame those blood vessels (vasculitis). Both blockage and inflammation can cause brain, spinal cord, or peripheral nerve symptoms. When the affected vessels are large, a person can suffer strokes in any part of the brain. Generalized obstruction of the small blood vessels results in thinking disorders and dementia.
If only the small blood vessels in the parts of the brain that control motion are affected, a person may suffer from involuntary flailing or twisting motions (chorea) and sometimes loss of balance (ataxia). In people with these symptoms, MRIs and CT scans often show evidence of injury to the related part of the brain.
When lupus causes blood flow to the spinal cord to be cut off, a person becomes paralyzed (transverse myelitis). Loss of blood flow to a peripheral nerve can result in a sudden loss of power or sensation in the corresponding part of the body (mononeuritis multiplex). Unfortunately, brain or nerve injury due to blood vessel blockage is usually permanent.
Symptoms Due to Lupus Complications
Systemic lupus erythematosus can damage parts of the body that, in turn, produce problems for the brain. The most common of these complications include kidney damage, which results in uncontrolled blood pressure and causes seizures or stroke; kidney failure, which causes twitching, seizures, and coma; and low blood platelets, which can cause spontaneous hemorrhage into the brain. Some people with lupus develop premature hardening of the arteries and heart disease, which can lead to cholesterol blockage of their blood vessels and eventually to ischemic stroke.
Symptoms Due to Treatment and Its Complications
Many of the medications used to treat lupus can cause neurological symptoms as side effects. The drug most commonly used for lupus is prednisone, a corticosteroid, which can cause psychosis. The psychosis is dose-related and disappears when the person stops taking the medication. The same class of drugs (steroids) can cause muscle weakness that closely resembles the weakness we see in lupus-induced muscle inflammation, so identifying the effect of the dosage can be tricky. Steroids can also bring on diabetes, which can lead to diabetic coma, and they markedly suppress our immune systems, making a person vulnerable to brain abscess and other infections. Immunosuppressants, which are used in severe cases of lupus, can also make the person vulnerable to infection.
In addition, lupus sufferers are very sensitive to other drugs. Even low doses of the simple medications used to control nausea can cause people with lupus to suffer uncontrolled facial movements. Because of all these possible complications, people with lupus and their doctors become very mindful of drugs” potential side effects.
Evaluation and Treatment
Most people with lupus develop only a few of the total number of possible symptoms. This diversity of clinical symptoms and possible mechanisms of brain injury makes it difficult for doctors to evaluate people with new neurological symptoms and immediately diagnose lupus as the cause. Furthermore, other autoimmune and rheumatic diseases may affect the nervous system in a similar way: dermatomyositis, scleroderma, vasculitis, rheumatoid arthritis, and others.
No single test can determine whether a person has lupus. Doctors faced with neurological symptoms commonly run blood tests, brain wave and other electrical tests, MRI and X-ray tests, and cerebrospinal fluid analysis, but these tests do not provide any specific indication of lupus. They may show evidence of a hemorrhage, vessel blockage, inflammation, or infection that led to an individual”s disorder, but not what caused that problem. Often these tests are normal, even though a person may be suffering from lupus.
Due to the absence of a single diagnostic test, doctors must identify lupus by recognizing its constellation of symptoms, and then attempt to confirm the diagnosis by testing for the specific antibodies that the body makes against its own tissues (called autoantibodies). We use the antinuclear antibody to screen people for lupus, and the antibody to DNA to diagnose the disease. Unfortunately, some drugs, infections, and other diseases can also produce positive results on these tests, and some people who have lupus might nonetheless test negative.
To further complicate the diagnosis of lupus-related neurological disease, only a few of the many lupus autoantibodies can affect the brain, and even the little information we have on those autoantibodies is controversial. Antineuronal antibodies are more common in people with brain disease than in those without, but we do not know whether they actually cause the brain disease. Antibodies to the microsomal P antigen may sometimes identify people whose mood disorders are due to lupus. Antiphospholipid antibody and lupus anticoagulant are clues to spontaneous clot formation. The only way to make the final diagnosis is careful clinical assessment using all available diagnostic tools. The autoantibodies can only serve as clues.
Treating lupus is often a team effort involving the affected person, the family, and several types of health care providers. Each person”s treatment depends on the specific symptoms. Once lupus has been diagnosed, a treatment plan is tailored to the individual”s needs, and it often changes over time. Neurologists are most likely to work with individuals suffering from symptoms involving the brain or nervous system.
People with lupus and their doctors must be extremely vigilant for any possible neurological symptoms. The initial signs may be quite subtle. Early and aggressive treatment of these complications can prevent severe brain injury. Our current treatment cannot repair damaged brain tissue, but it can reduce inflammation, thus improving a confused person”s thinking or awakening someone in a coma. Treatment can also prevent problems from recurring.
Several types of drugs are used to treat lupus. When the disease is active, blood vessels are inflamed, or a person is suffering from acute brain symptoms (seizures, coma, confusion), doctors prescribe high doses of corticosteroid hormones (such as prednisone) and immunosuppressive drugs (such as cyclophosphamide). If the problem is blood clots, the treatment is anticoagulant drugs (aspirin, warfarin/Coumadin, heparin/Calciparene). People may also take antihypertensives and anticonvulsants for the relevant conditions. Many of these drugs can cause severe side effects, and doctors aim to use the lowest possible dose for the shortest possible time to achieve the highest possible benefit. Some people seek alternative approaches, including special diets and homeopathy, but no research has proven these methods to be successful.
Even with the symptoms of lupus and the potential side effects of treatment, many people with the condition maintain a high quality of life. Perhaps as many as half of those affected have only mild illness, and others develop strategies to prevent or minimize their flares. Around 76 percent of people diagnosed with lupus survive for at least ten years, and around 69 percent for at least twenty. Symptoms involving the central nervous system make a person”s prognosis worse, but lupus is most deadly when it affects the kidneys. Much research is under way to determine what causes lupus, what new drugs can treat it, and what someday may cure it.