| Systemic Lupus and the Nervous System Daniel J. Wallace, M.D. Clinical Chief of Rheumatology, Cedars Sinai Medical Center, Associate Clinical Professor of Medicine, University of California at Los Angeles, Los Angeles, CA |
| People with lupus often experience headaches, confusion, difficulty with concentrating, fatigue and occasion ally have seizures, strokes, or other signs of nervous system involvement. Nervous system involvement is systemic lupus erythematosus (SLE) is unclear and controversial. This brochure will briefly discuss how lupus may affect the nervous system, categorize the may signs and symptoms associated with nervous system involvement, review the diagnostic work-up and discuss disease management. How Does Lupus Affect the Nervous System? A number of possibilities have been suggested to explain how lupus may cause the many symptoms of nervous system involvement. Nerve tissue may be damaged when antibodies attack nerve cells or blood vessels. The nervous system requires an uninterrupted flow of blood to supply its tissues with oxygen and nutrients necessary for normal functioning. Nutrients and oxygen are delivered through blood vessels that feed the brain, spinal cord and nerves. If blood flow is slowed or interrupted, the cells of the nervous system are injured, unable to function normally, and symptoms develop. the symptoms that occur vary depending on the location and extent of the tissue injury. The nervous system is divided into three parts. The central nervous system (CNS) consists of the brain and spinal cord. The peripheral nervous system is comprised of nerve fibers that supply the skin and muscles with the power needed for sensation and movement. The autonomic nervous system helps to regulate spinal, peripheral nerves and innervates the internal organs. Its role in SLE is poorly defined. Symptoms of Central Nervous System Lupus Central Nervous System (CNS) Vasculitis CNS vasculitis represents inflammation of the blood vessels of the brain. It occurs in up to 10% of all lupus patients, and is the only form of CNS disease that is included in the American College of Rheumatology criteria for defining SLE. Characterized by high fevers, seizures, psychosis and meningitis-like stiffness of the neck, it can rapidly progress to stupor and coma if not aggressively managed. CNS vasculitis is the most serious form of SLE and usually requires hospitalization and high doses of corticosteroids. Infection should be ruled out before treatment is initiated Seizures occur when injured or scarred brain tissue becomes the focus of abnormal electrical discharges. They may be a one-time occurrence or a persistent problem. Anti-convulsant medications are used to prevent seizures by controlling the brain’s abnormal electrical discharges. Cognitive Dysfunction At some point during the course of their lupus, up to 50% of lupus patients describe feelings of confusion, fatigue, memory impairment, and difficulty expressing their thoughts. This collection of symptoms is called “cognitive dysfunction” and is found in people with mild to moderately active SLE. These symptoms may be clearly documented by neuropsychological testing, and a newer neurodiafnostic test called the positron emission tomography (PET) scan shows reproducible blood flow abnormalities. The reason for these symptom is not known but it may have something to do with changes in how a group of chemicals known as cytokines are handled or may be related to certain parts of the brain wave tests (EEG), magnetic resonance imaging (MRI) or computerized tomography (CT) scans of the brain may all be normal. Antimalarials and/or steroids may be useful, but the management of cognitive dysfunction is often frustrating and currently no optimal therapy is available. Counseling and other interventions that assist a person in developing coping skills may be helpful. Cognitive dysfunction may come and go on its own. Lupus Headache People with lupus experience headaches which are unrelated to their lupus, i.e., sinus headache, tension headache and migraine. Approximately 20% of patients with SLE experience severe headaches which are related to the disease and known as “lupus headache.” This phenomenon is similar to migraine and may be seen more often in people who also have Raynaud’s phenomenon. PET scans indicate abnormalities in blood vessel tone of the ability of a vessel to dilate or migraine, although corticosteroids are occasionally useful. The Antiphosholipid Syndrome One-third of all people with lupus have a false positive syphilis test, a positive antisardiolipin antibody or a prolonged clotting time test called the PTT. This is known as the lupus anticoagulant or the antiphospholipid antibody. One-third of these patients (one-ninth or all people with lupus) will develop blood clots in various parts of the body. these patients have the antiphospholipid syndrome. When a blood clot occurs in the nervous system, it can cause a stroke. Symptoms of stroke usually include the painless onset of neurologic deficits (e.g., paralysis on one side of the body, inability to speak) without any signs of active lupus. A stoke is managed with blood thinning medications such as low dose aspirin, coumadin or heparin. The type of blood vessel involved and presenting symptoms are considered when determining which medical therapy should be used. Organic Brain Syndrome Patients with a history of stroke or vasculitis experience damage to the brain that is repaired by scar tissue. This results in seizures as well as varying degrees of difficulty with muscular movement, memory, concentration and orientation. these patients have organic brain syndrome and usually show on evidence of lupus activity in the blood or spinal fluid. Steroids make the symptoms worse. Organic brain syndrome is treated with emotional support. Fibromyalgia (Fibrositis Syndrome) Up to 20% of people with SLE have a simultaneous fibromyalgia (fibrositis) syndrome manifested by tender points and increased pain in the soft tissues. In addition, patients may experience cognitive dysfunction, decreased ability to concentrate, difficulty sleeping and lack of stamina. This syndrome is treated with anti-depressants, counseling and physical therapy if needed. People with symptoms of fibrositis and no physical of laboratory evidence of increased lupus activity should not be given corticosteroids since it may make them worse. Central Nervous System Symptoms Due to Medication Medications used to treat SLE can cause side effects that are similar to the symptoms of central nervous system lupus. These include nonsteroidal anti-inflammatory drugs which occasionally cause headache, dizziness, and although rarely, meningitis-like symptoms. Anti-malarials in very high doses may cause psychosis. Corticosteroids are associated with agitation, confusion, moodswings, psychosis, depression, and in high doses, seizures. Anti-hypertensive medications may be associated with loss of libido or depression. The physician must determine what is a side-effect of medication and what is a symptom of CNS lupus. Uncommon Cause of CNS Symptoms in SLE A research study of people with both lupus and Sjogren’s syndrome showed these individuals may be inclined to develop vasculitis or cognitive dysfunction. Certain circulating proteins in the blood can occasionally lead to cryoglobulinemia or hyperviscosity syndrome where the blood is too thick and slow blood flow to nervous system tissues. These complications are alleviated with plasmapheresis, or filtering of the blood. Sometimes, marked decreases in platelet counts (blood components important in blood clotting) may be associated with bleeding. People with lupus, idiopathic thrombocytopenic purpura (ITP) and kidney failure may bleed, while those with thrombotic thrombocytopenic purpura or who lack Protein S or Protein C may clot. Occasionally, infections of the central nervous system can be present and mimic lupus. Symptoms of Peripheral Nervous System Lupus In peripheral nervous system lupus, a variety of symptoms may occur depending on which nerves are involved. Involvement of the cranial nerves can cause: visual disturbances, facial pain, drooping of the eyelid(s), ringing on the ear(s), and dizziness. Inflammation of the blood vessels supplying the peripheral nerves can lead to numbness or tingling in the arms or legs. Occasionally, loss of sensation or muscular weakness in the extremities (e.g., carpal tunnel syndrome in the hands) can occur. these symptoms may be due to conditions other than lupus. Electrical studies, such as electromyopram (EMG) and nerve conduction tests are usually helpful in determining if symptoms are due to some other cause. For example, a herniated disc or a metabolic abnormality as in diabetes can cause similar nervous system symptoms, but show different electrical study results. Inflammation of the peripheral nerves (called mononeuritis multiplex) is treated with corticosteroids. How Your Doctor Evaluates Nervous System Symptoms If you have any nervous system symptoms, it is important for your doctor to know. The cause of your symptoms may be due to a condition other than lupus, a medication or a particular aspect of your life style. The workup consists of an interview with your doctor, a physical examination and a laboratory evaluation including a blood chemistry panel, complete blood count and urinalysis. Diagnosis is difficult as there is not one specific diagnostic test to detect nervous system involvement in lupus. Diagnostic tests such as a sedimentation rate, ANA, anti-DNA, anti-ribosomal P antibodies and complement may be useful in determining nervous system involvement. Neurodiagnostic tests currently available include CT and MRI brain scans, brain waves or electroencephalogram (EEG), and spinal taps. PET scans are only available in a few hospitals. The spinal fluid may be examined for cells, protein components and antineuronal antibodies. Neuropsychologic tests may be helpful in patients with cognitive dysfunction. How Your Doctor Treats Nervous System Symptoms As noted above, the treatment of nervous system lupus depends upon its source. Treatment may include: steroids, immunosuppressants, blood thinners, antibiotics, anti-convulsants, anti-depressants, counseling or surgery. If any diagnostic difficulties are evident, a rheumatologist and/or neurologist should be involved in your care. Response to treatment may be dramatic or gradual improvement may occur over several months. For many people with lupus, nervous system involvement is completely reversible. |
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