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From the Archives: Spring 2005 Issue of Lupus Now Magazine Command Central: When lupus affects the nervous system, many problems arise It was last year, nine years after being diagnosed with lupus, that Patti Renfro started to notice problems with her memory. As an assistant manager of a 280-unit apartment complex in Nashville, Renfro found it hard to remember simple things that once came easy. It wasn’t long before these memory lapses began to take a toll on her work.
"My short-term memory started to go, and I started to forget how to do my job," she says. "I was forgetting what things were called. I would even forget how to tie my shoes." During this time, Renfro says she was also having terrible headaches, dizzy spells, and sometimes a loss of vision where "all of a sudden, for seconds at a time, I couldn’t see." Renfro is like many people with lupus who suffer from bouts of memory loss, headaches, strokes, and cognitive dysfunction (which generally means a difficulty concentrating or reasoning) -- all symptoms that can arise when lupus affects the body’s nervous system.
The nervous system is made up of the brain, the spinal cord, and the nerves throughout the body. It Central nervous system (CNS), which consists of the brain and spinal cord. Peripheral nervous system, a network of nerves that connects the brain and spinal cord to the rest of Autonomic nervous system, nerves that communicate between the brain stem and the body’s internal organs and control functions such as rate of breathing, blood flow, and heart rate.
We know a lot about how our nervous system works and we know that it controls all of our thoughts, memories, behaviors, and movements. We also know that different parts of the brain control these functions (see "Your Brain at Work"). However, what doctors don’t know much about is why and how lupus attacks the nervous system and what, if anything, can be done to prevent it.
In 1999, the American College of Rheumatology (ACR) created a comprehensive definition for nervous system involvement in lupus, and the term "neuropsychiatric systemic lupus erythematosus" is now commonly used to refer to the condition. Other experts agree on a shorter list of definite symptoms that appear when the nervous system has been affected in a person with lupus. However, according the National Institute of Neurological Disorders and Stroke, although these symptoms may be present, it still can be difficult to know which ones can be directly attributed to lupus. John G. Hanly, M.D., physician and lupus researcher at Queen Elizabeth II Health Sciences Center and Dalhousie University in Halifax, Nova Scotia, notes that although nervous system involvement in lupus was recognized more than 100 years ago, it is probably the least understood feature of the disease.
"Our knowledge of the basic mechanisms and the consequences of nervous system disorders is not as advanced as with other organ system involvement, like the kidneys or the skin," says Hanly. C. Michael Neuwelt, M.D., who teaches medicine at the University of California–San Francisco and Stanford University, agrees. "Central nervous system lupus is probably the most common manifestation of lupus, but exacting criteria are lacking," says Neuwelt, who also treats rheumatic diseases at East Bay Rheumatology Group in San Leandro, CA. "When the brain is involved, we really don’t have well-defined markers." Most researchers do agree, however, that cognitive function may offer the best clues to how lupus affects the nervous system and how lupus itself may lead to problems in cognition and behavior.
Cognitive Dysfunction: Also Known as "Lupus Fog" Robin Brey, M.D., a neurologist at the University of Texas Health Science Center in San Antonio and president of the LFA, South Central Texas Chapter, says that cognitive dysfunction definitely is the most common symptom of CNS involvement that she sees.
"The way I relate to the term ‘cognitive dysfunction’ is that it’s a problem of difficulty finding words and retrieving information," Brey explains. "My patients say it feels like they have brain fog." Indeed, the term "lupus fog" is almost universally known to people with the disease. According to Brey, the difficulty in retrieving information was evident in patients who participated in the National Institutes of Health–funded study on cognitive function -- named Brain CONECTIONS -- that was recently completed. "Often in lupus, people have difficulty accessing information that is in their brain," Those in the CONECTIONS study were evaluated every four months with a wide variety of tests, including neurological and rheumatological exams. In one test, participants were given a list of words, and after about 10 minutes were asked to recall as many of the words as they could. "They often don’t do very well," says Brey. "But if we then show them a list of 20 words, they can pick out the 10 we originally showed them. So, there is an interference with access to the information that Brey says patients are frustrated by their inability to retrieve information they know they’ve learned.
"Our patients know the memory is there and stored, but the more they try, the more frustrated they get," she says. "Then it is even harder to remember." Brey suggests that people first realize that being frustrated or anxious makes the problem worse.
"Try to decrease that frustration by not worrying about it," she says. "If you have trouble remembering the word you want, use a different word. And also make lists that can prompt you to remember." These type of strategies and memory aids are really the best tools to cope with "lupus fog" because there are not yet any medications that can treat the condition. "There is no medicine for this," Brey says. "That’s partly because at this point we don’t know why it happens. It could be an effect of antibiotic use, or it could be a brain chemical malfunction. We need If cognitive dysfunction is the most common symptom seen in neuropsychiatric lupus, headache comes in second. However, the existence of a specific type of headache that is a symptom of neuropsychiatric lupus is still open to debate. According to the book, Systemic Lupus Erythematosus, Fourth Edition, most experts agree that there is a higher prevalence of headaches seen in people with lupus than in any other group. Yet, scientists have been unable to make a correlation between lupus and the clinical or neuropsychiatric symptoms. This raises the question whether headache really represents active neuropsychiatric lupus. Also, the term "lupus headache" was deemed too vague for ACR’s definitions of neuropsychiatric lupus, which instead describe specific types of headache -- such as migraine and tension -- and include detailed criteria that classify each type. Brey notes that often people with lupus are so concerned with other symptoms and issues related to their disease that they don’t feel the need to talk with their doctor about headaches. But, "if people with lupus have headaches that are not handled by Tylenol, it is really important to bring it up with the She adds that her research indicates that fewer than half of lupus patients with headache are offered treatment by their regular doctors. "The same strategies that work in people without lupus -- biofeedback, relaxation techniques, and medicinal treatment -- will work for those with lupus," she According to the ACR, in order for your doctor to assess whether there has been some nervous system involvement due to lupus -- and also to exclude other causes of the neurological symptoms -- Blood tests -- can detect several bleeding problems such as inflammation of the blood vessels in the brain and also the presence of antibodies, especially the antiphospholipid antibody, that can lead to Spinal fluid analysis -- can show distinctive changes in the spinal fluid that point to various disorders. Computed tomography (CT) and magnetic resonance imaging (MRI) -- can obtain images of the brain that can reveal strokes, tumors, bleeding, and abscesses. Electroencephalogram (EEG) and electromyoneography (EMNG) -- electrical studies that can detect bleeding or enlargement of the brain.
Perhaps the main difficulty in diagnosing neuropsychiatric lupus, though, is that many of its symptoms occur in the absence of active lupus. Canadian neuropsychiatric lupus researchers Susan D. Denburg, Ph.D., and Judah A. Denburg, M.D., in the 2003 Lupus special issue on central nervous system lupus, pointed out that nervous system involvement in lupus "is typically diagnosed on the basis of clinical psychiatric and/or neurologic syndromes. Neuropsychological tests can be used to assess nervous system integrity even in the absence of major neuropsychological syndromes." The five-year Brain CONECTIONS study actually did just that. Researchers measured cognitive dysfunction and biological changes using brain imaging in individuals newly diagnosed with neuropsychiatric lupus. Study results presented in 2004 at both the International Lupus Congress and the ACR Annual Scientific Meeting showed a high frequency of anatomic brain abnormalities.
Abnormalities found by MRI were associated with decreased sustained attention and reaction time, as well as with higher lupus disease activity at the time participants entered the study. Researchers say this suggests that both functional and structural damage to the brain is evident early on in the disease process and thus underscores the critical need to understand the underlying mechanism of The Denburgs concluded that the cognitive deficits described in lupus patients -- most probably due to no other process than lupus itself -- represent an extremely important index of central nervous system involvement. They suggest that these deficits are most likely related to, or are a consequence of, immunological mechanisms: brain-specific antiphospholipid antibodies, "neurotoxic" or "neuroactive" cytokines, and/or inflammation.
To treat neuropsychiatric lupus, doctors generally turn to corticosteroids, such as methylprednisolone pulse therapy or a combination of low-dose intravenous cyclophosphamide and prednisolone. They also may prescribe other drugs that suppress the immune system, or anticoagulants to treat blood clots. Psychopharmacologic treatments include antidepressants, stimulants, and mood stabilizers.
According to Giovanni Sanna, M.D., co-author of an article on the clinical approach to central nervous system therapy in the 2003 special issue of Lupus, one of the most important advances in treating central nervous system lupus has come from recognition of the antiphospholipid syndrome and the importance of blood-clotting mechanisms in the development of a number of central nervous "Many lupus patients with neurological manifestations and antiphospholipid antibodies, who would previously have received a high dose of corticosteroids and/or immunosuppression, are today being successfully treated with anticoagulation," he says.
Also of great importance when living with neuropsychiatric lupus are the cognitive therapies -- coping skills that help you help your brain. If you have trouble learning or processing information, recalling or finding words, or have difficulty focusing, planning, or organizing, this type of therapy may be very helpful. Cognitive therapists can explain how you can use memory aids, decrease distractions, form mental pictures, and above all, learn how to not get frustrated. Talk to your doctor about recommending a good therapist to assist you.
Debra Garcia of South Padre Island, TX, is also living with the daily struggles that began after lupus attacked her nervous system. She has been receiving Social Security disability for about three years -- not because she has been disabled by the condition (although she has), but because of the depression that affects her as a result. "[The Social Security Administration] never recognized my symptoms of lupus," Garcia says. "For five years I kept getting denied. But I saw I met the requirements for depression, so finally I submitted my claim for depression." Her request was approved right away.
"The thing that really hit home was when I began to lose my vision," Garcia says. "I began to have these blind spells. I went to a specialist who said it was probably caused by inflamed blood vessels putting pressure on the optic nerve, but there was nothing they could do." She also had experiences of losing track of her surroundings and often got lost while driving. "The surroundings would be familiar, and I would not be far from home, but I would have to stop and call my sister and say I was lost, and get someone to explain to her where I was and how I could get home," Garcia recalls. She continues, "I knew there had to be somebody who could help me, because what was happening was so vivid to me." During this time Garcia’s sister, an emergency-room nurse, read an article about the Brain CONECTIONS study that Brey was involved with in San Antonio and thought Garcia might be eligible to participate. "I begged Dr. Brey to take me for the study," Garcia says. The first thing Brey did was start Garcia on neurontin to help prevent the painful headaches, and Coumadin®, a blood thinner, for her symptoms of the antiphospholipid syndrome. "I’m a totally new person," Garcia says. "I felt the full effect in just a couple of months. The brain fogginess started to go away, I can see things more clearly -- it’s a difference of night and day." Garcia eventually was accepted into the study and says it is the most rewarding experience she ever had. "[Being part of this study] has been a ray of sunshine to understanding this disease and being able to help other lupus patients," she says.
Patti Renfro has also found some strength to cope with the symptoms of nervous system involvement, despite her increasing disability. As soon as she can, she plans to start an online newsletter that will include personal stories from people who have lupus, and positive, inspirational "I know now that I will never be cured of lupus; but if I can help others, I will," Renfro says. "I can either wallow in this and continue to have a self-pity party, or I can fight this and make a difference. In the process I will be helping myself heal." Major Signs That Lupus Has Affected the Nervous System Cognitive dysfunction (for example, not thinking clearly) Altered mental alertness (for example, stupor or coma) Peripheral neuropathy (for example, numbness, tingling, burning of the hands and/or feet) Autonomic neuropathy (for example, flushing, mottled skin) Adapted from The Lupus Book: A Guide for Patients and Their Families, Revised and Expanded Edition by Daniel J. Wallace, M.D. Reprinted with permission of Oxford University Press.
The frontal lobe controls skilled motor behavior, speech, mood, planning and organizing, problem-solving, personality, and a variety of "higher cognitive functions" including behavior and There are two temporal lobes -- one on each side of the brain -- that generate memory and emotions.
They allow you to recognize other people and objects, retrieve long-term memories, and start conversations. The right temporal lobe is mainly involved in visual memory, such as for pictures and faces. The left temporal lobe is involved in verbal memory, such as for words and names. The brainstem connects the lower part of the brain to the spinal cord. The brainstem manages those functions necessary for survival (breathing, digestion, heart rate, blood pressure) and for arousal The two parietal lobes are located behind the frontal lobe at the top of the brain. The parietal lobes interpret sensory input (touch, pressure) from the rest of the body and control body movement. In the back of the brain is the occipital lobe, which interprets vision. The cerebellum is at the back of the brain and coordinates the body’s movements (balance and Adapted from "About Brain Injury: A Guide to Brain Anatomy" from To learn more about neurological disorders and the effects of lupus: National Institute of Neurological Disorders and Stroke (NINDS) Information Clearinghouse, PubMed Central, the U.S. National Library of Medicine’s free digital archive of biomedical and life sciences journal literature, or via email at LUPUS An International Journal, Vol. 12, No. 12 2003. Special Issue on CNS Lupus published by

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