Lupus cerebritis: a case study.
Lupus erythematosus (Research)
|Publication:||Name: Journal of Neuroscience Nursing Publisher: American Association of Neuroscience Nurses Audience: Professional Format: Magazine/Journal Subject: Health care industry Copyright: COPYRIGHT 2002 American Association of Neuroscience Nurses ISSN: 0888-0395|
|Issue:||Date: August, 2002 Source Volume: 34 Source Issue: 4|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
Abstract: Nervous system involvement in systemic lupus
erythematosus (SLE) occurs in 24%-50% of all patients in the United
States at some time during the course of their illness. Lupus cerebritis
with associated headache, seizures, stroke, and chorea is just one of a
wide array of central nervous system disorders SLE patients can develop.
It also is one of the most difficult manifestations of lupus to
diagnose. Advances in imaging and laboratory analysis have contributed
to an earlier and more specific diagnosis of lupus cerebritis. Despite
improvements in the ability to treat SLE, management of nervous system
manifestations remains unsatisfactory. Controversy exists as to the best
approach for treatment. Newer combination therapies based on anecdotal
evidence are suggested.
Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease of the connective tissue. It is characterized by production of pathogenic autoantibodies and immune complexes. Although SLE occurs in people of all ages and races and in both genders, there is a higher incidence among females between 13 and 40 years of age (Johnson, 1999). According to the American College of Rheumatology, for a diagnosis of SLE, the patient must have at least four of the following organs involved: renal (proteinuria or cellular casts in urine), cardiac (pleuritis/pericarditis), skin (malar or discoid rash), joint (arthritis), hematologic system (anemia, thrombocytopenia, neutropenia), or brain and spinal cord (seizure, psychosis, myelitis; Johnson).
Because of its multisystem involvement, the neuroscience nurse may encounter the SLE patient with central nervous system (CNS) manifestations. Kaposi in 1872 provided the earliest known report of the CNS effects of SLE with his description of delirium in 2 of 11 SLE patients (Calabrese & Stern, 1995). Osler originally postulated the cerebral vasculitis seen in SLE in 1903 when he described a patient with lupus who also had neurological deficits (Liem, Gzesh, & Flanders, 1996).
More than 50% of all patients with SLE in the United States suffer from neurological involvement (Bruyn, 1995; Moore, 1999). Kohen, Asherson, Gharavi, and Lahita (1993) report that 25%-75% of SLE patients have neuropsychiatric manifestations at some stage of their illness. Various mechanisms are postulated for the CNS involvement found in SLE; diagnosis is difficult.
Controversy exists as to the best approach for treatment. The neuroscience nurse may be challenged with the patient with cerebral lupus, who not only waits for the definitive diagnosis but also hopes for response to treatment. This article discusses the pathophysiology and proposed mechanisms of neurological involvement seen in SLE. A case study is used to discuss treatment modalities and nursing interventions for the patient with lupus cerebritis.
Mechanisms of CNS Involvement in SLE
To better understand the pathophysiology of lupus cerebritis, a review of the vasculopathy seen in SLE is necessary. Lupus begins with the failure of T-helper cells to moderate the immune reaction. The T-helpers, macrophages, and B cells, mediated by cytokines (polypeptide products of activated lymphocytes), learn to recognize antigens on cell surfaces. Immunoglobulins released by the B cells attach to these antigens, forming immune complexes that collect in the tissues. Cytokine release also triggers edema, thickening of the basement membrane, infiltration by neutrophils, and disruption of the endothelium lining of the cell. This inflammation and endothelial thickening causes vascular occlusion from an accumulation of fibrin and thrombi, resulting in micro infarcts in various organs and, hence, SLE symptoms (Johnson, 1999; Tsokos, 2001).
Knowledge about CNS involvement in SLE patients is based on work with mice as well as on studies of post-mortem human brains. The exact pathophysiological process of lupus cerebritis is unknown. The proposed mechanisms (Table 1) are likely due to the assault of several autoimmune system changes, including the following (Bruyn, 1995; Howser, 1996):
* Circulating immune complexes
* Anti-neuronal antibodies
* Antiphospholipid antibodies
* Cytokine release.
Circulating Immune Complexes
The immune complexes, which consist of DNA and anti-DNA, cause an inflammatory response as well as a disruption of the blood-brain barrier. These circulating complexes have been found trapped in the highly vascular choroid plexus of SLE patients upon autopsy. True vasculitis, however, is found only in about 10% of patients with cerebral lupus (Bruyn, 1995; Liem et al., 1996).
The three identified anti-neuronal antibodies postulated in CNS involvement are the lympho-cytotoxic antibodies (LCAs), which somehow react with brain tissue and interfere with the neuron's ability to respond. The exact mechanism, however, is unknown. LCAs have a specific role and are found in both the serum and cerebrospinal fluid (CSF) of lupus patients with cerebritis. These antibodies also correlate with cognitive and visual spatial defects. Second, the anti-neuronal membrane antibodies are targeted directly to neuronal antigens. They, too, are found in the serum of SLE patients with cerebritis. And third, the intracytoplasmic antibodies target the constituents of the neuron cells (i.e., ribosomes and neurofilaments). They are also called anti-SSA or anti-SSB antibodies and are found in the CSF and serum. These antibodies are seen in 90% of SLE patients with psychosis (Bruyn, 1995). Recently, neurotoxic metabolites have been found in the CSF of mice that were behaviorally impaired from lupus-like autoimmune disease (Maric et al., 2001).
Another mechanism of CNS involvement is the thrombosis associated with antiphospholipid antibodies. The two antibodies implicated are anticardiolipin and lupus anticoagulant. Anticardiolipin antibodies attach to the endothelial lining of cells, causing endothelial damage, platelet aggregation, inflammation, and fibrosis. The lupus anticoagulant antibody prolongs coagulation. Together the antibody responses are known as the antiphospholipid antibody syndrome (Bruyn, 1995). Stroke-like disorders, such as pulmonary emboli, miscarriage, thrombocytopenia, and arterial/venous thrombi, are seen in 30%-50% of SLE patients (Terregino, 1999).
The final mechanism of lupus cerebritis involves the cytokines. The cytokines trigger edema, endothelial thickening, and infiltration of neutrophils in brain tissue. Two cytokines, interferon alfa and interleukin-6, have been found in the CSF of SLE patients with psychosis. Research points to the possibility of an increased concentration of these cytokines during SLE exacerbations (Bruyn, 1995).
No one clear mechanism appears to cause lupus cerebritis. All mechanisms may be present or act independently.
Lupus cerebritis may present as seizures, psychosis, myelopathy, or stroke in a patient with SLE (Barr & Merchut, 1992). In its broadest definition, it is the inflammatory response of the CNS secondary to SLE. A neurological disorder in SLE may occur as an isolated event or in association with other systemic signs of SLE or even precede the onset of systemic disease. Multiple neurological events may also occur together (Khamashta, Cervera, & Hughes, 1991). CNS manifestations of SLE are based on clinical studies, autopsies, or anecdotal reports of patients followed for variable time periods.
Lupus cerebritis may occur in adults and children (Quintero-Del-Rio & Van, 2000; Steinlin et al., 1995). The duration of the CNS involvement may vary from a few minutes, as in classic migraine or a transient ischemic attack (TIA), to years, as in dementia. Resulting neurological deficits may be transient or permanent, occasionally resulting in death (Khamashta et al., 1991).
Neurological signs are categorized into focal, nonspecific, and neuropsychiatric (Table 2). Focal neurological signs include stroke, transverse myelitis, cranial nerve palsies, peripheral neuropathy, and chorea, cerebellar ataxia (Barr & Merchut, 1992; Calabrese & Stern, 1995). Infarction, both large vessel and microscopic, tends to occur in isolation from other neurological events. The incidence of stroke is 3%-20% of SLE patients. It is highest in the first 5 years of the disease and is directly correlated with the presence of antiphospholipid antibodies (Terregino, 1999). The stroke recurrence rate reported in the literature ranges from 13%-69% (Mitsias & Levine, 1994; Bruyn, 1995).
Transverse myelitis occurs from demyelination or vasculopathy; small arteries are often affected. There are reports in the literature of spinal cord infarcts and subdural hematomas, resulting in paraplegia, sphincter dysfunction, and sensory loss (Moore, 1999). Cranial nerve palsies occur in 10%-15% of SLE patients. Laryngeal palsy, visual loss, ptosis, and facial weakness are the more common manifestations (Barr & Merchut, 1992).
Peripheral neuropathy occurs in more than 20% of the SLE population. This may occur as carpal tunnel syndrome, numbness/tingling, facial pain, and ringing in the ears (Moore, 1999). Movement disorders, such as cerebellar ataxia and chorea, are seen in less than 5% of SLE patients (Barr & Merchut, 1992).
Nonspecific neurological signs occur in about 40%-70% of SLE patients. These include headache, seizures, and organic brain syndrome. A "lupus headache" is the most frequent manifestation of SLE. It can be intractable and of vascular or muscular origin (Moore, 1999). If headache persists, cerebral venous thrombosis must be considered. Although 40%-70% of lupus patients complain of headache, a direct relationship with lupus and the severity of the disease is not always clear (Barr & Merchut, 1992). Seizures occur in 20% of patients. Various types are reported; tonic-clonic is most common (Terregirto, 1999). These seizures are caused by micro infarcts or subarachnoid hemorrhage (Barr & Merchut, 1992). The biggest challenge in dealing with seizures and lupus is that so many medications used to treat lupus also can cause seizures (e.g., steroids, antimalarials, and some cytotoxics; Moore, 1999). Also, seizure medications may adversely affect SLE. Valproate, in fact, may actually trigger the onset or exacerbation of lupus in some predisposed patients (Barr & Merchut). Organic brain syndrome occurs in about 30% of SLE patients due to multi-infarct dementia (Moore).
The neuropsychiatric sequelae seen in SLE patients range from affective to behavioral and cognitive disorders (Calabrese & Stern, 1995). Approximately 20% of all lupus patients initially present with neuropsychiatric disorders (Wolf, Niedermauer, Bergner, & Lowitzsch, 2001). Patients with undiagnosed lupus cerebritis many times appear in psychiatric or neurologic clinics. Affective symptoms include personality disorders, irritability, anger, anxiety, depression, sadness, and feelings of hopelessness (Calabrese & Stern).
Behaviorally, SLE patients have episodes of emotional liability such as crying and apathy, poor eye contact, and lack of initiative. Cognitive deficits are seen in 20%-40% of SLE patients (Moore, 1999). Symptoms include difficulty in thinking, concentrating, and speaking, with fluctuating levels of consciousness. Many patients refer to this as "brain fog." SLE patients with these neuropsychiatric manifestations are often referred for psychiatric consultation (Moore).
Psychosis may occur in SLE. However, the cause of psychosis is controversial as CNS involvement from both SLE and steroid treatment can occur. Because steroids are the mainstay treatment for SLE, it may be difficult to differentiate between steroid psychosis or actual CNS involvement. West (1994) suggested that the best way to differentiate between the two is to taper the steroid dose to determine whether the signs and symptoms diminish. If the psychotic symptoms decrease, steroid intoxication should be considered.
Diagnosing Lupus Cerebritis
Precise diagnosis of CNS lupus is extremely difficult. There is no single diagnostic gold standard. Hanly (1998) recommended that diagnosis should be based on both clinical assessment as well as the presence of antibodies in the serum and CSF (Table 3).
A diagnosis of cerebral SLE cannot be made from radiologic findings alone, because true cerebral vasculitis is rarely seen radiologically or even upon autopsy (Bruyn, 1995). Various imaging studies that aid in diagnosing lupus cerebritis have been reported in the literature.
Computed tomography. Computed tomography (CT) scans may show a normal brain or cerebral atrophy, calcification, infarcts, and intracranial hemorrhage or subdural fluid collections (Calabrese & Stern, 1995; Raymond, Zariah, Samad, Chin, & Kong, 1996; Shaskey, Mijer, Williams, & Sawitzke, 1995). Some of these findings may be attributed to chronic steroid use in the SLE patient.
Cerebral blood flow. Cerebral blood flow studies also can be used. One study showed that patients with a long history of SLE frequently had decreased cerebral blood flow (Postiglione et al., 1998).
Magnetic resonance imaging. Magnetic resonance imaging is considered a more sensitive diagnostic tool for lupus cerebritis (Bruyn, 1995). In fact, 80%-100% of those SLE patients who presented with seizures showed some type of an abnormal MRI scan. MRI relaxometry, which segments gray matter, can pick up cerebral edema from the cerebritis in specific locations (Petropoulos, Sibbitt, & Brooks, 1999). Diffusion-weighted, echo-planar MRI scans show primarily patterns of acute and subacute infarction and vasogenic edema (Moritani et al., 2001). MRI spectroscopy has recently been used, because it determines the presence of neurochemical abnormalities and neurometabolite markers, which indicate cellular damage. Those patients with suspected lupus cerebritis are shown to have positive Nacetylaspartate, increased choline-compounds, lipids, and macromolecules, which are all indicative of cell membrane breakdown and neuronal loss (Sabet, Sibbitt, Stidley, Danska, & Brooks, 1998). Cerebral atrophy on MRI also has been correlated with the presence of antiphospholipid antibodies (Hachulla et al., 1998).
Electroencephalography. Electroencephalography (EEG) also can be used to pinpoint specific areas of damage from micro infarcts. EEG abnormalities are seen in 50%-90% of SLE patients, including theta and delta slowing and sharp wave activity. Evoked potentials can show auditory involvement (Calabrese & Stern, 1995; Glanz, Schur, & Khoshbin, 1998).
Position emission tomography. Positron emission tomography (PET) has a sensitivity of 90%. Patients with lupus cerebritis show abnormal cortical perfusion indicative of cerebral hypometabolism. The use of PET and single photon emission computed tomography (SPECT) scanning is controversial, however, because many medical centers do not have this capability. It has been concluded that expensive PET and SPECT scanning adds little information to the diagnosis of lupus cerebritis as compared to MRI (Sailer et al., 1997; Waterloo et al., 2001).
Transcranial Doppler. Recently, transcranial doppler (TCD) testing was found to be a noninvasive method to ascertain risk of stroke in patients with lupus cerebritis. The presence of microthrombi can be seen (Kron, Hamper, & Petri, 2001).
Cerebral Angiogram. Even though the definitive method for diagnosis of cerebral vasculitis is by cerebral angiogram, it is not recommended or routinely used. The angiographic features can be nonspecific, because many times the vessels involved are below the range of radiographic resolution (Liem et al., 1996). True vasculitis is found in only about 10% of patients with cerebral lupus (Bruyn, 1995).
Because there is no one specific laboratory test available to diagnose lupus cerebritis, diagnosing the condition remains a challenge (Bruyn, 1995). CSF studies may be used, because they show high protein levels in 40%-80% of patients with CNS manifestations of SLE (Calabrese & Stern, 1995). CSF also can be tested for the presence of interleukin-6 and interferon alfa (cytokines), because their levels are found to be significantly higher in SLE patients who develop neurological symptoms (Gilad, Lampl, Eshel, Barak, & Sarova-Pinhas, 1997). In a study by Brundin et al. (1998), which looked at the CSF of SLE patients with cerebritis, elevated levels of nitric oxide were seen. These elevated levels were associated with more severe neurological deficits. The author concluded that the presence of nitrates/nitrites in CSF could be used to monitor activity or progression of the cerebritis.
Ten of the 19 different nuclear antigens are specific to SLE. The presence of antinuclear antibodies (ANA) in the serum is used in the diagnosis of SLE. The presence of DNA, anti DNA is the most specific test in 40%-60% of SLE patients. If the ANA titer ratio is >1:64, a diagnosis of SLE is confirmed (Calabrese & Stern, 1995). Specific antibodies that target parts of the neuron and confirm CNS involvement are intracytoplasmic targeted antibodies (anti-ribosomal P, anti Ro, SS-A or anti-La, SS-B). Their presence is seen in both the CSF and serum of patients with cerebritis (Bruyn, 1995).
The presence of antiphospholipid antibodies, lupus anticoagulant and anticardiolipin, correlates with changes in the patient's CT/MRI. In a review of the literature of more than 1,000 SLE patients with cerebritis, lupus anticoagulant was seen in the serum of 34% of patients and anticardiolipin antibodies (i.e., IGG, IGA, IGM) were seen in 44%-50% of patients (Mitchell, Webb, Hughes, Malsey, & Cameron, 1994).
Neuron reactive autoantibodies are considered a much better marker for CNS involvement, with levels significantly higher in SLE patients with cerebritis (Ochola, Hussain, Khamashta, Hughes, & Vergani, 1995). Specifically, lympho-cytotoxic antibodies (LCAs) are seen in 80% of patients (Bruyn, 1995). In general, determination of an immunologic marker in the CSF is a better indicator of CNS activity than the similar test in the serum (Barr & Merchut, 1992). Assessment of complement components (C3 and C4), which are part of the coagulation cascade, show low serum and CSF concentrations (Johnson, 1999).
Finally, diagnostic indicators for lupus cerebritis may include serial cognitive and neuropsychological testing, which address motor function, dexterity, and verbal and nonverbal abilities. In one study of patients who presented with neuropsychiatric manifestations, 87% had abnormal tests in the Halstead-Reitan Neuropsychological Test Battery and the Luria-Nebraska Battery (Barr & Merchut, 1992). One study illustrated the benefits of using the Beck Depression Inventory in assessing depression in patients with SLE (Iverson, Sawyer, McCracken, & Kozora, 2001).
Management of the Patient with Lupus Cerebritis: A Case Study
Treatment of lupus cerebritis is discussed by using a case study of a young female who presented with symptoms of CNS involvement before even knowing she had lupus.
Yvonne is a previously healthy 21-year-old female who just moved in with her boyfriend. According to the patient, she and her boyfriend had been fighting frequently because of her inability to search for a job due to weakness and fatigue. Yvonne presented to the emergency department with multisystem involvement. She complained of chills, a nonproductive cough, a fever of 101.6[degrees]F, diarrhea, and increased muscle pain in her thighs, arms, chest, and back. She also reported bleeding from her nose and vomiting and stated that her urine had looked "rusty colored" over the past week.
Admission labs showed renal and liver involvement with elevated blood urea nitrogen and creatinine levels, and elevated liver function tests (LFTs). Urinalysis was positive for protein, blood, and casts. Yvonne was admitted to the medical floor for further workup. Intravenous (IV) fluids were started, an anti-emetic was given for her nausea, and a cooling blanket for her fever. An abdominal ultrasound ruled out obstruction. On day 2 of hospitalization, Yvonne had mental status changes, which included uncontrollable crying, agitation, and repeated attempts to disrobe herself. Her sister was greatly disturbed and was requesting a psychiatrist see the patient. At this time the family was given help to cope with the sudden behavior changes of the patient. They were taught how to interpret the behavior changes and how to react to Yvonne's emotional outbursts by sitting quietly and keeping their voices calm and quiet. It was especially difficult for the family, because there was still not a definitive diagnosis.
A neurology consultation was obtained and an EEG ordered. The EEG showed abnormal, persistent, diffuse, slow activity, but no seizures. An MRI scan with magnetic resonance angiography ruled out any lesions or vasculitis. A lumbar puncture, done to rule out infection, was normal. Yvonne was transferred to the neurological intensive care unit for closer observation. She continued to complain of muscle weakness and hip pain, necessitating IV narcotic analgesic. An infectious disease consult was obtained to rule out an infectious cause for the myositis. Viral serologies (Epstein Barr, IgG, IgM, HW) were all negative. The elevated LFTs were considered to be autoimmune in origin. A rheumatology consult was obtained, because it was believed that the patient's clinical presentation could be consistent with an autoimmune disorder. An antigen/antibody survey showed a positive ANA with a titer of 1:1,600 (normal 1:64); SS-A and SS-B antigens were also identified.
Lupus anticoagulant/anticardiolipin antibodies were negative. She had low complement levels: a C3 of 67 (normal = 83-184), and a C4 of 8 (normal = 17-59). Based on the laboratory data and clinical picture, Yvonne was diagnosed with SLE, and her altered mental status was thought to be secondary to CNS involvement. Even though no one laboratory test confirmed cerebritis, the presence of the mental confusion and the confirmed diagnosis of lupus supported the diagnosis of lupus cerebritis.
After helping the family get through the many days of diagnostic testing (many of the antibody tests had to be sent out for confirmation), the next step was deciding on treatment options for Yvonne.
The three main treatment options presented to the family included the use of immunosuppressants, steroids, and anticoagulants. Immunosuppressive agents such as cyclophosphamide and azathioprine are used to suppress circulating B and T cells and autoantibody formation (Bruyn, 1995). These agents are usually given intravenously as a bolus on a monthly basis. Steroids are used to reduce inflammation and the immune response (Bruyn, 1995). Some advocate "large pulse steroids" of W methylprednisolone given over 20-30 minutes, 1.5 g every day for 3 days. After the W dose, a low oral dose is given and then eventually tapered off. High-dose steroids are indicated in cases of coma, seizures, psychosis, or transverse myelitis (Bruyn, 1995). A favorable response to IV methylprednisolone and cyclophosphamide has been seen in children with severe neuropsychiatric lupus (Baca et al., 1999). Intrathecal injection of methotrexate plus dexamethasone is a promising new method for treating CNS lupus (Dong et al., 2001).
Anticoagulation, with low-dose aspirin, warfarin, or subcutaneous or IV heparin are possible third treatment options (Bruyn, 1995). Anticoagulation is started prophylactically only if the patient suffers from thrombosis. Low-molecular-weight heparinoids (LMWH) such as enoxaparin sodium, 30 mg every 12 hours subcutaneously, has recently been studied and is considered the most effective therapy for lupus patients with vascular thrombosis (Bick, 2001).
Psychotropic medications also are considered in certain patients. Antipsychotics are given for acute psychosis, and antidepressants or benzodiazepines are given as mood stabilizers or as adjunctive therapy when the patients are receiving steroids (Calabrese & Stern, 1995). Part of the treatment regimen for some of the neuropsychiatric manifestations such as major depression may include supportive psychotherapy and electroconvulsive therapy (Calabrese & Stern, 1995). Experimental therapies seen in the literature include five to seven exchanges of CSF pheresis over 7-10 days. This provides additive and synergistic immunomodulation (Barr & Merchut, 1992). Low doses of methotrexate, IV immunoglobulin (IgG), and total lymphoid irradiation are treatment options that also help modulate the overactive immune system (Bruyn, 1995; Sherer et al., 1999). A new immunomodulating hormone therapy, a synthetic form of dehydroepiandrosterone (prasterone) given orally, 200 mg a day, is being used to help reduce the need for steroid treatment among patients with mild to moderate disease. Biologic agents appear to be on the horizon for more severe SLE (Wallace, 2001).
Yvonne was started on methylprednisolone 125 mg IV every 6 hours. Her mental status continued to deteriorate over the next several days. She went from being awake and alert, to being confused, and then localizing to pain. The steroid was increased to 130 mg every 6 hours. On hospital day three, Yvonne's left upper extremity was noted to be edematous and tender to touch. An ultrasound revealed a thrombosis of her left subclavian vein. She was started on 1,000 units an hour of IV heparin and eventually transitioned to warfarin, 10 mg orally. Her hypercoagulable state was thought to be caused by her SLE.
On day four of her hospitalization, Yvonne desaturated to a p[O.sub.2] of 85%; arterial blood gases showed an arterial p[O.sub.2] of 48. She did not require intubation, but she was placed on a 100% nonrebreather mask. Pulmonary embolism was being considered; a ventilation perfusion scan showed low probability. The chest X ray, however, showed bibasilar infiltrates in the posterior aspects of both lungs, consistent with aspiration. A pulmonary consult was obtained and Yvonne was placed on antibiotics. A central-line catheter was placed for total parenteral nutrition (TPN). During this time the family was kept informed of all the changes in her condition because of the multisystem involvement of her SLE. The social worker and chaplain were helping them cope with the changes that seemed to be happening daily.
The next day the nurses noted that Yvonne's middle digit on her left hand was bluish in color. The rheumatologist determined that this was due to her continuing hypercoagulable state. Her steroids were increased to a pulse dose of 500 mg over 30 minutes for 3 days and then returned to 125 mg every 6 hours. A dose of IV cyclophosphamide, 500 mg, was given for immunosuppression.
After 7 days on steroids, Yvonne's mental status improved. She responded to voice and became more alert and oriented. Now that she was more cooperative, physical and occupational therapy began for more active range of motion, muscle strengthening, and assistance with activities of daily living. Yvonne was anemic throughout her hospitalization and received a total of 4 units of packed red blood cells. She also was thrombocytopenic and neutropenic, which was attributed to both her heparin and the dose of cyclophosphamide. She was given filgrastim, 250 mcg a day subcutaneously, for 4 days.
Yvonne continued to show progress. By day 12 of her hospitalization, she was weaned to room air and was transferred to the neurological floor. A swallow evaluation was done and trial feedings were begun. She eventually progressed to a mechanical soft diet without supervision; the TPN and central line were discontinued. A cognitive evaluation and treatment program were begun for difficulties Yvonne had with processing. A family care conference was held to plan discharge needs. The family was given the name of a contact person for the Lupus Support Group. On day 15 of her hospitalization, Yvonne was ready to transfer to her father's care and follow-up at a clinic near her father's home. Her steroids were being tapered as followed: prednisone 25 mg orally twice a day for 8 days, then 20 mg orally twice a day. Other medications she was continued on included warfarin, 7.5 mg, to be adjusted as necessary to maintain an INR goal of 2-3.
According to the literature, CNS involvement ranks second to renal failure as cause of death in the patient with SLE (Barr & Merchut, 1992). Prognosis is guarded because the multisystem involvement of lupus can continue with exacerbations and remissions. Yvonne survived 16 days of hospitalization with a new diagnosis of lupus. She encountered various infections and problems from her hypercoagulable state, including CNS involvement. She left the hospital with concentration and memory deficits. It was strongly recommended she seek continued cognitive therapy at her hometown clinic. Yvonne continues living with her father. She ended her relationship with her boyfriend and is employed at a fast food restaurant. One month after discharge from the hospital, she was still on low-dose steroids and received one additional dose of cyclophosphamide.
Lupus cerebritis may be the first indication of SLE. No one diagnostic test is conclusive of the CNS involvement in SLE; however, clinical manifestations support diagnosis. Various treatment options are utilized to aid with immunosuppression and the hypercoagulable state. The CNS involvement seen in lupus cerebritis is difficult for the family to deal with not only because of the sudden changes, but also because the waiting period for exact diagnosis may lead the family into a very difficult coping period. The neuroscience nurse has an important role in understanding not only the CNS involvement of SLE but also its diagnostic and treatment modalities, to help the patient and family cope with this sometimes devastating disease.
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Table 1. Proposed Mechanisms of Lupus Cerebritis Circulating Immune Complexes (DNA, anti-DNA) * vasculitis * disruption of blood brain barrier Anti-neuronal Antibodies * lympho-cytotoxic (LCAs): react with brain tissue * anti-neuronal membrane: directed toward neuronal antigens * intracytoplasmic: target ribosome and neurofilaments of neuron Antiphospholipid Antibodies * anticardiolipin: cause endothelial damage, platelet aggregation, inflammation and fibrosis * lupus anticoagulant: prolongs coagulation, "antiphospholipid syndrome" Cytokine Release * specifically interferon alfa and interleukin-6 * causes edema * endothelial thickening * infiltration of neutrophils in brain tissue Table 2. Neurological Manifestations of Lupus Cerebritis Focal Nonspecific Neuropsychiatric Transient ischemic Headache Affective attack/stroke * Vascular * Personality disorders * Muscular * Irritability Transverse myelitis * Anger Seizures * Anxiety Cranial nerve palsies * Tonic/clonic * Depression * Laryngeal palsy * Sadness * Visual loss Organic brain * Hopelessness * Ptosis syndrome * Facial weakness Behavioral * Crying Peripheral * Apathy neuropathy * Poor eye contact * Numbness/tingling * Lack of initiative * Facial pain * Tinnitus Cognitive * Difficulty thinking, Movement disorders concentrating, or * Chorea speaking * Cerebellar ataxia * Fluctuating level of consciousness Table 3. Diagnostic Tests for Lupus Cerebritis Test Frequent Findings Imaging Studies Computed tomography Normal brain, cerebral atrophy, infarcts, calcifications, intracranial hemorrhage, subdural fluid Cerebral blood flow (CBF) [down arrow]CBF Magnetic resonance imaging (MRI) Cerebral atrophy -- MRI relaxometry Cerebral edema, cerebritis -- Diffusion-weighted Acute/subacute infarction, echo-planar vasogenic edema -- MRI spectroscopy Presence of N-acetylaspartate, [up arrow]choline compounds, lipids, and macromolecules Electroencephalography Theta and delta slowing, sharp wave activity Evoked potentials Auditory involvement Positron emission tomography Abnormal cortical perfusion/ cerebral hypometabolism Transcranial Doppler [up arrow]velocity/microthrombi Laboratory Tests Cerebrospinal fluid [up arrow]protein levels, presence of interleukin-6, interferon alfa cytokines, [up arrow]nitrates/ nitrites, [down arrow]complements (C3, C4), presence of intra- cytoplasmic antibodies (anti- ribosomal P, anti-neurofilament, anti-SSA/anti-SSB), lympho- cytotoxic antibodies (LCAs) Serum Presence of DNA, anti-DNA antibodies (>1:64), anti-ribosomal, anti- neurofilament, anti-SSA/anti-SSB antibodies, lupus anticoagulant, anticardiolipin antibodies (IGG, IGA, IGM), (LCAs), [down arrow] complements (C3, C4) Neuropsychometric Tests Abnormal motor function, dexterity, Cognitive and verbal and nonverbal abilities; Psychological depression, affective, behavioral, Behavioral and cognitive disorders Key: [up arrow] = increased; [down arrow] = decreased
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