Reversible posterior leukoencephalopathy in connective tissue diseases

OBJECTIVES: To describe a case of reversible posterior leukoencephalopathy (RPLS) involving a patient with systemic lupus erythematosus (SLE) and to review the medical literature to define the epidemiological, clinical, radiological, and therapeutic aspects of this syndrome in various connective tissue diseases. METHODS: Report of 1 case and review of the English literature using Medline search from 1967 to 2005. RESULTS: Including our reported case, RPLS has been identified in 13 patients with connective tissue disease. In separate case reports, 9 SLE patients, 2 Wegener's granulomatosis (WG) patients, and 1 patient with SLE and systemic sclerosis presented with RPLS. Associated risk factors included malignant hypertension, acute renal failure, and recent treatment with cyclophosphamide, cyclosporine, or methylprednisolone. Patients were treated with blood pressure control, hemodialysis, or withdrawal of the offending drug. In our patient, plasmapheresis and high-dose methylprednisolone resulted in a full recovery. In most cases, complete resolution of neurological symptoms occur within 2 weeks of presentation, along with improvement or resolution of imaging abnormalities. CONCLUSION: RPLS is a clinicoradiological entity, associated with reversible white matter edema involving most commonly the posterior central nervous system circulation. Seizures and altered mental status in patients with SLE or WG can pose difficult diagnostic and therapeutic challenges. The differential diagnosis is broad and includes infection, uremia, hypertension, infarction, thrombosis, demyelinating disorders, and vasculitis. Accurate diagnosis of RPLS and its differentiation from other, more common causes of the central nervous system is essential to ensure the best possible outcome in this rare but life-threatening neurological disorder.     

Diagnosis and pathogenesis of CNS lupus

Summary The central nervous system (CNS) is clinically involved in approximately 40% of all systemic lupus erythematosis (SLE) patients. Minor psychiatric symptoms and abnormalities on neuropsychological testing are being detected with increasing frequency. This review summarizes current thinking concerning the diagnosis and pathogenesis of CNS lupus. The main symptoms of CNS lupus can be diffuse (generalized seizures, psychosis) or focal (stroke, peripheral neuropathies). Neuropsychiatric symptoms often occur in the first year of SLE, but are rarely the presenting symptoms of the disease. In studies on the pathology of CNS lupus, vasculopathy, infarcts and haemorrhages are often observed, whereas vasculitis is rare. Endocardial lesions and mural thrombi have also been reported in 33–50% of CNS lupus patients. In fliagnostic imaging of the CNS, magnetic resonance imaging (MRI) scans often provide evidence for edema or small infarcts, both in focal and diffuse CNS lupus, whereas computerized tomography (CT) scans only show gross abnormalitites. The first reports on position emission tomography (PET) scans in CNS lupus patients show decreased glucose uptake in the brain. The cerebral blood flow decreases during active diffuse and focal CNS lupus. The blood-brain barrier is somewhat more frequently impaired in diffuse CNS lupus. Intrathecal IgG and IgM production is observed in 25–66% of all CNS lupus patient. Various specificities of autoantibodies have been observed in CNS lupus. Of these, anticardiolipin (ACA) antibodies show a well-documented association with focal involvement of the CNS in SLE. These antibodies could cause thrombosis by interfering with the protein C pathway of fibrinolysis. In addition, they are associated with endocardial and valvular heart disease, which is often observed in SLE and which could cause ombolism. The relation between ACA and diffuse CNS lupus is not yet clear. Low-avidity anti-DNA antibodies are also found in CNS lupus, possibly because of their fross-reaction with cardiolipin. Antineuronal antibodies and lymphocytotoxic antibodies have been associated with diffuse CNS lupus and abnormalities on neuropsychological testing. However, the population of these antibodies is rather heterogeneous and it has not been possible to assess a common target antigen. Therefore, it is still obscure whether there is also a second immune-mediated mechanism responsible for the development of the diffuse form of CNS lupus.     

Reversible posterior leucoencephalopathy syndrome in systemic lupus and vasculitis

OBJECTIVES: Reversible posterior leucoencephalopathy syndrome (RPLS) may develop in patients with renal insufficiency, hypertension, and immunosuppression, and is managed by prompt antihypertensive and anticonvulsant treatment. Four patients with renal insufficiency and fluid overload associated with Wegener's granulomatosis (one patient) and systemic lupus erythematosus (SLE) (three patients) are described, whose clinical picture and neuroimaging indicated RPLS. CASE REPORTS: All patients had headache, seizures, visual abnormalities, and transient motor deficit, and were hypertensive at the onset of the symptoms. Head computed tomography (CT) scan and magnetic resonance imaging showed predominantly posterior signal abnormalities, which were more conspicuous on T(2) weighted spin echo images than on CT scan. All patients had some form of cytotoxic treatment shortly before the syndrome developed, and dramatically responded to blood pressure control and anticonvulsant treatment. In two patients with SLE, dialysis was required for renal insufficiency. DISCUSSION: Follow up neuroimaging studies showed almost complete resolution of signal abnormalities, and suggested that RPLS was associated with cerebral oedema without concomitant infarction. The treatment of hypertension and neurotoxic condition such as uraemia appears of primary importance, while immunosuppressive treatment may cause further damage of the blood-brain barrier.     

Clinical features of reversible posterior leukoencephalopathy syndrome in patients with systemic lupus erythematosus

To characterize reversible posterior leukoencephalopathy syndrome (RPLS) in systemic lupus erythematosus (SLE) in terms of treatments for resolution and its clinical course, we reviewed 28 cases of RPLS in SLE including our cases in view of the treatment. Of these, 15 cases improved with blood pressure control and 13 required immunosuppressive therapy for activity of SLE presenting neurological manifestations. Patients without immunosuppressants at onset of RPLS more frequently required immunosuppressive therapy to recover it than those precedingly using these agents [31% (4/13) versus 87% (13/15), p = 0.008, chi-square test]. Brain magnetic resonance imaging (MRI) is important for diagnosis of RPLS-SLE in the patient with SLE who develops neurological disturbance and rapidly increasing blood pressure. When 7-day therapy for hypertension and convulsion does not reverse the manifestations, immunosuppressive treatments would be recommended to reverse RPLS.     

Clinical features of reversible posterior leukoencephalopathy syndrome in patients with systemic lupus erythematosus

Abstract

To characterize reversible posterior leukoencephalopathy syndrome (RPLS) in systemic lupus erythematosus (SLE) in terms of treatments for resolution and its clinical course, we reviewed 28 cases of RPLS in SLE including our cases in view of the treatment. Of these, 15 cases improved with blood pressure control and 13 required immunosuppressive therapy for activity of SLE presenting neurological manifestations. Patients without immunosuppressants at onset of RPLS more frequently required immunosuppressive therapy to recover it than those precedingly using these agents [31% (4/13) versus 87% (13/15), p = 0.008, chi-square test]. Brain magnetic resonance imaging (MRI) is important for diagnosis of RPLS-SLE in the patient with SLE who develops neurological disturbance and rapidly increasing blood pressure. When 7-day therapy for hypertension and convulsion does not reverse the manifestations, immunosuppressive treatments would be recommended to reverse RPLS.     

Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement

Symptoms originating from central nervous system (CNS) are frequently occuring in patients with systemic lupus erythematosus (SLE). Reliable diagnostic markers for this condition are presently lacking. Importantly, CNS involvement in lupus patients is associated with increased morbidity and mortality. The aim of this retrospective evaluate was to study the diagnostic value of cerebrospinal fluid (CSF) cytokine levels in SLE patients with CNS involvement. 34 patients with SLE were hospitalized and investigated for the presence of CNS lupus. These patients were evaluated clinically and with magnetic resonance imaging (MRI) and CSF analyses, as well as with neuropsychiatric tests. 13 patients were found to have CNS lupus whereas another four of the patients fulfilled the criteria for CNS involvement but were excluded from this group due to other causes of CNS involvement. Lastly, in 17 SLE cases, the diagnosis of CNS lupus could not be confirmed. CSF levels of interleukin-6 (IL-6) and IL-8, as well as the CSF/serum IL-6 ratio, were elevated in the CNS lupus group, compared with the 17 SLE patients not fullfilling a diagnosis of cerebral lupus. Interestingly, follow-up of five patients being successfully treated for CNS lupus revealed profound decrease of intrathecal IL-6 levels. These results indicate that analysis of CSF cytokine levels, especially IL-6 and IL-8, may be useful in the diagnostics and possibly follow-up of SLE patients with cerebral lupus.     

Central nervous system lupus: a clinical approach to therapy

Management of central nervous system (CNS) involvement still remains one of the most challenging problems in systemic lupus erythematosus (SLE). The best available evidence for the treatment of CNS lupus is largely based on retrospective series, case reports and expert opinion. Current therapy is empirical and tailored to the individual patient. Symptomatic, immunosuppressive and anticoagulant therapies are the main strategies for the management of CNS lupus. The choice depends on the most probable underlying pathogenic mechanism and the severity of the presenting neuropsychiatric symptoms. Thrombotic and nonthrombotic CNS disease needs to be differentiated and requires different management strategies. However, this is often challenging since many, if not most CNS manifestations, may be due to a combination of different pathogenic mechanisms and multiple CNS events may occur in the individual patient. Patients with mild manifestations may need symptomatic treatment only, whereas more severe acute nonthrombotic CNS manifestations may require pulse intravenous cyclophosphamide. Plasmapheresis may also be added in patients with more severe illness refractory to conventional treatment. Recently, the use of intrathecal methotrexate and dexamethasone has been reported in a small series of patients, with a good outcome in patients with severe CNS manifestations. Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid syndrome (APS). This article reviews the clinical approach to therapy in patients with CNS lupus.     

Recent advances and future perspective in neuroimaging in neuropsychiatric systemic lupus erythematosus

Involvement of the central nervous system (CNS) is one of the most important complications of systemic lupus erythematosus (SLE), occurring in 14-75% of SLE patients. Neurological and psychiatric involvement is mainly manifested as cerebrovascular disease, seizures, cognitive impairment, headaches and psychosis. However, diagnosis of brain involvement in SLE (i.e., neuropsychiatric lupus: NPSLE) as well as understanding of pathogenetic mechanisms still remains a difficult challenge. Although a wide range of neurodiagnostic tools have been used in the last decade to assess CNS involvement, no single technique has proven to be definitive or reliable. Since neurometabolic impairment, neurochemistry and perfusion abnormalities in NPSLE may precede anatomic lesions, new functional techniques such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, and magnetization transfer imaging may be useful in order to indentify pathologic changes unrevealed by conventional imaging. So these new diagnostic tools could modify diagnostic and therapeutic approaches to this major unsolved problem, also shedding some light on the physiopathology of CNS disease in SLE.     

Initial presentation of acute transverse myelitis in systemic lupus erythematosus: demographics, diagnosis, management and comparison to idiopathic cases

To describe and compare the diagnosis, demographics and management of systemic lupus erythematosus (SLE) related versus idiopathic acute transverse myelitis during the initial presentation of the disease. We undertook a chart review of the hospital records of patients admitted to our hospital from 1994 until 2007 and had the diagnosis of SLE related and idiopathic acute transverse myelitis. Demographics, laboratory and imaging studies, diagnosis and treatment were recorded in both groups and analyzed in a case control fashion. We identified 15 patients with SLE-related acute transverse myelitis (SLE-ATM) and 39 idiopathic (I-ATM) cases between 1994 and 2007. Patients with SLE were more likely to be African American, have CNS demyelinating lesions on MRI, a high IgG% on their CSF analysis and a higher sedimentation rate on presentation. Treatment with high-dose steroids was instituted in both groups of patients, though SLE patients had a longer hospital stay by an average of 5 days. SLE-ATM patients were more likely to be African American as compared to I-ATM patients, have CNS demyelinating lesions on MRI, a high IgG% on CSF analysis and a higher sedimentation rate on presentation. The hospital stay for SLE patients was 5 days longer than the idiopathic patients. This study underlines the importance of early diagnosis of patients who develop ATM related to SLE.     

系统性红斑狼疮合并可逆性脑白质后部综合征1例报道

目的 探讨系统性红斑狼疮（SLE）合并可逆性脑后部白质综合征（RPLS）的诱发因素、临床特点及诊治要点,以提高临床医生对该病的认识,降低误诊率。方法 对近期我科收治的1例SLE合并RPLS的临床资料进行了深入分析,并复习相关文献。结果 患者原发病诊断明确,入院后双手颤抖伴癫痫失神发作,予以大剂量激素联合他克莫司治疗及抗癫痫处理后效果不佳,停用他克莫司及积极控制血压等处理后,未再出现类似症状,头颅MRI提示病变范围较前明显缩小,综合考虑诊断为SLE合并RPLS。结论 SLE合并RPLS极易与神经精神狼疮、高血压脑病等疾病混淆,临床应提高对该病的认识和警惕,避免误诊误治。     

Systemic lupus erythematosus

This review covers major advances in clinical issues related to systemic lupus erythematosus (SLE) published between 1995 and 2000. The classification criteria for both SLE and antiphospholipid syndrome (APS) have been updated, and up to 19 different subsets of neuropsychiatric lupus have been defined. New epidemiological data show that the incidence of new cases and the survival of patients with SLE are both increasing. Several randomised controlled trials have defined the role of cyclophosphamide, methotrexate, antimalarials, and hormonal treatment in the management of SLE. New data are available for drugs such as ciclosporin and thalidomide. Finally, several new treatments for severe refractory cases, such as mycophenolate mofetil and stem-cell transplantation, are being increasingly used. New data also refer to management of thrombosis in APS and high-risk pregnancies in women with SLE or APS.     

Choroidopathy of systemic lupus erythematosus

PURPOSE: To describe the ocular and systemic manifestations associated with systemic lupus erythematosus (SLE) choroidopathy. METHODS: Three new cases of choroidopathy in patients with active SLE were described. Twenty-five published cases of lupus choroidopathy were summarized. RESULTS: There have been 28 cases of lupus choroidopathy (47 involved eyes) that have been reported in the English literature since 1968, including the three current cases. Only two of the patients were male. The choroidopathy was bilateral in 19 patients (68%). All 28 patients (100%) had active systemic vascular disease at the onset of their choroidopathy; 18 (64%) had nephropathy and 10 (36%) had central nervous system (CNS) lupus vasculitis. All but one of the patients had a known diagnosis of SLE at the onset of choroidopathy. 30 of the 47 involved eyes had presenting visual acuity of 20/40 or better; 14 eyes showed improvement in visual acuity with therapy. 23 patients (82%) had resolution of their choroidopathy when their systemic disease was brought under control. Despite treatment, 4 of the 28 patients (14%) died from complications of SLE. CONCLUSIONS: Although less known than retinopathy, lupus choroidopathy may be more common than generally appreciated. It usually serves as a sensitive indicator of lupus activity. The presence of SLE choroidopathy is generally indicative of coexistent (although sometimes occult) nephropathy, CNS vasculitis, and other SLE visceral lesions. Immunomodulation of the systemic disease can lead to improvement and resolution of the systemic vasculitis as well as the choroidopathy.     

Multimodality Cardiac Imaging in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematous (SLE) is an autoimmune disease with a wide range of cardiovascular complications. The main manifestations include diseases of the coronary arteries, valves, pericardium, and myocardium. Multimodality cardiovascular imaging techniques are critical for evaluating the extent of cardiac manifestations in SLE patients, which can provide valuable prognostic information. However, their utility has previously not been well defined. This review provides a state-of-the-art update on the cardiovascular manifestations of lupus, as well as the role of multimodality cardiac imaging in guiding management of patients with SLE.     

Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement

OBJECTIVE: Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). CNS involvement in lupus is associated with increased morbidity and mortality. Currently, reliable markers for activity in this condition are absent. The goal of this study was to determine the level of the light subunit of the neurofilament triplet protein (NFL) and that of glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid of SLE patients with clinically verified CNS involvement and compare them with the levels in SLE patients without CNS involvement. METHODS: We assessed cerebrospinal fluid obtained from 99 patients with SLE and 99 age-matched controls for the presence of soluble molecules indicating neuronal destruction and astrogliosis-NFL and GFAP, respectively. Patients were evaluated clinically, with magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analyses, and neuropsychiatric tests. RESULTS: In the group of lupus patients with CNS involvement, intrathecal levels of NFL and GFAP were increased an average of 7-fold (P 相似文献   

Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus. Their use as estimates of central nervous system disease activity

Paired serum and cerebrospinal fluid (CSF) specimens from 13 patients with systemic lupus erythematosus (SLE) and central nervous system involvement (CNS-SLE) were studied for CSF IgM, IgA, and IgG indexes (indicators of intrathecal immunoglobulin synthesis) and CSF-serum albumin quotient (Q albumin) (an indicator of blood-brain-barrier function). We also studied 20 patients with noninflammatory neurologic diseases and seven patients with SLE without CNS involvement for comparison. In addition to an increase in the CSF IgG index, IgM and IgA indexes also were elevated in patients with CNS-SLE. All three indexes decreased significantly when CNS manifestations subsided by successful treatment. The Q albumin was normal in most patients. The elevation of CSF immunoglobulin indexes may be a result of polyclonal B-lymphocyte activation within the CNS, rather than the leak of immunoglobulins from the systemic circulation into the CNS. Since these indexes reflect CNS disease activity in SLE, they may be a successful tool for the management of SLE.     

Cerebrospinal fluid and serum prolactin in systemic lupus erythematosus with and without central nervous system involvement

Aim: Recent research has shown that prolactin (PRL) may participate in the pathogenesis of systemic lupus erythematosus (SLE) and hyperprolactinemia may be related to disease activity. The current study investigated both serum and cerebrospinal fluid (CSF) PRL in SLE patients and their possible relationship to central nervous system (CNS) involvement. Methods: Prolactin levels were determined by immunoradiometric assay. Serum PRL levels were detected in 80 patients with SLE and 25 matched healthy controls. Disease activity was scored by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). CSF PRL levels were detected in seven cases of CNS involving SLE, eight cases of non‐CNS involved inactive SLE and eight cases of non‐SLE CNS disorders. Results: Hyperprolactinemia was present in 40% of SLE patients. Serum PRL levels were significantly correlated with SLEDAI scores. There was no significant difference in serum PRL levels between SLE patients with or without CNS involvement, but the mean CSF PRL levels were higher in CNS‐involved SLE patients than in non‐CNS‐involved SLE and non‐SLE patients. There was no significant correlation between serum and CSF PRL levels. Conclusions: Our results suggest that high serum PRL levels correlate with active disease in SLE, but not with CNS involvement. CSF PRL levels in SLE patients correlate with CNS involvement, which indicates that CSF PRL may be involved in the pathogenesis of CNS‐SLE.     

Diagnostic value of single‐photon–emission computed tomography in severe central nervous system involvement of systemic lupus erythematosus: A case‐control study

Objective

To evaluate the diagnostic value of single‐photon–emission computed tomography (SPECT) in severe central nervous system (CNS) involvement of systemic lupus erythematosus (SLE).

Methods

Forty‐three patients with SLE, including 22 with CNS‐SLE and 21 with non–CNS‐SLE, underwent SPECT and magnetic resonance imaging (MRI) examinations. SPECT was repeated 1–2 months after treatment in patients with abnormal findings.

Results

SPECT and MRI abnormalities were detected in 20 (90.9%) and 10 (45.5%) of the 22 patients with CNS‐SLE, respectively (P < 0.01). For 4 patients with cerebral infarction or hemorrhage, SPECT was equally as sensitive as MRI (100%). For the patients with CNS‐SLE with diffuse presentations, SPECT was more sensitive than MRI in revealing abnormalities (16 [88.9%] of 18 patients versus 6 [33.3%] of 18 patients; P < 0.01). In 19 (95.0%) patients, the abnormal SPECT finding manifested as moderate to severe perfusion defect (15 in frontal lobe, 11 in parietal lobe, 11 in basal ganglia, 3 in temporal lobe, and 17 in multiple regions). Although mild perfusion defect was also detected in 4 (19.0%) of the patients with non–CNS‐SLE, it only involved a single region and spared the frontal and parietal lobes. Repeated SPECT after treatment showed that perfusion defect had improved significantly or even disappeared in 11 (84.6%) of 13 patients with diffuse CNS‐SLE with abnormal findings before treatment.

Conclusion

Moderate to severe perfusion defect in SPECT involving multiple regions, especially in the frontal and parietal lobes and basal ganglia, in patients with lupus suggests CNS involvement. SPECT is more sensitive than MRI in revealing damage in diffuse CNS‐SLE, and is useful in followup, especially for monitoring disease severity and guiding treatment.

     

Outcome of Collagen Vascular Diseases by Treatment with Plasmapheresis

Abstract: The outcome of collagen vascular diseases after treatment with plasmapheresis was studied in 9 patients with polyarteritis nodosa (PN), in 2 patients with Wegener's granulomatosis (WG), in 1 patient with allergic granulomatous angitis (AGA), and in 20 patients with systemic lupus erythematosus (SLE) associated with antiphospho-lipid syndrome (APS). Improvement after treatment with plasmapheresis was observed in 41.7% of the patients with PN, WG, and AGA. On the other hand, with the exception of 1 patient with thrombocytopenia and 1 patient with renal failure, all of the clinical manifestations, including thrombocytopenia, central nervous system (CNS) lupus, thrombophlebitis, lung infarction, and recurrent abortions in the SLE patients with APS, improved after plasmapheresis. Plasmapheresis is thought to be an influential strategy of treatment for patients with collagen vascular diseases.     

Pneumocystis jiroveci pneumonia in patients with systemic lupus erythematosus after rituximab therapy

Pneumocystis jiroveci pneumonia (PCP) is an uncommon but potentially life-threatening infection in immunocompromised patients with low blood T cells. Rituximab, a chimeric human/murine monoclonal antibody against the B cell-specific antigen CD20, has been increasingly used and appears to be effective in the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE). PCP has been reported in some patients with autoimmune diseases or lymphoma subjected to rituximab treatment, but has not yet been reported in SLE patients. We report PCP in two patients with SLE after rituximab treatment. Fever and respiratory symptoms associated with diffuse pulmonary infiltrates developed within weeks after rituximab therapy. One patient died of respiratory failure. Another patient recovered uneventfully after treatment with clindamycin and primaquine.     

Magnetic resonance and computed tomographic imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus.

Magnetic resonance (MR) imaging and computed tomography (CT) are useful for the evaluation of central nervous system (CNS) lupus. This report describes the use of cranial MR and CT in 21 patients with systemic lupus erythematosus (SLE) with acute neuropsychiatric symptoms manifested by headache, seizures, focal neurological deficits, psychosis, or organic brain syndrome. Computed tomography was found to be insensitive and detected only diffuse atrophy (two cases), cerebral infarct (one case), and intracerebral haemorrhage (one case) in the 21 patients. Cranial MR images obtained with a General Electric 1.5 tesla Signa unit detected labile and fixed areas of increased proton intensity interpreted as focal oedema (eight cases), infarct (10 cases), haemorrhage (one), atrophy (seven), and acute sinusitis (two). Focal oedema was characterised by labile, high intensity lesions in the gray or white matter of the cerebellum, cerebrum, or brain stem, which completely resolved after aggressive corticosteroid treatment. Most high intensity reversible or fixed lesions evident on MR were not apparent on cranial CT images. In several patients sequential MR images were valuable in monitoring the efforts of treatment. Although histological confirmation of the high intensity brain lesions apparent on MR is desirable, prior necropsy studies suggest that pathological confirmation may be difficult owing to the paucity of recognisable brain lesions in patients with CNS lupus. It is concluded that for the evaluation of acute neuropsychiatric SLE MR is useful and provides more information than cranial CT.