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.     

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.     

Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.     

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.     

Reversible posterior leukoencephalopathy syndrome in a patient with Takayasu arteritis

Reversible posterior leukoencephalopathy syndrome (RPLS) has been identified in several connective tissue diseases. However, there are no reports of RPLS associated with Takayasu arteritis (TA). We report the first case of TA associated with RPLS. A 23-year-old woman presented with sudden headache and vomiting, followed by generalized tonic–clonic seizures and mental changes two weeks after administration of oral prednisolone. MRI showed hyperintense signals on T2 and FLAIR images in the bilateral temporal–parietal–occipital lobes, left frontal lobe, and left cerebellar hemisphere. Three weeks after starting control of convulsions and blood pressure with plasmapheresis, high-dose methylprednisolone, and cyclophosphamide, the clinical manifestations and abnormal signals on MRI completely resolved. These reversible clinical and radiological changes are consistent with vasogenic edema in the central nervous system, indicating RPLS. Although high-dose methylprednisolone and cyclophosphamide are thought to cause RPLS, we think that it is justified to use these agents, at least in difficult cases, for making a clear-cut differentiation from CNS vasculitis, as long as blood pressure and fluid volume are well controlled. Moreover, we suggest that RPLS should be included in differential diagnosis of acute neurological changes in connective tissue diseases, including TA.     

Reversible posterior leukoencephalopathy syndrome in a patient with Takayasu arteritis

Abstract

Reversible posterior leukoencephalopathy syndrome (RPLS) has been identified in several connective tissue diseases. However, there are no reports of RPLS associated with Takayasu arteritis (TA). We report the first case of TA associated with RPLS. A 23-year-old woman presented with sudden headache and vomiting, followed by generalized tonic–clonic seizures and mental changes two weeks after administration of oral prednisolone. MRI showed hyperintense signals on T2 and FLAIR images in the bilateral temporal–parietal–occipital lobes, left frontal lobe, and left cerebellar hemisphere. Three weeks after starting control of convulsions and blood pressure with plasmapheresis, high-dose methylprednisolone, and cyclophosphamide, the clinical manifestations and abnormal signals on MRI completely resolved. These reversible clinical and radiological changes are consistent with vasogenic edema in the central nervous system, indicating RPLS. Although high-dose methylprednisolone and cyclophosphamide are thought to cause RPLS, we think that it is justified to use these agents, at least in difficult cases, for making a clear-cut differentiation from CNS vasculitis, as long as blood pressure and fluid volume are well controlled. Moreover, we suggest that RPLS should be included in differential diagnosis of acute neurological changes in connective tissue diseases, including TA.     

Posterior reversible encephalopathy syndrome during systemic lupus erythematosus: four new cases and review of the literature

Posterior reversible encephalopathy syndrome (PRES) associates various neurological manifestations (headaches, seizures, altered mental status, cortical blindness, focal neurological deficits, vomiting) and transient changes on neuroimaging consistent with cerebral edema. Posterior reversible encephalopathy syndrome mainly occurs in the setting of hypertension, eclampsia, renal failure and/or use of immunosuppressive drugs.We report four cases of PRES complicating systemic lupus erythematosus (SLE). In all our cases, renal involvement and hypertension were present. Neurological symptoms were typical. Magnetic resonance imaging showed posterior cerebral edema and in one case hemorrhagic complication. With symptomatic treatment and immunosuppressor withdrawal when they were previously used, symptoms fully resolved within 15 days in all cases, but one who had only partial regression related to cerebral hemorrhage.Including our cases, we reviewed a total of 46 patients with SLE and PRES. Their clinical and radiological presentation was not specific. The peculiar role of SLE itself in the occurrence of PRES was not clear, since hypertension (95%), renal involvement (91%), recent onset of immunosuppressive drugs (54%) and/or recent treatment with high intravenous dose of steroids (43%) were often present. The hypertension and other worsening factors should be treated. Finally, the evolution of this clinical and radiological spectacular syndrome is generally rapidly favorable.     

系统性红斑狼疮足细胞病七例临床特征分析

目的 回顾性分析狼疮足细胞病(LP)患者的临床及实验室特征、治疗反应及预后.方法 选取2011年1月至2019年5月无锡市人民医院住院期间行肾活检证实的LP病例7例,回顾性分析其临床及实验室特征、治疗反应及预后.结果 7例LP中6例为女性,平均发病年龄(33±12)岁,SLE平均病程(69±64)个月,其中3例为初发初诊,6例为初次诊断狼疮肾损害.6例患者表现为肾病综合征(NS);2例表现为急性肾功能不全(ARF).LP患者肾脏表现与SLE疾病活动度不平行,自身抗体阳性率、低补体发生率均较低.经激素、免疫抑制剂治疗后6例患者肾脏病变缓解;随访过程中,2例患者出现肾脏复发.结论 LP以生育期女性好发,NS或伴AKI是其主要临床表现,肾脏表现与肾外表现不平行,激素、免疫抑制剂治疗敏感,部分患者治疗后可出现复发.     

Reversible posterior leukoencephalopathy syndrome induced by bevacizumab plus chemotherapy in colorectal cancer

Reversible posterior leukoencephalopathy syndrome(RPLS)is a rare brain-capillary leak syndrome,characterized by clinical symptoms of headache,visual loss,seizures and altered mental functioning.This syndrome is usually reversible and is associated with hypertension,nephropathy,and use of immunosuppressive medication and cytotoxic agents.We describe two rare cases of RPLS occurring in colorectal cancer,both of which presented with coma,that we believe can be directly attributed to bevacizumab,a monoclonal antibody that inhibits the angiogenesis of tumours by specifically blocking vascular endothelial growth factor.We analysed the clinical features,risk factors and outcomes of RPLS in these two patients,and although no typical finding was identified on imaging examination,we found that inadequate blood pressure control was one of the risk factors leading to RPLS and that supportive treatment including intensive blood pressure control improved outcomes.Due to the increasing use of bevacizumab in colorectal cancer,clinicians should be aware of this potential complication.     

Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon but distinctive clinicoradiological entity comprising of headache, seizures, visual disturbance, and altered mental function, in association with posterior cerebral white matter edema. With appropriate management, RPLS is reversible in the majority of cases. Previous reported associations of RPLS include hypertension, eclampsia, renal failure, and use of immunosuppressive drugs; reports in the adult hematology setting are rare. We report two cases of adults undergoing treatment for hematological malignancies who developed RPLS, and we emphasize the importance of early recognition and institution of appropriate management in reducing the risk of development of permanent neurological disability.     

Autoantibodies against alpha-fodrin in Sjögren's syndrome with neurological manifestations

OBJECTIVE: To investigate the diagnostic value of autoantibodies against alpha-fodrin in patients with Sj?gren's syndrome (SS) with neurological manifestations compared to SS patients without neurological manifestations, a control group, and patients with other neurological autoimmune diseases including systemic lupus erythematosus (SLE) with neurological manifestations and multiple sclerosis (MS). METHODS: We evaluated alpha-fodrin autoantibodies in 31 patients with SS with neurological manifestations, 53 SS patients without neurological symptoms, 38 patients with SLE, 60 with MS, and 160 controls. RESULTS: Twenty of the 31 SS patients with neurological manifestations (64.5%) had an increased concentration of IgA and/or IgG anti-alpha-fodrin. This was not statistically different from that of SS patients without neurological symptoms (73.6%), but was higher than the number with SSA/SSB antibodies, which were found in 15 (48%) of our SS patients without neurological manifestations. When the results of the 2 tests were combined, 28 of the 31 (90.3%) patients had positive autoantibodies (alpha-fodrin and/or SSA/SSB). Alpha-fodrin antibodies were increased in 8 (13.3%) of the 60 patients with MS, in 6 (15.7%) of 38 patients with SLE, and in 10 (6.3%) of 160 controls. CONCLUSION: Our results confirm that alpha-fodrin antibodies are an additional diagnostic tool for SS. This test is of particular interest for patients with SS with neurological manifestations, in whom anti SSA/SSB antibodies are less frequently found.     

Pattern of neuropsychiatric manifestations and outcome in juvenile systemic lupus erythematosus

The aim of this study was to study the neuropsychiatric (NP) manifestations, diagnostic evaluation, treatment and outcome in juvenile systemic lupus erythematosus (SLE). We reviewed the charts of all children with SLE and evidence of NP manifestations as defined by the presence of at least one of the following: headache, cerebrovascular accident (CVA), chorea, seizure, papilledema, and psychiatric or spinal cord manifestations. Out of 90 children with SLE, 20 (16 female) had NP manifestations. The mean age at onset was 8.8 years. The mean period between onset of SLE and NP manifestations was 10.2 months. NP manifestations were the presenting feature in 3 patients. Eleven patients had headache, 10 had psychiatric manifestations, 10 had seizure and 6 had CVA. Coma was seen in 5 patients, chorea in 4, transverse myelitis in 2 and papilledema in 2. Anticardolipin antibodies were high in 12 patients. Five patients had an abnormal CSF study. Nine patients had EEG abnormalities and 13 showed MRI abnormalities. All patients received oral prednisone and 17 were treated with IVMP and immunosuppressive therapy (cyclophosphamide or azathioprine); 85% of our patients recovered completely, but 15% had persistent NP sequelae; 10% died from severe infection. In conclusion, NP involvement in juvenile SLE is common. However, early diagnosis and early treatment with adjunctive intravenous pulse cyclophosphamide may improve the outcome.Abbreviations CVA Cerebrovascular accident - IVMP Intravenous methylprednisolone - NP Neuropsychiatric - SLE Systemic lupus erythematosus     

The short-term role of corticosteroid therapy for pulmonary arterial hypertension associated with connective tissue diseases: report of five cases and a literature review

Pulmonary arterial hypertension (PAH) is a life-threatening complication in connective tissue diseases (CTD). It remains controversial whether immunosuppressive therapy is useful for PAH associated with CTD (PAH-CTD). The Dana Point algorithm does not refer such treatments in patients with PAH-CTD due to the lack of evidence. However, some case reports have shown the potential efficacy of immunosuppression for PAH-CTD. Here we report five cases of PAH-CTD treated with corticosteroids and discuss the current management of PAH-CTD with immunosuppressive agents. Our cases consisted of three active systemic lupus erythematosus (SLE), a quiescent SLE and an active polymyositis. WHO functional classes at baseline were class III in three cases and class II in two. Median follow-up period was 44 (28-92) weeks. PAH was diagnosed by right heart catheterization in all cases (median pulmonary arterial pressure was 45 (29-49) mmHg). All patients received 1?mg/kg of prednisolone (PSL) for 2-4?weeks, followed by appropriate dose reduction. Methylprednisolone pulse therapy was performed in patients resistant to the high dosage of PSL. Four patients received vasodilators in combination. The therapy as above improved WHO functional class 4?weeks after the initiation of PSL in all the patients. Two patients required dose increase or additional administration of vasodilators due to the dose reduction of PSL. Corticosteroid therapy may be effective for PAH-CTD at least in the short term, even in low general activity of CTD or moderate PAH. Our experience suggests that corticosteroid therapy, by itself or in conjunction with standard vasodilators, is effective for PAH-CTD patients.     

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。     

Profile of neurological manifestations in systemic lupus erythematosus

IntroductionTo study the pattern of neurological involvement in systemic lupus erythematosus (SLE) and its correlation with investigation, disease activity and response to treatment.MethodsThis observational study was carried out from June 2007 to May 2008. Diagnosed cases of SLE (based upon ARA criteria) who present with neurological manifestations at the time of diagnosis or develop neurological manifestations anytime during the course of the disease were followed up for six months. Both prospective and retrospective cases were included.ResultsOf the 35 patients with neurological manifestations of SLE, presenting to KEM hospital, Mumbai from the period of June 2007 to May 2008, 94% were females. The commonest age group was 20–29 years. Manifestations observed were seizures (66%), altered sensorium (20%), psychosis (9%), hemiparesis (9%), headache (6%), peripheral neuropathy (6%), depression (3%), cognitive decline (3%) and myelopathy (3%). With appropriate and adequate treatment, at the end of the study, 86% patients improved neurologically and in terms of SLE disease activity, while 11% died and 4% remained the same state neurologically.ConclusionNeurological involvement in SLE is seen relatively early during the course of the disease and correlates with disease activity. It is commonly seen in patients with SLE who receive inappropriate and/or inadequate treatment.     

Gender and ethnic origin have no effect on longterm outcome of childhood-onset systemic lupus erythematosus

OBJECTIVE: To investigate the associations of gender and ethnic origin with longterm outcome in childhood-onset systemic lupus erythematosus (SLE). METHODS: The study cohort consisted of 51 patients (13 males and 38 females) with childhood-onset SLE followed for > or = 5 years at the British Columbia Children's Hospital in Vancouver. Fifteen patients were Caucasian, 14 Chinese, 9 East Indian, and 13 patients were of other ethnic backgrounds: none was African-American or Hispanic. Outcome measures assessed retrospectively included Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (SDI), SLE-related death, need for dialysis or renal transplantation, and use of intensive immunosuppressive therapy. A SDI > or = 2 was assigned as poor outcome. RESULTS: The median age at diagnosis was 10.8 years and the median duration of followup was 7.2 years. Five-year survival was 100%; 10-year survival was 85.7% (12/14 patients). The median SDI score at last followup was 2.0 (range 0-9); 2.0 for male, 1.5 for female; 2.0 for Caucasian and 2.03 for non-Caucasian patients. Twenty-six out of 51 patients (51%) had poor outcome (SDI score > 2). Three female patients required dialysis: 2 had subsequent renal transplants. Thirty patients received intensive immunosuppressive therapy. The SDI scores, mortality, and need for intensive immunosuppressive therapy were not influenced by either gender or ethnic origin. CONCLUSION: The median SDI score was high for this cohort with childhood-onset SLE. In contrast to other published data, no association of male gender and/or non-Caucasian ethnicity with poor outcome was found in our study cohort.     

Controversies and advances in the management of systemic lupus erythematosus in children and adolescents

Systemic lupus erythematosus (SLE) begins in childhood or adolescence in approximately 15% of cases, and although short- and long-term outcomes have improved considerably in the past 20 years there remain many areas of controversy regarding optimal management of these patients. In this chapter, areas of debate reviewed include: the appropriate timing of adding immunosuppressive therapy to corticosteroids, the optimal choice of immunosuppressive medication, the management of patients who fail 'standard' therapies, the significance and appropriate treatment of antiphospholipid antibodies in children with SLE and the emerging morbidities of childhood SLE. The goal of this chapter is to provide a balanced literature review and clinical approach to children and adolescents with SLE and to highlight areas requiring studies in paediatric clinical research.     

Immunablation in Kombination mit autologer Stammzelltransplantation bei Lupus

Systemic lupus erythematosus (SLE) is a classic systemic autoimmune disease. Standard treatment consists of chronic therapy with antimalarials, glucocorticoids and immunosuppressive/cytotoxic drugs, which is associated with considerable side effects. In contrast, immunoablation of autoreactive immunologic memory followed by autologous stem cell transplantation (ASCT) has been the only regimen capable of inducing long-term remission of up to 10 years after cessation of immunosuppressive therapy, even in severely affected patients. Introduced in 1996, the procedure has since been performed in 147 patients with severe SLE refractory to standard treatment in clinical studies worldwide. Most of these patients achieved clinical long-term remission. However, SLE relapses and secondary autoimmune disorders have been reported. Transplant-related mortality occurred in 6% of the 147 cases, with a wide center effect (2–13%). Here we summarise the results published in the literature on immunoablation followed by ASCT in SLE and discuss future perspectives for optimising this therapeutic approach. It may be possible to improve the outcome and reduce the risks of treatment by identifying patients with a poor prognosis at an early stage, before irreversible organ damage has taken place.     

Reversible posterior leucoencephalopathy syndrome associated with anticancer drugs

Background: Reversible posterior leucoencephalopathy syndrome (RPLS) is an underappreciated clinical‐radiologic syndrome characterized by reversible cortical dysfunction preferentially involving the occipital lobes in conjunction with imaging findings of reversible subcortical oedema. As RPLS is being increasingly identified within the oncology population in association with cytotoxic chemotherapy and targeted agents, a review of the published work in English was carried out. Methods: A MEDLINE search of the published work in English was conducted to identify cases of RPLS in patients more than 16 years of age who were treated with anticancer drugs for documented malignancy. Only cases with adequate documentation regarding demographic and treatment data, cerebral magnetic resonance imaging and outcome were selected. Results: We identified 24 patients with RPLS associated with a variety of anticancer drugs, most commonly complicating polychemotherapy and/or bevacizumab‐containing regimens. There was a female predominance: 18 females and 6 males (P= 0.023). Women were of premenopausal age and were younger than males: 49.3 ± 16.4 years versus 60.7 ± 6.4 years (P= 0.09). Most patients presented with acute headache (67%), seizures (63%), confusion (54%) or cortical blindness (46%) with mean systolic and diastolic blood pressure of 168 ± 15 and 98 ± 15 mm Hg, respectively. Findings on magnetic resonance imaging showed hyperintense lesions on T₂‐weighted images in all patients, which involved the occipital lobes in 75% of patients; all patients experienced clinical and radiologic resolution within days to weeks. No deaths were directly attributed to RPLS. Conclusions: Combination and single‐agent chemotherapy as well as novel anticancer drugs are associated with RPLS. We found RPLS to be overrepresented in premenopausal woman; the prevalence in this subgroup may be related to an anticancer drug–oestrogen interaction inducing altered cerebral vasoreactivity and endothelial dysfunction.     

Transverse myelitis as the first manifestation of systemic lupus erythematosus or lupus-like disease: good functional outcome and relevance of antiphospholipid antibodies

OBJECTIVE: Transverse myelitis (TM) is a rare complication of systemic lupus erythematosus (SLE). Although usually a late manifestation of SLE, it can occur at presentation. We investigated the clinical presentation, treatment and outcome of 15 patients with TM as the presenting manifestation of SLE or lupus-like disease. METHODS: All patients received corticosteroids, while 13 also received immunosuppressive therapy. Five patients were fully anticoagulated with warfarin. RESULTS: A sensory level with spastic lower limb weakness and sphincter disturbance was the most common presentation: 14/15 patients had a thoracic or cervical sensory level. Cerebrospinal fluid examination showed high protein concentrations in 3 patients and oligoclonal bands in 8. Eleven of the 15 (73%) had antiphospholipid antibodies (aPL). Of the 15 patients, 3 had complete resolution of the symptoms, 6 had good functional improvements, 5 had good to fair outcome with some functional deficit, and one patient who received corticosteroids alone later died from pneumonia. CONCLUSION: We describe 15 patients with TM as the presenting manifestation of SLE or lupus-like disease with a high prevalence of aPL. Our data support the view that early diagnosis and immunosuppressive therapy may be superior to corticosteroids alone in improving functional outcome. In those patients with aPL, antiplatelet agents and/or warfarin should also be considered.