Reversible posterior leukoencephalopathy syndrome in p-ANCA-associated vasculitis

The perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) is closely associated with rapidly progressing glomerulonephritis, microscopic polyangiitis, and allergic granulomatous angiitis. While mononeuropathy due to vasculitis is a well-known neurological manifestation of these conditions, manifestations involving the central nervous system (CNS) have rarely been reported. Our patient presented the very characteristic CNS lesion of reversible posterior leukoencephalopathy syndrome (RPLS) which has often been associated with hypertension, eclampsia, cyclosporine neurotoxicity, and other diseases. The patient also developed the recently established disease entity, Takotsubo cardiomyopathy.     

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.     

老年人可逆性后部白质脑病综合征五例及临床和影像学特点分析

目的 分析我国老年人可逆性后部白质脑病综合征(reversible posterior leukoencephalopathy syndrome,RPLS)患者的临床表现和影像学特点.方法 回顾报告5例老年RPLS患者的临床表现和影像学特点. 结果 本组老年男性患者1例,女性4例,平均年龄(63.0±2.4)岁,5例患者均在起病时并存高血压.最常见的临床表现依次为视觉障碍5例,头痛4例,癫痫4例,意识障碍3例,病理反射2例,偏瘫2例.CT检查示4例患者表现异常,MRI检查示5例患者均出现枕叶病变,颞叶受累2例,顶叶受累1例.4例患者出院平均(48.8±29.2)d后CT检查为阴性结果,死亡1例.结论 RPLS是典型的多因共果疾病,血管原性假说被影像学研究结果证实.神经影像学对诊断RPLS很重要,弥散加权像(DWI)有助于鉴别诊断RPLS和缺血性脑血管病.     

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.     

可逆性后部白质脑病综合征的发病机制

可逆性后部白质脑病综合征(reversible posterior leukoencephalopathy syndrome,RPLS)是一种临床影像学疾病实体,主要以迅速进展的血压增高、头痛、呕吐、意识障碍、痢性发作为特征,神经影像学显示为双侧大脑半球对称性白质可逆性水肿(尤其是在大脑后部),通过及时和正确的治疗,临床症状和神经影像学改变可完全恢复.有关RPLS发病机制的两大假说--脑血管痉挛学说和脑血管过度灌注学说一直存在争论,目前多数学者仍然认同后者是造成脑水肿的主要原因.文章从RPLS的病因学、病理学和影像学特征阐述了其发病机制以及近年来对上述两大假说的新观点.     

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.     

可逆性后部白质脑病综合征的临床和影像学特征:9例回顾性病例系列研究

目的 探讨可逆性后部白质脑病综合征(reversible posterior leukoencephalopathy syndrome,RPLS)的临床和影像学特征.方法 回顾性分析9例RPLS患者的临床和影像学资料.结果 继发于妊娠高血压综合征4例(44%),短肠综合征1例(11%),急性淋巴细胞白血病1例(11%)...     

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.     

可逆性后部白质脑病综合征的发病机制及研究进展

可逆性后部白质脑病综合征(RPLS)是多种病因引起的神经系统受损临床综合征,目前关于其发病机制主要有以下两种学说:脑过度灌注理论和血管痉挛理论,前者主要包括血管机制、血管内皮损伤机制及免疫机制。该病主要临床表现为头痛、抽搐发作、视觉障碍、意识改变及精神行为异常等;典型的神经影像学改变是大脑半球后部白质水肿,以双侧顶枕叶受累最为多见,具有可逆性。     

Reversible posterior leukoencephalopathy syndrome: a possible manifestation of Wegener’s granulomatosis-mediated endothelial injury

We present the case of a 15-year-old girl who had Wegener's granulomatosis with severe intestinal involvement. During the clinical course, she developed generalized seizures and was diagnosed with reversible posterior leukoencephalopathy syndrome (RPLS). Plasma exchange combined with steroid pulse therapy was initiated and showed marked improvement. This is one of the few cases of RPLS without severe hypertension or renal failure, suggesting that RPLS is likely to be a manifestation of Wegener's granulomatosis-mediated endothelial injury.     

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.     

CNS vasculopathies: Challenging mimickers of primary angiitis of the central nervous system

Primary angiitis of the central nervous system (CNS) is an inflammatory vasculopathy affecting the brain and spinal cord. It is a difficult diagnosis to make because of its insidious nonspecific course and its multiple mimics. This review identifies and discusses some noninfectious mimickers of primary CNS angiitis, including: reversible cerebral vasoconstriction syndrome, Sneddon's Syndrome, amyloid-beta-related angiopathy, Susac Syndrome, and neurosarcoidosis. Each condition will be reviewed in terms of epidemiology, pathology, clinical presentation, diagnostic approach, and treatment. Distinguishing these mimics from the primary angiitis of the CNS is important for proper treatment and prognosis.     

Reversible posterior leukoencephalopathy syndrome: a possible manifestation of Wegener’s granulomatosis-mediated endothelial injury

Abstract

We present the case of a 15-year-old girl who had Wegener’s granulomatosis with severe intestinal involvement. During the clinical course, she developed generalized seizures and was diagnosed with reversible posterior leukoencephalopathy syndrome (RPLS). Plasma exchange combined with steroid pulse therapy was initiated and showed marked improvement. This is one of the few cases of RPLS without severe hypertension or renal failure, suggesting that RPLS is likely to be a manifestation of Wegener’s granulomatosis-mediated endothelial injury.     

Reversible posterior leukoencephalopathy syndrome probably caused by L-asparaginase

A 46-year-old male with refractory biphenotypic acute leukemia was treated with doxorubicin (days 1-3, 15-17), vincristine (days 1, 8, 15, 22), prednisolone (days 1-28), and L-asparaginase (L-ASP: days 15-28) as reinduction therapy. Physical examination revealed normotensive state and normal consciousness. On the 27th day, systemic seizures developed with mild hypertension (BP 151/98 mmHg). Computed tomography (CT) imaging of the brain showed areas of hypodensity in the bilateral white matter, and in the occipital and posterior parietal areas. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) showed some high intensity area involving the white matter, but also involving the cortex in the same area. Because the patient's condition progressed into unconsciousness and apnea from recurrent seizures, a respirator and anticonvulsants were needed. Four days later, the patient's general condition dramatically improved. There were no abnormal findings on MRI, and we diagnosed the cause of the seizures as reversible posterior leukoencephalopathy syndrome (RPLS). In adults, RPLS caused by chemotherapy is rare, especially L-ASP. Our patient did not have any previous history of convulsion up to the LAdVP, which brought on the seizures. It was considered that the RPLS might be caused by L-ASP, which had been given to this patient for the first time and was being given to him at the time of developing the seizures. RPLS is one of the causes of neurologic complications by L-ASP.     

Reversible posterior leukoencephalopathy syndrome in a child with cerebral X-linked adrenoleukodystrophy treated with cyclosporine after bone marrow transplantation

Reversible posterior leukoencephalopathy syndrome (RPLS) was described by Hinchey and colleagues in 1996. The disorder occurs predominantly in patients with acute hypertension and/or on pharmacological immunosuppression. We report a 6-year-old male with cerebral X-linked adrenoleukodystrophy who received an HLA-matched unrelated bone marrow transplant (BMT). Cyclosporine was used as graft-versus-host disease prophylaxis. At 55 days post-BMT, his cyclosporine concentrations were high for several days and the concentration was still high on day 70 (353 μg/L). He presented 83 days post-BMT with new onset of headache, lethargy, acute visual loss and focal seizures. He was not hypertensive. MRI of the head revealed signal changes that now extended more peripherally into the subcortical and cortical regions of the occipital and temporal lobes. The patient's cyclosporine was stopped for 5 days. The patient's vision returned to normal and his headaches and lethargy resolved with no further seizures 3 weeks later. Follow-up MRI of the head 2 months later showed almost complete resolution of the cortical signal abnormalities. It is important to consider RPLS in patients with cerebral adrenoleukodystrophy who present with acute neurological deterioration. Attention to the pattern of white matter and the presence of cortical grey matter involvement on neuroimaging is important for the diagnosis. When appropriate management is initiated, that is controlling hypertension when present and discontinuing or reducing the dose of offending immunosuppressive agents, the acute neurological symptoms will usually resolve. This revised version was published online in August 2006 with corrections to the Cover Date.     

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。     

Reversible posterior leukoencephalopathy syndrome: diagnosis and management in the setting of lung transplantation

Reversible posterior leukoencephalopathy syndrome (RPLS) is a potentially devastating early complication of calcineurin inhibitor (CNI) therapy in solid organ transplantation. Management centres on cessation of CNI therapy; however, this strategy is complicated in lung transplantation because of the threat of allograft rejection, or, if CNI is replaced with mammalian target of rapamycin-based immunosuppression, poor wound healing and bronchial dehiscence. We describe four cases of RPLS after lung transplantation, emphasizing the diagnostic and management approach required to maintain a healthy allograft and ensure that RPLS is, as the name suggests, reversible.     

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.     

Central nervous system vasculitis in children

Central nervous system (CNS) vasculitis is an increasingly recognized, often devastating inflammatory brain disease of children and adults. In primary or isolated CNS vasculitis/angiitis of childhood (cPACNS), the vascular inflammation is limited to the brain and spinal cord. Secondary CNS vasculitis occurs in a variety of conditions including infections, collagen vascular diseases, systemic vasculidities, and malignancies. Mimics of CNS vasculitis in children include dissections and noninflammatory vasculopathies. Diagnosis of primary CNS vasculitis in both adults and children is based on the Calabrese criteria. This review summarizes recent data on CNS vasculitis in children; reviews the clinical spectrum at presentation and the role of laboratory tests, neuroimaging, and brain biopsy; and discusses treatment strategies, outcome data, and overlapping conditions of cPACNS.