Cerebral amyloid angiopathy presenting as a mass lesion

A rare clinical presentation of cerebral amyloid angiopathy is reported. Our patient presented with the clinical and radiological signs of a right frontal mass lesion suggesting a brain tumor, and a biopsy provided the diagnosis of cerebral amyloid angiopathy. A brief review of the pathology and clinical features of cerebral amyloid angiopathy is presented.     

Cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is characterized by deposition of cerebrovascular amyloid protein in the media of leptomeningeal vessels. (amyloid B protein, cystatin C, transthyretin, gelsolin, and prion protein). It is a cause of cerebrovascular disorders including cerebral hemorrhage, cognitive impairment and unusually transient neurological symptoms. It is the main contributing factor to cerebral hemorrhage after hypertension in the elderly. We aimed to review epidemiological, pathophysiological and clinical and MRI imaging data in CAA.     

Cerebral amyloid angiopathy: the vascular pathology and complications

Twenty-five cases with cerebral amyloid angiopathy (CAA) were studied. Senile plaques (SP) were present in all cases. In only eight cases which also displayed either SP (two cases), or both SP and Alzheimer's neurofibrillary tangles (NFT) (six cases), was there a history of dementia. In five cases, SP and NFT were observed without a history of dementia. Seven cases had significant cerebral hemorrhage, single or multiple, which could be related to CAA. Ten cases had cerebral infarcts, but only in seven of these cases could the infarcts be related to CAA. In five cases, with moderate to severe CAA and no history of dementia other distinctive vascular changes were also noted in the brain. These CAA-associated vasculopathies (CAA-AV) consisted of: clusters of multiple arteriolar lumina, the so-called "glomerular" formations, with various degrees of amyloid infiltration; aneurysmal vessels with amyloid infiltration; obliterative intimal changes; "double barreling", chronic inflammatory perivascular or transmural infiltrates; hyaline (nonamyloid) arteriolar degeneration, with or without aneurysmal dilatation; and fibrinoid necrotizing vascular change. In all five cases with CAA-AV, there were cerebral infarcts or hemorrhages which were considered to be direct complications of amyloid angiopathy, or of the vasculopathies developing secondary to the amyloid infiltration of vessel walls. It is possible that the associated vasculopathies represented secondary vascular changes that followed amyloid deposition in the blood vessel walls.     

Cerebral hemorrhage with biopsy-proved amyloid angiopathy.

Clinical, radiological, and immunohistochemical findings in brain biopsy specimens from six patients with cerebral amyloid angiopathy-associated intracerebral hemorrhage were reviewed. Acute clinical presentations included headache, nausea and vomiting, loss of consciousness, and focal neurological deficits such as hemiplegia and blindness. Transient ischemic attacks experienced by one patient and referable to one hemisphere did not indicate impending hemorrhage in that region. Computed tomographic scans revealed acute, irregular, superficial, lobar hemorrhage with occasional ring enhancement. Immunohistochemical studies were performed on biopsy specimens using primary antibodies against portions of the Alzheimer A4 (beta-) peptide or gamma-trace peptide (the vascular amyloid protein in patients with hereditary cerebral hemorrhage with amyloidosis-Icelandic type). In all patients, anti-A4 and anti-gamma-trace labeled cerebral microvessels. Immunoreactive senile plaques were few compared with the numbers of stained microvessels. Reactive astrocytes in some patients were labeled by both antiserum samples, suggesting uptake or production of these proteins by the astrocytes. This study demonstrates the heterogeneous clinical and radiological features of cerebral amyloid angiopathy-related brain hemorrhage and the value of anti-A4 and anti-gamma-trace immunohistochemical study of biopsy material from patients with suspected cerebral amyloid angiopathy-related intraparenchymal bleeding.     

Cerebral amyloid angiopathy

We studied 24 patients with autopsy-proven cerebral amyloid angiopathy. Eight patients were demented or had some other medical problem and died of pneumonia or systemic disease. Sixteen patients died of intracranial hemorrhage. Amyloid was found in cortical arteries and arterioles of all patients. CT showed diffuse atrophy in demented patients and intracerebral hematomas in the others. The location and size of the hematoma, with cortical and subarachnoid extension, help to differentiate amyloid angiopathy from other causes of intracranial hemorrhage in the elderly.     

淀粉样脑血管病

<正>淀粉样脑血管病(CAA)是一种以大脑皮质、皮质下及软脑膜中、小血管壁内淀粉样物质(β-淀粉样蛋白)沉积为特征的颅内血管病变。多呈散发性,少数为常染色体显性遗传;平均发病年龄69.50岁,发病率随年龄的增长而逐渐升高。该病是血压正常老年人发生自发性脑叶出血的重要原因,常累及枕叶,额颞顶叶次之,深部白质、基底节和丘脑极少受累。影像学主要表现为皮质-皮质下大或微小出血灶、白质脱髓鞘改变和脑萎缩,可单独或同时出现。CT是迅速确定急性颅内出血的首选影像学方法。MRI可显示出不同时期的微小出血灶,T2*序列[包括梯度回波序列(GRE)和磁敏感加权成像(SWI)]对急性和(或)慢性微小缺血十分敏感,微小出血灶位于皮质-皮质下,深部白质、基底节和脑干极少受累;同时可合并蛛网膜下隙出血、硬膜下     

Cerebral amyloid angiopathy with severe secondary vascular pathology: a histopathological study

Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and is characterized by deposition of fibrillar amyloid in cortical and leptomeningeal vessels. In this study we describe the macroscopic and microscopic neuropathological findings of 5 patients with severe CAA-associated secondary vascular changes, including smooth muscle cell degeneration, hyalinization, 'double-barreling' phenomenon, macrophage infiltration, and aneurysmal dilatation of the vessel wall. In 3 of the 5 patients these vascular changes were associated with multiple small hemorrhages, whereas in 2 patients areas of ischemic necrosis were observed. However, none of these patients suffered from large (lobar) hemorrhagic accidents. Nevertheless, severe CAA, particularly when associated with secondary vascular pathology, may lead to vascular dementia-like ischemic changes. Hence, the distinction between patients with severe CAA and secondary vascular abnormalities from those suffering from vascular dementia can be difficult. We speculate that CAA, particularly when associated with secondary vascular pathology, although not resulting in large hemorrhages, may contribute to cognitive decline. The functional impact of CAA and CAA-related secondary vascular changes on cognitive performance warrants further exploration.     

脑淀粉样血管病变相关炎症

为了提高对脑淀粉样血管病变(CAA)相关炎症(CAA-I)的认识。现将该院1例CAA-I患者的临床表现、影像特点、诊疗过程进行整理回顾。患者为男性,70岁,以癫痫发作、认知功能减退为临床表现。脑脊液(CSF)检查提示细胞数及蛋白轻度升高。头颅计算机断层扫描(CT)提示凸面型蛛网膜下腔出血、脑白质变性。头颅磁共振成像(MRI)提示紧邻皮质的斑片状T2WI及FLAIR异常高信号影,非对称性并延伸至皮质下白质,伴软脑膜强化。磁敏感加权成像(SWI)提示≥1处皮质―皮质下微出血灶及皮质表面铁沉积。基因检测为载脂蛋白E(APOE) E2/E3。诊断为很可能的脑淀粉样血管病相关炎症。经甲泼尼龙冲击治疗后病灶明显好转,1个月后随访认知功能改善、无癫痫发作。CAA-I是脑淀粉样血管病的罕见亚型,临床医生多对此病认识不足,多序列的磁共振检查,尤其是SWI有利于其诊断,激素治疗效果显著。 [国际神经病学神经外科学杂志, 2022, 49(6): 59-64]     

Cerebral amyloid angiopathy and motor neurone disease presenting with a progressive supranuclear palsy-like syndrome.

We describe a 68-year-old woman who presented with falls, mild limb bradykinesia, axial rigidity, and a severe supranuclear gaze palsy, which failed to benefit from levodopa. She subsequently developed severe apraxia, progressive dysarthria, dysphagia, and a frontal cognitive impairment. Pyramidal weakness with fasciculations and widespread chronic partial denervation appeared shortly before her death from bronchopneumonia, 6 months after disease onset. A severe cerebral amyloid angiopathy diffusely involving the cerebral hemispheres and cerebellum was present at autopsy as well as a second pathological condition indicative of motor neurone disease. Cerebral amyloid angiopathy may rarely present with a progressive supranuclear palsy-like phenotype.     

Cerebral amyloid angiopathy presenting as a brain tumor: case report

We describe the unusual case of a 45-year-old male patient harboring an intracranial mass due to cerebral amyloid angiopathy whose clinical and radiological features were those of a low grade glioma. Biopsy revealed cerebral amyloid angiopathy. The clinical, radiological and pathological findings are discussed as we review the available literature.     

Cerebral amyloid angiopathy presenting as a pseudotumor: 2 cases with spontaneously favorable outcomes

A rare clinical and radiographical presentation of cerebral amyloid angiopathy mimicking a brain neoplasm was observed in 2 patients. The signs and symptoms included seizures and focal parieto-occipital dysfunction in 1 case, massive left hemisphere dysfunction and akinetic mutism in the other. Brain CT and MRI showed nonspecific focal white matter abnormalities suggestive of the diagnosis of low-grade glioma. Gradient echo T1 and T2-weighted images showing multiple areas of signal void suggesting multiple disseminated petechial hemorrhages led to the diagnosis of cerebral amyloid angiopathy. An eventless brain biopsy confirmed the diagnosis. The neuropathology examination disclosed amyloid angiopathy of the pial and cortical vessels selectively stained by anti A-beta protein antibodies. The clinical course was remarkable in the two cases with almost complete clinical recovery without any particular treatment.     

Cerebral amyloid angiopathy: An overview

Cerebral amyloid angiopathy (CAA) is characterized by amyloid deposition in cortical and leptomeningeal vessels. Several cerebrovascular amyloid proteins (amyloid β‐protein (Aβ), cystatin C (ACys), prion protein (AScr), transthyretin (ATTR), gelsolin (AGel), and ABri (or A‐WD)) have been identified, leading to the classification of several types of CAA. Sporadic CAA of Aβ type is commonly found in elderly individuals and patients with Alzheimer’s disease. Cerebral amyloid angiopathy is an important cause of cerebrovascular disorders including lobar cerebral hemorrhage, leukoencephalopathy, and small cortical hemorrhage and infarction. We review the clinicopathological and molecular aspects of CAA and discuss the pathogenesis of CAA with future perspectives.     

Cerebral amyloid angiopathy causing intracranial hemorrhage

Ten cases of sporadic cerebral amyloid angiopathy (CAA) were seen as intracranial hemorrhage. CAA was seen as a stroke or catastrophic intracranial hemorrhage in all cases. CAA complicated by intracranial hemorrhage carried a high mortality; 9 of 10 patients died in spite of aggressive medical or surgical treatment. Senile dementia of Alzheimer's type was an associated finding in only 1 patient. Computed tomographic scanning in 4 patients initially was not diagnostic for hemorrhage. Lambda chains and amyloid P protein were demonstrated in the areas of amyloid angiopathy immunocytochemically. The pathogenesis of hemorrhage in CAA could be either increased fragility of amyloid-laden blood vessels or rupture of microaneurysms. Surgical treatment of intracranial hemorrhage in CAA should therefore be undertaken with caution.     

Cerebral amyloid angiopathy in the elderly

Cerebral amyloid angiopathy (CAA) results from deposition of β‐amyloid in the media and adventitia of small arteries and capillaries of the leptomeninges and cerebral cortex and is a major cause of lobar intracerebral hemorrhage and cognitive impairment in the elderly. CAA is associated with a high prevalence of magnetic resonance imaging markers of small vessel disease, including cerebral microbleeds and white matter hyperintensities. Although advanced CAA is present in approximately ¼ of brains with Alzheimer disease (AD), fewer than half of CAA cases meet pathologic criteria for AD. This review will discuss the pathophysiology of CAA and focus on new imaging modalities and laboratory biomarkers that may aid in the clinical diagnosis of individuals with the disease. Ann Neurol 2011;70:871–880