Hemorragia encefálica por angiopatía amiloidea / Amyloid angiopathy brain hemorrhage

Amyloid angiopathy (AA) is a selective deposition of amyloid in the walls of the brain vessels. It is a form of sporadic and localized amyloidosis, constituted by the Aβ4 protein, the same of Alzheimer's disease senile plaques. The most consistent clinical effect of AA is spontaneous brain hemorrhage (BH). It is the second most common cause of BH after arterial hypertension (HT). Other clinical manifestations are cognitive impairment and transient focal neurological episodes. AA BH is characteristically localized in the cerebral cortex and subcortical white matter (lobar hemorrhage), consistent with the preferential deposit of amyloid in the walls of leptomeningeal and intracortical small cerebral vessels. Other types of AA hemorrhagic complications are microbleeds (MB), cerebral convexity subarachnoid hemorrhage (cSAH) and superficial hemosiderosis (cSS). The diagnosis of AA BH is based on the Boston criteria. Using these criteria, several non-hemorrhagic biomarkers of AA have been identified that can be useful in its diagnosis. The principal AA BH risk factor is age, followed by cSS, MB, Apolipoprotein E gen ε2 and ε4 alleles, HT and the use of antithrombotics. This condition has a high recurrence rate that shares the same risk factors. There is no specific treatment for AA BH. It has a better prognosis than HT BH during the acute period, but worse on the long term, due to its high recurrence rate and cognitive impairment.

Cerebral amyloid angiopathy-related inflammation: current status and future implications / 中华医学杂志(英文版)

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

Hemorragia cerebral durante fase ativa de infecção por SARS-CoV-2 em paciente com angiopatia amiloide: relato de caso / Cerebral hemorrhage during the active phase of SARS-CoV-2 infection in a patient with amyloid angiopathy: case report

RESUMO As alterações neurológicas associadas à COVID-19 têm sido frequentemente descritas, principalmente nos casos de maior severidade, e estão relacionadas a causas multifatoriais, como a disfunção endotelial, a liberação de mediadores inflamatórios (cytokine storm), a disfunção endotelial e a hipoxemia. Relatamos o caso de uma paciente do sexo feminino, 88 anos, com quadro de hemorragia cerebral associada à angiopatia amiloide, no contexto de infecção por SARS-CoV-2.

ABSTRACT The neurological changes associated with COVID-19 have been frequently described, especially in cases of greater severity, and are related to multifactorial causes, such as endothelial dysfunction, inflammatory mediator release (cytokine storm), endothelial dysfunction and hypoxemia. We report the case of a female patient, 88 years old, with cerebral hemorrhage associated with amyloid angiopathy in the context of SARS-CoV-2 infection.

Cerebral amyloid angiopathy: a cross-sectional study in a single center in Northeastern Brazil / Angiopatia amiloide cerebral: um estudo transversal em um único centro no Nordeste brasileiro

ABSTRACT Background: Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by progressive deposition of β-amyloid peptides in the walls of small and medium-sized cortical and leptomeningeal vessels. Until today, the prevalence of CAA is unknown in our region. Objective: This study aims to analyze the prevalence of this entity in a specific elderly population in a tertiary hospital in Northeastern Brazil. Methods: A cross-sectional, retrospective study with the enrollment of patients aged 65 or older followed in the neurological outpatient service of the Universidade Federal do Piauí, Brazil, who underwent brain magnetic resonance imaging (MRI) from July 2016 to June 2018. Results: One hundred and seventy-four patients were enrolled, of whom 100 were women (57.4%) and 74, men (42.6%), aged from 65 to 91 years old (median age 73.27). Nine patients were excluded from the study due to unavailability of MRI sequences needed for an appropriate analysis. Out of the 165 remaining patients, 12 (7.2%) had established the diagnosis of CAA, according to the modified Boston criteria. Conclusion: The prevalence of CAA in our study was like those of medical literature, with a progressive age-related increase.

RESUMO Introdução: A angiopatia amiloide cerebral (AAC) é uma desordem vascular causada pela deposição progressiva de peptídeos β-amiloides nas paredes de pequenos e médios vasos corticais e leptomeníngeos. Até a presente data, a epidemiologia da AAC é desconhecida em nossa região. Objetivos: Avaliar a prevalência da AAC em uma população específica de pacientes idosos de um hospital terciário no nordeste brasileiro. Métodos: Estudo transversal, retrospectivo, com seleção de pacientes com idade igual ou superior a 65 anos, acompanhados no serviço de Neurologia do Hospital Universitário da Universidade Federal do Piauí, Brasil, e que foram submetidos a exame de ressonância nuclear magnética entre julho de 2016 e junho de 2018. Resultados: Foram recrutados 174 pacientes, dos quais 100 eram mulheres (57,4%) e 74 homens (42,6%), com idades entre 65 e 91 anos (média de 73,27). Nove pacientes foram excluídos devido à indisponibilidade de sequências de ressonância magnética necessárias para uma análise apropriada. Dos 165 pacientes restantes, 12 (7,2%) foram diagnosticados com AAC de acordo com os critérios de Boston modificados. Conclusão: A prevalência da AAC em nosso estudo foi semelhante ao resultado encontrado na literatura médica, com um aumento progressivo relacionado à idade.

Magnetic Resonance Image Findings of Cerebral Amyloid Angiopathy Related Inflammation

No abstract available.

MRI Assessment of Cerebral Small Vessel Disease in Patients with Spontaneous Intracerebral Hemorrhage

PURPOSE: Cerebral small vessel disease (SVD) is known to be associated with ischemic stroke, intracerebral hemorrhage (ICH), and cognitive impairment. In this retrospective observational study, we explored SVD markers on MRI relevant to spontaneous ICH. MATERIALS AND METHODS: The ICH group consisted of 150 consecutive patients with a first primary parenchymal ICH, and the control group consisted of 271 age- and sex-matched individuals who underwent brain MRI in a health care center. We compared cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), enlarged perivascular space (EPVS), and lacunae in the ICH and control groups. RESULTS: A total of 1278 CMB lesions were identified in 121 of the 150 patients in the ICH group (80.6%), while 77 CMB lesions were found in 32 of the 271 individuals in the control group (11.8%). WMH and EPVS were more severe and lacunae were more frequent in the ICH patients than in the control group. When receiver operating characteristic (ROC) curves were plotted, number of CMBs most significantly predicted ICH. All imaging markers were significantly associated with ICH in every age group. The location of CMBs coincided with the location of ICH, and ICH volume correlated with CMB count. CONCLUSION: All MRI markers for SVD were worse in ICH patients than in healthy controls, and these markers were prominent even in young ICH patients. Lacunae, WMH, EPVS, and CMB should be considered as factors related with spontaneous ICH.

Hemorragia subaracnoídea no traumática con angiografía por tomografía computada inicial "negativa / Non-traumatic subarachnoid hemorrhage with "negative" initial computed tomography angiography

La hemorragia subaracnoidea (HSA) no traumática es un subtipo de ictus hemorrágico que representa aproximadamente el 5% de todos los accidentes vasculares encefálicos (AVE). El 85% de los casos de HSA espontánea (no traumática) son secundarios a un aneurisma intracraneano roto, el 10% a hemorragia perimesencefálica no aneurismática y el otro 5% a otras causas. Entre estas se incluyen malformaciones arterio-venosas, fístulas durales, vasculits, trombosis de vena cortical, síndrome de vasoconstricción reversible, angiopatía amiloidea y síndrome de encefalopatía posterior reversible. La aproximación inicial a una HSA no traumática requiere un estudio angiográfico no invasivo con tomografía computada para la toma de decisiones terapéuticas. Si no se detecta un aneurisma sacular intradural que explique el sangrado, las conductas a seguir dependerán del patrón de distribución de la sangre. En esta revisión sugerimos una aproximación basada en 1) revisar el estudio inicial tomando en cuenta los puntos ciegos para la detección de aneurismas, 2) analizar el patrón de distribución de la sangre y 3) analizar los hallazgos en imágenes de acuerdo a las posibles causas según patrón.

Non-traumatic subarachnoid hemorrhage represents approximately 5% of strokes. From these, 85% of nontraumatic subarachnoid hemorrhage are secondary to a ruptured aneurysm, 10% to nonaneurysmal perimesencephalic hemorrhage and the other 5% to other causes. These include but are not limited to arteriovenous malformations, dural fistulae, vasculitis, cortical vein thrombosis, reversible cerebral vasoconstriction syndrome, amyloid angiopathy and posterior reversible encephalopathy syndrome. Initial workup of nontraumatic subarachnoid hemorrhage requires a non-enhanced CT and CT angiography for decision making and management. If there is no aneurysm as a source of hemorrhage, subsequent imaging studies will depend on blood distribution pattern. In this review we suggest an approach: 1) review blind spots for aneurysm detection in the initial CT angiography, 2) analyze blood distribution pattern and 3) evaluate imaging findings and possible causes according to each pattern.

Focal Subarachnoid Hemorrhage Mimicking Recurrent Transient Ischemic Attack

Focal subarachnoid hemorrhage occasionally presents as transient focal neurologic episodes mimicking transient ischemic attack (TIA). Unless properly diagnosed, it may aggravate cerebral hemorrhage by administering antithrombotic agents. Therefore, clinicians need to be aware that such focal subarachnoid hemorrhage sometimes cannot be detected on noncontrast computed tomography and blood-sensitive magnetic resonance imaging can detect even a small amount of hemorrhage. We describe an 85-year-old woman with focal subarachnoid hemorrhage and possible cerebral amyloid angiopathy who presented transient left arm weakness recurrently, which mimicked TIA.

Pathologically Confirmed Cerebral Amyloid Angiopathy with No Radiological Sign in a Patient with Early Onset Alzheimer's Disease

Cerebral amyloid angiopathy (CAA) is associated with perivascular disruption, which is caused by progressive amyloid-beta (Aβ) deposition in vessels. Previous autopsy studies have shown that the prevalence of CAA in Alzheimer's disease (AD) is 70% to 90%. CAA is principally characterized by restricted lobar microbleeds (MBs), which can be detected by gradient-echo T2* (GRE) and susceptibility-weighted imaging (SWI). We herein report on a 62-year-old man who presented with 8 years of memory impairment. The apolipoprotein E (APOE) genotype was ε4/ε4, and a brain GRE performed 28 months before death revealed mild atrophy and no MBs. At autopsy, the patient scored “A3, B3, C3” according to the National Institute on Aging-Alzheimer's Association guidelines; the patient thus exhibited a high level of AD neuropathological changes. Furthermore, immunohistochemical staining for Aβ showed antibody accumulation and severe cerebral amyloid angiopathic changes in numerous vessels with amyloid deposits. Our case suggests that radiological CAA markers, such as cerebral microbleed (CMB) or cerebral superficial siderosis, may not suffice to detect amyloid angiopathy in cerebral vessels. CAA should therefore be considered as a combined pathology in APOE ε4 homozygotes with AD, even if such patients do not exhibit CMB on MRI.

Characteristics of Cerebral Microbleeds

Cerebral microbleeds (CMBs) are increasingly recognized neuroimaging findings, occurring with cerebrovascular disease, dementia, and aging. CMBs are associated with subsequent hemorrhagic and ischemic stroke, and also with an increased risk of cognitive deterioration and dementia. They occur in the setting of impaired small vessel integrity due to hypertension or cerebral amyloid angiopathy. This review summarizes the concepts, cause or risk factors, histopathological mechanisms, and clinical consequences of CMBs.

Updates on Prevention of Hemorrhagic and Lacunar Strokes / 대한뇌졸중학회지

Intracerebral hemorrhage (ICH) and lacunar infarction (LI) are the major acute clinical manifestations of cerebral small vessel diseases (cSVDs). Hypertensive small vessel disease, cerebral amyloid angiopathy, and hereditary causes, such as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), constitute the three common cSVD categories. Diagnosing the underlying vascular pathology in these patients is important because the risk and types of recurrent strokes show significant differences. Recent advances in our understanding of the cSVD-related radiological markers have improved our ability to stratify ICH risk in individual patients, which helps guide antithrombotic decisions. There are general good-practice measures for stroke prevention in patients with cSVD, such as optimal blood pressure and glycemic control, while individualized measures tailored for particular patients are often needed. Antithrombotic combinations and anticoagulants should be avoided in cSVD treatment, as they increase the risk of potentially fatal ICH without necessarily lowering LI risk in these patients. Even when indicated for a concurrent pathology, such as nonvalvular atrial fibrillation, nonpharmacological approaches should be considered in the presence of cSVD. More data are emerging regarding the presentation, clinical course, and diagnostic markers of hereditary cSVD, allowing accurate diagnosis, and therefore, guiding management of symptomatic patients. When suspicion for asymptomatic hereditary cSVD exists, the pros and cons of prescribing genetic testing should be discussed in detail in the absence of any curative treatment. Recent data regarding diagnosis, risk stratification, and specific preventive approaches for both sporadic and hereditary cSVDs are discussed in this review article.

Eyebrow Incision for Surgical Evacuation of a Lobar Intracerebral Hematoma with a Novel Endoport System

Large lobar intracerebral hemorrhages (ICHs) can cause rapid neurological deterioration, and affected patients have low rates of survival and functional independence. Currently, the role of surgical intervention in the management patients with lobar ICHs is controversial. Minimally invasive technologies have been developed which may potentially decrease the operative morbidity of ICH surgery. The aim of this case report is to describe the technical aspects of the use of a novel minimally invasive endoport system, the BrainPath (NICO, Indianapolis, IN, USA), through an eyebrow incision for evacuation of a large lobar hematoma. An 84-year-old female presented with a left frontal ICH, measuring 7.5 cm in maximal diameter and 81 cm³ in volume, secondary to cerebral amyloid angiopathy. Through a left eyebrow incision, a miniature modified orbitozygomatic craniotomy was performed, which allowed endoport cannulation of the hematoma from a lateral subfrontal cortical entry point. Endoport-assisted hematoma evacuation resulted in nearly 90% volume reduction and improvement of the patient's functional status at clinical follow-up. We found that minimally invasive endoport technology can be employed in conjunction with conventional neurosurgical skull base principles to achieve safe and effective evacuation of large lobar hematomas in carefully selected patients.

Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update / 대한뇌졸중학회지

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. ICH is more common in Asians, advanced age, male sex, and low- and middle-income countries. The case fatality rate of ICH is high (40% at 1 month and 54% at 1 year), and only 12% to 39% of survivors can achieve long-term functional independence. Risk factors of ICH are hypertension, current smoking, excessive alcohol consumption, hypocholesterolemia, and drugs. Old age, male sex, Asian ethnicity, chronic kidney disease, cerebral amyloid angiopathy (CAA), and cerebral microbleeds (CMBs) increase the risk of ICH. Clinical presentation varies according to the size and location of hematoma, and intraventricular extension of hemorrhage. Patients with CAA-related ICH frequently have concomitant cognitive impairment. Anticoagulation related ICH is increasing recently as the elderly population who have atrial fibrillation is increasing. As non-vitamin K antagonist oral anticoagulants (NOACs) are currently replacing warfarin, management of NOAC-associated ICH has become an emerging issue.

Imaging of Intracranial Hemorrhage / 대한뇌졸중학회지

Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage.

Interrelationship between implant and orthognathic surgery for the rehabilitation of edentulous cleft palate patients: a case report

A 43-year-old woman with a unilateral cleft lip and palate, presenting a totally edentulous maxilla and mandible with marked maxillomandibular discrepancy, attended the Prosthodontics section of the Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo for treatment. She could not close her mouth and was dissatisfied with her complete dentures. Treatment planning comprised placement of six implants in the maxilla, four in the mandible followed by prostheses installation and orthognathic surgery. The mandibular full arch prosthesis guided the occlusion for orthognathic positioning of the maxilla. The maxillary complete prosthesis was designed to assist the orthognathic surgery with a provisional prosthesis (no metal framework), allowing reverse treatment planning. Maxillary and mandibular realignment was performed. Three months later, a relapse in the position of the maxilla was observed, which was offset with a new maxillary prosthesis. This isa complex interdisciplinary treatment and two-year follow-up is presented and discussed. It should be considered that this type of treatment could also be applied in non-cleft patients.

Clinical Neuropathological Analysis of 10 Cases of Cerebral Amyloid Angiopathy-Related Cerebral Lobar Hemorrhage

OBJECTIVE: The clinical and pathological characteristics of 10 cases of cerebral amyloid angiopathy (CAA)-related cerebral lobar hemorrhage (CLH) that was diagnosed at autopsy were investigated to facilitate the diagnosis of this condition. METHODS: The clinical characteristics of 10 cases of CAA-related CLH were retrospectively reviewed, and a neuropathological examination was performed on autopsy samples. RESULTS: The 10 cases included two with a single lobar hemorrhage and eight with multifocal lobar hemorrhages. In all of the cases, the hemorrhage bled into the subarachnoid space. Pathological examinations of the 10 cases revealed microaneurysms in two, double barrel-like changes in four, multifocal arteriolar clusters in five, obliterative onion skin-like intimal changes in four, fibrinoid necrosis of the vessels in seven, neurofibrillary tangles in eight, and senile plaques in five cases. CONCLUSION: CAA-related CLHs were located primarily in the parietal, temporal, and occipital lobes. These hemorrhages normally consisted of multiple repeated CLHs that frequently bled into the subarachnoid space. CAA-associated microvascular lesions may be the pathological factor underlying CLH.

Cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer(')s disease.</p><p><b>METHODS</b>Levels of amyloid protein β (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.</p><p><b>RESULTS</b>The levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4 ± 265.2) ng/L, (7111.0 ± 1033.4) ng/L, (71.8 ± 51.5) ng/L, and 0.077 ± 0.033, respectively in CAA dementia and (663.6 ± 365.6) ng/L, (5115.0 ± 2931.1) ng/L, (47.7 ± 38.8) ng/L, and 0.192 ± 0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (all P>0.05).</p><p><b>CONCLUSION</b>Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.</p>

Lacunar Infarction and Small Vessel Disease: Pathology and Pathophysiology / 대한뇌졸중학회지

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.

Cerebral Amyloid Angiopathy: Emerging Concepts / 대한뇌졸중학회지

Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid beta-protein (Abeta)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Abeta deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Abeta40 for CAA and anti-Abeta antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Abeta immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis, treatment, risk factors, and future perspectives.

In vivo Image of Cerebral Amyloid Angiopathy in an Alzheimer's Disease Mouse Model / 대한뇌졸중학회지

No abstract available.