Amyloid-ß (Aß)-Related Cerebral Amyloid Angiopathy Causing Lobar Hemorrhage Decades After Childhood Neurosurgery.

BACKGROUND: Recent reports raise the possibility of cerebral amyloid angiopathy (CAA) leading to intracerebral hemorrhage in young adults following childhood neurosurgery, suggesting transmission of amyloid-ß (Aß) through neurosurgical procedures including dura mater grafting. Parenchymal Aß deposition, and to a lesser extent tau aggregation, similar to that seen in Alzheimer disease, have also been described. METHODS: We conducted a database review of 634 consecutive intracerebral hemorrhage patients aged <65 years at a tertiary stroke center over 20 years to identify such patients. RESULTS: We identified 3 patients aged in their thirties who presented with spontaneous lobar intracerebral hemorrhage, with imaging or neuropathology consistent with CAA, and a history of childhood neurosurgery. Two of these patients had undergone a dural repair using cadaveric dura mater (Lyodura). In addition to CAA, both patients had neuropathologically confirmed parenchymal Aß and tau deposits, characteristic of Alzheimer disease. CONCLUSIONS: Our findings support the concept of neurosurgical Aß transmission but suggest that such cases are rare in standard clinical practice.

Subdural Hemorrhage from Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage: A Risk Factor for Postoperative Hemorrhage.

OBJECTIVE: Surgical treatment for cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) is controversial. A subset of CAA-related ICH with associated subdural hemorrhage (SDH) has been reported. This study aimed to evaluate clinical results and surgical outcomes of this type of ICH with associated SDH. METHODS: Study participants included 98 patients with CAA-related ICH who met Boston criteria. Patients were divided into an SDH group and a control (no SDH) group. Clinical and neuroimaging features and surgical outcomes of the 2 groups were compared. RESULTS: Lobular shape of hematoma was found significantly more often in the SDH group (65.7% [23/35]) compared with the control group (25.4% [16/63]; P < 0.001). Subarachnoid hemorrhage was found significantly more often in the SDH group (34.3% [12/35]) compared with the control group (7.9% [5/63]; P = 0.001). The rate of postoperative hemorrhage was significantly higher in the SDH group (61.5% [8/13]) than in the control group (16.2% [6/37]; P = 0.006). The frequency of occurrence of postoperative hemorrhage was significantly higher in the SDH group (13/13) than in the control group (6/37; P = 0.017). A good surgical outcome occurred in none (0/12) of the patients in the SDH group, whereas a good surgical outcome occurred in 51.9% (14/27) of patients in the control group (P = 0.006). CONCLUSIONS: Patients with CAA-related ICH with associated SDH more frequently have postoperative hemorrhage and have a worse surgical outcome. These findings are useful in choosing therapeutic methods and preoperative planning of surgical strategy.

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage.

OBJECTIVE: We aim to clarify the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage and to investigate the efficacy of pathological diagnosis using biopsy specimens. METHOD: We retrospectively reviewed 253 consecutive patients with cortico-subcortical hemorrhage who had been admitted to Aizawa Hospital between January 2006 and July 2013. We had performed craniotomy and hematoma evacuation in 48 patients, as well as biopsy of the evacuated hematoma, cerebral parenchyma adjacent to the hematoma, or both, and they were classified according to the histological results (positive or negative for vascular amyloid deposition) and to the Boston criteria. We compared the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage. We also investigated the detection rate of cerebral amyloid angiopathy with respect to the origins of the specimens. RESULTS: Pathological examination revealed that 22 subjects were positive for vascular amyloid. The number of the cerebral microbleeds located in the deep or infratentorial region was significantly larger in the negative group than in the positive group (P <.05). There was no significant difference in the distribution of lobar cerebral microbleeds and in the prevalence of hypertension. In the probable cerebral amyloid angiopathy-related intracerebral hemorrhage patients, the probability of having vascular amyloid detected by biopsy of both hematoma and parenchyma was 100%. Rebleeding in the postoperative periods was observed in 2 cases (9.1%) of the positive group. CONCLUSIONS: Our results demonstrate the importance and safety of biopsy simultaneously performed with hematoma evacuation. Deep or infratentorial microbleeds are less correlated with cerebral amyloid angiopathy-related intracerebral hemorrhage than with noncerebral amyloid angiopathy-related intracerebral hemorrhage.

Cerebral amyloid angiopathy causing large contralateral hemorrhage during surgery for lobar hemorrhage: a case report.

We report a rare case of cerebral amyloid angiopathy (CAA) causing large contralateral hemorrhage during surgery for lobar hemorrhage. A 62-year-old woman presented with lobar hemorrhage in the left frontal and parietal lobes recurring over the previous 1 month. Because we could not detect the origin of the lobar hemorrhage, we performed a biopsy around the lobar hemorrhage site with the removal of a hematoma. During the surgery, we identified acute brain swelling without bleeding from the operative field. Intraoperative computed tomography demonstrated new large lobar hemorrhage of the right parietal lobe, which we could promptly remove. Specimens around hematomas on both sides were pathologically diagnosed as CAA on immunohistochemical examination. After the surgery, she suffered from lobar hemorrhage three times in the space of only 3 months. To the best of our knowledge, there has been no reported case of CAA causing intracranial hemorrhage of another lesion during surgery. Neurosurgeons should know a possibility of intraoperative hemorrhage in surgeries for lobar hemorrhage caused by CAA.

Cerebral amyloid angiopathy-associated intracerebral hemorrhage: pathology and management.

Amyloid angiopathy-associated intracerebral hemorrhage (ICH) comprises 12%-15% of lobar ICH in the elderly. This growing population has an increasing incidence of thrombolysis-related hemorrhages, causing the management of hemorrhages associated with cerebral amyloid angiopathy (CAA) to take center stage. A concise reference assimilating the pathology and management of this clinical entity does not exist. Amyloid angiopathy-associated hemorrhages are most often solitary, but the natural history often progresses to include multifocal and recurrent hemorrhages. Compared with other causes of ICH, patients with CAA-associated hemorrhages have a lower mortality rate but an increased risk of recurrence. Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical vessels, CAA-associated hemorrhages are superficial in location due to preferential involvement of vessels in the cerebral cortex and meninges. This feature makes CAA-associated hemorrhages easier to access surgically. In this paper, the authors discuss 3 postulates regarding the pathogenesis of amyloid hemorrhages, as well as the established clinicopathological classification of amyloid angiopathy and CAA-associated ICH. Common inheritance patterns of familial CAA with hemorrhagic strokes are discussed along with the role of genetic screening in relatives of patients with CAA. The radiological characteristics of CAA are described with specific attention to CAA-associated microhemorrhages. The detection of these microhemorrhages may have important clinical implications on the administration of anticoagulation and antiplatelet therapy in patients with probable CAA. Poor patient outcome in CAA-associated ICH is associated with dementia, increasing age, hematoma volume and location, initial Glasgow Coma Scale score, and intraventricular extension. The surgical management strategies for amyloid hemorrhages are discussed with a review of published surgical case series and their outcomes with a special attention to postoperative hemorrhage.

[The study of association between spontaneous intracranial hemorrhage and cerebral amyloid angiopathy].

OBJECTIVE: To get the general situation of the cerebral amyloid angiopathy (CAA) incidence in spontaneous intracranial hemorrhage (SICH) patients receiving surgical treatment in Chinese people. METHODS: During the period May 2008 and March 2009, 105 patients admitted to 30 hospitals throughout China for acute SICH were studied, including 68 male and 37 female mean aged (55 +/- 13). The patients were suffered from SICH proved by computed tomography scan (CT). Emergent craniotomies for hemorrhage evacuation were performed for these patients within 72 h after hemorrhage onset and brain tissue of the cortex was also obtained meanwhile. A further histological study, Congo red stained and Abeta immunochemistry included was followed to verify the existence of CAA. RESULT: Fifteen out of the 105 cases is identified as CAA positive, and the total ratio is 14.29%. As to age groups, about 20.83% (5/24) of the cases of the 40-49 years old group have been diagnosed as CAA, 17.14% (6/35) of the 50-59 years old group, 4.17% (1/24) of the 60-69 group, and for those older than 70 years, the ratio is 8.00% (2/25). CONCLUSION: We come to the conclusion that 14.29% of the surgically treated SICH events might be closely related to CAA.

Effect of liver transplantation on transthyretin Tyr114Cys-related cerebral amyloid angiopathy.

OBJECTIVE: Patients with amyloidogenic transthyretin (ATTR) Tyr114Cys develop amyloid deposits in cerebral blood vessels, cerebral hemorrhage, and rapidly progressive dementia that presents with hereditary cerebral amyloid angiopathy (CAA). However, no treatment has been identified for CAA. Although liver transplantation has become an acceptable treatment of TTR-related amyloidosis, liver transplantation may not successfully treat CNS manifestations of the disorder. In this study, we examined the effect of liver transplantation on these manifestations of TTR-related CAA. METHODS: We compared clinical courses of three patients with CAA associated with ATTR Tyr114Cys who underwent liver transplantation with those of five patients with the disorder who did not undergo liver transplantation. RESULTS: The mortality and occurrence of cerebral hemorrhage and dementia in patients having transplantations were reduced compared with those in patients not having transplantations. The two groups did not differ with regard to the frequency of episodes of fluctuating consciousness and TIAs. The group undergoing transplantations had significantly smaller volumes of intracranial hemorrhage than did the no-transplantation group. CONCLUSION: Liver transplantation was effective for CNS manifestations of cerebral amyloid angiopathy associated with amyloidogenic transthyretin Tyr114Cys.

[Cerebral amyloid angiopathy presenting as a brain tumor: case report]. / Angiopatia amilóide cerebral simulando tumor cerebral: relato de caso.

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.

Angiopatia amilóide cerebral simulando tumor cerebral: relato de caso / Cerebral amyloid angiopathy presenting as a brain tumor: case report

Descrevemos o raro caso de um paciente de 45 anos portador de lesão expansiva intracraniana por angiopatia amilóide cerebral com características clínicas e de imagem compatíveis com um glioma de baixo grau. A biópsia revelou angiopatia amilóide cerebral. Os achados clínicos, radiológicos e histopatológicos são discutidos e analisados juntamente à literatura disponível.

Amyloid in neurosurgical and neurological practice.

The amyloidoses are a diverse group of diseases characterized by the deposition of specific proteins with distinct affinity to the dye Congo red, collectively called amyloid. The amyloidogenic proteins have acquired an abnormal, highly ordered, beta-pleated sheet configuration with a propensity to self-aggregate. The amyloid may be distributed in different organs with a remarkable diversity. Two broad categories of amyloidoses are recognised: The systemic (consisting of the primary or light chain form, the secondary or reactive form and the familial or hereditary form) and the localised that target specific organs. A tropism of amyloid proteins to the neural tissue produces certain patterns of central nervous system diseases: cerebral amyloid angiopathy, a substrate of spontaneous intracerebral haemorrhage; mature neuritic plaques found in Alzheimer disease and a subset of prion diseases; a topographically restricted accumulation of extracellular proteins giving rise to tumour-mimicking masses, the amyloidomas; and finally, spinal extradural amyloid collections that occasionally are found in the context of rheumatoid arthritis. In this review article we present original illustrative cases of amyloid diseases of the central nervous system that may be encountered in neurosurgical and neurological practice. Molecular aspects and clinical management problems are discussed.

Lobar cerebral hemorrhage from amyloid angiopathy: clinical, neuroimaging, pathologic and outcome correlations.

Cerebral amyloid angiopathy (CAA) contributes to sporadic lobar intracerebral hemorrhage in older patients, especially those who are more than 70 years old. In clinical practice, a diagnosis of CAA refers to the Boston Criteria, which requires that "definitive" cases be confirmed by pathologic evidence at autopsy. A "Probable" case, means that there is clinical support and that pathologic evidence is available by biopsy from the craniotomy for patients with severe lobar intracerebral hemorrhage. Cerebral amyloid that is deposited in cortical vessels is revealed by apple-green birefringence under polarized light using Congo-red stain. Rebleeding after a first primary intracerebral hemorrhage is common. This paper describes five cases of aged patients with lobar cerebral hemorrhage and craniotomy with hematoma evacuation and biopsy. Pathological results all showed amyloid angiopathy. Various outcomes are discussed, and the literature is reviewed. Findings show that although patients with CAA were at high risk of recurrent hemorrhage after surgery, the mortality rate was relatively low despite the severity of lobar intracerebral hemorrhage.

Postoperative outcome of 37 patients with lobar intracerebral hemorrhage related to cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Several recent studies have suggested that neurosurgical procedures are not contraindicated in patients with cerebral amyloid angiopathy (CAA). The purpose of this study was to elucidate the clinical factors influencing the outcome of patients with CAA-related intracerebral hemorrhage (ICH) treated surgically. METHODS: A total of 50 neurosurgical procedures (42 intracerebral hematoma evacuations, 4 ventriculoperitoneal shunts, 3 ventricular drainages, and 1 brain biopsy) were performed in 37 patients with CAA-related ICH. To ascertain the clinical factors that may influence their postoperative outcome, their clinical data (demographics, medical history, recurrent lobar hemorrhage, radiographic characteristics, multiple lobar hemorrhage, surgical details, and postoperative hemorrhage) were examined retrospectively and subjected to multivariate analysis. RESULTS: Twenty patients (54%) had a good outcome, and only 4 (11%) died. Parietal hematomas, advanced age (>/=75 years), and intraventricular hemorrhages had significant adverse influence on the postoperative outcome. Clinically significant postoperative hemorrhage requiring evacuation occurred after 2 (5%) of 42 intracerebral hematoma evacuations. Postoperative hemorrhage did not have significant adverse influence on the outcome. CONCLUSIONS: Neurosurgery can be performed relatively safely in patients with CAA-related ICH, and their postoperative outcome is better than that reported previously. Surgical treatment should be considered for such patients aged <75 years without a parietal hematoma and intraventricular hemorrhage.

Cerebral amyloid angiopathy (CAA) with presentation as a brain inflammatory pseudo-tumour.

Cerebral amyloid angiopathy (CAA) is frequent but often asymptomatic. It can induce lobar haemorrhage, rapidly progressive dementia or recurrent transient neurological symptoms, other presentations being less frequent. We report 3 patients in their sixties presenting with a space occupying lesion which was the first manifestation of CAA. They were operated with a diagnosis of cerebral tumour. In all three cases, macroscopy was similar, the lesions were superficial in the cerebral cortex and the preoperative diagnoses were glioblastoma, meningioma and cavernoma. Histologically, the lesions consisted of a large inflammatory granuloma with numerous lipophages and siderophages surrounding capillaries with prominent endothelial cells. Vessels in the near cortex and meninges and within the granuloma harboured heavy amyloid deposits immunolabelled by anti-P component, anti-protein beta A4 with a A40 predominance and anti-apolipoprotein E. Adjacent cerebral cortex showed reactive gliosis and rare senile plaques. Amyloidosis is rarely considered among diagnoses of space occupying lesions. In our three cases, CT scan and MRI changes were related to the presence of an inflammatory granuloma around foci of haemorrhage and amyloid laden vessels.

Surgical intervention, biopsy and APOE genotype in cerebral amyloid angiopathy-related haemorrhage.

Twelve patients who had surgical removal of a cerebral haematoma had a biopsy or autopsy diagnosis of cerebral amyloid angiopathy-related haemorrhage (CAAH). Ten had a cortical biopsy at the time of surgery and eight reports of these were interpreted as showing CAA to be the cause of the haemorrhage. The diagnosis in the remaining two was made at autopsy. Six patients had a biopsy and autopsy, resulting in a 67% (four of six) biopsy sensitivity. Amyloid beta-protein (A beta) immunohistochemistry was more sensitive than tinctorial stains in detecting CAA. As previously reported in CAAH there was an excess of patients with the APOE epsilon 2 allele (33% versus 16% in a control group). Four patients (33%) were alive at 3 months. Despite surgical intervention, CAAH has a poor outcome in patients with impaired consciousness. Clinical awareness of CAAH and use of A beta immunostaining may increase the diagnostic yield from cerebral biopsy.

Surgical experience with massive lobar haemorrhage caused by cerebral amyloid angiopathy.

Nineteen patients with massive lobar haemorrhage without angiographic lesions received direct or stereotactic surgery, and biopsy specimens were examined histologically. Ten patients (53%) were found to have vessels positive for Congo-red staining, and demonstrating amyloid angiopathy. In the patients with amyloid angiopathy, CT scan and surgical findings were investigated. Subarachnoid haemorrhage (9/10), irregularly shaped haematoma (9/10) and fluid-blood density level in the haematoma cavity (7/10) were frequently found on CT scan. The characteristic surgical findings in patients treated by direct surgery were subarachnoid haemorrhage adjacent to intracerebral haematoma (8/8) and the existence of a tangle of vessels in the haematoma cavity (4/8). Evacuation of haematomas was relatively easy, and difficulty of haemostasis was not encountered during surgery.

Spontaneous cerebral haemorrhage from cerebral amyloid angiopathy.

Three cases of spontaneous intracerebral haemorrhage treated by acute evacuation of haematoma are described. All cases proved to have cerebral amyloid angiopathy as the primary cause of the haemorrhage. Only one patient survived. Previous reports are discussed.