scholarly journals Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage

2021 ◽  
Vol 10 (5) ◽  
pp. 989
Author(s):  
Paula Marazuela ◽  
Anna Bonaterra-Pastra ◽  
Júlia Faura ◽  
Anna Penalba ◽  
Jesús Pizarro ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Cerebral Amyloid Angiopathy ◽  
Serum Levels ◽  
Protective Role ◽  
Outcome Evaluation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA–ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

Left Ventricle Hypertrophy is Common in Patients with Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage and Is Independently Associated with Long-Term Mortality.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Octavio M Pontes-Neto ◽  
Sergi Martinez-Ramirez ◽  
Anand Viswanathan ◽  
Eitan Auriel ◽  
Kristen M Schwab ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Intracerebral Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Lv Mass ◽  
The Mean ◽  
Cerebral Amyloid ◽  
Long Term Mortality

Background: A post-hoc analysis of the PROGRESS trial suggested that long-term anti-hypertensive therapy prevents intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA). However, the burden of underlying hypertension in patients with CAA is unclear, and it is also unclear whether this hypertensive burden contributes to long-term outcome in survivors of CAA-related ICH. Left ventricle (LV) hypertrophy is a measure of the chronicity and severity of hypertension and could be used to assess hypertensive end-organ damage in patients with CAA. Objective: To test the hypothesis that LV hypertrophy is common in patients with CAA-related ICH and is associated with increased long-term mortality and shorter survival in those patients. Methods: This was a retrospective analysis of a prospectively collected cohort of consecutive patients with primary ICH presenting to a single academic center. We included patients presenting between January/2000 to December/2010, age > 55 years, who received a transthoracic echocardiogram (echo) during follow-up and were diagnosed with definitive, probable or possible CAA according to the Boston criteria. LV mass index (10g/m2) was calculated according to Penn convention. Ninety-day survivors were followed prospectively for long-term mortality or censoring at January/2012. Cox proportional hazards models were used to identify predictors of mortality as time-dependent variables adjusting for potential confounders. Results: Among 211 patients who met inclusion criteria, the mean time to follow-up was 4.28 ± 2.7 years; the median time to echocardiogram was 3 days (IQR:49). The mean age was 75.7 ± 9.1 years; 103 (49%) were male. LV hypertrophy was present in 55 (31.8%) patients and 152 (72%) patients survived more than 90 days. In multivariate analysis, after adjusting for baseline characteristics, LV mass index (10g/m2) was associated with higher long-term mortality (HR: 1.20; 95%CI: 1.01-1.4; p=0.039). On Cox-regression, LV hypertrophy was independently associated with shorter long-term survival (HR 1.91; 95%CI 1.05-3.47; p=0.034). Conclusions: LV hypertrophy is common in patients with CAA-related ICH and is associated with increased risk of subsequent mortality among 90-day survivors.

Transient Focal Neurological Events in Cerebral Amyloid Angiopathy and the Long-term Risk of Intracerebral Hemorrhage and Death

2021 ◽  
Author(s):  
Juan María Sanchez-Caro ◽  
Iñigo de Lorenzo Martínez de Ubago ◽  
Elena de Celis Ruiz ◽  
Ainara Barguilla Arribas ◽  
Lionel Calviere ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

scholarly journals 10-Year Follow-Up of a Patient with Cerebral Amyloid Angiopathy

2020 ◽  
Vol 12 (Suppl. 1) ◽  
pp. 202-206
Author(s):  
Min Kyoung Kang ◽  
Byung-Woo Yoon
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
The Elderly ◽  
Amyloid Angiopathy ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Radiological Features ◽  
Magnetic Imaging ◽  
Long Term Follow Up ◽  
Cerebral Amyloid

We report the case of long-term follow-up of brain magnetic imaging of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is often considered a major cause of spontaneous intracerebral hemorrhage in the elderly. This case illustrates the markedly progressive clinical and radiological features of the vasculopathic process in 10 years.

Cerebrovascular and Neurodegenerative Pathologies in Long-Term Stable Mild Cognitive Impairment

2021 ◽  
pp. 1-15
Author(s):  
Manu J. Sharma ◽  
Brandy L. Callahan
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cerebral Amyloid Angiopathy ◽  
Neurofibrillary Tangles ◽  
Small Vessel Disease ◽  
Significant Proportion ◽  
Amyloid Angiopathy ◽  
Prodromal Phase ◽  
Cerebral Amyloid

Background: Mild cognitive impairment (MCI) is considered by some to be a prodromal phase of a progressive disease (i.e., neurodegeneration) resulting in dementia; however, a substantial portion of individuals (ranging from 5–30%) remain cognitively stable over the long term (sMCI). The etiology of sMCI is unclear but may be linked to cerebrovascular disease (CVD), as evidence from longitudinal studies suggest a significant proportion of individuals with vasculopathy remain stable over time. Objective: To quantify the presence of neurodegenerative and vascular pathologies in individuals with long-term (>5-year) sMCI, in a preliminary test of the hypothesis that CVD may be a contributor to non-degenerative cognitive impairment. We expect frequent vasculopathy at autopsy in sMCI relative to neurodegenerative disease, and relative to individuals who convert to dementia. Methods: In this retrospective study, using data from the National Alzheimer’s Coordinating Center, individuals with sMCI (n = 28) were compared to those with MCI who declined over a 5 to 9-year period (dMCI; n = 139) on measures of neurodegenerative pathology (i.e., Aβ plaques, neurofibrillary tangles, TDP-43, and cerebral amyloid angiopathy) and CVD (infarcts, lacunes, microinfarcts, hemorrhages, and microbleeds). Results: Alzheimer’s disease pathology (Aβ plaques, neurofibrillary tangles, and cerebral amyloid angiopathy) was significantly higher in the dMCI group than the sMCI group. Microinfarcts were the only vasculopathy associated with group membership; these were more frequent in sMCI. Conclusion: The most frequent neuropathology in this sample of long-term sMCI was microinfarcts, tentatively suggesting that silent small vessel disease may characterize non-worsening cognitive impairment.

Clinical and neuropathologic analysis of intracerebral hemorrhage in patients with cerebral amyloid angiopathy

2019 ◽  
Vol 176 ◽  
pp. 110-115
Author(s):  
Taro Yanagawa ◽  
Masaki Takao ◽  
Masami Yasuda ◽  
Tomoya Kamide ◽  
Hiroki Sato ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

scholarly journals Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Andrea Wagner ◽  
Christiane Groetsch ◽  
Sibylle Wilfling ◽  
Karl-Michael Schebesch ◽  
Mustafa Kilic ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Recurrent Events ◽  
Clinical Presentation ◽  
Secondary Prophylaxis ◽  
Amyloid Angiopathy ◽  
Index Event ◽  
Asymptomatic Patients ◽  
Cerebral Amyloid

Abstract Background The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH). Methods Retrospective analyses and clinical follow-ups of individuals with at least mBC “possible” CAA from 2005 to 2018. Results 149 patients were classified in subgroups due to the index event: lICH (n = 91), AIS (n = 32), > 3 cMBs only (n = 16) and cSS (n = 10). Patients in the lICH subgroup had a significantly higher percentage of single new lICHs compared to other groups, whereas patients in the AIS-group had a significantly higher percentage of multiple new AIS. cMBs as index event predisposed for AIS during follow up (p < 0.0016). Patients of the cMBs- or cSS-group showed significantly more TFNEs (transient focal-neurological episodes) and lower numbers of asymptomatic patients (for epilepsy and TFNEs) at the index event than patients with lICH or AIS (p < 0.0013). At long-term follow-up, the cMBs- and cSS-group were characterized by more TFNEs and fewer asymptomatic patients. Conclusions A new classification system of CAA should add subgroups according to the initial clinical presentation to the mBCs allowing individual prognosis, acute treatment and secondary prophylaxis.

Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Andreas Charidimou ◽  
Gregoire Boulouis ◽  
Matthew Frosch ◽  
Jean-Claude Baron ◽  
Marco Pasi ◽  
...  
Keyword(s):  
White Matter ◽  
Intracerebral Hemorrhage ◽  
Diagnostic Accuracy ◽  
Cerebral Amyloid Angiopathy ◽  
Brain Mri ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Validation Sample ◽  
Temporal Validation ◽  
Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

Subacute Cognitive Decline in an 86-Year-Old Woman With Prior Lobar Intracerebral Hemorrhage

2021 ◽  
pp. 192-194
Author(s):  
Stephen W. English ◽  
James P. Klaas
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cognitive Decline ◽  
Temporal Lobe ◽  
Cerebral Amyloid Angiopathy ◽  
Mass Effect ◽  
Amyloid Angiopathy ◽  
Left Temporal Lobe ◽  
Epileptiform Discharges ◽  
Cerebral Amyloid ◽  
T2 Hyperintensity

An 86-year-old woman with a history of hypertension, hyperlipidemia, coronary artery disease, and hypothyroidism sought care for subacute, progressive cognitive decline. Five months earlier, she was hospitalized for a small, left temporal, lobar, intracerebral hemorrhage with associated receptive aphasia. Over the next several months, she had a precipitous cognitive decline. She was prescribed memantine by her primary physician because of concern for dementia. One month before seeking care, she was found unconscious in her bathroom, which was believed to be an unwitnessed seizure. Brain magnetic resonance imaging 1 month before the current evaluation showed a prior, small, left temporal hemorrhage and diffuse lobar microhemorrhages on gradient echo imaging, focal leptomeningeal gadolinium enhancement in the left temporal lobe, and multifocal T2 hyperintensity with mass effect, maximal in the left temporal lobe. Electroencephalography showed multifocal, independent epileptiform discharges. She underwent open biopsy of the left temporal lobe, which indicated focal granulomatous inflammation causing vascular destruction, with β‎-amyloid plaques within the cortical and leptomeningeal vessels. The findings were consistent with a diagnosis of amyloid-β‎-related angiitis in the setting of severe cerebral amyloid angiopathy. Because of concern for subclinical seizures and epileptiform discharges on electroencephalography, the patient was started on levetiracetam without substantial change in her mental status. After the biopsy findings demonstrated inflammatory changes consistent with amyloid-β‎-related angiitis, she was started on intravenous methylprednisolone, followed by transition to prednisone. After 6 months of treatment, she had significant clinical and radiographic improvement. Follow-up magnetic resonance imaging at that time showed interval improvement in the T2 hyperintensity and mass effect in the left temporal lobe. She was again independent with her activities of daily living, and memantine was discontinued. Cerebral amyloid angiopathy encompasses a heterogeneous group of diseases characterized by amyloid-β‎ peptide deposition. The most common clinical manifestation of cerebral amyloid angiopathy is lobar intracerebral hemorrhage, which can be multifocal and recurrent but can also result in cerebral ischemia and ischemic leukoencephalopathy.

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