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Keywords = CAA-RI

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28 pages, 1969 KiB  
Review
Clinical Management of Cerebral Amyloid Angiopathy
by Aikaterini Theodorou, Stella Fanouraki, Eleni Bakola, Georgia Papagiannopoulou, Lina Palaiodimou, Maria Chondrogianni, Maria-Ioanna Stefanou, Lampis Stavrinou, Athanasia Athanasaki, Klearchos Psychogios, Odysseas Kargiotis, Apostolos Safouris, Georgios Velonakis, Georgios P. Paraskevas and Georgios Tsivgoulis
J. Clin. Med. 2025, 14(12), 4259; https://doi.org/10.3390/jcm14124259 - 15 Jun 2025
Viewed by 3445
Abstract
Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and [...] Read more.
Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and most uncommon subtypes of the disease. Results: The vast majority of CAA remains sporadic, with increasing prevalence with age and very frequent coexistence with Alzheimer’s disease. Clinically, CAA can present with spontaneous lobar intracerebral hemorrhage, transient focal neurologic episodes attributed to convexity subarachnoid hemorrhage or cortical superficial siderosis, and progressive cognitive decline leading to dementia. Inflammatory CAA subtype should be recognized early and treated promptly so that better functional outcomes may be achieved. Moreover, genetic and iatrogenic CAA forms are rare, yet increasingly recognized during the last years. Therapeutic management remains challenging for clinicians, especially when markers indicative of higher bleeding risk are present. A targeted therapy does not currently exist. However, various clinical trials are in progress, focusing on offering new promising insights into the disease treatment. Conclusions: This review aims to deepen our understanding of CAA diagnosis and therapeutic approach but also summarizes current evidence on the most uncommon subtypes of this cerebral small-vessel disease. Full article
(This article belongs to the Section Clinical Neurology)
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11 pages, 4714 KiB  
Case Report
Cerebral Amyloid Angiopathy Related Inflammation: A Single-Center Case Series Analysis
by Syed Zahid Ali, Hanah Alley, James Johnson, Harshini Sirvisetty, Michael Sowell, Alex Glynn and Peter Hedera
Brain Sci. 2025, 15(5), 472; https://doi.org/10.3390/brainsci15050472 - 29 Apr 2025
Viewed by 806
Abstract
Background: Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare subtype of cerebral amyloid angiopathy (CAA), which presents mostly as a subacute and reversible encephalopathy. Primary symptoms include behavioral changes and cognitive decline in the form of rapidly progressive dementia, headache, seizures, and focal [...] Read more.
Background: Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare subtype of cerebral amyloid angiopathy (CAA), which presents mostly as a subacute and reversible encephalopathy. Primary symptoms include behavioral changes and cognitive decline in the form of rapidly progressive dementia, headache, seizures, and focal neurological deficits. It can also manifest as a varied range of typical and atypical presentations. Misdiagnosis is common because it shares symptoms with other infectious, ischemic and autoimmune pathologies and there is also a significant overlap of MRI findings. Methods: Gold standard diagnosis requires brain biopsy in appropriate clinical setting, but diagnostic criteria is established for probable and possible CAA-RI using clinical symptoms and MRI findings in the absence of other inflammatory, infectious or autoimmune processes. Immunomodulatory therapy is the mainstay of treatment, with variable response. Results: We present a case series of three patients with CAA-RI highlighting disease course, neuroradiological manifestation, treatment response, and clinical outcomes. We also provide a literature review to increase insight into this rare pathology. Conclusions: Early diagnosis and prompt initiation of immunosuppressive therapy is beneficial in most cases. Full article
(This article belongs to the Section Behavioral Neuroscience)
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25 pages, 9116 KiB  
Review
Cerebral Amyloid Angiopathy: Clinical Presentation, Sequelae and Neuroimaging Features—An Update
by Stefan Weidauer and Elke Hattingen
Biomedicines 2025, 13(3), 603; https://doi.org/10.3390/biomedicines13030603 - 1 Mar 2025
Cited by 1 | Viewed by 2391
Abstract
The prevalence of cerebral amyloid angiopathy (CAA) has been shown to increase with age, with rates reported to be around 50–60% in individuals over 80 years old who have cognitive impairment. The disease often presents as spontaneous lobar intracerebral hemorrhage (ICH), which carries [...] Read more.
The prevalence of cerebral amyloid angiopathy (CAA) has been shown to increase with age, with rates reported to be around 50–60% in individuals over 80 years old who have cognitive impairment. The disease often presents as spontaneous lobar intracerebral hemorrhage (ICH), which carries a high risk of recurrence, along with transient focal neurologic episodes (TFNE) and progressive cognitive decline, potentially leading to Alzheimer’s disease (AD). In addition to ICH, neuroradiologic findings of CAA include cortical and subcortical microbleeds (MB), cortical subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS). Non-hemorrhagic pathologies include dilated perivascular spaces in the centrum semiovale and multiple hyperintense lesions on T2-weighted magnetic resonance imaging (MRI). A definitive diagnosis of CAA still requires histological confirmation. The Boston criteria allow for the diagnosis of a probable or possible CAA by considering specific neurological and MRI findings. The recent version, 2.0, which includes additional non-hemorrhagic MRI findings, increases sensitivity while maintaining the same specificity. The characteristic MRI findings of autoantibody-related CAA-related inflammation (CAA-ri) are similar to the so-called “amyloid related imaging abnormalities” (ARIA) observed with amyloid antibody therapies, presenting in two variants: (a) vasogenic edema and leptomeningeal effusions (ARIA-E) and (b) hemorrhagic lesions (ARIA-H). Clinical and MRI findings enable the diagnosis of a probable or possible CAA-ri, with biopsy remaining the gold standard for confirmation. In contrast to spontaneous CAA-ri, only about 20% of patients treated with monoclonal antibodies who show proven ARIA on MRI also experience clinical symptoms, including headache, confusion, other psychopathological abnormalities, visual disturbances, nausea and vomiting. Recent findings indicate that treatment should be continued in cases of mild ARIA, with ongoing MRI and clinical monitoring. This review offers a concise update on CAA and its associated consequences. Full article
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15 pages, 7269 KiB  
Article
Combined Toxic Effects and Mechanisms of Chloroacetic Acid and N-Nitrosodimethylamine on Submerged Macrophytes
by Kaili Huang, Haiqing Huang, Xuhui Huang, An Lao, Zheng Zheng and Hanqi Wu
Water 2024, 16(18), 2689; https://doi.org/10.3390/w16182689 - 21 Sep 2024
Viewed by 1388
Abstract
Disinfection by-products (DBPs) such as chloroacetic acids (CAAs) and N-Nitrosodimethylamine (NDMA) are prevalent pollutants in surface waters, particularly with the increasing use of chlorine-based disinfectants. The entry of these DBPs into water bodies may increase accordingly, posing ecological risks to aquatic life. To [...] Read more.
Disinfection by-products (DBPs) such as chloroacetic acids (CAAs) and N-Nitrosodimethylamine (NDMA) are prevalent pollutants in surface waters, particularly with the increasing use of chlorine-based disinfectants. The entry of these DBPs into water bodies may increase accordingly, posing ecological risks to aquatic life. To assess the toxic effects of CAAs and NDMA on submerged macrophytes, Vallisneria natans was exposed to different concentrations of CAAs (1.0, 10.0, and 100.0 μg L−1) and NDMA (0.1, 1.0, and 10.0 μg L−1). A RI value of <1 indicates that simultaneous exposure to CAAs and NDMA can produce an antagonistic effect. Both CAAs and NDMA adversely affect the photosynthetic system of plants. In the NDMA treatment group, chlorophyll a content decreases with increasing concentration, accounting for 96.03%, 60.80%, and 58.67% of the CT group, respectively. Additionally, it effectively triggers the plant’s antioxidant response, with significant increases in SOD, POD, and GSH levels. Among these, the combined treatment group AN2 (10 + 1 μg L−1) showed the most significant change in SOD activity, reaching 3.57 times that of the CT group. Ultrastructural changes also revealed stress responses in leaf cells and damage to organelles. Furthermore, metabolomics provided insights into the metabolic responses induced by CAAs or NDMA in V. natans leaves, where the composition and metabolism of lipids, fatty acids, cofactors and vitamins, amino acids, nucleotides, and some antioxidants were regulated, affecting plant growth. This study provides preliminary information for the ecological risk assessment of submerged plants by complex contamination with the disinfection by-products CAA and NDMA. Full article
(This article belongs to the Section Biodiversity and Functionality of Aquatic Ecosystems)
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12 pages, 2567 KiB  
Case Report
Cerebral Amyloid Angiopathy-Related Inflammation (CAA-rI): Three Heterogeneous Case Reports and a Focused Literature Review
by Ivo Bozovic, Marta Jeremic, Aleksandra Pavlovic, Carna Jovanovic, Nikola Kresojevic, Nikola Vojvodic, Dejana Jovanovic, Dragoslav Sokic and Milija Mijajlovic
Brain Sci. 2023, 13(5), 747; https://doi.org/10.3390/brainsci13050747 - 29 Apr 2023
Cited by 3 | Viewed by 5980
Abstract
Cerebral amyloid angiopathy-related inflammation (CAA-rI) is a largely reversible, subacute encephalopathy, which is considered as a rare variant of cerebral amyloid angiopathy (CAA). Although the diagnosis of this inflammatory vasculopathy is generally clinico-pathologic, a probable or possible diagnosis can often be established based [...] Read more.
Cerebral amyloid angiopathy-related inflammation (CAA-rI) is a largely reversible, subacute encephalopathy, which is considered as a rare variant of cerebral amyloid angiopathy (CAA). Although the diagnosis of this inflammatory vasculopathy is generally clinico-pathologic, a probable or possible diagnosis can often be established based on current clinico-radiological diagnostic criteria. This is important since CAA-rI is considered as a treatable disorder, which most commonly occurs in the elderly population. Behavioral changes and cognitive deterioration are highlighted as the most common clinical signs of CAA-rI, followed by a heterogeneous spectrum of typical and atypical clinical presentations. However, despite the well-established clinical and radiological features incorporated in the current diagnostic criteria for this CAA variant, this rare disorder is still insufficiently recognized and treated. Here, we have shown three patients diagnosed with probable CAA-rI, with significant heterogeneity in the clinical and neuroradiological presentations, followed by different disease courses and outcomes after the introduction of immunosuppressive treatment. Moreover, we have also summarized up-to-date literature data about this rare, yet underdiagnosed, immune-mediated vasculopathy. Full article
(This article belongs to the Section Neuropathology)
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13 pages, 2928 KiB  
Article
Cerebral Amyloid Angiopathy—Related Inflammation: A Single-Center Experience and a Literature Review
by Aikaterini Theodorou, Lina Palaiodimou, Apostolos Safouris, Odysseas Kargiotis, Klearchos Psychogios, Vasiliki Kotsali-Peteinelli, Aikaterini Foska, Vasiliki Zouvelou, Elias Tzavellas, Dimitrios Tzanetakos, Christina Zompola, John S. Tzartos, Konstantinos Voumvourakis, Georgios P. Paraskevas and Georgios Tsivgoulis
J. Clin. Med. 2022, 11(22), 6731; https://doi.org/10.3390/jcm11226731 - 14 Nov 2022
Cited by 8 | Viewed by 2951
Abstract
Background: Limited data exist regarding the prevalence of clinical, neuroimaging, and genetic markers among patients diagnosed with Cerebral Amyloid Angiopathy–related inflammation (CAA-ri). We sought to determine these characteristics in patients diagnosed in our center and to summarize available literature published either as single-case [...] Read more.
Background: Limited data exist regarding the prevalence of clinical, neuroimaging, and genetic markers among patients diagnosed with Cerebral Amyloid Angiopathy–related inflammation (CAA-ri). We sought to determine these characteristics in patients diagnosed in our center and to summarize available literature published either as single-case reports or small case series (<5 patients). Methods: We reported our single-center experience of patients diagnosed with CAA-ri according to international criteria during a seven-year period (2015–2022), and we abstracted data from 90 previously published cases. Results: Seven patients (43% women, mean age 70 ± 13 years) were diagnosed with CAA-ri in our center. The most common symptom at presentation was focal neurological dysfunction (71%), and the most prevalent radiological finding was the presence of T2/FLAIR white matter hyperintensities (100%). All patients were treated with corticosteroids and had a favorable functional outcome. Among 90 previously published CAA-ri cases (51% women, mean age 70 ± 9 years), focal neurological dysfunction was the most common symptom (76%), followed by a cognitive decline (46%) and headache (34%). The most prevalent neuroimaging findings were cerebral microbleeds (85%), asymmetric T2/FLAIR white matter hyperintensities (81%), and gadolinium-enhancing T1-lesions (37%). Genetic testing for the Apolipoprotein-E gene was available in 27 cases; 59% carried the APOE ε4/ε4 genotype. The majority of the published CAA-ri cases (78%) received corticosteroid monotherapy, while 17 patients (19%) were treated with additional immunosuppressive treatment. Favorable functional outcome following treatment was documented in 70% of patients. Conclusion: Improving the vigilance of clinicians regarding the early recognition and accurate diagnosis of CAA-ri is crucial for swift therapy initiation, which may result in improved functional outcomes. Full article
(This article belongs to the Section Clinical Neurology)
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11 pages, 969 KiB  
Article
Stemming the Rise of Antibiotic Use for Community-Acquired Acute Respiratory Infections during COVID-19 Pandemic
by Shena Y. C. Lim, Yvonne P. Zhou, Daphne Yii, De Zhi Chin, Kai Chee Hung, Lai Wei Lee, Jia Le Lim, Li Wen Loo, Narendran Koomanan, Nathalie Grace Chua, Yixin Liew, Benjamin P. Z. Cherng, Siew Yee Thien, Winnie H. L. Lee, Andrea L. H. Kwa and Shimin J. Chung
Antibiotics 2022, 11(7), 846; https://doi.org/10.3390/antibiotics11070846 - 24 Jun 2022
Cited by 3 | Viewed by 3007
Abstract
At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the [...] Read more.
At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the usual purview of the antimicrobial stewardship unit (ASU). Serum procalcitonin, a biomarker to distinguish viral from bacterial infections, can be used to guide antibiotic recommendations in suspected lower respiratory tract infection. We modified our stewardship approach, and used a procalcitonin-guided strategy to identify “high yield” interventions for audits in patients admitted with CA-ARI. With this approach, there was an increase in the proportion of patients with antibiotics discontinued within 4 days (16.5% vs. 34.9%, p < 0.001), and the overall duration of antibiotic therapy was significantly shorter [7 (6–8) vs. 6 (3–8) days, p < 0.001]. There was a significant decrease in patients with intravenous-to-oral switch of antibiotics to “complete the course” (45.3% vs. 34.4%, p < 0.05). Of the patients who had antibiotics discontinued, none were restarted on antibiotics within 48 h, and there was no-30-day readmission or 30-day mortality attributed to respiratory infection. This study illustrates the importance of the antimicrobial stewardship during the pandemic and the need for ASU to remain attuned to prescriber’s practices, and adapt accordingly to address antibiotic misuse to curb antimicrobial resistance. Full article
(This article belongs to the Special Issue The Use of Antibiotics in COVID-19 Infections)
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11 pages, 3523 KiB  
Case Report
Rapid Cognitive Decline and Recurrent Falls in a 71 Year-Old Man due to Cerebral Amyloidangiopathy-Related Inflammation (CAA-RI)
by Stefan Dörr, Rabea Schickel, Lara Lucke-Paulig, Steffen Schöntag and Ralf Lobmann
Geriatrics 2019, 4(4), 56; https://doi.org/10.3390/geriatrics4040056 - 2 Oct 2019
Cited by 7 | Viewed by 6471
Abstract
Cognitive decline and falls in the elderly are common and are often accepted as natural and inevitable by relatives and health care professionals, but frequently there are specific and treatable diseases that should be revealed. In our case, cerebral amyloid angiopathy-related inflammation (CAA-RI) [...] Read more.
Cognitive decline and falls in the elderly are common and are often accepted as natural and inevitable by relatives and health care professionals, but frequently there are specific and treatable diseases that should be revealed. In our case, cerebral amyloid angiopathy-related inflammation (CAA-RI) was causative for neuro-psychiatric symptoms and worsening of gait in a 71 year-old man with recurrent falls and decline of gait and cognition. Cerebral amyloidangiopathy (CAA) is an important cause of cerebrovascular disorders in the elderly, characterized by leukoencephalopathy combined with lobar or small cortical hemorrhage due to amyloid deposition in cortical and leptomeningeal vessels. In several conditions, amyloid deposition can provoke inflammation or edema that lead to -normally reversible- encephalopathy. CAA-RI is then characterized by subacute neurobehavioral symptoms, headache, seizures or stroke-like signs. The first therapeutic option after confirming the diagnosis is treatment with glucocorticoids. Despite treatment with prednisolone, our patient could not regain his unrestricted mobility and self-help competence. Our report aims to sharpen awareness for CAA and its inflammatory form (CAA-RI) in healthcare professionals involved in medical care of the elderly and provide a short summary of this disease. Full article
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