Cerebral Amyloid Angiopathy-related Inflammation Research Articles

A Case of Cerebral Amyloid Angiopathy-Related Inflammation With Partial Remission After High Dose Steroid Therapy

A Case of Cerebral Amyloid Angiopathy-Related Inflammation With Partial Remission After High Dose Steroid Therapy

Cerebral amyloid angiopathy-related inflammation with posterior reversible encephalopathy syndrome-like presentation: a case report

BackgroundCerebral amyloid angiopathy-related inflammation (CAA-RI), which presents with acute or subacute cognitive or functional decline, focal or multifocal neurologic deficits, new onset of seizures, or a combination of seizures and neurologic deficits, shares clinical and radiologic similarities with posterior reversible encephalopathy syndrome (PRES). Differential diagnosis is critical because the treatment principle for these 2 conditions differs greatly. Here, we present a case of PRES-like CAA-RI and the strategy used to discriminate between the 2 conditions.Case presentationA patient with probable CAA-RI was first thought to suffer from PRES. Initial high-dose methylprednisolone therapy caused rapid improvement of the neurologic symptoms but abrupt discontinuation of corticosteroids resulted in clinical relapse and deterioration. Subsequent reinitiation of high-dose methylprednisolone followed by tapering off of oral prednisone led to clinical and radiologic recovery at the 3-month follow-up.ConclusionsWe suggest that in cases where it is difficult to distinguish between CAA-RI and PRES solely based on magnetic resonance imaging, a good response to corticosteroids and an apolipoprotein E (ApoE) ε4/ε4 genotype are critical for establishing a diagnosis of CAA-RI. If there is clinical deterioration, sudden withdrawal of high-dose corticosteroid during the active phase of CAA-RI should be avoided.

Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis.

There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.

Cerebral Amyloid Angiopathy-Related Inflammation: A Single-Center Experience and a Literature Review.

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). 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. 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. 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.

Reader Response: Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.

Reader Response: Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.

Association of Microglial Activation With Spontaneous ARIA-E and CSF Levels of Anti-Aβ Autoantibodies.

Background and ObjectivesAmyloid-related imaging abnormalities suggestive of vasogenic edema or sulcal effusion (ARIA-E) are the most common adverse events complicating Alzheimer disease (AD) immunotherapy with anti–β-amyloid (Aβ) monoclonal antibodies. ARIA-E can also occur spontaneously in cerebral amyloid angiopathy–related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with increased CSF levels of anti-Aβ autoantibodies. Although the pathophysiologic mechanisms of ARIA-E remain to be fully elucidated, experimental evidence from ex vivo studies suggests that gantenerumab and aducanumab enable microglial activation. However, the in vivo evidence for a direct association between neuroinflammation and ARIA-E in patients with high CSF anti-Aβ (auto)antibody levels has never been demonstrated.MethodsThe spatial distribution and temporal variations of microglial activation associated with levels of anti-Aβ autoantibodies at (sub)acute presentation of ARIA-E and after corticosteroid therapy were evaluated in a longitudinal case series of patients with CAA-ri, the spontaneous variant of the iatrogenic ARIA-E reported in Aβ-lowering immunotherapy with monoclonal antibodies. Multimodal and multiparametric MRI was used for CAA and ARIA-E severity quantification, according to validated scoring system; CSF testing for anti-Aβ autoantibodies and AD biomarkers; 11C-PK11195 PET for activated microglia.ResultsAt (sub)acute presentation, we found focal peaks of microglial activation having a greater spatial colocalization with ARIA-E compared with chronic age-related white matter change imaging abnormalities. The severity of ARIA-E and the magnitude of the associated microglial activation were greater in patients having AD and severe CAA concomitant disease compared with patients having CAA only. CSF anti-Aβ autoantibodies at presentation were high in all patients and markedly decreased at posttreatment follow-up, in parallel with clinical resolution of acute symptoms, reduced ARIA-E severity, and reduced microglial activation.DiscussionOur findings extend the current notion of ARIA-E by providing the first in vivo 11C-PK11195 PET evidence for an association between microglial activation and the magnitude and severity of ARIA-E in patients with increased CSF concentration of anti-Aβ autoantibodies and comorbid AD and CAA disease. Our results highlight CSF testing for anti-Aβ autoantibodies as a promising diagnostic, prognostic, and therapy response biomarker to help guide future treatment and management decisions in real clinical practice and clinical trials.

Diagnosis, treatment, and follow-up of patients with cerebral amyloid angiopathy-related inflammation

PurposeCerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare potentially reversible encephalopathy associated with an autoimmune process against proteins deposited in the walls of cortical and leptomeningeal brain vessels. Definite diagnosis requires histopathological features of vascular inflammation and amyloid deposition from brain biopsy. Clinical-neuroradiological criteria have been recently introduced and validated to reduce the need for biopsy. The purpose of this paper is to report a historical retrospective review of clinical-neuroradiological follow-up of two patients with probable CAA-ri and five patients with a reasonably probable suspect of CAA-ri (4 females, 3 males, patient’s age at admission: 66–79 years) seen at our institution between 2007 and 2021, focusing on clinical and neuroradiological awareness to this entity and variable response to immunotherapy.Materials and methodsClinical features at presentation included subacute to acute confusion (6/7), seizures (4/7), cognitive impairment (5/7), and focal neurological signs (3/7). Neuroradiology included braincomputed tomography followed by magnetic resonance imaging. Infectious diseases and autoimmune workups were then performed.ResultsCSF analysis was performed in two patients. Cerebral angiography was performed in two patients, to rule out vascular malformations. Hemorrhagic posterior reversible encephalopathy syndrome has been suspected in two patients. Four patients underwent immunotherapy with corticosteroids followed by reduction of brain dysfunctions. Three patients did not undergo immunotherapy but underwent clinical and/or neuroradiological remission.ConclusionsPatients with CAA-ri present a rare steroid-responsive acute to subacute brain dysfunction. Thus, it has to be known and recognized both clinically and neuroradiologically. Spontaneous clinical and/or neuroradiological improvement is possible in patients with mild symptoms.

Different clinical outcomes between cerebral amyloid angiopathy-related inflammation and non-inflammatory form.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3pg/ml vs 490.8pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.

A Challenging Case of Cerebral Amyloid Angiopathy-related Inflammation (CAAri): Implications for Secondary Stroke Prevention and Immunomodulation Therapies (P1-10.002)

A Challenging Case of Cerebral Amyloid Angiopathy-related Inflammation (CAAri): Implications for Secondary Stroke Prevention and Immunomodulation Therapies (P1-10.002)

Clinical Features and Course of Cerebral Amyloid Angiopathy-Related Inflammation (P8-4.011)

Clinical Features and Course of Cerebral Amyloid Angiopathy-Related Inflammation (P8-4.011)

Cerebral Amyloid Angiopathy-Related Inflammation in Down Syndrome-Related Alzheimer Disease.

A 59-year-old woman with Down syndrome (DS) and prodromal Alzheimer disease (AD) presenting progressive cognitive impairment in the previous year, with no focal symptoms, headache, seizures, or accelerated cognitive decline, underwent 3T brain MRI showing cortico-subcortical tumefactive fluid-attenuated inversion recovery (FLAIR) hyperintensities, associated with microbleeds and superficial siderosis (Figure 1). These FLAIR abnormalities have moved spatially compared with a previous MRI, suggesting an inflammatory process (Figure 2). The diagnosis of cerebral amyloid angiopathy (CAA)–related inflammation (CAA-ri) was made.1 DS is a genetic form of AD and has increased CAA prevalence.2 As future anti-amyloid trials will likely include individuals with DS, neurologists must be aware of CAA-ri in this population.

Cerebral Amyloid Angiopathy‐related Inflammation: American Society of Neuroradiology 2020 Case of the Year

Cerebral amyloid angiopathy‐related inflammation (CAARI) presents as a syndrome of acute/subacute encephalopathy. Currently, the underlying etiopathogenesis of this entity is not well established, though the amyloid deposits and resulting perivascular inflammation and cellular infiltrate are said to be the underlying cause. A definitive diagnosis of CAARI may require brain biopsy, which is not often clinically feasible in every case. Furthermore, CAARI does not affect the parenchyma uniformly, and biopsy could be falsely negative at times. When present, the combination of helpful imaging findings and a high index of suspicion may help avoid the morbidity associated with invasive brain biopsy and establish a timely diagnosis. This article describes one of the commonly encountered imaging and clinical presentations of CAARI.

Four cases of suspected cerebral amyloid angiopathy-related inflammation

Four cases of suspected cerebral amyloid angiopathy-related inflammation

A case of probable cerebral amyloid angiopathy-related inflammation with extensive hemorrhagic lesions following posterior reversible encephalopathy syndrome

A case of probable cerebral amyloid angiopathy-related inflammation with extensive hemorrhagic lesions following posterior reversible encephalopathy syndrome

Cerebral amyloid angiopathy-related inflammation (CAA-ri) in a patient positive for SARS-CoV-2 – radiological findings and differential diagnosis

84-year old female with confirmed, asymptomatic SARS-CoV-2 infection was admitted to Neurology Department after sudden onset of left-sided hemiparesis and impaired consciousness. Imaging played a key role in diagnostic process, in course of which the diagnosis of cerebral amyloid angiopathy-related inflammation (CAA-ri) was made.&#x0D; According to latest research, SARS-CoV-2 infection is considered to cause various neurological complications. To my best knowledge this is the first case of CAA-ri and SARS-CoV-2 coexistence to be reported.

Palinopsia as an initial symptom of cerebral amyloid angiopathy-related inflammation.

•We report the first case of cerebral amyloid angiopathy-related inflammation (CAA-RI) presenting palinopsia initially.•Palinopsia is generally caused by intracranial diseases involving the parietal and occipital areas.•CAA dominantly affects parietal and occipital lobes, therefore palinopsia could be an important phenomenon of the disease.

Cerebral amyloid angiopathy related inflammation: steroid responsive or spontaneously remissive brain dysfunction?

Definite diagnosis of cerebral amyloid angiopathy related inflammation (CAA-ri) requires histopathological features of vascular inflammation and amyloid deposition. However clinico-radiological criteria for CAA-ri have been recently introduced1 and validated2. Clinical syndrome shows dramatic improvement after immunotherapy3. However, spontaneous remission has been described in some patients4.

Clinical variability and the role of diagnostic criteria of cerebral amyloid angiopathy-related inflammation (CAA-RI): A case series

Cerebral amyloid angiopathy (CAA) is usually a cause of hemorrhagic stroke. Rarely it could be complicated by an inflammatory brain disease called CAA-related inflammation (CAA-ri) as a consequence of amyloid-β auto-antibodies production. Symptoms and their onset vary widely among patients, from headache to coma, and from chronic to acute onset. In the past, diagnosis was possible only performing a brain biopsy. Recently, in order to avoid procedural risks of a brain biopsy and to accelerate the diagnostic process and consequent treatment, clinicoradiological diagnostic criteria were proposed.

Cerebral amyloid angiopathy-related inflammation during bevacizumab treatment for metastatic cervical cancer

Bevacizumab is an anti-angiogenic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF). Bevacizumab inhibits cancer angiogenesis fundamental for either cancer development, its exponential growth, or metastatic spread.

Cerebral amyloid angiopathy – Related inflammation after COVID-19 vaccination: Case or causality?

Cerebral amyloid angiopathy (CAA) is characterized by microangiopathy with increased susceptibility to hemorrhages. Some patients may develop an inflammatory form presenting with focal deficits, seizures and alterations of vigilance (CAA-related inflammation episodes-CAA-ri). To report on clinical and biological findings of a case of CAA-ri after COVID-19 Tozinameran vaccination.