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Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a subset of cerebral amyloid angiopathy (CAA) causing a reversible encephalopathy characterized by seizures and focal neurological deficit. Previously, biopsy was required to make this diagnosis, distinct radiological features have allowed development for clinicoradiological criteria to assist in diagnosis. CAA-ri is an important condition to recognize as patients respond to high dose corticosteroids with significant resolution of symptoms. A 79-year-old woman presents with new onset seizures and delirium with prior history of mild cognitive impairment. An initial computed tomography (CT) brain demonstrated vasogenic oedema in the right temporal lobe, and magnetic resonance imaging (MRI) showed bilateral subcortical white matter change and multiple microhemorrhages. The MRI findings were suggestive of cerebral amyloid angiopathy. Cerebrospinal fluid analysis demonstrated raised protein and oligoclonal bands. A thorough septic and autoimmune screen demonstrated no abnormality. Following a multidisciplinary discussion, a diagnosis of CAA-ri was made. She was commenced on dexamethasone and her delirium improved. CAA-ri is an important diagnostic consideration in an elderly patient who presents with new seizures. Clinicoradiological criteria are useful diagnostic tools and may avoid the need for invasive histopathological diagnosis.

Abstract Background Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a distinct but rare subset of CAA. The greater availability of high resolution Magnetic Resonance Imaging (MRI) has currently allowed the increasing recognition and diagnosis of this entity, without the risk of a brain biopsy. However, in rare cases with typical clinical characteristics but uncommon neuroimaging findings at presentation, the brain-biopsy is required for an early and reliable diagnosis. Case description A 71-year-old man with arterial hypertension presented due to 1-week history of headache, vomiting, disorientation and impaired consciousness. Brain MRI revealed multiple acute cortical/subcortical microinfarcts, scarce microbleeds, extensive right parietooccipital and left frontotemporal leptomeningeal enhancement. After an extensive diagnostic work-up, excluding infectious, neoplastic and autoimmune etiologies, the patient underwent brain-biopsy. Histology disclosed amyloid deposition in an arteriolar wall and the patient fulfilled diagnostic criteria for probable CAA-ri with supporting pathology. He received intravenous methylprednisolone, followed by oral tapering with steroids showing clinical and radiological improvement with complete resolution of gadolinium enhancement. Follow-up MRI revealed an increase of cerebral microbleeds and the patient fulfilled CAA-ri neuroimaging criteria. Conclusions This case highlights the importance of continuous vigilance from clinical neurologists to detect CAA-ri diagnosis and the diagnostic value of brain-biopsy in CAA-ri patients with atypical neuroimaging presentation, such as acute microinfarcts. The early diagnosis and the prompt treatment initiation can improve the prognosis and the evolution of this rare disorder.

We describe a patient with cerebral amyloid angiopathy-related inflammation (CAA-ri) presenting as Alzheimer disease (AD) with a mass lesion with symptom onset at age 59. He was found to have a nonenhancing lesion in the right temporal lobe on magnetic resonance imaging without evidence of hemorrhage. He underwent a biopsy which showed amyloid beta in blood vessel walls and a perivascular inflammatory infiltrate consistent with CAA-ri. Neurofibrillary tangles were present and a flortaucipir positron emission tomography showed bilateral signal highest in the lateral temporal and parietal cortices. A lumbar puncture showed tau, p-tau, and amyloid beta levels consistent with AD without evidence of inflammation. He was homozygous for the APOE ε4 allele. He died at age 67. A focus of CAA-ri can be present in the context of AD with a mass lesion and without evidence of hemorrhage, significant ischemic changes, or overt inflammation on cerebrospinal fluid examination.

Purpose of review: In this article, we discuss the current consensus approach to the evaluation and treatment of inflammatory cerebral amyloid angiopathy (CAA). We also outline critical knowledge gaps and identify questions for future research. Recent findings: Recent cohort studies found that immunosuppressive treatment for inflammatory CAA was associated with higher probability of clinical and radiographic improvement and reduced risk of disease recurrence. A recent case series showed correlations between changes in cerebrospinal fluid levels of anti-Aβ autoantibodies, changes in microglial activation, and clinical and radiographic response to immunosuppressive treatment; these data provide supporting evidence for a pathophysiological link between inflammatory CAA and adverse events associated with Alzheimer's disease (AD) immunotherapy treatments. Summary: Despite many knowledge gaps, widely accepted methods for diagnosis and management of inflammatory CAA have emerged, including validated clinical and radiographic criteria and treatment with immunosuppressive medications. Still, there is considerable space for diagnosis and treatment paradigms to advance in tandem with our understanding of the disease. Efforts to optimize protocols for clinical and radiographic assessment, identify biomarkers at multiple stages of disease, and leverage insights from Alzheimer's disease biomarkers and therapeutics will be pivotal to achieving these goals. [ABSTRACT FROM AUTHOR]

Background: Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a distinct but rare subset of CAA. The greater availability of high resolution Magnetic Resonance Imaging (MRI) has currently allowed the increasing recognition and diagnosis of this entity, without the risk of a brain biopsy. However, in rare cases with typical clinical characteristics but uncommon neuroimaging findings at presentation, the brain-biopsy is required for an early and reliable diagnosis. Case description: A 71-year-old man with arterial hypertension presented due to 1-week history of headache, vomiting, disorientation and impaired consciousness. Brain MRI revealed multiple acute cortical/subcortical microinfarcts, scarce microbleeds, extensive right parietooccipital and left frontotemporal leptomeningeal enhancement. After an extensive diagnostic work-up, excluding infectious, neoplastic and autoimmune etiologies, the patient underwent brain-biopsy. Histology disclosed amyloid deposition in an arteriolar wall and the patient fulfilled diagnostic criteria for probable CAA-ri with supporting pathology. He received intravenous methylprednisolone, followed by oral tapering with steroids showing clinical and radiological improvement with complete resolution of gadolinium enhancement. Follow-up MRI revealed an increase of cerebral microbleeds and the patient fulfilled CAA-ri neuroimaging criteria. Conclusions: This case highlights the importance of continuous vigilance from clinical neurologists to detect CAA-ri diagnosis and the diagnostic value of brain-biopsy in CAA-ri patients with atypical neuroimaging presentation, such as acute microinfarcts. The early diagnosis and the prompt treatment initiation can improve the prognosis and the evolution of this rare disorder. [ABSTRACT FROM AUTHOR]

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Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rapid but reversible autoimmune encephalopathy where spontaneous autoantibody reaction against amyloid beta deposited in cerebral blood vessels produces characteristic neuroinflammatory changes such as vasogenic edema and microhemorrhages on MRI. The term amyloid-related imaging abnormalities (ARIA) is sometimes used to describe these changes but are more often reserved for similar MRI signal abnormalities seen after administration of anti-amyloid immunotherapy, using treatment exposure as an antecedent. It is unclear if there is any biological basis for this dichotomized distinction. We report a case of severe CAA-ri after exposure to SARS-CoV-2 vaccine and performed a literature review of CAA-ri related to vaccination. CAA-ri precipitated by immunogenic triggers other than anti-amyloid therapy would lend support to the hypothesis that ARIA seen on MRI may represent the same disease underpinned by a shared anti-Aβ autoantibody response irrespective of etiology. A thorough history should be taken before labelling CAA-ri as spontaneous. [ABSTRACT FROM AUTHOR]

Abstract Background Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare clinical entity, characterized by headaches, seizures, rapidly progressive cognitive decline, behavioral changes and magnetic resonance imaging (MRI) findings underlying the autoimmune and inflammatory reaction at the level of CAA-affected vessel. CAA-ri is likely responsive to corticosteroid. MRI shows asymmetric and multifocal white matter hyperintensity (WMH) lesions and multiple cerebral microbleeds. Apolipoprotein E (ApoE) ε4 homozygosity is associated with CAA-ri strongly [Neurology 68(17):1411-1416, 2007, Ann Neurol 73(4):449-458, 2013, J Alzheimers Dis 44(4):1069-1074, 2015]. SORL1 processes a causal involvement in Alzheimer’s disease (AD) as a proposed modulator of the amyloid precursor protein (APP). It is unclear whether SORL1 is involved with CAA-ri or not. Case presentation A 48-year-old woman suffered from a one-day history of a headache, nausea, and vomiting. Neurological examination revealed normal. We diagnosed this case as probable CAA-ri according to the clinic manifestations and MRI. Gene detection indicated a rare variant in SORL1 and ApoE ε4 homozygosity. When treated with corticosteroid, the patient’s clinical symptoms and MRI manifestations were almost relieved. However, when keeping the corticosteroid withdrawal for three months, the patient relapsed with a headache and typical images on MRI emerged. Corticosteroid therapy was effective again. Unfortunately, susceptibility weighted imaging (SWI) showed increased microbleeds. With tapering corticosteroid slowly, no recurrence was found on this patient with four-month follow-up. Conclusion A variant of SORL1 may be associated with CAA-ri, recurrence of disease could be detected with MRI by an increased microbleeds. Our case report suggests that corticosteroid therapy might be effective for CAA-ri.

Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease, characterized by the deposition of β-amyloid within the cortical and leptomeningeal blood vessel walls. It has attracted interest concerning new therapeutic perspectives. However, there are scarce data regarding the cerebrospinal fluid biomarkers (CSF) and genetic factors in sporadic CAA.In this narrative review, we investigated the literature regarding the cerebrospinal fluid core biomarkers profile of patients with probable or possible CAA and its subtype, the CAA- related inflammation (CAA-ri), taking into account the clinical and radiological characteristics of the patients. We also analyzed the Apolipoprotein E (APOE) genotype differentiations among the different subtypes of cerebral amyloid angiopathy.Our results demonstrate specific CSF patterns of β-amyloid (Aβ42 and Aβ40) and tau-proteins (t-tau and p-tau) which may serve as molecular biomarkers for CAA/ CAA-ri and could prove helpful for novel therapeutic procedures. Specifically, decreased levels of Aβ40 and Aβ42 in both CAA and CAA-ri, mildly increased concentrations of tau protein in patients with CAA-ri and a strong association between APOE ε4/ε4 genotype and CAA-ri are the main findings.

Cerebral amyloid angiopathy (CAA) related inflammation (CAA-RI) is an autoimmune inflammatory condition occurring in patients with CAA. We aimed to determine the prevalence of radiological CAA-RI amongst patients with CAA and to describe their presenting clinical features. We performed a retrospective review of electronic medical records across multiple centers within a single healthcare network. Patients who met radiological modified Boston 2.0 criteria for CAA and had white matter hyperintensity (WMH) were included. Scans were analyzed by a vascular neurologist and confirmed by a neuroradiologist blinded to clinical information for meeting criteria for possible or probable radiographic CAA-RI. Out of 1100 patients reviewed, 511 patients met radiological modified Boston criteria for CAA and 193 patients had WMH on MRI. A total of 55 (28.5 % of those with CAA and WMH, and 10.8 % of all CAA with or without WMH) patients had MRI brain imaging suggestive of possible or probable radiographic CAA-RI. The diagnosis of CAA-RI was reported in only 10 (18.2 %) patients initially while 20 (36.4 %) were diagnosed up to 74 months later (median 0, IQR 0-9 months). At the time of earliest probable CAA-RI findings on imaging, the most common concurrent findings were cognitive impairment (74.5 %), macro-hemorrhages (52.7 %), headache (30.9 %), seizures (14.5 %), and ischemic infarcts (14.5 %). Only 18 (32.7 %) patients were treated with immunosuppression. The prevalence of radiographic CAA-RI was high, and most cases were unrecognized and untreated. Further studies are needed to assess if earlier detection and treatment of radiologic CAA-RI may halt disease progression and prevent cognitive decline in these patients. [ABSTRACT FROM AUTHOR]

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.

Background: Cerebral amyloid angiopathy – related inflammation (CAA-ri) is an uncommon manifestation of CAA. Methods: Single-center, retrospective review of all charts with ICD-code I68.0 (CAA) from 2/2/2016–1/1/2020. Results: Of 152 CAA cases, 13 (8.6%) were consistent with CAA-ri. Corticosteroid-treatment led to short-term reduction in modified Rankin Scale scores (2.6 ± 1.4 vs. 1.6 ± 1.5; p = 0.01) and T2/FLAIR lesion volume (78.1 ± 52.2 cm3 vs. 30 ± 30.9 cm3, p < 0.01) as well as short-term improvement in post-treatment Clinical Global Impression - Global Change scores compared to pre-treatment scores (clinical: 6 ± 1 vs. 2.6 ± 1.3, p = 0.03; radiological: 4.6 ± 1.9 vs. 1.2 ± 0.4, p = 0.03). Interpretation: Corticosteroid-treatment leads to clinical and radiological short-term improvement (class IV evidence). Unlabelled Image • class IV evidence that corticosteroid treatment leads to short-term improvement • 8.6% of CAA cases were consistent with definite (n = 5) or probable (n = 8) CAA-ri • age at presentation is significantly younger in CAA-ri compared to CAA • decrease in consciousness / behavioral changes were the most common symptoms (69%) • leptomeningeal and/or parenchymal contrast enhancement in 75% of cases [ABSTRACT FROM AUTHOR]

Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease, characterized by the deposition of β-amyloid within the cortical and leptomeningeal blood vessel walls. It has attracted interest concerning new therapeutic perspectives. However, there are scarce data regarding the cerebrospinal fluid biomarkers (CSF) and genetic factors in sporadic CAA. In this narrative review, we investigated the literature regarding the cerebrospinal fluid core biomarkers profile of patients with probable or possible CAA and its subtype, the CAA- related inflammation (CAA-ri), taking into account the clinical and radiological characteristics of the patients. We also analyzed the Apolipoprotein E (APOE) genotype differentiations among the different subtypes of cerebral amyloid angiopathy. Our results demonstrate specific CSF patterns of β-amyloid (Aβ 42 and Aβ 40 ) and tau-proteins (t-tau and p-tau) which may serve as molecular biomarkers for CAA/ CAA-ri and could prove helpful for novel therapeutic procedures. Specifically, decreased levels of Aβ 40 and Aβ 42 in both CAA and CAA-ri, mildly increased concentrations of tau protein in patients with CAA-ri and a strong association between APOE ε4/ε4 genotype and CAA-ri are the main findings., (© 2021 Published by Elsevier B.V.)

An 86-year-old woman was admitted to our hospital with headache and acute detarioration of consciousness. Cerebral microbleeds (CMBs) dominated the occipital lobe on the head MRI, revealing white matter lesions. It was accompanied by gadolinium (Gd) imaging effect in the leptomeninges and some CMBs. She was clinically diagnosed with amyloid β-related vasculitis and a good outcome was obtained with steroid therapy. Even when symptoms re-exacerbated, exacerbation of the contrast effect of CMBs was observed, but no white matter lesions appeared, and leptomeningeal enhancement did not change remarkably throughout the entire course.