Cerebral Amyloid Angiopathy-related Inflammation Research Articles

Longitudinal markers of cerebral amyloid angiopathy and related inflammation in rTg-DI rats

Cerebral amyloid angiopathy (CAA) is a prevalent vascular dementia and common comorbidity of Alzheimer’s disease (AD). While it is known that vascular fibrillar amyloid β (Aβ) deposits leads to vascular deterioration and can drive parenchymal CAA related inflammation (CAA-ri), underlying mechanisms of CAA pathology remain poorly understood. Here, we conducted brain regional proteomic analysis of early and late disease stages in the rTg-DI CAA rat model to gain molecular insight to mechanisms of CAA/CAA-ri progression and identify potential brain protein markers of CAA/CAA-ri. Longitudinal brain regional proteomic analysis revealed increased differentially expressed proteins (DEP) including ANXA3, HTRA1, APOE, CST3, and CLU, shared between the cortex, hippocampus, and thalamus, at both stages of disease in rTg-DI rats. Subsequent pathway analysis indicated pathway enrichment and predicted activation of TGF-β1, which was confirmed by immunolabeling and ELISA. Further, we identified numerous CAA related DEPs associate with astrocytes (HSPB1 and MLC1) and microglia (ANXA3, SPARC, TGF-β1) not previously associated with astrocytes or microglia in other AD models, possibly indicating that they are specific to CAA-ri. Thus, the data presented here identify several potential brain protein biomarkers of CAA/CAA-ri while providing novel molecular and mechanistic insight to mechanisms of CAA and CAA-ri pathological progression and glial cell mediated responses.

Diagnostic Challenges in Cerebral Amyloid Angiopathy-related Inflammation (P8-5.010)

Diagnostic Challenges in Cerebral Amyloid Angiopathy-related Inflammation (P8-5.010)

Abstract WP286: Cerebral Amyloid Angiopathy and Risk of Seizures

Introduction: Cerebral amyloid angiopathy (CAA) is associated with multiple conditions that are known to have an elevated risk of seizures, including intracerebral hemorrhage, CAA-related inflammation, and Alzheimer’s disease. However, there are limited population-based data regarding the risk of seizures associated with clinically diagnosed CAA. Methods: We performed a retrospective cohort study using inpatient and outpatient claims from 2016 to 2018 from a nationally representative 5% sample of Medicare beneficiaries. The study exposure was a diagnosis of CAA identified using ICD-10-CM code I68.0. The primary outcome was seizure, defined using previously validated ICD-10-CM code G40.x, but excluding diagnosis codes for epileptic conditions that are unlikely to be a result of CAA. Participants with prevalent seizures were excluded. Cox proportional hazards regression was used to determine the association between CAA and seizure after adjustment for age, sex, race, and vascular risk factors. Results: Of 1,403,686 patients included during the study period, 425 (0.03%) were diagnosed with CAA. Median follow-time was 3 years (IQR, 2.4-3). The cumulative incidence rate of seizures was 6.9 (95% CI, 4.8-9.9) per 100 person-years in patients with CAA and 0.30 (95% CI, 0.29-0.30) per 100 person-years in patients without CAA. In Cox proportional hazards analysis, CAA was associated with an increased risk of seizures (HR, 12.6; 95% CI, 8.8-18.0). Conclusions: In a nationally representative cohort of Medicare beneficiaries, CAA was associated with an increased risk of seizures.

Cerebral Amyloid Angiopathy-Related Inflammation Presenting as Nontraumatic Subdural Hematoma

Cerebral Amyloid Angiopathy-Related Inflammation Presenting as Nontraumatic Subdural Hematoma

ARIA‐E, ARIA‐H, and CAA‐related inflammation: time of reconsiderations?

AbstractBackgroundEvidence from published clinical trials suggests that high‐dose of monoclonal antibodies (mAbs) are needed to significantly remove parenchymal‐deposited Aβ plaques. However, high‐dosing mAbs resulted in a 25‐35% increased risk of amyloid‐related imaging abnormalities‐edema (ARIA‐E) and ARIA‐hemorrhage (ARIA‐H) side events. Although most ARIA‐E are incidentally recognized as clinically silent during pre‐planned safety monitoring MRI scans and suggested to be managed by dose reduction or suspension, it is noticeable that half of ARIA‐E progressed to symptomatic at continued dosing and to associate with late occurrence of ARIA‐H. Of particular importance, a few of them aggravated to potentially severe brain injury or death due to fatal CAA‐related events. Increased evidence from natural history studies suggests that ARIA‐E is the iatrogenic manifestation of cerebral amyloid angiopathy‐related inflammation (CAA‐ri), a rare autoimmune encephalopathy due to raised anti‐Aß autoAbs levels in the cerebrospinal fluid (CSF).MethodNatural history study of CAA‐ri demonstrated that immunotherapy‐related ARIA‐E share several commonalities with the spontaneous occurrence of autoAbs‐related ARIA‐E, including fluid, MRI, and PET biomarker changes and the potential response to treatment outcomes.ResultThe prospective longitudinal monitoring of patients with CAA‐ri provide evidence for a regional and temporal association of ARIA‐E on MRI with focal peaks of neuroinflammation on microglial‐PET imaging. This association was strong in patients with positive CSF markers of AD (ATN positive) and comorbid CAA pathology on MRI, while it was negligible in patients with CAA disease w/o AD (ATN negative). Raised CSF concentrations of anti‐Aß autoAbs were found in all patients at (sub)acute presentation, and reduced within 5 months from the ARIA‐E index event, in parallel with evidence of radiographic resolution of ARIA‐E. At follow‐up MRI scan, the occurrence of new hemorrhagic markers (aka ARIA‐H in trials) were found only in patients with coexisting CAA and AD comorbid pathology. The MRI scales for ARIA commonly used in clinical trials only partially paralleled the clinical, biological, and MRI findings.ConclusionThis suggests that to mitigate and monitor the risk of ARIA, more sensitive, specific, cost‐effective and easy to interpret diagnostic tools and biomarkers than MRI alone will be needed for precision drug‐dose tailoring.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy.

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.

The prevalence of radiological cerebral amyloid angiopathy-related inflammation in patients with cerebral amyloid angiopathy

ObjectivesCerebral 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. MethodsWe 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. ResultsOut 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. ConclusionsThe 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.

Cerebral amyloid angiopathy-related inflammation: a rare but important cause of acute confusion on the general medical take.

Cerebral amyloid angiopathy-related inflammation: a rare but important cause of acute confusion on the general medical take.

Cerebral amyloid angiopathy–related inflammation: clinical features and treatment response in a case series

IntroductionCerebral amyloid angiopathy–related inflammation (CAA-ri) is an entity characterised by an inflammatory response to β-amyloid deposition in the walls of cerebral microvessels. MethodsWe conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. ResultsThe study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (n = 6), behavioural alterations (n = 5), epileptic seizures (n = 5), focal neurological signs (n = 4), and headache (n = 2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (n = 7), subcortical white matter hyperintensities on T2-FLAIR sequences (n = 7), and leptomeningeal enhancement (n = 6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (n = 5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. ConclusionsEarly diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.

Rare forms of cerebral amyloid angiopathy: pathogenesis, biological and clinical features of CAA-ri and iCAA.

Thanks to a more widespread knowledge of the disease, and improved diagnostic techniques, the clinical spectrum of cerebral amyloid angiopathy (CAA) is now broad. Sporadic CAA, hereditary CAA, CAA-related inflammation (CAA-ri) and iatrogenic CAA (iCAA) create a clinical and radiological continuum which is intriguing and only partially discovered. Despite being relatively rare, CAA-ri, an aggressive subtype of CAA with vascular inflammation, has gained growing attention also because of the therapeutic efficacy of anti-inflammatory and immunomodulating drugs. More recently, diagnostic criteria have been proposed for an unusual variant of CAA, probably related to an iatrogenic origin (iCAA), toward which there is mounting scientific interest. These atypical forms of CAA are still poorly known, and their recognition can be challenging and deserve to be pursued in specialized referral centres. The aim of this brief review is to focus current developments in the field of rare forms of CAA, its pathogenesis as well as clinical and biological features in order to increase awareness of these rare forms.

Cerebral amyloid angiopathy-related inflammation (CAARI) and HHV-6 positivity: A case report of a treatment dilemma and a possible relationship (P1-12.003)

<h3>Objective:</h3> To examine the treatment dilemma utilizing high-dose steroids in a patient with cerebral amyloid angiopathy-related inflammation (CAARI) and HHV-6 positivity. Additionally, to question a possible relationship between HHV-6 and CAARI. <h3>Background:</h3> Cerebral amyloid angiopathy-related inflammation (CAARI) has been described as a distinct syndrome with subacute cognitive decline or seizure symptoms. Previous studies have established diagnostic criteria for this entity and proposed a treatment strategy. However, the precipitating factors behind developing CAARI in a subset of patients with CAA are unclear. We present a case of CAARI in a patient with no underlying diagnosis of dementia that was found to be positive for HHV-6 in serum and CSF and treated successfully with steroids. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> An 83-year-old woman presented with a first-time generalized tonic-clonic seizure with postictal confusion. On presentation, her systolic blood pressure was elevated at 150–170, and she was tachycardic to 160 with a temperature of 38.4. A contrasted MRI brain showed multifocal vasogenic edema, sulcal FLAIR hyperintensity, and innumerable lobar microhemorrhages. Black blood contrast MRI brain angiogram was unremarkable, with no evidence of vasculitis. At this point, the patient had clinically improved but remained slightly encephalopathic with word-finding difficulties. Continuous EEG monitoring showed diffuse background slowing. Initial CSF studies revealed an isolated mildly elevated protein of 49 and negative cytology. Therefore, based on the clinical and radiographic evidence, a decision was made to undergo five days of high-dose methylprednisolone for probable CAARI. However, days later, HHV-6 in CSF resulted positive with 249 copies/ml, and a serum sample showed 1100 copies/ml. <h3>Conclusions:</h3> The concurrence of cerebral amyloid angiopathy-related inflammation (CAARI) and HHV-6 in serum and CSF might yield a diagnostic and therapeutic challenge. However, the treatment with high-dose pulsatile steroids with taper did improve the overall clinical picture. Further studies are needed to investigate a potential correlation. <b>Disclosure:</b> Dr. Alshawa has nothing to disclose. Dr. Makkieh has nothing to disclose. Miss Alsakka has nothing to disclose. Dr. Torres-Melendez has nothing to disclose.

A Case of Progressive Left Leg Weakness and Vision Changes: Focal Inflammatory Cerebral Amyloid Angiopathy Masquerading as a Glioma (P12-5.003)

<h3>Objective:</h3> To emphasize the need to consider tumefactive focal inflammatory cerebral amyloid angiopathy (CAA) in the differential diagnosis of CNS lesions. <h3>Background:</h3> Although classically considered an etiology of cognitive impairment in the elderly, CAA represents a spectrum of disease. CAA-related inflammation (CAA-ri), a distinct CAA phenotype, is characterized by vascular inflammation from amyloid deposition. CAA-ri may rarely appear as a tumefactive lesion, mimicking CNS malignancy. We present a case of biopsy-proven focal CAA-ri initially misidentified as a glioma, with the goal of increasing awareness of this entity. <h3>Design/Methods:</h3> Not applicable <h3>Results:</h3> A 68-year-old man with Parkinson’s disease presented with progressive left lower extremity weakness, word finding difficulty and vision changes. Neurological examination revealed Parkinsonian features, left homonymous superior quadrantanopia and left leg weakness. Brain MRI revealed a non-enhancing FLAIR hyperintensity in the subcortical right parieto-occipital lobe, with numerous susceptibility-weighted foci within this area, consistent with microhemorrhages versus vascular inflammation. Flash frozen pathology was initially suggestive of glioma, prompting lesionectomy. Final pathology revealed inflammation of small and medium sized blood vessels, multinucleated giant cells and positive Congo-red staining, consistent with necrotizing vasculitis and amyloid angiopathy. Treatment with steroids was deferred following risk-benefit analysis. <h3>Conclusions:</h3> We report a unique case of tumefactive CAA-ri, a clinicopathologic variant of CAA, manifesting as a mass-like lesion with distinguishing radiographic features. Our literature review identified only three prior reports of this entity. Clinical presentation depends on lesion size, location, and presence of edema and inflammation. While our patient lacked systemic co-pathologies, uterine involvement and carpal tunnel syndrome have been reported. Management relies on vascular risk modification, and steroids or immunosuppressants for active inflammation. Our case underscores the need to recognize CAA-ri in the differential of mass-like lesions. Recognizing the spectrum of CAA-related disease is key in understanding the natural history of the disease, and potential benefit of future anti-amyloid therapies. <b>Disclosure:</b> Dr. Mohammadi has nothing to disclose. Dr. Lilian has nothing to disclose. Mr. Chen has received research support from National Institues of Health. Michelle Offit, MS has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Streicher has nothing to disclose. Dr. Sabharwal has nothing to disclose.

Teaching NeuroImages: Acute convexity subarachnoid hemorrhage

Nontraumatic acute convexity subarachnoid hemorrhage (cSAH) is a common manifestation of cerebral amyloid angiopathy (CAA), but has been rarely reported in patients with CAA-related inflammation (CAA-ri).1,2

CEREBRAL AMYLOID ANGIOPATHY-RELATED INFLAMMATION PRESENTING WITH A STROKE-LIKE EPISODE.

MRI is a crucial tool for the diagnostic evaluation of cerebral amyloid angiopathy-related inflammation (CAA-ri).A high index of suspicion and awareness of CAA-ri is necessary for correct diagnosis in stroke-like presentations of the condition.The treatment of choice for CAA-ri is empirical corticosteroid therapy, which is associated with clinical and radiological improvement.

Abstract TMP30: High Prevalence Of Unrecognized Cerebral Amyloid Angiopathy Related Inflammation Among Patients With Cerebral Amyloid Angiopathy And White Matter Disease

Introduction: Cerebral amyloid angiopathy related inflammation (CAARI) is an autoimmune inflammatory condition that occurs in patients with cerebral amyloid angiopathy (CAA) and can lead to rapidly progressive cognitive decline. Little is known about the prevalence of subclinical and clinical CAARI. We sought to determine the prevalence of subclinical and clinical CAARI among patients with CAA and white matter hyperintensities (WMH). Methods: In this multicenter, single healthcare system, retrospective cohort study, we reviewed electronic medical records and MRI brain scans of patients presenting with a diagnosis code for amyloidosis or CAA that were evaluated between 1/2010 - 6/2020. We included patients meeting modified Boston criteria for CAA who had WMH on T2 FLAIR sequences. Patients without available hemosiderin sensitive sequences (SWI or GRE) and T2 FLAIR sequences and those without WMH on T2 FLAIR imaging were excluded. Two independent vascular neurologists blinded to background clinical information reviewed each MRI brain scan for the presence of CAARI. The clinical course and outcomes were reviewed and reported. Results: Out of 1100 patients reviewed, 511 met modified Boston criteria for CAA and 193 met the final study inclusion criteria. 55 (28.5% of those with CAA and WMH, and 10.8% of all CAA) patients had MRI brain imaging suggestive of CAA-RI. 21 (38.2%) were male, 38 (69.1%) were Caucasian, and the mean (SD) age was 72.9 (8.9) years. CAA-RI was recognized in only 10 (18.2%) patients initially while 20 (36.4%) were diagnosed up to 9 months later (median 0, IQR 0-9 months). At time of earliest detection of CAARI on imaging, 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 started on immunosuppression. Nineteen (34.5%) patients expired during the observation period of which only 8 (42.1%) were ever diagnosed with CAA-RI by their treating clinician. Conclusion: The prevalence of subclinical CAA-RI in our study was high. Most cases of radiographic CAARI went unrecognized and untreated. Further studies are needed to assess if treatment of subclinical CAARI may prevent cognitive decline in these patients.

Abstract TP22: Temporal Lobe Involvement In Cerebral Amyloid Angiopathy Related Inflammation Is Associated With Relapse Of Inflammation And Rapidly Progressive Cognitive Decline

Introduction: Cerebral Amyloid Angiopathy related inflammation (CAARI) is an autoimmune cause of rapidly progressive cognitive decline. Little is known about the magnetic resonance imaging (MRI) brain features associated with relapse of CAARI and the effect of treatment on relapse rates therefore we sought to study this. Methods: In this single center prospective cohort study, we analyzed MRI brain scans of 22 patients with CAARI followed at the Cleveland Clinic Cerebrovascular Center between September 2019 and July 2022. We divided patterns of edema on T2 FLAIR imaging into focal, multifocal or diffuse and assessed for temporal lobe involvement (TLI). We analyzed hemosiderin sensitive sequences for the pattern of CAA including cerebral microbleeds (CMB), macrohemorrhage (MH) and/or cortical superficial siderosis (cSS). We collected data on clinical features, treatment duration and cognition after treatment. Relapse was defined as recurrence of edema on T2 FLAIR with cognitive decline or seizure. We report percentages of each clinical feature, imaging pattern and treatment effect on relapse rates. Results: Median age was 74 (35% male, 75% White). Progressive cognitive decline (68%) and seizures (68%) were common but headaches (27.2%) occurred less frequently. Most common CAA features were asymmetric CMB (100%), followed by MH (45%) and cSS (22.7%). The most common pattern of cerebral edema was multifocal (50%), followed by focal (31.8%) and diffuse (27.2%). TLI was seen in 17 (77%) patients. 21 (95.4%) patients were treated with prednisone for median (Q1, Q3) duration of 20 (12, 24) weeks whereas 5 (22.7%) were treated with long term mycophenolate. A total of 6 (27.2%) relapses were seen during a median (Q1, Q3) follow up period of 14 (7, 21) months and occurred at a median (Q1, Q3) of 5.5 (5.12, 5.5) months after stopping steroids. Amongst those who relapsed, none were on mycophenolate, 4 (66.6%) had diffuse edema, 2 (33.4%) had focal edema and all had asymmetric CMB and TLI. No relapses were seen after initiating mycophenolate. Conclusion: Asymmetric CMBs, diffuse or focal cerebral edema with temporal lobe involvement and not being on steroid sparing therapy were associated with relapse of CAARI and rapidly progressive cognitive decline.

Cerebrospinal Fluid Biomarkers and Amyloid-β Elimination from the Brain in Cerebral Amyloid Angiopathy-Related Inflammation.

Cerebrospinal fluid (CSF) biomarkers in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) have demonstrated inconsistent results. We investigated the relationship between CSF amyloid-β protein (Aβ) and vascular pathological findings to elucidate the mechanisms of Aβ elimination from the brain in CAA-ri. We examined Aβ 40 and Aβ 42 levels in CSF samples in 15 patients with CAA-ri and 15 patients with Alzheimer's disease and cerebral amyloid angiopathy (AD-CAA) using ELISA as a cross-sectional study. Furthermore, we pathologically examined Aβ 40 and Aβ 42 depositions on the leptomeningeal blood vessels (arteries, arterioles, and veins) using brain biopsy samples from six patients with acute CAA-ri and brain tissues of two autopsied patients with CAA-ri. The median Aβ40 and Aβ42 levels in the CSF showed no significant difference between pre-treatment CAA-ri (Aβ40, 6837 pg/ml; Aβ42, 324 pg/ml) and AD-CAA (Aβ40, 7669 pg/ml, p = 0.345; Aβ42, 355 pg/ml, p = 0.760). Aβ40 and Aβ42 levels in patients with post-treatment CAA-ri (Aβ40, 1770 pg/ml, p = 0.056; Aβ42, 167 pg/ml, p = 0.006) were lower than those in patients with pre-treatment CAA-ri. Regarding Aβ40 and Aβ42 positive arteries, acute CAA-ri cases showed a higher frequency of partially Aβ-deposited blood vessels than postmortem CAA-ri cases (Aβ40, 20.8% versus 3.9%, p = 0.0714; Aβ42, 27.4% versus 2.0%, p = 0.0714, respectively). Lower levels of CSF Aβ40 and Aβ42 could be biomarkers for the cessation of inflammation in CAA-ri reflecting the recovery of the intramural periarterial drainage pathway and vascular function.

PS-R06-6: CEREBRAL AMYLOID ANGIOPATHY-RELATED INFLAMMATION PRESENTING WITH POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME

Background: Cerebral amyloid angiopathy related inflammation (CAAri) is a rare CAA variant, characterized by headaches, seizures, acute or subacute encephalopathy, or focal neurological deficits. Radiologically, CAAri presents with widespread white matter lesions on brain MRI in addition to the hemorrhagic imaging features of CAA. We report a patient with CAAri who showed posterior reversible encephalopathy syndrome. Case Report: A 77 year old man presented with generalized tonic clonic seizure that persisted for 30 minutes and decreased in consciousness level. He had past medical history of dementia, diabetes and hypertension. His initial blood pressure was 170/90 mmHg and pulse rates were 144/minute. On neurological examination, his consciousness level was stupor and there are no lateralizing signs. Cerebrospinal fluid analysis was unremarkable except elevated protein level of 75 mg/dL. Diffusion weighted images (DWI) and fluid attenuated inversion recovery (FLAIR) images showed diffuse hyperintensities involving the bilateral temporoparietooccipital lobes. Gradient echo images revealed multiple microbleeds in bilateral cortical and subcortical regions as can be seen in CAA. A diagnosis of CAAri was considered, and the patient was started on steroids and valproic acid with clinical improvement. Nine days after admission, follow up DWI and FLAIR images demonstrated improvement of previously shown lesions. Conclusions: Aside from the most common subacute presentations, CAAri can have a PRES like presentation. It is hypothesised that in this form, CAAri causes altered vascular autoregulation and impaired blood brain barrier integrity in the face of precipitating factors such as hypertension.

Inflammatory Cerebral Amyloid Angiopathy: A Broad Clinical Spectrum.

Cerebral amyloid angiopathy (CAA) is a common central nervous system (CNS) vasculopathy, which in some cases is associated with subacute encephalopathy, seizures, headaches, or strokes due to vascular inflammation directed against vascular amyloid accumulation. The pathological subtypes of inflammatory CAA include CAA-related inflammation (CAAri) with mostly perivascular lymphocytic infiltrates, or amyloid-beta (Aβ)-related angiitis (ABRA) with transmural granulomatous inflammation. CAAri and ABRA probably represent part of the spectrum of CNS vasculopathies, intermediate between CAA and primary CNS vasculitis, and they are closely related to Aβ-related imaging abnormalities and other manifestations of an inflammatory response directed against Aβ in the leptomeninges and cerebral parenchyma. As treatment strategies in Alzheimer's disease shift toward potentially effective antiamyloid immunotherapy, the incidence rate of inflammatory CAA (which is probably an underrecognized condition) is likely to increase. Its clinical features are varied and include subacute encephalopathy, behavioral symptoms, headaches, seizures, and focal neurological deficits, which necessitate a high degree of suspicion for this disorder that often responds to treatment. The recent definition of the typical clinical and radiological syndrome has increased its recognition and may eliminate the need for invasive histological sampling in at least some affected patients. Here we review the pathophysiology, clinical spectrum, and approach to diagnosis, and discuss illustrative cases that highlight the wide range of clinical presentations.

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