204 Clinicoradiological Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation (CAA-ri) - a Non-Invasive Approach to Diagnosis and Management

Abstract Background Cerebral Amyloid Angiopathy (CAA) is an age-related disorder characterised by deposition of beta-amyloid protein in the walls of small and medium cortical vessels leading to increased risk of intracranial bleeding. CAA-Related Inflammation (CAA-ri) is an under recognised subtype of CAA potentially responsive to immunosuppression and traditionally diagnosed by invasive brain biopsy. CAA-ri is associated with rapid cognitive decline but shows reversibility for some when treated with immunosuppression. We present the case of an 82 year old lady who presented with first seizure, a history of notable cognitive change and neuroimaging consistent with probable CAA-ri. Methods Validated clinicoradiological diagnostic criteria for CAA-ri were applied to MRI T2 FLAIR and SWI sequences. CSF, APOE genotyping, EEG and cognitive testing were performed. Interdisciplinary perspectives were sought from Neurology, Neurosurgery and Infectious Diseases colleagues. Consensus opinion opposed brain biopsy on strength of imaging evidence and pulsed intravenous steroid treatment was initiated. BP, anti-convulsant and bone protection were optimised and anti-thrombotics avoided. Repeat imaging and cognitive testing were repeated after four months. Results MRI T2-FLAIR revealed an asymmetric multifocal distribution of cortical and subcortical white matter hyperintensities (WMH) with leptomeningeal enhancement while SWI showed extensive multifocal microhaemorrhages with confluent haemorrhage in the right frontal and temporal regions. EEG demonstrated right frontal theta slowing and absence of epileptiform activity. CSF analysis reported raised protein at 53mg/dl. Normal WCC. Formal cognitive testing with ACEIII revealed a score of 79/100. EPOA was advised. Conclusion Clinicoradiological diagnosis of CAA-ri permits early initiation of immunosuppressive therapy and avoids invasive brain biopsy. In the absence of clinical suspicion and blood sensitive imaging sequences CAA-ri may be misdiagnosed as Acute Ischaemic Stroke or TIA where the addition of anti-thrombotic therapy could cause harm while early medical management offers potential reversibility.

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Late-Life Vascular Risk Score in Association With Postmortem Cerebrovascular Disease Brain Pathologies

Stroke ◽

10.1161/strokeaha.120.030226 ◽

2021 ◽

Author(s):

Shahram Oveisgharan ◽

Lei Yu ◽

Ana Capuano ◽

Zoe Arvanitakis ◽

Lisa L. Barnes ◽

...

Keyword(s):

Cerebrovascular Disease ◽

Cerebral Amyloid Angiopathy ◽

Risk Score ◽

Odds Ratio ◽

Amyloid Angiopathy ◽

Individual Level ◽

Framingham Risk ◽

Increased Risk ◽

Cerebral Amyloid ◽

The Individual

Background and Purpose: The general cardiovascular Framingham risk score (FRS) identifies adults at increased risk for stroke. We tested the hypothesis that baseline FRS is associated with the presence of postmortem cerebrovascular disease (CVD) pathologies. Methods: We studied the brains of 1672 older decedents with baseline FRS and measured CVD pathologies including macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. We employed a series of logistic regressions to examine the association of baseline FRS with each of the 5 CVD pathologies. Results: Average age at baseline was 80.5±7.0 years and average age at death was 89.2±6.7 years. A higher baseline FRS was associated with higher odds of macroinfarcts (odds ratio, 1.10 [95% CI, 1.07–1.13], P <0.001), microinfarcts (odds ratio, 1.04 [95% CI, 1.01–1.07], P =0.009), atherosclerosis (odds ratio, 1.07 [95% CI, 1.04–1.11], P <0.001), and arteriolosclerosis (odds ratio, 1.04 [95% CI, 1.01–1.07], P =0.005). C statistics for these models ranged from 0.537 to 0.595 indicating low accuracy for predicting CVD pathologies. FRS was not associated with the presence of cerebral amyloid angiopathy. Conclusions: A higher FRS score in older adults is associated with higher odds of some, but not all, CVD pathologies, with low discrimination at the individual level. Further work is needed to develop a more robust risk score to identify adults at risk for accumulating CVD pathologies.

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Abstract W MP89: Validation of Clinical-Radiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-related Inflammation

Stroke ◽

10.1161/str.45.suppl_1.wmp89 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Eitan Auriel ◽

Mahmut Edip Gurol ◽

Jun Ni ◽

Ellis Van Etten ◽

Sergi Martinez-Remirez ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Cerebral Amyloid Angiopathy ◽

Vascular Inflammation ◽

Brain Biopsy ◽

Control Group ◽

Amyloid Angiopathy ◽

Radiological Criteria ◽

Disease Subtype ◽

History Of ◽

Cerebral Amyloid

Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a disease subtype characterized by rapidly progressive cognitive decline, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. CAA-ri is an important diagnosis to reach in clinical practice, as many patients respond to immunosuppressive therapy. Definitive diagnosis of CAA-ri generally requires brain biopsy, however, highlighting the importance of developing noninvasive diagnostic criteria. Objectives: To test the sensitivity and specificity of modified criteria (Table 1) for possible and probable CAA-ri in groups of subjects with histologically proven CAA-ri and non-CAA-ri. Methods: After refining previously proposed clinical- radiological criteria we retrospectively analyzed clinical charts and MRI FLAIR and gradient-echo scans obtained from 17 subjects with pathologically confirmed CAA-ri and 37 control subjects with pathologic diagnosis of non-inflammatory CAA. The control group was further divided into those with past intracerebral hemorrhage (ICH) (n=21) and those with cerebral microbleeds (CMB) only and no history of ICH (n=16). Results: In the CAA-ri group 14/17 (82.4%) met criteria for both probable and possible CAA-ri. One (4.7%) of the subjects in the control CAA-ICH group (n=21) met the criteria for possible and none met criteria for probable CAA-ri. In the control CAA-no ICH group 1/16 (6.25%) and 11/16 (68.75%) met criteria for probable and possible CAA-ri respectively. This yields sensitivity and specificity of 82% and of 97.3% respectively for the probable criteria and sensitivity and specificity of 82% and 67.6% respectively for the possible criteria. Conclusions: Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and radiographic information alone with good sensitivity and excellent specificity.

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Epileptiform activity during transient focal neurologic episodes in cerebral amyloid angiopathy

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000781 ◽

2019 ◽

pp. 10.1212/CPJ.0000000000000781

Author(s):

Daniele Mattavelli ◽

Francesco Mele ◽

Pierluigi Bertora ◽

Silvia Rosa ◽

Cristina Bortolami ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Epileptiform Activity ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Amyloid Spells and High Blood Pressure: Imminent Danger

Case Reports in Neurology ◽

10.1159/000369922 ◽

2014 ◽

Vol 7 (1) ◽

pp. 39-43 ◽

Cited By ~ 1

Author(s):

Andre Caetano ◽

Miguel Pinto ◽

Sofia Calado ◽

Miguel Viana-Baptista

Keyword(s):

Blood Pressure ◽

High Blood Pressure ◽

Cerebral Amyloid Angiopathy ◽

Antiplatelet Agents ◽

Pressure Profile ◽

Clonic Seizure ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Increased Risk ◽

Cerebral Amyloid

We present the case of a 71-year-old male, admitted after a generalized tonic-clonic seizure, with a history of recurrent left arm and face paresthesias, associated with sulcal cortical subarachnoid hemorrhages. During the next 48 h, he remained agitated with a high blood pressure profile; he also suffered a cardiac arrest in relation to a severe left fronto-parietal and a smaller right parietal parenchymal hemorrhage that developed over the subarachnoid hemorrhage locations. There were no intracranial vascular abnormalities. Three months later, an MRI revealed disseminated superficial siderosis. He was discharged with a modified Rankin scale of 4. He died 1 month later of unknown cause. A diagnosis of probable cerebral amyloid angiopathy was assumed. Patients with pathologically proven cerebral amyloid angiopathy that present with transient focal neurological symptoms in relation to cortical bleeds, the so-called ‘myloid spells' seem to be at an increased risk of future parenchymal hemorrhages. Avoiding antiplatelet agents in these cases has been proposed. Our case suggests that these patients should be monitored closely in the hyperacute phase , and tight blood pressure control should be considered as the immediate risk of bleeding may be high, even without a definitive diagnosis of cerebral amyloid angiopathy.

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Cerebral amyloid angiopathy–associated intracerebral hemorrhage: pathology and management

Neurosurgical FOCUS ◽

10.3171/2012.1.focus11370 ◽

2012 ◽

Vol 32 (4) ◽

pp. E7 ◽

Cited By ~ 46

Author(s):

Prachi Mehndiratta ◽

Sunil Manjila ◽

Thomas Ostergard ◽

Sylvia Eisele ◽

Mark L. Cohen ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Management Strategies ◽

Case Series ◽

The Elderly ◽

Postoperative Hemorrhage ◽

Amyloid Angiopathy ◽

Increased Risk ◽

Cerebral Amyloid

Amyloid angiopathy–associated intracerebral hemorrhage (ICH) comprises 12%–15% of lobar ICH in the elderly. This growing population has an increasing incidence of thrombolysis-related hemorrhages, causing the management of hemorrhages associated with cerebral amyloid angiopathy (CAA) to take center stage. A concise reference assimilating the pathology and management of this clinical entity does not exist. Amyloid angiopathy–associated hemorrhages are most often solitary, but the natural history often progresses to include multifocal and recurrent hemorrhages. Compared with other causes of ICH, patients with CAA-associated hemorrhages have a lower mortality rate but an increased risk of recurrence. Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical vessels, CAA-associated hemorrhages are superficial in location due to preferential involvement of vessels in the cerebral cortex and meninges. This feature makes CAA-associated hemorrhages easier to access surgically. In this paper, the authors discuss 3 postulates regarding the pathogenesis of amyloid hemorrhages, as well as the established clinicopathological classification of amyloid angiopathy and CAA-associated ICH. Common inheritance patterns of familial CAA with hemorrhagic strokes are discussed along with the role of genetic screening in relatives of patients with CAA. The radiological characteristics of CAA are described with specific attention to CAA-associated microhemorrhages. The detection of these microhemorrhages may have important clinical implications on the administration of anticoagulation and antiplatelet therapy in patients with probable CAA. Poor patient outcome in CAA-associated ICH is associated with dementia, increasing age, hematoma volume and location, initial Glasgow Coma Scale score, and intraventricular extension. The surgical management strategies for amyloid hemorrhages are discussed with a review of published surgical case series and their outcomes with a special attention to postoperative hemorrhage.

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A Case of Cerebral Amyloid Angiopathy-related Inflammation with Multiple Microbleeds: Diagnosis by Brain Biopsy

Nihon Naika Gakkai Zasshi ◽

10.2169/naika.106.820 ◽

2017 ◽

Vol 106 (4) ◽

pp. 820-827

Author(s):

Seitaro Nohara ◽

Akiko Ishii ◽

Atsushi Ueda ◽

Shoko Seki ◽

Eiichi Oguni ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Brain Biopsy ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Cerebral Amyloid Angiopathy: Multiple neurolgic problems

Psychology and Mental Health Care ◽

10.31579/2637-8892/015 ◽

2017 ◽

Vol 1 (3) ◽

pp. 01-01

Author(s):

Paul Gilbert

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Clinical Symptoms ◽

Brain Biopsy ◽

Acute Onset ◽

Amyloid Angiopathy ◽

Migraine Headaches ◽

Diffuse White Matter ◽

Cerebral Amyloid ◽

Intravenous Steroids

A 72-Year-old female with a history of migraine headaches presented with an acute onset of expressive aphasia, difficulty with memory and worsening of her headaches. An MRI of the brain was done which revealed diffuse white matter T2 hyperintensities (Figures 1). Due to worsening of the patient’s clinical symptoms a repeat MRI was performed four days later that revealed multiple micro-bleeds (Figure 2), as well as a lobar hemorrhage in left temporal lobe (Figure 2). An extensive workup including HIV testing, CSF examination for infectious etiology including protein 14-3-3 and demylineating disease was negative. Paraneoplastic and autoimmune workup was also non-diagnostic. A brain biopsy was performed due to the extensive white matter disease, which revealed Cerebral Amyloid Angiopathy (CAA) with focal granulomatous angiitis. The patient was treated with intravenous steroids with no significant improvement clinically. Two months after diagnosis, her disease course has remained static, without improvement or deterioration.

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Cerebral amyloid angiopathy-related transient focal neurological episodes: A transient ischemic attack mimic with an increased risk of intracranial hemorrhage

Journal of the Neurological Sciences ◽

10.1016/j.jns.2019.116452 ◽

2019 ◽

Vol 406 ◽

pp. 116452 ◽

Cited By ~ 5

Author(s):

Marta Vales-Montero ◽

Andrés García-Pastor ◽

Ana María Iglesias-Mohedano ◽

Ester Esteban-de Antonio ◽

Paula Salgado-Cámara ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Intracranial Hemorrhage ◽

Transient Ischemic Attack ◽

Amyloid Angiopathy ◽

Increased Risk ◽

Cerebral Amyloid ◽

Ischemic Attack

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Abstract W P257: Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage

Stroke ◽

10.1161/str.45.suppl_1.wp257 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Farid Radmanesh ◽

Guido J Falcone ◽

Christopher D Anderson ◽

Thomas W Battey ◽

Alison M Ayres ◽

...

Keyword(s):

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Ct Angiography ◽

Cerebral Amyloid Angiopathy ◽

Symptom Onset ◽

Hematoma Expansion ◽

Amyloid Angiopathy ◽

Spot Sign ◽

Increased Risk ◽

Cerebral Amyloid

Objectives: Intracerebral hemorrhage (ICH) patients with CT angiography (CTA) spot sign are at increased risk of hematoma expansion and poor outcome. Since ICH is often the acute manifestation of a chronic cerebral vasculopathy, we investigated whether different clinical or imaging characteristics predict spot sign presence in patients with different underlying vasculopathies. Using ICH location as a surrogate for hypertension-related ICH and cerebral amyloid angiopathy-related ICH, we identified risk factors associated with spot sign. METHODS: We retrospectively analyzed a prospective cohort of consecutive spontaneous ICH patients with available CTA. Spot sign presence was ascertained by two independent readers blinded to clinical data. We assessed potential predictors of spot sign be performing uni- and multivariable logistic regression, analyzing deep and lobar ICH separately. RESULTS: 649 patients were eligible, 291 (45%) deep and 358 (55%) lobar ICH. Median time from symptom onset to CTA was 4.5 (IQR 5.2) and 5.7 (IQR 7.4) hours in patients with deep and lobar ICH, respectively. At least one spot sign was present in 76 (26%) deep and 103 (29%) lobar ICH patients. In mutivariable logistic regression, independent predictors of spot sign in deep ICH were warfarin (OR 2.82 [95%CI 1.06-7.57]; p=0.03), time from symptom onset to CTA (OR 0.9 [95%CI 0.81-0.97]; p=0.02), and baseline ICH volume (OR 1.27 [95%CI 1.14-1.43]; p=2.5E-5; per 10 mL increase). Predictors of spot sign in lobar ICH were preexisting dementia (OR 2.7 [95%CI 1.15-6.43]; p=0.02), warfarin (OR 4.01 [95%CI 1.78-9.29]; p=0.009), and baseline ICH volume (OR 1.27 [95%CI 1.17-1.39]; p=5.4E-8; per 10 mL increase). As expected, spot sign presence was a strong predictor of hematoma expansion in both deep (OR 3.52 [95%CI 1.72-7.2]; p=0.0005) and lobar ICH (OR 6.53 [95%CI 3.23-13.44]; p=2.2E-7). CONCLUSIONS: The most potent associations with spot sign are shared by deep and lobar ICH, suggesting that ICH caused by different vasculopathic processes share biological features. The relationship between preexisting dementia and spot sign in lobar ICH, but not deep ICH, suggests that ICH occurring in the context of more advanced cerebral amyloid angiopathy may be more likely to have prolonged bleeding.

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The Characteristics of Superficial Siderosis and Convexity Subarachnoid Hemorrhage and Clinical Relevance in Suspected Cerebral Amyloid Angiopathy

Cerebrovascular Diseases ◽

10.1159/000381223 ◽

2015 ◽

Vol 39 (5-6) ◽

pp. 278-286 ◽

Cited By ~ 27

Author(s):

Jun Ni ◽

Eitan Auriel ◽

Jenelle Jindal ◽

Alison Ayres ◽

Kristin M. Schwab ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Epileptiform Activity ◽

Brain Mri ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Cerebral Bleeding ◽

Cerebral Amyloid

Background and Aims: Systematic studies of superficial siderosis (SS) and convexity subarachnoid hemorrhage (cSAH) in patients with suspected cerebral amyloid angiopathy (CAA) without lobar intracerebral hemorrhage (ICH) are lacking. We sought to determine the potential anatomic correlation between SS/cSAH and transient focal neurological episodes (TFNE) and whether SS/cSAH is predictor of future cerebral hemorrhagic events in these patients. Methods: We enrolled 90 consecutive patients with suspected CAA (due to the presence of strictly lobar microbleeds (CMBs) and/or SS/cSAH) but without the history of symptomatic lobar ICH who underwent brain MRI including T2*-weighted, diffusion-weighted imaging and fluid-attenuated inversion recovery sequences from an ongoing single center CAA cohort from 1998 to 2012. Evaluation of SS, cSAH and CMBs was performed. Medical records and follow-up information were obtained from prospective databases and medical charts. TFNE was defined according to published criteria and electroencephalogram reports were reviewed. Results: Forty-one patients (46%) presented with SS and/or cSAH. The prevalence of TFNE was significantly higher in those with SS/cSAH (61 vs. 10%; p < 0.001) and anatomically correlated with the location of cSAH, but not SS. The majority of TFNE in patients with SS/cSAH presented with spreading sensory symptoms. Intermittent focal slowing on electroencephalogram was present in the same area as SS/cSAH in 6 patients, but no epileptiform activity was found in any patients. Among those with available clinical follow-up (76/90 patients, 84%), ten patients with SS/cSAH (29%, median time from the scan for all patients with SS/cSAH: 21 months) had a symptomatic cerebral bleeding event on follow up (average time to events: 34 months) compared with only 1 event (2.4%, 25 months from the scan) in patients without SS/cSAH (time to event: 25 months) (p = 0.001). The location of hemorrhages on follow-up scan was not in the same location of previously noted SS/cSAH in 9 of 10 patients. Follow-up imaging was obtained in 9 of 17 patients with cSAH and showed evidence of SS in the same location as initial cSAH in all these 9 cases. Conclusions: SS/cSAH is common in patients with suspected CAA without lobar intracerebral hemorrhage and may have a significantly higher risk of future cerebral bleeding events, regardless of the severity of the baseline CMB burden. The findings further highlight a precise anatomical correlation between TFNE and cSAH, but not SS. Distinct from transient ischemic attack or seizure, the majority of TFNE caused by SS/cSAH appear to present with spreading sensory symptoms.

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