A Critical Investigation of Sick Euthyroid Syndrome in Chronic Heart Failure Patients: Addressing the Need for Accurate Thyroid Assessment.

Background The body undergoes numerous metabolic changes during severe illness or physiological stress to protect itself by lowering metabolism and reducing overall demands. This evolutionary adaptation dates back to early human development, long before the advent of ICU facilities and advanced treatments. One such protective mechanism is Sick Euthyroid Syndrome (SES), also known as Non-thyroidal Illness Syndrome (NTIS). SES commonly occurs in critically ill patients and is frequently observed in conditions such as heart failure, chronic kidney disease, and severe sepsis. This syndrome is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. Typically, these patients exhibit low serum levels of triiodothyronine (T3), normal or low levels of thyroxine (T4), and normal or low thyroid-stimulating hormone (TSH) levels. SES is believed to be an adaptive response to illness, aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress. This original article delves into SES's prevalence and clinical impact in these settings. Materials and methods The study aims to determine the prevalence of SES in patients with long-standing heart failure, elucidate the relationship between thyroid function and heart failure severity, and assess its impact on various hematological and clinical parameters. This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, a 2011-bed hospital, over one and a half years. This study included 70 patients with chronic heart failure, aged 18 years and above, defined by a left ventricular ejection fraction of 40% or less and a Boston criteria score of 8 or more. Patients were excluded if they had a history of thyroid dysfunction, clinical sepsis, or were taking thyroid-affecting drugs.  Results The study provides important insights into the prevalence and impact of SES in long-standing heart failure patients. It found that a significant 44.29% of these patients exhibited low T3 levels, highlighting the substantial occurrence of SES in this population. Additionally, the study revealed a negative correlation between N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, Boston score, and total T3, suggesting that as indicators of heart failure severity worsen, total T3 levels may decrease further. Another key finding is the high prevalence of anemia among heart failure patients, with a notable gender disparity: 92.11% of male patients were affected compared to 50% of female patients.  Conclusion The study concluded that SES is significantly prevalent among long-standing heart failure patients, further indicating that thyroid suppression increases with the severity of heart failure. Recognizing SES can guide tailored treatments, prompting intensive monitoring and optimized heart failure management. Additionally, the study found a high prevalence of anemia, particularly among male patients, highlighting the need for gender-specific considerations in managing heart failure. These findings underscore the importance of routine thyroid function assessments and regular monitoring of anemia in heart failure patients. Future research should focus on improving clinical outcomes through comprehensive management of both thyroid function and anemia in these patients.

Frequency of deep-seated cerebral microbleeds in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy.

Background: Cerebral amyloid angiopathy (CAA) is a common disease and the most common cause of lobar hemorrhages in the elderly. Usually, deep-seated microhemorrhages preclude the diagnosis of CAA. In this study, we sought to estimate the frequency of deep-seated microbleeds on MRI in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy. In addition, we describe a cohort of patients with cortical and deep-seated microbleeds on MRI and a histopathological specimen available from lobar hematoma evacuation. Methods: Retrospective database search for histopathological specimens from lobar hematoma evacuation and review of imaging findings (CT and MRI) and patient charts was performed. Results: Between 1 January 2012 and 31 December 2020, 88 specimens from 88 patients were available. A total of 56 specimens were excluded (no brain tissue in the specimen n = 4, other diagnosis n = 8, no MRI n = 43, and no BOLD-based sequence n = 1). Of the remaining 32 patients, 25 patients (78%) did not harbor deep-seated lesions on MRI, of which 17 patients had histopathological features of CAA. A total of seven patients harbored deep-seated CMB. Of these seven patients, three (3/20, 15%) had histopathological features of CAA. Conclusion: Approximately 15% of patients with histopathologically diagnosed CAA harbor deep-seated microbleeds. This finding may add to the discussion on how to identify patients with CAA and deep-seated CMB.

Applicability of the Edinburgh CT Criteria for Lobar Intracerebral Hemorrhage Associated with Cerebral Amyloid Angiopathy.

OBJECTIVE: Based on histopathology, Edinburgh diagnostic criteria were proposed to consider a nontraumatic intracerebral lobar hemorrhage (ICH) as related to cerebral amyloid angiopathy (CAA) using the initial computed tomography (CT) scan and the APOE genetic status. We aimed to externally validate the Edinburgh prediction model, excluding the APOE genotyping and based on the modified Boston criteria on the MRI for CAA diagnosis METHODS: We included patients admitted for spontaneous lobar ICH in the emergency department between 2016 and 2019 who underwent noncontrast CT scan and MRI. According to the MRI, patients were classified into the CAA group or into the non-CAA group in the case of other causes of ICH. Two neuroradiologists, blinded to the final retained diagnosis, rated each radiological feature on initial CT scan described in the Edinburgh study on initial CT scan RESULTS: A total of 102 patients were included, of whom 36 were classified in the CAA group, 46 in the non-CAA causes group and 20 of undetermined cause (excluded from the primary analysis). The Edinburgh prediction model, including finger-like projections and subarachnoid extension showed an area under receiver operating characteristic curves (AUC) of 0.760 (95% confidence interval, CI: 0.660-0.859) for the diagnosis of CAA. The AUC reached 0.808 (95% CI: 0.714-0.901) in a new prediction model integrating a third radiologic variable: the ICH cortical involvement. CONCLUSION: Using the Boston MRI criteria as a final assessment, we provided a new external confirmation of the radiological Edinburgh CT criteria, which are directly applicable in acute settings of spontaneous lobar ICH and further proposed an original 3­set model considering finger-like projections, subarachnoid extension, and cortical involvement that may achieve a high discrimination performance.

Characterizing mixed location hemorrhages/microbleeds with CSF markers.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. PATIENTS AND METHODS: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. RESULTS: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. CONCLUSION: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

MRI and CT imaging biomarkers of cerebral amyloid angiopathy in lobar intracerebral hemorrhage.

BACKGROUND: Cerebral amyloid angiopathy (CAA), a common cause of intracerebral hemorrhage (ICH), is diagnosed using the Boston criteria including magnetic resonance imaging (MRI) biomarkers (cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS). The simplified Edinburgh criteria include computed tomography (CT) biomarkers (subarachnoid extension (SAE) and finger-like projections (FLPs)). The underlying mechanisms and diagnostic accuracy of CT compared to MRI biomarkers of CAA are unknown. METHODS: We included 140 survivors of spontaneous lobar supratentorial ICH with both acute CT and MRI. We assessed associations between MRI and CT biomarkers and the diagnostic accuracy of CT- compared to MRI-based criteria. RESULTS: FLPs were more common in patients with strictly lobar CMB (44.7% vs 23.5%; p = 0.014) and SAE was more common in patients with cSS (61.3% vs 31.2%; p = 0.002). The high probability of the CAA category of the simplified Edinburgh criteria showed 87.2% (95% confidence interval (CI): 78.3-93.4) specificity, 29.6% (95% CI: 18.0-43.6) sensitivity, 59.3% (95% CI: 38.8-77.6) positive predictive value, and 66.4% (95%: CI 56.9-75.0) negative predictive value, 2.3 (95% CI: 1.2-4.6) positive likelihood ratio and 0.8 (95% CI 0.7-1.0) negative likelihood ratio for probable CAA (vs non-probable CAA), defined by the modified Boston criteria; the area under the receiver operating characteristic curve (AUROC) was 0.62 (95% CI: 0.54-0.71). CONCLUSION: In lobar ICH survivors, we found associations between putative biomarkers of parenchymal CAA (FLP and strictly lobar CMBs) and putative biomarkers of leptomeningeal CAA (SAE and cSS). In a hospital population, CT biomarkers might help rule-in probable CAA (diagnosed using the Boston criteria), but their absence is probably not as useful to rule it out, suggesting an important continued role for MRI in ICH survivors with suspected CAA.

Simplified Edinburgh and modified Boston criteria in relation to amyloid PET for lobar intracerebral hemorrhage.

BACKGROUND: Histopathological evidence of cerebral vascular amyloid ß accumulation is the gold standard to diagnose cerebral amyloid angiopathy (CAA). Neuroimaging findings obtained with CT and MRI can suggest the presence of CAA when histopathology is lacking. We explored the role of amyloid PET in patients with lobar intracerebral hemorrhage (ICH) as this may provide molecular evidence for CAA as well. METHODS: In this retrospective, monocenter analysis, we included consecutive patients with non-traumatic lobar ICH who had undergone amyloid PET. We categorized patients according to amyloid PET status and compared demographics and neuroimaging findings. We calculated sensitivity and specificity of the simplified Edinburgh criteria and amyloid PET with probable modified Boston criteria as reference standard, as well as sensitivity and specificity of the simplified Edinburgh and modified Boston criteria with amyloid PET status as molecular marker for presence or absence of CAA. RESULTS: We included 38 patients of whom 24 (63%) were amyloid PET positive. Amyloid PET positive patients were older at presentation (p = 0.004). We observed no difference in prevalence of subarachnoid hemorrhages, fingerlike projections or microbleeds between both groups, but cortical superficial siderosis (p = 0.003) was more frequent in the amyloid PET positive group. In 5 out of 38 patients (13%), the modified Boston criteria were not fulfilled due to young age or concomitant vitamin K antagonist use with INR > 3.0. With the modified Boston criteria as reference standard, there was no difference in sensitivity nor specificity between the simplified Edinburgh criteria and amyloid PET status. With amyloid PET status as reference standard, there was also no difference in sensitivity nor specificity between the simplified Edinburgh and modified Boston criteria. CONCLUSIONS: Amyloid PET was positive in 63% of lobar ICH patients. Under certain circumstances, patients might not be diagnosed with probable CAA according to the modified Boston criteria and in these cases, amyloid PET may be useful. Accuracy to predict CAA based on amyloid PET status did not differ between the simplified Edinburgh and modified Boston criteria.

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis.

BACKGROUND: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. METHODS: Beta-amyloid 1-40 (Aß40), beta-amyloid 1-42 (Aß42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. RESULTS: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. CONCLUSION: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.

Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis.

Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and linked to immunotherapy-related side-effects in Alzheimer's disease (AD). Given ongoing efforts to develop AD immunotherapy, accurate estimates of CAA prevalence are important. CAA can be diagnosed neuropathologically or during life using MRI markers including strictly lobar microbleeds. In this meta-analysis of 170 studies including over 73,000 subjects, we show that in patients with AD, CAA prevalence based on pathology (48%) is twice that based on presence of strictly lobar cerebral microbleeds (22%); in the general population this difference is three-fold (23% vs 7%). Both methods yield similar estimated prevalences of CAA in cognitively normal elderly (5% to 7%), in patients with intracerebral hemorrhage (19% to 24%), and in patients with lobar intracerebral hemorrhage (50% to 57%). However, we observed large heterogeneity among neuropathology and MRI protocols, which calls for standardized assessment and reporting of CAA.

Cerebral amyloid angiopathy-related acute lobar intra-cerebral hemorrhage: diagnostic value of plain CT.

BACKGROUND: Diagnosing probable cerebral amyloid angiopathy (CAA) after lobar intra-cerebral hemorrhage (l-ICH) currently relies on the MR-based modified Boston criteria (mBC). However, MRI has limited availability and the mBC have moderate sensitivity, with isolated l-ICH being classified as "possible CAA". A recent autopsy-based study reported potential value of finger-like projections (FLP) and subarachnoid hemorrhage (SAH) on acute CT. Here we assessed these markers' performance in a cohort most of whom survived the index episode. METHODS: We included all patients from a prospective pathology database with non-traumatic l-ICH, admission CT and available tissue sample showing no alternative cause. CT was assessed by two blinded independent neuroradiologists. Interobserver reproducibility was almost perfect for SAH and substantial for FLP. RESULTS: Sixteen patients were eligible [age 65.8 ± 7.2 yrs; hematoma volume: 39(26, 71)mls; hematoma evacuation sample 15 patients; autopsy one patient]. MRI was available in 11 patients. ICH-related death affected six patients. Aß40-42 immunohistochemistry revealed CAA in seven patients (44%). SAH and FLP were present in 12/16 (75%) and 10/16 (62%) patients, respectively. SAH had 100% sensitivity for CAA but low specificity; FLP had lower performance. Using either pathology or MRI as reference standard yielded essentially similar results. All patients with possible CAA on MRI but CAA on pathology had SAH. CONCLUSIONS: In patients with moderate-size l-ICH who mostly survived the index event, SAH had perfect sensitivity and better performance than FLP. In addition, SAH appeared to add onto MRI in possible CAA, the clinically most relevant scenario. Studies in larger samples are however warranted.

[Cerebral amyloid angiopathy, comorbid atrial fibrillation]. / Tserebral'naya amiloidnaya angiopatiya, komorbidnaya s fibrillyatsiei predserdii.

Cerebral amyloid angiopathy (CAA) is caused by the deposition of ß-amyloid in small vessels in the cerebral cortex and leptomeninges. Nowadays, CAA is recognized more often due to the development of neuroimaging technologies. The frequency of CAA increases in old age that explains its frequent association with cardiovascular diseases. Combination of CAA with atrial fibrillation (AF) causes particular difficulties in managing of the patients, since antithrombotic drugs prescribed to patients with AF mostly contraindicated in CAA because of increased risk of intracerebral hemorrhages. The article presents a case report of the patient with AF who was admitted to the stroke center with acute ischemic stroke. According to MRI, the focus of acute ischemia was small and localized in the cerebellum. This stroke was regarded as having an undetermined etiology according TOAST classification. Small-vessel occlusion subtype was not diagnosed because the TOAST criteria do not attribute an ischemic focus in the cerebellum to a lacunar stroke, while cardioembolic subtype was rejected due to a small (less than 1.5 cm in diameter) size of the focus. Probable CAA in the patient was diagnosed on the basis of the following MRI data: multiple cortical-subcortical micro-hemorrhages (T2*GRE); a single cortical focus with features of the hemorrhage at the stage of intracellular methemoglobin deposition (T1- weighted MR images); bilateral enlargement of perivascular spaces in semioval centers (FLAIR); a negative fronto-occipital gradient (T2-weighted MR images). A diagnosis of CAA was made in accordance with the 2010 Boston criteria and 2019 recommendations of the International CAA Association. The article discusses the hemorrhagic and non-hemorrhagic MRI features of CAA. Frequency of occurrence of cortical microinfarcts in CAA is discussed as well as their differences from small cardioembolic infarcts in AF. Algorithms for antithrombotic therapy for secondary prevention of ischemic stroke in patients with CAA and AF are considered.

Clinical and radiological differences between patients with probable cerebral amyloid angiopathy and mixed cerebral microbleeds.

BACKGROUND: The key imaging features of cerebral amyloid angiopathy (CAA) are lobar, cortical, or cortico-subcortical microbleeds, macrohaemorrhages and cortical superficial siderosis (cSS). In contrast, hypertensive angiopathy is characterized by (micro) haemorrhages in the basal ganglia, thalami, periventricular white matter or the brain stem. Another distinct form of haemorrhagic microangiopathy is mixed cerebral microbleeds (mixed CMB) with features of both CAA and hypertensive angiopathy. The distinction between the two entities (CAA and mixed CMB) is clinically relevant because the risk of haemorrhage and stroke should be well balanced if oral anticoagulation is indicated in CAA patients. We aimed to comprehensively compare these two entities. METHODS: Patients with probable CAA according to the modified Boston criteria and mixed CMB without macrohaemorrhage were retrospectively identified from our database. Comprehensive comparison regarding clinical and radiological parameters was performed between the two cohorts. RESULTS: Patients with CAA were older (78 ± 8 vs. 74 ± 9 years, p = 0.036) and had a higher prevalence of cSS (19% vs. 4%, p = 0.027) but a lower prevalence of lacunes (73% vs. 50%, p = 0.018) and deep lacunes (23% vs. 51%, p = 0.0003) compared to patients with mixed CMB. Logistic regression revealed an association between the presence of deep lacunes and mixed CMB. The other collected parameters did not reveal a significant difference between the two groups. CONCLUSIONS: CAA and mixed CMB demonstrate radiological differences in the absence of macrohaemorrhages. However, more clinically available biomarkers are needed to elucidate the contribution of CAA and hypertensive angiopathy in mixed CMB patients.

Delayed Identification of Cortical Superficial Siderosis in a Patient with Recurrent Transient Focal Neurological Symptoms: A Case Report.

Cortical superficial siderosis (cSS), also referred to as sulcal siderosis, is a neurological condition characterized by hemosiderin subpial deposits in the cortical sulci over the convexities of cerebral hemispheres. These deposits are further found sparingly in the spinal cord, brainstem, and cerebellum. Patients typically present with transient focal neurological symptoms that make cSS challenging to differentiate from other acute neurological processes such as transient ischemic attacks (TIA), focal seizures, and acute convexity subarachnoid hemorrhage (cSAH). This condition is presently recognized as a characteristic feature of the age-associated disorder referred to as cerebral amyloid angiopathy (CAA). This paper describes a patient who presented with transient neurologic symptoms, first suspected to be secondary to acute subarachnoid hemorrhage (SAH), found to have cSS and cerebral amyloid angiopathy.

[Cerebral amyloid angiopathy revealed or hypertension-related cerebral small vessel diseases: A clinical challenge]. / Angiopathie amyloïde cérébrale ou atteinte des microvaisseaux cérébraux en rapport avec l'HTA : un challenge clinique.

Cerebral amyloid angiopathy (CAA) is a entity characterized by degenerative Amyloïd deposits in the walls of the meningeal and cortical vessels. It is considered as the second cause of primitives cerebral hemorrhage in elderly. The differential diagnosis between AAC and hypertension-related cerebral small vessel diseases is difficult and represent a true challenge for the clinician. We report two cases of cerebral small vessel diseases revealed by malignant hypertension.

Cerebral amyloid angiopathy - The modified Boston criteria in clinical practice.

BACKGROUND: Early identification of patients with cerebral amyloid angiopathy (CAA) is relevant considering the increased risk for cerebral hemorrhage. A new set of diagnostic criteria for CAA was recently proposed, which include the presence of superficial siderosis. We aimed to assess the impact of applying these criteria regarding use of antithrombotic therapy. METHODS: Review of consecutive patients admitted to a Neurology Department from 2014 to 2016, with acute parenchymal or subarachnoid hemorrhage and/or atypical transient focal neurological episodes. Patients with a possible or probable CAA according to the original and modified Boston criteria were included. Information was collected regarding presentation, imaging findings and concomitant therapy. RESULTS: Among a total of 1436 admitted patients, 52 with acute hemorrhagic lesions or atypical TFNE were screened: 22 met criteria for CAA; 4 were deemed too young; 21 had other causes for hemorrhagic parenchymal lesions; and 5 had uncertain diagnosis. Using the modified Boston criteria, 8 patients fulfilled criteria for probable CAA and 14 for possible CAA. When we applied the original Boston criteria to the same patients, only 7 fulfilled criteria for probable CAA and 8 for possible CAA. Among the additional patients identified with the modified Boston criteria, 4 were using antithrombotic therapy. CONCLUSIONS: The use of the modified Boston criteria allowed for the identification of 7 additional patients, more than half of which were taking antithrombotic therapy. Systematic use of these criteria could have an important impact in clinical practice. Raising awareness on the different presentations of CAA among clinicians is of the utmost importance.

Lobar intracerebral haematomas: Neuropathological and 7.0-tesla magnetic resonance imaging evaluation.

BACKGROUND AND PURPOSE: The Boston criteria for cerebral amyloid angiopathy (CAA) need validation by neuropathological examination in patients with lobar cerebral haematomas (LCHs). In "vivo" 1.5-tesla magnetic resonance imaging (MRI) is unreliable to detect the age-related signal changes in LCHs. This post-mortem study investigates the validity of the Boston criteria in brains with LCHs and the signal changes during their time course with 7.0-tesla MRI. MATERIALS AND METHODS: Seventeen CAA brains including 26 LCHs were compared to 13 non-CAA brains with 14 LCHs. The evolution of the signal changes with time was examined in 25 LCHs with T2 and T2* 7.0-tesla MRI. RESULTS: In the CAA group LCHs were predominantly located in the parieto-occipital lobes. Also white matter changes were more severe with more cortical microinfarcts and cortical microbleeds. On MRI there was a progressive shift of the intensity of the hyposignal from the haematoma core in the acute stage to the boundaries later on. During the residual stage the hyposignal mildly decreased in the boundaries with an increase of the superficial siderosis and haematoma core collapse. CONCLUSIONS: Our post-mortem study of LCHs confirms the validity of the Boston criteria for CAA. Also 7.0-tesla MRI allows staging the age of the LCHs.

Hemorrhagic stroke, cerebral amyloid angiopathy, Down syndrome and the Boston criteria.

A stroke, or a cerebrovascular accident (CVA) is a life-threatening condition which often results in permanent or significant disability in the adult population. Several classifications of CVAs exist, one of them being based on the mechanism of injury of brain tissue: ischemic (85-90%) and hemorrhagic (10-15%). In a hemorrhagic stroke an intercranial bleeding occurs, leading to the formation of a focal hematoma typically located in the basal ganglia of the brain (approx. 45% of cases). A common yet underestimated cause of intracerebral hemorrhage is cerebral small vessel disease with microhemorrhages, including the cerebral amyloid angiopathy (CAA). This condition is associated with the deposition of amyloid-beta in arterial walls (in soft meninges, subcortical areas and the cerebral cortex). Research has shown that causes of hemorrhagic changes in the brain include genetic disorders, such as Down syndrome. The association is caused by the so-called 'gene dosage effect', as the gene for the precursor protein for amyloid-beta is located in chromosome 21. We wish to present the case of a 60 year old patient with Down syndrome who suffered a hemorrhagic stroke without antecedent hypertension. Based on the history taken, diagnostic imaging and the source literature, a diagnosis of cerebral amyloid angiopathy as the source of the bleeding was made (however it must be noted that without a full post-mortem examination, the Boston criteria allow only for a 'probable cerebral amyloid angiopathy' diagnosis to be made). The authors hereby also report the need to modify the Boston criteria for cerebral amyloid angiopathy.

Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage.

INTRODUCTION: The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. METHODS: We identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. RESULTS: We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of "probable CAA" (≥2 strictly lobar MBs) was 87.5% (95% confidence interval [CI], 60.4-97.8) and 25% (95% CI, 13.2-78) in hospital and general populations, respectively. DISCUSSION: Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited.