Explore the vast range of titles available.

BackgroundIdentifying infarct core on admission is essential to establish the amount of salvageable tissue and indicate reperfusion therapies. Infarct core is established on CT perfusion (CTP) as the severely hypoperfused area, however the correlation between hypoperfusion and infarct core may be time-dependent as it is not a direct indicator of tissue damage. This study aims to characterize those cases in which the admission core lesion on CTP does not reflect an infarct on follow-up imaging.MethodsWe studied patients with cerebral large vessel occlusion who underwent CTP on admission but received endovascular thrombectomy based on a non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) >6. Admission infarct core was measured on initial cerebral blood volume (CBV) CTP and final infarct on follow-up CT. We defined ghost infarct core (GIC) as initial core minus final infarct >10 mL.Results79 patients were studied. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (11–20), median time from symptoms to CTP was 215 (87–327) min, and recanalization rate (TICI 2b–3) was 77%. Thirty patients (38%) presented with a GIC >10 mL. GIC >10 mL was associated with recanalization (TICI 2b–3: 90% vs 68%; p=0.026), admission glycemia (<185 mg/dL: 42% vs 0%; p=0.028), and time to CTP (<185 min: 51% vs >185 min: 26%; p=0.033). An adjusted logistic regression model identified time from symptom to CTP imaging <185 min as the only predictor of GIC >10 mL (OR 2.89, 95% CI 1.04 to 8.09). At 24 hours, clinical improvement was more frequent in patients with GIC >10 mL (66.6% vs 39%; p=0.017).ConclusionsCT perfusion may overestimate final infarct core, especially in the early time window. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who might still benefit from reperfusion.

The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11–78.42; p  = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50–0.95; p  = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64–26.42, p  = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23–13.03; p  = 0.021), and smoking (OR 2.91, 95% CI 1.08–7.90; p  = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83–0.94; p  < 0.001). In conclusion, a combination of clinical and radiological features available before EVT can help to identify an ICAS-LVO. This approach could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures. Prospective studies are needed to validate these findings in other populations.

Background Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β (Aβ) deposition in cerebral vessels, leading to lobar cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). Apolipoprotein J (ApoJ) is a multifunctional chaperone related to Aβ aggregation and clearance. Our study investigated the vascular impact of chronic recombinant human Apolipoprotein J (rhApoJ) treatment in a transgenic mouse model of β-amyloidosis with prominent CAA. Methods Twenty-month-old APP23 C57BL/6 mice received 25 doses of rhApoJ (1 mg/kg) ( n  = 9) or saline ( n  = 8) intraperitoneally for 13 weeks, while Wild-type (WT) mice received saline ( n  = 13). Postmortem brains underwent T2*-weighted magnetic resonance imaging (MRI) to detect hemorrhagic lesions. Aβ levels and distribution, cerebral fibrinogen leakage, brain smooth muscle actin (sma), and plasma matrix metalloproteinases and inflammatory markers were analyzed after treatments. Additionally, plasma samples from 22 patients with lobar ICH were examined to determine the clinical relevance of the preclinical findings. Results rhApoJ-treated APP23 presented fewer cortical CMBs (50–300 μm diameter) ( p  = 0.012) and cortical larger hemorrhages (> 300 μm) ( p  = 0.002) than saline-treated mice, independently of Aβ brain levels. MRI-detected hemorrhagic lesions correlated with fibrinogen cerebral extravasation ( p  = 0.011). Additionally, rhApoJ-treated mice presented higher number of sma-positive vessels than saline-treated mice ( p  = 0.038). In rhApoJ-treated mice, human ApoJ was detected in plasma and in occasional leptomeningeal vessels, but not in the parenchyma, suggesting that its mechanism of action operates through the periphery. The administration of rhApoJ induced an increase in plasma Groα ( p  = 0.035) and MIP-1α ( p  = 0.035) levels, while lower MMP-12 ( p  = 0.046) levels, compared to the saline-treated group. In acute lobar ICH patients, MMP-12 plasma levels correlated with larger hemorrhage volume ( p  = 0.040) and irregular ICH shape ( p  = 0.036). Conclusions Chronic rhApoJ treatment in aged APP23 mice ameliorated CAA-related neurovascular damage by reducing the occurrence of CMB. We propose that rhApoJ may prevent blood-brain barrier (BBB) leakage and CMB appearance partly through circulating MMP-12 modulation.

Background There is some evidence supporting the idea that double parathyroid adenomas represent a different entity from multiglandular hyperplasia; however, the distinction among them is not straightforward. Case presentation We described a case of primary hyperparathyroidism (PHPT) with pronounced clinical manifestations, caused by a bilateral giant parathyroid adenoma. A 34-year-old Hispanic/Latino male was diagnosed with PHPT caused by two giant parathyroid adenomas. The preoperative tests were neck ultrasound and computed tomography scan (CT-scan), showing two masses in the territory of parathyroid glands, bilaterally distributed (right was 31 × 18 × 19 mm and the left was 38 × 15 × 14 mm); sestamibi scan was not available. Parathyroid hormone (PTH) was highly elevated. Multiple complications of PHPT were present, such as bone lytic lesions, renal and pancreatic calcifications, and cardiovascular disease, the latter of which is an overlooked complication of PHPT. Multiple endocrine neoplasia 1 and 2 (MEN 1/2) were ruled out by the absence of clinical, biochemical, and radiological findings in other endocrine glands. The patient underwent subtotal parathyroidectomy with an intraoperative histopathological study; both intraoperative and definitive histopathology results were consistent with parathyroid adenomas; afterward, adequate suppression of PTH was assured, and later on, the patient presented hungry bone syndrome (HBS). Conclusions The diagnosis of double parathyroid adenomas is difficult. Regarding the similarities between multiglandular hyperplasia and parathyroid adenomas, this case report contributes to the further distinction between these two clinical entities. This case report also represents, in particular, the challenge of difficult diagnosis in places with limited resources, such as developing countries.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-β (Aβ) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aβ is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral β-amyloidosis.

Brain accumulation of amyloid-beta (Aβ) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aβ deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-β-amyloidosis to specifically identify vascular Aβ-associated proteins. We focused on one of the main proteins detected in the Aβ-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aβ-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aβ deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aβ40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aβ pathology from parenchymal Aβ deposition.

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.

Background: Selection of endovascular approaches for acute stroke patients remains unclear. The efficacy of intra-arterial therapy (IAT) has been demonstrated in the past. However, in the last years, the use of mechanical thrombectomy by retrievers (RET) is increasing at the expense of IAT. We aimed to compare several clinical outcomes between patients treated with IAT or RET. Methods: In a 6-year period, acute stroke patients (<8 h) with confirmed internal carotid artery (ICA) occlusion or middle cerebral artery (MCA) occlusion undergoing endovascular therapy were prospectively included in our database. Patients who underwent intra-arterial tissue plasminogen activator (tPA) ± microguidewire mechanical clot disruption (IAT group) were compared with those who underwent thrombectomy with the Solitaire® or Trevo® retrievers (RET group). Recanalization (REC) was considered if at the end of the endovascular procedure thrombolysis in cerebral infarction score was 2a-3. Dramatic clinical improvement (DCI) was defined as a decrease of ≥10 NIHSSS points from baseline to discharge or 7 days. Results: One hundred and eighty patients were included, 100 (55.6%) patients in the IAT group and 80 patients (44.4%) in the RET group. There were no differences in baseline characteristics (age, gender, risk factors profile, previous treatment with i.v. tPA, baseline NIHSS, extracranial ICA angioplasty and time to REC). Rates of REC, DCI and symptomatic intracranial hemorrhage were also similar between groups. Among patients with ICA occlusions (41 IAT, 34 RET), REC was significantly higher with RET (83.9 vs. 61%; p = 0.04).There was a trend towards a higher DCI rate in the RET group (32.3%) compared with the IAT group (14.6%; p = 0.06). According to MCA occlusions, there were no major differences in the main outcome variables. The number needed to treat to achieve one additional DCI with RET compared with IAT was 12 for MCA occlusions, and only 5 for ICA occlusions. Conclusions: Among acute stroke patients undergoing endovascular therapies, the benefits of RET over IAT are greater in ICA occlusions. Retrievers may be considered as the first therapeutic option in these patients.

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) ( n  = 59) and compared the results with those from hypertension-associated ICH ( n  = 42), AD patients ( n  = 73) and controls ( n  = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p  = 0.033; CAA vs. AD, p  = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients ( r  = 0.583, p  = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed ( p  < 0.001). Whereas the APOE4 frequency was higher in AD ( p  < 0.001) and CAA ( p  = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities ( p  = 0.045) and the presence of lobar microbleeds ( p  = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aβ(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA–ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.