Posterior reversible encephalopathy syndrome and acute ischemic stroke: an underreported association.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare and complex disorder with variable clinical presentation and a typical magnetic resonance imaging (MRI) pattern of vasogenic edema with typical and atypical locations. It is often triggered by other diseases and drugs and the most prototypical association is with persistently elevated arterial pressure values. Among the potential cerebrovascular complications, intracranial bleeding has been described, but ischemic stroke is uncommonly reported. METHODS: We are presenting a case of a male patient with prolonged and sustained arterial hypertension acutely presenting with lacunar ischemic stroke involving the right corona radiata and composite MRI findings with the association of chronic small vessel disease (SVD) markers, acute symptomatic lacunar stroke, and atypical, central variant, posterior fossa dominant PRES. In the MRI follow-up, the white matter hyperintensities in T2-fluid attenuated inversion recovery (FLAIR sequences) due to PRES. DISCUSSION: The pathophysiology of PRES is not yet fully known, but the association with markedly increased values of arterial pressure is typical. In this context, ischemic stroke has not been considered in the clinical and neuroradiological manifestations of PRES and it has been only occasionally reported in the literature. In this case, the main hypothesis is that sustained hypertension may have triggered both manifestations, PRES, and ischemic stroke and the last one allowed to diagnose the first one. CONCLUSIONS: Atypical variants of PRES are not so rare and it may also occur in typical triggering situations. The association with ischemic stroke is even rarer and it may add some clues to the pathomechanisms of PRES.

The Venular Side of Cerebral Amyloid Angiopathy: Proof of Concept of a Neglected Issue.

Small vessel diseases (SVD) is an umbrella term including several entities affecting small arteries, arterioles, capillaries, and venules in the brain. One of the most relevant and prevalent SVDs is cerebral amyloid angiopathy (CAA), whose pathological hallmark is the deposition of amyloid fragments in the walls of small cortical and leptomeningeal vessels. CAA frequently coexists with Alzheimer's Disease (AD), and both are associated with cerebrovascular events, cognitive impairment, and dementia. CAA and AD share pathophysiological, histopathological and neuroimaging issues. The venular involvement in both diseases has been neglected, although both animal models and human histopathological studies found a deposition of amyloid beta in cortical venules. This review aimed to summarize the available information about venular involvement in CAA, starting from the biological level with the putative pathomechanisms of cerebral damage, passing through the definition of the peculiar angioarchitecture of the human cortex with the functional organization and consequences of cortical arteriolar and venular occlusion, and ending to the hypothesized links between cortical venular involvement and the main neuroimaging markers of the disease.

Intracranial Stenosis Treated with Stenting in Patients with Suspected Cerebral Vasculitis: Two Case Reports.

Central nervous system vasculitis (CNSV) is an uncommon and poorly understood form of vasculitis. Early recognition is important because medical treatment might improve the outcome. However, randomized clinical trials on CNSV treatment do not exist. Endovascular treatment has been reported in few cases, but no data exist for intracranial stenting. We report 2 cases of patients with suspected CNSV and recurrent clinical episodes, treated with intracranial stenting. A 48-year-old man had relapsing episodes of right hemiparesis. Neuroradiological exams showed severe left carotid terminus stenosis. Despite immunosuppressive therapy, neuroradiological follow-up exams showed a worsening of the aforementioned stenosis with many transient episodes of weakness in the right limbs and aphasia. A 64-year-old woman had a sudden onset of dysarthria and transient aphasia. Neuroradiological exams showed a severe arterial stenosis involving the origin of left anterior cerebral artery and middle cerebral artery (MCA). Despite dual antiplatelet therapy, she presented an acute onset of severe aphasia, due to an occlusion of the left carotid terminus and proximal MCA. In both cases, endovascular procedure and intracranial stenting was performed, with marked improvement of cerebral blood flow. No more clinical episodes were reported. Intracranial stenting may be a valid therapeutic option in selected patients with CNSV and involvement of medium or large size vessels with clinical worsening despite best medical treatment.

In-hospital and out-of-hospital stroke in patients with COVID-19: two different diseases?

BACKGROUND: Ischemic stroke is a known complication of COVID-19. It may have a different pathogenesis and worse outcome compared to stroke in patients without COVID-19. Furthermore, patients with COVID-19 and out-of-hospital stroke onset might have different characteristics compared to patients with COVID-19 and in-hospital stroke onset. The aim of our study was to analyze the characteristics of patients with stroke with and without COVID-19 and of patients with COVID-19 with in-hospital and out-of-hospital stroke. METHODS: We performed a retrospective study of all consecutive patients admitted to our hospital with ischemic stroke between October 2020 and February 2021. We compared functional outcome, lab test, demographic, and clinical characteristics between patients with or without COVID-19. We performed a sub-analysis comparing patients with COVID-19 and in-hospital and out-of-hospital stroke onset. RESULTS: We included in the final analysis 137 patients of whom 26 with COVID-19. Half (13) had out-of-hospital stroke and half in-hospital stroke onset. Overall, patients with COVID-19 had higher mortality compared to the control group (27% vs 9%, p: 0.02), and non-significantly lower rate of good functional outcome (50% vs 63%, p: 0.22). Patients with COVID-19 and out-of-hospital stroke had higher rate of good functional outcome (69% vs 39%, p: 0.05), higher lymphocyte count, and lower D-dimer compared with patients with in-hospital stroke onset. CONCLUSIONS: Patients with stroke and COVID-19 had higher mortality compared to patients without COVID-19. Among patients with COVID-19 those with out-of-hospital stroke had better outcome and fewer blood test abnormalities compared to patients with in-hospital stroke.

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome.

OBJECTIVES: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting. MATERIALS AND METHODS: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors. RESULTS: We included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 - 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 - 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 - 203.14). CONCLUSION: We found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting.

Liver Angiopoietin-2 Is a Key Predictor of De Novo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct-Acting Antivirals.

Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA-treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin-2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C-reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo-Doppler work-up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = -0.412, P = 0.037 and r = -0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3-month follow-up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044-1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080-2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395-16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127-13.203; P = 0.032) were independent predictors of de novo HCC. CONCLUSION: Our study indicates that DAA-mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo-angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000-000).