PI3KC2ß inactivation stabilizes VE-cadherin junctions and preserves vascular integrity.

Endothelium protection is critical, because of the impact of vascular leakage and edema on pathological conditions such as brain ischemia. Whereas deficiency of class II phosphoinositide 3-kinase alpha (PI3KC2α) results in an increase in vascular permeability, we uncover a crucial role of the beta isoform (PI3KC2ß) in the loss of endothelial barrier integrity following injury. Here, we studied the role of PI3KC2ß in endothelial permeability and endosomal trafficking in vitro and in vivo in ischemic stroke. Mice with inactive PI3KC2ß showed protection against vascular permeability, edema, cerebral infarction, and deleterious inflammatory response. Loss of PI3KC2ß in human cerebral microvascular endothelial cells stabilized homotypic cell-cell junctions by increasing Rab11-dependent VE-cadherin recycling. These results identify PI3KC2ß as a potential new therapeutic target to prevent aggravating lesions following ischemic stroke.

Carotid Ultrasound for Assessment of Nonobstructive Carotid Atherosclerosis in Young Adults with Cryptogenic Stroke.

BACKGROUND: The role of nonobstructive (<50% stenosis) carotid atherosclerosis (NOCA) in young adults with ischemic stroke is not well understood. In the present study, we investigated the prevalence and the ultrasonic characteristics of NOCA in a consecutive series of young adults with cryptogenic stroke (CS). METHODS: Patients aged 18-54, consecutively treated in a tertiary hospital for first-ever CS (defined as an ischemic stroke without ASCOD (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes) grade 1 potential cause) in the carotid artery territory, were prospectively enrolled. NOCA was assessed using carotid duplex ultrasonography. RESULTS: Of 148 patients with first-ever ischemic stroke, 70 had CS, including 44 patients with carotid CS. NOCA was found in 22 of 44 (50%) patients. All but 1 plaque were echolucent. NOCA was bilateral in 15 patients and unilateral in 7 patients. All unilateral plaques were on the symptomatic side (P = .02). Plaque thickness, plaque length, and plaque volume were greater on the symptomatic side than on the asymptomatic side (P = .001, P < .001, and P < .001, respectively). Discrimination between the symptomatic and the asymptomatic side using any of these plaque metrics was good with areas under the curve (95% confidence interval) of .82 (.69-0.95), .85 (.74-0.96), and .87 (.75-0.99) for plaque thickness, plaque length, and plaque volume, respectively. CONCLUSIONS: NOCA is frequent in young adults with CS. Measurement of the plaque burden with carotid duplex may help to identify symptomatic NOCA.

Tobacco Use and Cryptogenic Stroke in Young Adults.

OBJECTIVE: Cryptogenic stroke is the leading subtype of ischemic stroke in the young. We sought to evaluate the association between traditional cardiovascular risk factors and cryptogenic stroke by using a case-control study. METHODS: Patients aged 18-54 years, consecutively treated for first-ever cryptogenic ischemic stroke in an academic stroke unit, were compared with subjects from the general population living in the same geographic area. Control subjects were matched for age and sex with patients. We further evaluated the association between significant risk factors and nonobstructive (<50% stenosis) carotid plaque and thrombus among patients with cryptogenic stroke. Odds ratios [OR] were calculated using logistic regression analysis. RESULTS: A total of 155 patients with cryptogenic stroke (66.4% men, mean age 43.5 years [SD 8.4]) were included in the study. Cryptogenic stroke was associated with current tobacco use (42.6% in patients versus 23.9% in control subjects; OR = 2.38, 95% confidence interval [CI] 1.40-4.05, P = .002). Current tobacco use was associated with nonobstructive carotid plaque (OR = 6.22; 95% CI, 2.43-15.9; P = .001) and nonobstructive carotid thrombus (OR = 13.7; 95% CI, 1.42-132.7; P = .03) among the patients. CONCLUSION: Our case-control study showed a strong link between current tobacco use and cryptogenic stroke in young adults.

Reversible Cerebral Vasoconstriction Syndrome with Intracranial Hypertension: Should Decompressive Craniectomy Be Considered?

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare cause of intracerebral hemorrhage (ICH) causing intracranial hypertension. METHODS: Case report. RESULTS: We report a case of RCVS-related ICH leading to refractory intracranial hypertension. A decompressive craniectomy was performed to control intracranial pressure. We discuss here the management of RCVS with intracranial hypertension. Decompressive craniectomy was preformed to avoid the risky option of high cerebral perfusion pressure management with the risk of bleeding, hemorrhagic complications, and high doses of norepinephrine. Neurological outcome was good. CONCLUSION: RCVS has a complex pathophysiology and can be very difficult to manage in cases of intracranial hypertension. Decompressive craniectomy should probably be considered.

Risk factor profile by etiological subtype of ischemic stroke in the young.

BACKGROUND AND PURPOSE: Studies of risk factors for ischemic stroke in the young have generally considered ischemic stroke as a whole. The purpose of the present study was to evaluate the association of traditional cardiovascular risk factors with etiological subtypes of ischemic stroke in young adults. METHODS: Retrospective review of data from patients aged 16-54 years consecutively treated for first-ever ischemic stroke in an academic stroke unit. Definite causes of stroke were classified using the ASCO (A for atherothrombosis, S for small vessel disease, C for cardiac source, O for other cause) classification system. We used multinomial logistic regression analysis to evaluate associations of age, gender, smoking, hypertension, diabetes and blood lipids with each etiological subtype. RESULTS: A total of 400 patients were included: 244 men (61.1%), 156 women (38.9%); mean age (SD) 44.5 (8.5) years. A definite cause of stroke could be identified in 202 (50.5%) patients. Definite causes of stroke included: atherothrombosis, 72 (18.0%) patients; cardioembolism, 37 (9.25%) patients; small vessel disease, 28 (7.0%) patients; other definite cause, 65 (16.25%) patients including 44 patients with carotid or vertebral artery dissection. Atherothrombosis was associated with age, smoking, diabetes, hypertension and low HDL-cholesterol. Small vessel disease was associated with age and hypertension. Cardioembolism was associated with age. CONCLUSION: The risk factor profile differs between etiological subtypes of ischemic stroke in young adults. Our findings emphasize the impact of smoking, diabetes, hypertension and low HDL-cholesterol as risk factors for atherothrombosis, and of hypertension as a risk factor for small vessel disease in young adults.