BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*

Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca Results: An increase of cytoplasmic Ca Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Animals ; Calcium/metabolism* ; Cerebral Arteries ; Homeostasis ; Male ; Mitochondria/physiology* ; Myocytes, Smooth Muscle/physiology* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/physiology* ; Weightlessness Simulation

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.
Animals ; Brain ; Carotid Arteries ; Cerebral Infarction ; Connexin 43 ; Imatinib Mesylate ; Ischemia ; Learning ; Memory ; Mice ; Motor Activity ; Neuroprotection ; Phosphotransferases ; Reperfusion ; Reperfusion Injury ; STAT3 Transcription Factor ; Transducers ; Walking

OBJECTIVE: To determine the correlation between cerebral blood flow (CBF) on arterial spin labeling (ASL) MRI and the degree of postoperative revascularization assessed on digital subtraction angiography in children with moyamoya disease (MMD). MATERIALS AND METHODS: Twenty-one children (9 boys and 12 girls; mean age, 8.4 ± 3.6 years; age range, 3–16 years) with MMD who underwent both pseudocontinuous ASL MRI at 1.5T and catheter angiography before and after superficial temporal artery encephaloduroarteriosynangiosis were included in this retrospective study. The degree of revascularization in the middle cerebral artery (MCA) territory was evaluated on external carotid angiography and was graded on a 3-point scale. On ASL CBF maps, regions of interest were manually drawn over the MCA territory of the operated side at the level of the centrum semi-ovale and over the cerebellum. The normalized CBF (nCBF) was calculated by dividing the CBF of the MCA territory by the CBF of the cerebellum. Changes in nCBFs were calculated by subtracting the preoperative nCBF values from the postoperative nCBF values. The correlation between nCBF changes measured with ASL and the revascularization grade from direct angiography was evaluated. RESULTS: The nCBF value on the operated side increased after the operation (p = 0.001). The higher the degree of revascularization, the greater the nCBF change was: poor revascularization (grade 1), −0.043 ± 0.212; fair revascularization (grade 2), 0.345 ± 0.176; good revascularization (grade 3), 0.453 ± 0.182 (p = 0.005, Jockheere-Terpstra test). The interobserver agreement was excellent for the measured CBF values of the three readers (0.91–0.97). CONCLUSION: The nCBF values of the MCA territory obtained from ASL MRI increased after the revascularization procedure in children with MMD, and the degree of nCBF change showed a significant correlation with the degree of collateral formation evaluated via catheter angiography.
Angiography ; Angiography, Digital Subtraction ; Catheters ; Cerebellum ; Cerebral Revascularization ; Cerebrovascular Circulation ; Child ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Cerebral Artery ; Moyamoya Disease ; Perfusion ; Retrospective Studies ; Temporal Arteries

OBJECTIVE: Coiled aneurysms are known to recanalize over time, making follow-up evaluations mandatory. Although de novo intracranial aneurysms (DNIAs) are occasionally detected during routine patient monitoring, such events have not been thoroughly investigated to date. Herein, we generated estimates of DNIA development during long-term observation of coiled cerebral aneurysms, focusing on incidence and the risk factors involved. MATERIALS AND METHODS: In total, 773 patients undergoing coil embolization of intracranial aneurysms between 2008 and 2010 were reviewed retrospectively. Their medical records and radiologic data accrued over the extended period (mean, 52.7 ± 29.7 months) were analyzed. For the detection of DNIA, follow-up magnetic resonance angiography and/or conventional angiography were used. The incidence of DNIAs and related risk factors were analyzed using Cox proportional hazards regression and Kaplan-Meier product-limit estimator. RESULTS: In 19 (2.5%) of the 773 patients with coiled aneurysms, DNIAs (0.56% per patient-year) developed during continued long-term monitoring (3395.3 patient-years). Of these, 9 DNIAs (47.4%) were detected within 60 months, with 10 (52.6%) emerging thereafter. The most common site involved was the posterior communicating artery (n = 6), followed by the middle cerebral artery (n = 5) and the basilar top (n = 4). Multivariate analysis indicated that younger age (< 50 years) (hazard ratio [HR] = 1.045; p = 0.010) and recanalization of coiled aneurysms (HR = 2.560; p = 0.047) were significant factors in DNIA formation, whereas female sex, smoking, and hypertension fell short of statistical significance. Cumulative survival rates without DNIA were significantly higher in older subjects (> 60 years; p < 0.001) and in the absence of post-coiling aneurysm recurrence (p = 0.006). CONCLUSION: In most patients with coiled aneurysms, development of DNIAs during long-term monitoring is rare. However, younger patients (< 50 years) or patients with recurring aneurysms appear to be predisposed to DNIAs.
Aneurysm ; Angiography ; Arteries ; Embolization, Therapeutic ; Female ; Follow-Up Studies ; Humans ; Hypertension ; Incidence ; Intracranial Aneurysm ; Magnetic Resonance Angiography ; Medical Records ; Middle Cerebral Artery ; Monitoring, Physiologic ; Multivariate Analysis ; Recurrence ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking ; Survival Rate

Distal intracranial occlusions can sometimes cause significant neurological deficits. Endovascular thrombectomy in these vessels may improve outcome but carry a higher risk of haemorrhagic complications due to the small calibre and tortuosity of the target vessel. We report two cases of isolated M2/3 artery occlusion causing dense hemiplegia that was successfully treated with stent retrieval thrombectomy. A “semi-deployment technique” of a 3 mm stentriever was employed at the M2/3 bifurcation of the middle cerebral artery. Partial stent unsheathing allowed adequate clot engagement while avoiding excessive tension by the stent metal struts along the tortuous course of a distal vessel. Complete revascularization was achieved after first-pass of the stent retriever without complication, resulting in good clinical outcome in both cases. The described semi-deployment technique reduces the radial and tractional force exerted by the stentreiver on small branches, and may reduce the risk of vessel laceration or dissection in distal vessel thrombectomy.
Arteries ; Endovascular Procedures ; Hemiplegia ; Lacerations ; Middle Cerebral Artery ; Stents ; Stroke ; Thrombectomy ; Traction

PURPOSE: Mechanical thrombectomy has become the standard of care for acute stroke caused by large vessel occlusion. As more patients are treated endovascularly, the number of older patients with tortuous vessels has risen. In these patients, catheterizing the internal carotid artery via a transfemoral approach can be very difficult or even impossible. Therefore, in selected patients, alternative strategies to the transfemoral approach have to be applied. MATERIALS AND METHODS: We report a case series of six patients undergoing mechanical thrombectomy via a combined transfemoral and transcarotid approach. Puncture of the carotid artery was conducted using roadmap guidance after an unsuccessful transfemoral attempt. Technical aspects and outcomes with this alternative approach were analyzed. RESULTS: Direct puncture of the carotid artery was achieved in five out of six patients (83%). In three out of six patients (50%), revascularization (modified Thrombolysis in Cerebral Infarction score ≥2b) was restored. No complications related to endovascular therapy were documented. One patient showed good neurological outcome (modified Rankin Scale [mRS] 5 at admission, mRS 1 at discharge). CONCLUSION: A combined transfemoral/transcarotid approach can be an alternative vascular access in patients with problematic vessel anatomy.
Carotid Arteries ; Carotid Artery, Internal ; Catheters ; Cerebral Infarction ; Humans ; Punctures ; Standard of Care ; Stroke ; Thrombectomy

PURPOSE: Emergent intracranial occlusions causing acute ischemic stroke are often related to extracranial atherosclerotic stenosis. This study aimed to investigate the association between post-procedure intracerebral hemorrhage (ICH) and emergent extracranial artery stenting and assess their effects on clinical outcomes in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively analyzed patients undergoing hyperacute endovascular treatment for cervicocephalic vascular occlusion in three Korean hospitals between January 2011 and February 2016. Patients who had extracranial artery involvement and were treated from 24 hours of symptom onset to puncture were included in this study, and they were divided into the extracranial stenting (ES) and non-ES groups. Any type of petechial hemorrhages and parenchymal hematoma was defined as ICH for the current study. RESULTS: In total, 76 patients were included in this study. Among them, 56 patients underwent ES, and 20 patients did not. Baseline characteristics, risk factors, laboratory data, treatment methods, successful reperfusion rates, and baseline stenotic degrees of extracranial internal carotid artery did not differ between these two groups. However, atrial fibrillation was more frequent in patients without than with ES (P=0.002), and post-procedure ICH was more frequent in patients with than without ES (P=0.035). Logistic regression models revealed that ES was independently associated with post-procedure ICH (odds ratio [OR], 7.807; 95% confidence interval [CI], 1.213–50.248; P=0.031), and ICH was independently associated with poor clinical outcomes (OR, 0.202; 95% CI, 0.054–0.759; P=0.018); however, ES itself was not associated with clinical outcomes (OR, 0.530; 95% CI, 0.117–2.395; P=0.409). Notably, ICH and ES had interaction for predicting good outcomes (P=0.041). CONCLUSION: Post-procedure ICH was associated with ES and poor clinical outcomes. Therefore, ES should be cautiously considered in patients with hyperacute stroke.
Arteries ; Atrial Fibrillation ; Carotid Artery, Internal ; Carotid Stenosis ; Cerebral Hemorrhage ; Cerebral Infarction ; Constriction, Pathologic ; Endovascular Procedures ; Hematoma ; Hemorrhage ; Humans ; Logistic Models ; Punctures ; Reperfusion ; Retrospective Studies ; Risk Factors ; Stents ; Stroke

PURPOSE: Although carotid endarterectomy (CEA) is recommended as a treatment for carotid stenosis rather than carotid artery stenting (CAS), CAS has been preferred in Korea. The aim of this study was to analyze long-term outcomes after CAS compared with CEA using Korean nationwide insurance data. MATERIALS AND METHODS: We obtained all data from the nationwide database of the Health Insurance Review & Assessment Service (HIRA) during the study period using several codes regarding the procedure or operation. We included the HIRA data, which included at least one-year follow-up after the procedures. The outcomes associated with both procedures were death, recurrence of ischemic stroke, and admission for cerebral hemorrhage. RESULTS: A total of 16,065 eligible patients who were treated with CAS or CEA between 1 January 2007 and 31 December 2016 were analyzed. The number of patients with CAS and CEA was 12,173 (75.8%) and 3,892 (24.2%), respectively. 8,976 patients (55.9%) were classified as symptomatic patients. CAS was associated with a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.282; 95% confidence interval [CI], 1.173–1.400). The adjusted rates for recurrent ischemic stroke and cerebral hemorrhage between CAS versus CEA were 24.9% versus 15.9% (HR, 1.474; 95% CI, 1.325–1.639) and 1.5% versus 0.9% (HR, 2.026; 95% CI, 1.322–3.106), respectively. In young symptomatic patients, there was no statistically significant difference in all-cause mortality and cardiovascular death between CAS and CEA. CONCLUSION: Our study using Korean nationwide insurance data demonstrated similar results to previous studies. Until further evidence of CAS is established through prospective studies, CAS should be performed in selected patients according to current guidelines.
Carotid Arteries ; Carotid Stenosis ; Cerebral Hemorrhage ; Endarterectomy ; Endarterectomy, Carotid ; Follow-Up Studies ; Humans ; Insurance ; Insurance, Health ; Korea ; Mortality ; Prognosis ; Prospective Studies ; Recurrence ; Stents ; Stroke

Endovascular recanalization therapy (ERT) has been a standard of care for patients with acute ischemic stroke due to large artery occlusion (LAO) within 6 hours after onset, since five landmark ERT trials conducted by 2015 demonstrated its clinical benefit. Recently, two randomized clinical trials demonstrated that ERT, even in the late time window of up to 16 hours or 24 hours after last known normal time, improved the outcome of patients who had a target mismatch, defined as either clinical-core mismatch or perfusion-core mismatch, which prompted the update of national guidelines in several countries. Accordingly, to provide evidence-based and up-to-date recommendations for ERT in patients with acute LAO in Korea, the Clinical Practice Guidelines Committee of the Korean Stroke Society decided to revise the previous Korean Clinical Practice Guidelines of Stroke for ERT. For this update, the members of the writing group were appointed by the Korean Stroke Society and the Korean Society of Interventional Neuroradiology. After thoroughly reviewing the updated evidence from two recent trials and relevant literature, the writing members revised recommendations, for which formal consensus was achieved by convening an expert panel composed of 45 experts from the participating academic societies. The current guidelines are intended to help healthcare providers, patients, and their caregivers make well-informed decisions and to improve the quality of care regarding ERT. The ultimate decision for ERT in a particular patient must be made in light of circumstances specific to that patient.
Arteries ; Caregivers ; Cerebral Infarction ; Consensus ; Health Personnel ; Humans ; Korea ; Mechanical Thrombolysis ; Reperfusion ; Standard of Care ; Stroke ; Writing