Peri-Infarct Hot-Zones Have Higher Susceptibility to Optogenetic Functional Activation-Induced Spreading Depolarizations

Background and Purpose: Spreading depolarizations (SDs) are recurrent and ostensibly spontaneous depolarization waves that may contribute to infarct progression after stroke. Somatosensory activation of the metastable peri-infarct tissue triggers peri-infarct SDs at a high rate. Methods: We directly measured the functional activation threshold to trigger SDs in peri-infarct hot zones using optogenetic stimulation after distal middle cerebral artery occlusion in Thy1-ChR2-YFP mice. Results: Optogenetic activation of peri-infarct tissue triggered SDs at a strikingly high rate (64%) compared with contralateral homotopic cortex (8%; P =0.004). Laser speckle perfusion imaging identified a residual blood flow of 31±2% of baseline marking the metastable tissue with a propensity to develop SDs. Conclusions: Our data reveal a spatially distinct increase in SD susceptibility in peri-infarct tissue where physiological levels of functional activation are capable of triggering SDs. Given the potentially deleterious effects of peri-infarct SDs, the effect of sensory overstimulation in hyperacute stroke should be examined more carefully.

Aligning the Criterion and Tests for Brain Death

Disturbing cases continue to be published of patients declared brain dead who later were found to have a few intact brain functions. We address the reasons for the mismatch between the whole-brain criterion and brain death tests, and suggest solutions. Many of the cases result from diagnostic errors in brain death determination. Others probably result from a tiny amount of residual blood flow to the brain despite intracranial circulatory arrest. Strategies to lessen the mismatch include improving brain death determination training for physicians, mandating a test showing complete intracranial circulatory arrest, or revising the whole-brain criterion.

The diagnostic value of duplex ultrasound in detecting the presence and location of a stenosis in an autologous arteriovenous fistula

Objective: To determine the value of duplex ultrasound in the detection of significant (⩾50%) stenosis and the location of the stenosis in arteriovenous fistula, compared to angiography. Methods: Patients who underwent construction of an autologous arteriovenous fistula between January 2007 and December 2013 in Treant Care Group, hospital location Emmen, were included in this study. In all patients with a significantly decreased blood flow (flow <400 mL/min and/or ⩾20% decrease) measured by Transonic flowmeter before December 2016, duplex ultrasound was performed. Concordance between duplex ultrasound and angiography was analysed in all patients with a haemodynamically significant stenosis detected by duplex ultrasound. Results: In all, 63 patients had a significant decrease in blood flow leading to duplex ultrasound. In 51 (80.9%) of the 63 duplex ultrasound, a haemodynamically significant stenosis was detected. In 45 (88.2%) of these, angiography was performed, all confirming the presence of significant stenosis. In eight patients, no angiography was performed (sufficient residual blood flow (n = 7), death (n = 1)). Most stenoses were located in the venous outflow tract (75.6%). In 95.6%, a venous approach was possible during angiography. After intervention, a significant increase in blood flow was observed (from 530 mL/min to 910 mL/min (p < 0.001)). Conclusion: We show that duplex ultrasound is likely reliable to ascertain the presence of arteriovenous fistula stenosis in addition to flow criteria. Also, it provides important information to select the most effective and safe approach for cannulation. Duplex ultrasound may reduce costs and burden of diagnosing stenoses.

Impact of electrical defibrillation on infarct size and no-reflow in pigs subjected to myocardial ischemia-reperfusion without and with ischemic conditioning

Ventricular fibrillation (VF) occurs frequently during myocardial ischemia-reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no reflow (NR) without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min of coronary occlusion/reperfusion. VF, as identified from the ECG, was terminated by intrathoracic defibrillation. The area at risk (AAR), IS, and NR were determined by staining techniques (patent blue, triphenyltetrazolium chloride, and thioflavin-S). Four experimental protocols were analyzed: I/R ( n = 49), I/R with ischemic preconditioning (IPC; n = 22), I/R with ischemic postconditioning (POCO; n = 22), or I/R with remote IPC (RIPC; n = 34). The incidence of VF was not different between I/R (44%), IPC (45%), POCO (50%), and RIPC (33%). IS was reduced by IPC (23 ± 12% of AAR), POCO (31 ± 16%), and RIPC (22 ± 13%, all P < 0.05 vs. I/R: 41 ± 12%). NR was not different between protocols (I/R: 17 ± 15% of AAR, IPC: 15 ± 18%, POCO: 25 ± 16%, and RIPC: 18 ± 17%). In pigs with defibrillation, IS was 50% larger than in pigs without defibrillation but independent of the number of defibrillations. Analysis of covariance confirmed the established determinants of IS, i.e., AAR, residual blood flow during ischemia (RMBFi), and a conditioning protocol, and revealed VF/defibrillation as a novel covariate. VF/defibrillation in turn was associated with larger AAR and lower RMBFi. Lack of dose-response relation between IS and the number of defibrillations excluded direct electrical injury as the cause of increased IS. Obviously, AAR size and RMBFi account for both IS and the incidence of VF. IS and NR are mechanistically distinct phenomena. NEW & NOTEWORTHY Ventricular fibrillation/defibrillation is associated with increased infarct size. Electrical injury is unlikely the cause of such association, since there is no dose-response relation between infarct size and number of defibrillations. Ventricular fibrillation, in turn, is associated with a larger area at risk and lower residual blood flow.

Delayed aneurysm rupture due to residual blood flow at the inflow zone of the intracranial paraclinoid internal carotid aneurysm treated with the Pipeline embolization device: Histopathological investigation

Cerebral aneurysm rupture is a serious complication that can occur after flow diverter (FD) placement, but the underlying mechanisms remain unclear. We encountered a case in which direct stress on the aneurysm wall caused by residual blood flow at the inflow zone near the neck during the process of thrombosis after FD placement appeared associated with aneurysm rupture. The patient was a 67-year-old woman with progressive optic nerve compression symptoms caused by a large intracranial paraclinoid internal carotid aneurysm. The patient had undergone treatment with a Pipeline embolization device (PED) with satisfactory adherence between the PED and vessel wall. Surgery was completed without complications, and optic nerve compression symptoms improved immediately after treatment. Postoperative clinical course was satisfactory, but the patient suddenly died 34 days postoperatively. Autopsy confirmed the presence of subarachnoid hemorrhage caused by rupture of the internal carotid aneurysm that had been treated with PED. Although the majority of the aneurysm lumen including the outflow zone was thrombosed, a non-thrombosed area was observed at the inflow zone. Perforation was evident in the aneurysm wall at the inflow zone near the neck, and this particular area of aneurysm wall was not covered in thrombus. Macrophage infiltration was not seen on immunohistochemical studies of the aneurysm wall near the perforation. A hemodynamically unstable period during the process of complete thrombosis of the aneurysm lumen after FD placement may be suggested, and blood pressure management and appropriate management with antiplatelet therapy may be important.

Intercavernous Sinus Dural Arteriovenous Fistula Successfully Treated with Transvenous Embolization

The venous sinuses commonly found in the margins of the diaphragm and sella are venous interconnections between the bilateral cavernous dural sinuses and are termed intercavernous communications or intercavernous sinuses. They form a venous ring, a single “circular sinus” that extends throughout the skull base. We report the first case to our knowledge of an intercavernous sinus fistula. We emphasize the importance of thorough knowledge of lesion characteristics before considering any interventional procedure. An 84-year-old woman presented with alarming progressive orbital symptoms for one month affecting her left eye. A cerebral angiogram showed an intercavernous sinus fistula supplied by internal and external carotid arterial branches. Transvenous embolization through retrograde catheterization of the right inferior petrosal sinus allowed complete coil occlusion of the lesion. Cerebral angiography confirmed the absence of residual blood flow through the fistula. This report represents the first case of an intercavernous sinus dural arteriovenous fistula successfully treated with transvenous embolization. A detailed awareness of the regional anatomy is essential for treatment approach and favorable outcomes.

Utilization of Extracorporeal Pump during Local Intra-Arterial Fibrinolysis in the Treatment of Acute Cerebral Arterial Occlusion

Local intra-arterial fibrinolysis may improve the outcome of patients with ischemic cerebrovascular disease. A favorable prognosis is thought to be related to early re-establishment of blood flow into the affected brain. To minimize the time to revascularization during local intraarterial fibrinolysis, we employed an extracorporeal pump to deliver oxygenated blood into the affected brain through a microcatheter. The patient, a 57-year-old man, showed disturbance of consciousness with left hemiparesis and was admitted to our hospital one hour after onset of symptoms. Cerebral angiography demonstrated an acute occlusion of the right middle cerebral artery, and the patient underwent local intra-arterial fibrinolysis with an extracorporeal pump. Oxygenated blood was successfully delivered through a microcatheter into the affected brain before recanalization. Subsequently, recanalization was obtained by intra-arterial fibrinolysis with a tissue plasminogen activator. The outcome of this patient was excellent. Thus, local intra-arterial thrombolysis with extracorporeal pump may be an effective method by which to increase the residual blood flow and widen the therapeutic window for fibrinolysis.