Minor stroke due to large artery occlusion. When is intravenous thrombolysis not enough? Results from the SITS International Stroke Thrombolysis Register

Purpose: Beyond intravenous thrombolysis, evidence is lacking on acute treatment of minor stroke caused by large artery occlusion. To identify candidates for additional endovascular therapy, we aimed to determine the frequency of non-haemorrhagic early neurological deterioration in patients with intravenous thrombolysis-treated minor stroke caused by occlusion of large proximal and distal cerebral arteries. Secondary aims were to establish risk factors for non-haemorrhagic early neurological deterioration and report three-month outcomes in patients with and without non-haemorrhagic early neurological deterioration. Method: We analysed data from the SITS International Stroke Thrombolysis Register on 2553 patients with intravenous thrombolysis-treated minor stroke (NIH Stroke Scale scores 0–5) and available arterial occlusion data. Non-haemorrhagic early neurological deterioration was defined as an increase in NIH Stroke Scale score ≥4 at 24 h, without parenchymal hematoma on follow-up imaging within 22–36 h. Findings: The highest frequency of non-haemorrhagic early neurological deterioration was seen in 30% of patients with terminal internal carotid artery or tandem occlusions (internal carotid artery + middle cerebral artery) (adjusted odds ratio: 10.3 (95% CI 4.3–24.9), p < 0.001) and 17% in extracranial carotid occlusions (adjusted odds ratio 4.3 (2.5–7.7), p < 0.001) versus 3.1% in those with no occlusion. Proximal middle cerebral artery-M1 occlusions had non-haemorrhagic early neurological deterioration in 9% (adjusted odds ratio 2.1 (0.97–4.4), p = 0.06). Among patients with any occlusion and non-haemorrhagic early neurological deterioration, 77% were dead or dependent at three months. Conclusions: Patients with minor stroke caused by internal carotid artery occlusion, with or without tandem middle cerebral artery involvement, are at high risk of disabling deterioration, despite intravenous thrombolysis treatment. Acute vessel imaging contributes usefully even in minor stroke to identify and consider endovascular treatment, or intensive monitoring at a comprehensive stroke centre, for patients at high risk of neurological deterioration

Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats

Background: Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit. Methods: Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging. Results: Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient–derived lesion volume 2–4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group. Conclusions: Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear

Posterior Cerebral Artery Ischemic Stroke in a Patient with Hypoplastic P1 Segment of the Posterior Cerebral Artery

Posterior circulation stroke usually presents with clinical challenges, and symptoms may include blindness. Hypoplastic or atretic cerebral artery may be a risk factor for future ischemic stroke. We present a 75‑year‑old male patient with posterior cerebral artery ischemic stroke who presented with sudden visual deterioration, and brain magnetic resonance angiography showed hypoplastic right P1. Keywords: Hypoplastic artery, ischemic stroke, posterior circulation, visual impairmen

Cerebral Collateral Circulation in Carotid Artery Disease

Carotid artery disease is common and increases the risk of stroke. However, there is wide variability on the severity of clinical manifestations of carotid disease, ranging from asymptomatic to fatal stroke. The collateral circulation has been recognized as an important aspect of cerebral circulation affecting the risk of stroke as well as other features of stroke presentation, such as stroke patterns in patients with carotid artery disease. The cerebral circulation attempts to maintain constant cerebral perfusion despite changes in systemic conditions, due to its ability to autoregulate blood flow. In case that one of the major cerebral arteries is compromised by occlusive disease, the cerebral collateral circulation plays an important role in preserving cerebral perfusion through enhanced recruitment of blood flow. With the advent of techniques that allow rapid evaluation of cerebral perfusion, the collateral circulation of the brain and its effectiveness may also be evaluated, allowing for prompt assessment of patients with acute stroke due to involvement of the carotid artery, and risk stratification of patients with carotid stenosis in chronic stages. Understanding the cerebral collateral circulation provides a basis for the future development of new diagnostic tools, risk stratification, predictive models and new therapeutic modalities. In the present review we discuss basic aspects of the cerebral collateral circulation, diagnostic methods to assess collateral circulation, and implications in occlusive carotid artery disease

Computational modelling of emboli travel trajectories in cerebral arteries: Influence of microembolic particle size and density

This article has been made available through the Brunel Open Access Publishing Fund.Ischaemic stroke is responsible for up to 80 % of stroke cases. Prevention of the reoccurrence of ischaemic attack or stroke for patients who survived the first symptoms is the major treatment target. Accurate diagnosis of the emboli source for a specific infarction lesion is very important for a better treatment for the patient. However, due to the complex blood flow patterns in the cerebral arterial network, little is known so far of the embolic particle flow trajectory and its behaviour in such a complex flow field. The present study aims to study the trajectories of embolic particles released from carotid arteries and basilar artery in a cerebral arterial network and the influence of particle size, mass and release location to the particle distributions, by computational modelling. The cerebral arterial network model, which includes major arteries in the circle of Willis and several generations of branches from them, was generated from MRI images. Particles with diameters of 200, 500 and 800 μ m and densities of 800, 1,030 and 1,300 kg/m 3 were released in the vessel's central and near-wall regions. A fully coupled scheme of particle and blood flow in a computational fluid dynamics software ANASYS CFX 13 was used in the simulations. The results show that heavy particles (density large than blood or a diameter larger than 500 μ m) normally have small travel speeds in arteries; larger or lighter embolic particles are more likely to travel to large branches in cerebral arteries. In certain cases, all large particles go to the middle cerebral arteries; large particles with higher travel speeds in large arteries are likely to travel at more complex and tortuous trajectories; emboli raised from the basilar artery will only exit the model from branches of basilar artery and posterior cerebral arteries. A modified Circle of Willis configuration can have significant influence on particle distributions. The local branch patterns of internal carotid artery to middle cerebral artery and anterior communicating artery can have large impact on such distributions. © 2014 The Author(s)

Translational Evaluation of Acid/Base and Electrolyte Alterations in Rodent Model of Focal Ischemia

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion. METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient middle cerebral artery occlusion models. RESULTS: Analysis indicated significant differences in the blood gas and electrolytes between pre- to post-middle cerebral artery occlusion. A decrease in pH and sodium with increases in carbon dioxide, potassium, ionized calcium, and glucose changes were found in both middle cerebral artery occlusion models; while hematocrit and hemoglobin were significant in the transient model. pH and ionized calcium were predictors of infarct volume in the permanent model, as changes in pH and ionized calcium decreased, infarct volume increased. CONCLUSIONS: There are acute changes in acid/base balance and electrolytes during stroke in transient and permanent rodent models. Additionally, we found pH and ionized calcium changes predicted stroke volume in the permanent middle cerebral artery occlusion model. These preliminary findings are novel, and warrant further exploration in human conditions

Animal models of ischaemic stroke and characterisation of the ischaemic penumbra

Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the ‘ischaemic cascade’ that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed

冠動脈バイパス術後脳梗塞の危険因子に関する検討

　According to the recent increase of age of cardiac surgical patients, the mortality due to non-cardiac causes has increased. One of the most serious risk factors in the senile patients is perioperative stroke mainly due to cerebral infarction. To identify the risk factors for stroke after coronary artery bypass grafting (CABG) 483 patients who underwent scheduled CABG during past 4 years were retrospectively reviewed. Eighteen patients (3.7%) had stroke perioperatively. The hospital mortality was 3.1% (15 patients) and 2 patients (13.3%) died of cerebral infarction. To analyze the risk factors for stroke after CABG, we intensively examined the previous cerebral infarction, carotid artery stenosis evaluated by duplex scanning, and atherosclerotic or calcified changes of the ascending aorta diagnosed by palpation during surgery. There was a significant correlation between severe atherosclerotic or calcified changes of the ascending aorta and perioperative cerebral infarction

Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis

Cerebral edema (CED) is a severe complication of acute ischemic stroke. There is uncertainty regarding the predictors for the development of CED after cerebral infarction. We aimed to determine which baseline clinical and radiological parameters predict development of CED in patients treated with intravenous thrombolysis. We used an image-based classification of CED with 3 degrees of severity (less severe CED 1 and most severe CED 3) on postintravenous thrombolysis imaging scans. We extracted data from 42 187 patients recorded in the SITS International Register (Safe Implementation of Treatments in Stroke) during 2002 to 2011. We did univariate comparisons of baseline data between patients with or without CED. We used backward logistic regression to select a set of predictors for each CED severity. CED was detected in 9579/42 187 patients (22.7%: 12.5% CED 1, 4.9% CED 2, 5.3% CED 3). In patients with CED versus no CED, the baseline National Institutes of Health Stroke Scale score was higher (17 versus 10; P<0.001), signs of acute infarct was more common (27.9% versus 19.2%; P<0.001), hyperdense artery sign was more common (37.6% versus 14.6%; P<0.001), and blood glucose was higher (6.8 versus 6.4 mmol/L; P<0.001). Baseline National Institutes of Health Stroke Scale, hyperdense artery sign, blood glucose, impaired consciousness, and signs of acute infarct on imaging were independent predictors for all edema types. The most important baseline predictors for early CED are National Institutes of Health Stroke Scale, hyperdense artery sign, higher blood glucose, decreased level of consciousness, and signs of infarct at baseline. The findings can be used to improve selection and monitoring of patients for drug or surgical treatment

Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis

Objective To investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis. Methods 54 patients with internal carotid artery stenosis were enrolled. VMR was calculated by transcranial Doppler monitoring of the velocity of blood flow. 3-Dimensional dynamic contrast enhanced magnetic resonance angiography was used to detect stenosis, and diffusion weighted imaging was used to detect infarction. Results VMR value was significantly lower in patients with carotid artery stenosis than in control group (T=3.112, P=0.002), and significantly lower in patients with aortic atherosclerotic stroke than in non-infarct group (T=10.930, P=0.000). However, VMR value was significantly higher in patients with new-onset small-artery occlusion stroke than in non-infarction group (T=−2.538, P=0.013). Scatter plots showed that aortic atherosclerotic stroke occurred mainly in patients with severe internal carotid artery stenosis, and VMR value in cerebral artery significantly decreased. Conclusion Decreased VMR value is an important prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be used as a reference for preoperative hemodynamic evaluation in patients with internal carotid artery stenosis