Prognostic significance of angiographically confirmed large vessel intracranial occlusion in patients presenting with acute brain ischemia

Introduction  Independent predictors of outcome for ischemic stroke include age and initial stroke severity. Intracranial large-vessel occlusion would be expected to predict poor outcome. Because large-vessel occlusion and stroke severity are likely correlated, it is unclear if largevessel occlusion independently predicts outcome or is simply a marker for stroke severity. Methods  A consecutive series of patients with suspected stroke or transient ischemic attack were imaged acutely with computed tomography angiography (CTA). CTAs were reviewed for intracranial large-vessel occlusion as the cause of the stroke. Baseline National Institutes of Health Stroke Scale (NIHSS) score, discharge modified Rankin score, and patient demographics were abstracted from hospital records. Poor neurological outcome was defined as modified Rankin score exceeding 2. Results  Seventy-two consecutive patients with acute ischemic stroke were imaged with CTA. The median (range) time from stroke symptom onset to CT imaging was 183 minutes (25 minutes to 4 days). Median NIHSS score was 6 (1–32) and intracranial large-vessel occlusion was found in 28 (38.9%) patients. Fifty-six percent of patients had a good neurological outcome. In multivariate logistic regression analysis, two variables predicted poor neurological outcome: baseline NIHSS score (OR 1.21,95% CI[1.07–1.37]) and presence of intracranial large-vessel occlusion (OR 4.48, 95% CI[1.19–16.9]). The predictive value of large-vessel occlusion, on outcome was similar to an 8-point increase in NIHSS score. Conclusion  In patients presenting with acute brain ischemia, intracranial large-vessel occlusion independently predicts poor neurological outcome at hospital discharge, as does the presence of a high NIHSS score. Performing routine intracranial vascular imaging on acute stroke patients may allow for more accurate determination of prognosis and may also guide therapy.     

Emergency Microsurgical Embolectomy for the Treatment of Acute Intracranial Artery Occlusion: Report of Two Cases

Background

The main treatment for acute arterial ischemic stroke is intravenous or intra-arterial thrombolysis within a particular time window. Endovascular mechanical embolectomy is another treatment option in the case of major artery occlusion. Endovascular mechanical embolectomy is a useful technique for restoring blood flow in patients with large-vessel occlusion, and especially in those who are contraindicated for thrombolytics or in whom thrombolytic therapy has failed.

Case Report

We report herein two cases of emergency microsurgical embolectomy for the treatment of acute middle cerebral artery and internal carotid artery occlusion as an alternative treatment for major artery occlusion.

Conclusions

Emergency microsurgical mechanical embolectomy may be an alternative treatment option for restoring blood flow in selected patients with large-vessel acute ischemic stroke.     

Acute anticoagulation following cardioembolic stroke

Whether acute anticoagulation after cardioembolic stroke affords substantial protection against early recurrent emboli or an unacceptable risk of hemorrhage remains controversial. To assess this further, we evaluated 121 consecutive patients with acute cardioembolic stroke. Forty-nine were therapeutically anticoagulated within 96 hours of stroke onset, and 41 received no anticoagulants within the first 2 weeks after stroke. These two groups did not differ significantly with regard to age, sex, severity of acute neurologic deficit, or spectrum of underlying cardiac disease. The incidences of clinically significant brain hemorrhage (2%) and early recurrent embolization (2%) were equally low in both groups. Our data suggest that acute acute anticoagulation may be employed safely in most patients with cardioembolic stroke but that such treatment does not clearly benefit this population as a whole.     

Heparin therapy in embolic cerebral infarct. A retrospective study

Heparin therapy in acute stroke is a controversial issue. It is uncertain, whether heparin has a therapeutic or preventive effect in the early phase of the stroke. From 1984-1989, 1095 patients with acute ischemic stroke were treated, 141 (12.9%) of whom received heparin within 3 days of stroke onset. The mean duration of heparin anticoagulation was 10 days. In 28 cases (20%), heparin was used as antithrombotic agent (25/28 patients suffered a basilar artery occlusion, of whom 22 died). In 113 cases (80%), heparin was used in embolic stroke to prevent recurrence (24% cardioembolic stroke, 54% arterio-arterial embolism, and 22% embolism of unknown etiology). The rate of recurrent stroke in the early phase was 13% with a persistent deficit in 5.3%. The results are comparable with those of other trials reported in the literature. Only 2 patients had an anticoagulation-related haemorrhage with clinical deterioration. Heparin anticoagulation in acute stroke is a low-risk therapy, but its preventive value has not yet been demonstrated.     

Heparin in der Akutphase des ischämischen Schlaganfalls

Therapy with low- or high-dose heparin in acute stroke is changing. Despite several clinical studies (>20), some with quite large numbers of patients, no statistically significant benefit was found for the clinical endpoints of death and functional outcome. This negative result remains even when considering the preventive effect of high-dose heparin on secondary acute embolic events (e.g., cardiac emboli-arrhythmia) and low-dose heparin on venous thrombosis. Based on study results, most reviews and therapy recommendations for the treatment of acute stroke generally decline the use of high-dose heparins and heparinoids with full anticoagulation for improving outcome or preventing secondary embolic events as well as low-dose applications for venous thrombosis prophylaxis. This paper reviews the literature and presents the data of a standardised survey on coagulation therapy in acute stroke patients from all university and major stroke units in Germany (n=33). Contrary to the restrictive recommendations, therapy with heparin is firmly established in most stroke units. Full anticoagulation with heparin ("full dose") is performed on selected patients in 32/33 stroke units (97%). The selection criteria and thus the frequency of high-dose heparin use varies widely among the different centers. Almost all German stroke units (97%) routinely use low-dose heparin to prevent venous thrombosis and pulmonary embolism.The heparin agents and dosage, however, vary. These data correspond to those from the USA and Canada,where daily routine also departs from evidence-based treatment recommendations. That may be due to individual pathophysiological and aetiological considerations and of course the low acceptance of treatment recommendations based on classic, randomised trials. This underlines the need for new concepts (e.g.observational trials, continuous registers, etc.) addressing the adaptation of study-related conditions to the much more complex situation of daily routine (with risk/benefit, safety, and economic variables).     

Intravenous thrombolysis in Sneddon's syndrome

Sneddon's syndrome (SS) is an uncommon disorder, characterized by the association of ischemic stroke and widespread livedo reticularis. The treatment options for SS to prevent stroke recurrence and future disability include antiplatelet therapy, anticoagulation, or immunosuppression. We describe a patient with SS who presented with an acute ischemic stroke, and was treated with intravenous recombinant tissue-plasminogen activator with significant neurologic improvement. To our knowledge this is the first report of the use of thrombolysis in SS patients with acute ischemic stroke. It suggests that thrombolytic therapy might be safe and effective in these patients.     

Prosthetic valve endocarditis 1976-1987. Antibiotics, anticoagulation, and stroke

We retrospectively reviewed the clinical characteristics and outcomes of 61 patients with 62 episodes of prosthetic valve endocarditis, paying particular attention to neurologic complications (stroke). Atypical features of the group included a benign outcome of early postoperative infection (18% mortality) and a high stroke morbidity and mortality rate with Staphylococcus epidermidis infections. Eleven patients (18%) suffered an embolic stroke, most less than or equal to 3 days after diagnosis and before the initiation of antimicrobial therapy; the rate of embolic stroke recurrence was low (9%). The risk of embolic stroke was lower with bioprosthetic than with mechanical valves. No protective effect of anticoagulation therapy with warfarin was observed. Six patients (8%) suffered brain hemorrhage due to septic arteritis, brain infarction, or undetermined causes; no specific risk of hemorrhagic stroke was evident with anticoagulation therapy. Antibiotic treatment appears to be more important than anticoagulation to prevent neurologic complications in patients with prosthetic valve endocarditis.     

Anticoagulation Choice and Timing in Stroke Due to Atrial Fibrillation: A Survey of US Stroke Specialists (ACT-SAFe)

ObjectiveRisk of early recurrent ischemic stroke in patients with atrial fibrillation may be high. ASA/AHA guidelines provide imprecise recommendations on the timing and anticoagulant choice for this indication. We assessed current opinions of stroke neurologists.MethodsCase scenarios describing patients with acute ischemic stroke (AIS) due to paroxysmal atrial fibrillation (AF) were presented to US board-certified stroke neurologists in an internet-based questionnaire. Questions assessed timing and choice of anticoagulation for secondary stroke prevention, factors prompting earlier anticoagulation, reasons for specific anticoagulant choice, and alternatives to anticoagulation in ineligible patients. Open-ended comments were also solicited.ResultsResponses were available from 238/1239 stroke neurologists surveyed. In patients with small AIS without hemorrhagic transformation (HT), 51% elected to start anticoagulation within 96 hours. With increased stroke severity and asymptomatic HT, only 29% and 26% respectively chose to anticoagulate within 7 days. Few requested stability imaging before starting anticoagulation. With symptomatic HT the majority (79%) waited >14 days. 93% would anticoagulate earlier if left atrium/left atrial appendage or acute left ventricular thrombi, or mechanical heart valve were present. Direct oral anticoagulants (DOACs) were the preferred anticoagulation strategy (64%), and the remaining 38% preferred Warfarin. Aspirin was preferred by 57% in anticoagulation ineligible.ConclusionApart from AIS with symptomatic HT, there is a remarkable lack of consensus among stroke neurologists regarding the timing of anticoagulation for secondary stroke prevention in patients with AIS due to PAF. DOACs are the preferred anticoagulation strategy. More studies are required to clarify anticoagulant management in this patient population.     

CT and MRI in the diagnosis of acute stroke and their role in thrombolysis

Thrombolysis is an effective but potential deleterious therapy and should therefore be limited to patients with acute intracerebral vessel occlusion and salvageable tissue. MRI currently develops towards the new diagnostic standard for the selection of stroke patients eligible for acute thrombolytic treatment and acute stroke studies. Diffusion- and perfusion-weighed MRI provides diagnostic information not available from the neurological assessments or from CCT and conventional spin-echo MRI. As high-speed DWI and PWI protocols become standardized, a 15-minute integrated stroke protocol of employing echo-planar imaging (EPI) can be outinely performed in the setting of acute clinical stroke. The combination of these MR techniques is suitable to define tissue at risk of infarction that is potentially salvageable brain tissue (an estimate of the ischemic penumbra) and may respond to early recanalization even beyond 3 hours after stroke onset. The extension of the therapeutic window for thrombolytic therapy towards 6 hours in a subpopulation of acute stroke patients might open the way for the successful reperfusion therapy in more stroke patients.     

Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection.

BACKGROUND: Effective therapy was not available for treatment of acute stroke until 1995, when tissue plasminogen activator (tPA) was shown to improve neurological and functional outcome in stroke patients who were treated within 3 hours of symptom onset. SUMMARY OF REVIEW: Currently, many patients do not qualify for tPA therapy because they present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using CT to select patients, have failed. Use of early MR imaging may provide significant advantages over CT for identification of patients who are likely to benefit from thrombolytic therapy because (1) the early perfusion-weighted imaging (PWI) lesion estimates the region of acute dysfunctional brain tissue, whereas the acute diffusion-weighted imaging (DWI) lesion appears to correspond to the core of the early infarction; (2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (an estimate of the ischemic penumbra); and (3) in patients with a PWI/DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion growth. CONCLUSIONS: Clinical trials that use new MRI techniques to screen patients may be able to identify a subset of acute stroke patients who are ideal candidates for thrombolytic therapy even beyond 3 hours after stroke onset.     

Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes

Background

Cancer and ischemic stroke are two of the most common causes of death among the elderly, and associations between them have been reported. However, the main pathomechanisms of stroke in cancer patients are not well known, and can only be established based on accurate knowledge of the characteristics of cancer-related strokes. We review herein recent studies concerning the clinical, laboratory, and radiological features of patients with cancer-related stroke.

Main Contents

This review covers the epidemiology, underlying mechanisms, and acute and preventive treatments for cancer-related stroke. First, the characteristics of stroke (clinical and radiological features) and systemic cancer (type and extent) in patients with cancer-specific stroke are discussed. Second, the role of laboratory tests in the early identification of patients with cancer-specific stroke is discussed. Specifically, serum D-dimer levels (as a marker of a hypercoagulable state) and embolic signals on transcranial Doppler (suggestive of embolic origin) may provide clues regarding changes in the levels of coagulopathy related to cancer and anticoagulation. Finally, strategies for stroke treatment in cancer patients are discussed, emphasizing the importance of preventive strategies (i.e., the use of anticoagulants) over acute revascularization therapy in cancer-related stroke.

Conclusion

Recent studies have revealed that the characteristics of cancer-related stroke are distinct from those of conventional stroke. Our understanding of the characteristics of cancer-related stroke is essential to the correct management of these patients. The studies presented in this review highlight the importance of a personalized approach in treating stroke patients with cancer.     

Treatment of arterial and venous brain ischemia. Experts' recommendations: stroke management in the intensive care unit

With thrombolysis, intravenous alteplase (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose given as a bolus followed by a 60-minute infusion, is recommended within 4.5 hours of onset of ischemic stroke. When indicated, intravenous thrombolysis must be initiated as soon as possible. It is possible to use intravenous alteplase in patients with seizures at stroke onset, if the neurological deficit is related to acute cerebral ischemia. Intravenous alteplase can be discussed for use on a case-by-case basis, according to risk of bleeding, in selected patients under 18 years and over 80 years of age, although for the current European recommendations this would be an off-label use. In hospitals with a stroke unit, intravenous thrombolysis is prescribed by a neurologist (current French labelling) or a physician having the French certification for neurovascular diseases (outside the current French labelling). The patient must be monitored in the stroke unit or in case of multiple organ failure in an intensive and critical care unit. In hospitals without a stroke unit, thrombolysis must be decided by the neurologist from the corresponding stroke unit via telemedicine. It is recommended to perform brain imaging 24 hours after thromboysis. Intra-arterial thrombolysis can be contemplated on a case-by-case basis after multidisciplinary discussion within a 6-hour time window for patients with acute middle cerebral artery or carotid occlusions, and within a larger time window for patients with basilar artery occlusion, because of their very poor spontaneous prognosis. Mechanical thrombectomy can also be contemplated in the same situations. With antiplatelet agents, it is recommended that patients receive aspirin (160 mg-325 mg) within 48 hours of ischemic stroke onset. When thrombolysis is performed or contemplated, it is recommended to delay the initiation of aspirin or other antithrombotic drugs for 24 hours. The use of antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor is not recommended. Urgent anticoagulation using heparin, low-molecular-weight heparins or danaparoid with the goal to treat ischemic stroke patients is not recommended. Secondary prevention by anticoagulation can be used, immediately or within the first days, after minor ischemic stroke or TIA in patients with a high risk for cardioembolism, if uncontrolled hypertension is absent. In patients with large infarcts and a high risk for cardioembolism, the timing for initiating anticoagulation must be decided on a case-by-case basis. In patients with anticoagulation who had an ischemic stroke, the decision to temporarily stop or maintain anticoagulation must be made on a case-by-case basis, depending on thromboembolic risk, level of anticoagulation at stroke onset and estimated risk of hemorrhagic transformation. It is not recommended to use neuroprotective agents in ischemic stroke patients. Patients with cerebral venous thrombosis must be treated with therapeutic doses of heparin, even in case of concomitant intracranial hemorrhage related to cerebral venous thrombosis. If the patient's status worsens despite adequate anticoagulation, thrombolysis may be used in selected cases. The optimal administration route (local or intravenous), thrombolytic agent (urokinase or alteplase) and dose are unknown. There is currently no recommendation with regard to local thrombolytic therapy in patients with dural sinus thrombosis. Urgent blood transfusions are recommended to reduce hemoglobin S to <30% in patients with sickle cell disease and acute ischemic stroke.     

Cerebrovascular disorders

Arterial ischemic stroke is being recognized more commonly in the pediatric population. The etiologies differ greatly from those seen in adults. The most common etiologies are congenital heart disease and sickle cell disease. Children may present with or without hemiparesis and may have fever, headache, and depressed level of consciousness. A high index of suspicion is needed to diagnose stroke. Although clinical studies are scarce in children, besides early diagnosis, early specialized care with careful attention to detail ensuring adequate oxygenation and ventilation, prevention of hyperthermia and seizures, and maintenance of blood pressure and metabolic balance are important and likely improve outcome in these children. Selective children may also benefit from anticoagulant therapy, and, as the interval to diagnosis decreases, thrombolytic therapy may become an option although safety data are required. Children with acute stroke should be rapidly transported to and cared for in a pediatric center with a specialized stroke team or access to acute stroke protocols.     

Anti-stroke prophylaxis--the ethics of collateral damage

Prophylactic anticoagulation therapy with agents such as dabigatran etexilate (as an alternative to warfarin) promises substantial benefits to both patients and monitoring physicians in the treatment of those at high risk of stroke from atrial fibrillation. Such treatment has, however, one potentially lethal consequence. There is, as yet, no easily administered rapid means of reversal in instances of acute surgical emergency. The problems that may then be encountered in neurosurgical practice are discussed.     

Pathomechanism and Management of Stroke in COVID-19: Review of Immunopathogenesis,Coagulopathy, Endothelial Dysfunction,and Downregulation of ACE2

Coronavirus disease 2019 (COVID-19) can reportedly manifest as an acute stroke, with most cases presenting as large vessel ischemic stroke in patients with or without comorbidities. The exact pathomechanism of stroke in COVID-19 remains ambiguous. The findings of previous studies indicate that the most likely underlying mechanisms are cerebrovascular pathological conditions following viral infection, inflammation-induced endothelial dysfunction, and hypercoagulability. Acute endothelial damage due to inflammation triggers a coagulation cascade, thrombosis propagation, and destabilization of atherosclerosis plaques, leading to large-vessel occlusion and plaque ulceration with concomitant thromboemboli, and manifests as ischemic stroke. Another possible mechanism is the downregulation of angiotensin-converting enzyme 2 as the target action of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Acute stroke management protocols need to be modified during the COVID-19 pandemic in order to adequately manage stroke patients with COVID-19.     

Can stroke physicians and neuroradiologists identify signs of early cerebral infarction on CT?

Doctors managing acute stroke are expected to recognise signs of early infarction on CT before choosing thrombolytic treatment, according to recent trials and guidelines. The ability of 13 physicians and two neuroradiologists to recognise early infarct signs and decide whether patients should be randomised in a hypothetical stroke treatment trial was tested. Only 65% of the CT scans from 14 stroke patients were correctly identified as normal or abnormal (95% CI 60-69%). Neither observer experience nor knowledge of symptoms significantly improved recognition of abnormality, although experience did significantly improve the observers' ability to reproduce their results. Parenchymal hypodensity was the least well recognised sign. Only 45% (95% CI 40%-50%) of patients were identified correctly for the hypothetical acute stroke treatment trial. Early infarction on CT is not well recognised even by experienced doctors. Part of the problem may be in understanding the definitions of the extent of infarction. These difficulties should be considered in the design of acute stroke treatment trials and in the introduction of any new acute stroke treatments.     

Anticoagulation in cerebral ischemia

Anticoagulation clearly benefits patients at risk of stroke from cerebral embolism. Conversely, patients with completed ischemic stroke are not benefited, and may show a higher mortality and morbidity because of hemorrhagic complications. Technical advances in the early, accurate diagnosis of cerebral hemorrhage, the constant infusion of heparin, and closer monitoring of anticoagulation have continued to reduce the risk of hemorrhage in treated patients. In patients with TIA, alternative therapy with anti-platelet agents, which appears to prevent stroke at less bleeding risk, is under study. Current results show no differences between the two therapies, but only historical controls are available for evaluation of benefit. Whether or not anticoagulation prevents progression of neurologic deficit in patients with strokes-in-evolution remains an unanswered question, which can be resolved only by prospective, randomized, controlled trials.     

Atrial fibrillation as a relevant risk factor for stroke

Atrial fibrillation, one of the most frequent heart rhythm disturbances and the most common source of embolic material in cerebral circulation, is associated with a fivefold increased risk of ischemic stroke. Except thromboembolic complications, atrial fibrillation affects hemodynamic activity of the heart, reduces cardiac output and might decrease cerebral blood flow. It is possible that atrial fibrillation disturbs autoregulation mechanisms of cerebral circulation in patients suffering from an acute stroke. This could be the reason of higher early mortality and more severe clinical outcome versus strokes in patients with the sinus rhythm. An ongoing increase of population with atrial fibrillation is observed. Such patients often need intensive antithrombotic prevention with oral anticoagulants. Worldwide prescribing effective anticoagulant therapy is insufficient in relation to the needs. The leading reason underlying the under-utilization of oral anticoagulation in patients with atrial fibrillation is the lack of knowledge about importance of this kind of stroke prevention and fear of bleeding among doctors, particularly among general practitioners.     

Acute care in stroke: the importance of early intervention to achieve better brain protection

It is known that 'time is brain', and only early therapies in acute stroke have been effective, like thrombolysis within the first 3 h, and useful neuroprotective drugs are searched for that probably would be effective only with their very early administration. General care (respiratory and cardiac care, fluid and metabolic management, especially blood glucose and blood pressure control, early treatment of hyperthermia, and prevention and treatment of neurological and systemic complications) in acute stroke patients is essential and must already start in the prehospital setting and continue at the patient's arrival to hospital in the emergency room and in the stroke unit. A review of published studies analyzing the influence of general care on stroke outcome and the personal experience from observational studies was performed. Glucose levels >8 mmol/l have been found to be predictive of a poor prognosis after correcting for age, stroke severity, and stroke subtype. Although a clinical trial of glucose-insulin-potassium infusions is ongoing, increased plasma glucose levels should be treated. Moreover, insulin therapy in critically ill patients, including stroke patients, is safe and determines lower mortality and complication rates. Both high and low blood pressure levels have been related to a poor prognosis in acute stroke, although the target levels have not been defined yet in clinical trials. The body temperature has been shown to have a negative effect on stroke outcome, and its control and early treatment of hyperthermia are important. Hypoxemia also worsens the stroke prognosis, and oxygen therapy in case of <92% O(2) saturation is recommended. Besides, blood pressure stabilization avoiding falls of the diastolic pressure and the lowering of glycemia and temperature have been related to a better prognosis in stroke units patients, and homeostasis maintenance is associated with a better outcome. General care has become an emergent and first-line brain-protectant treatment that must be started at the prehospital level from the very beginning. This could help to save more brain tissue to get the best conditions for further specific stroke therapies such as the use of neuroprotective or thrombolytic drugs in the hospital.