Is CT perfusion helpful in the treatment allocation of patients with acute ischemic stroke? An expert-opinion analysis

Background

Intravenous tPA is the standard treatment for acute ischemic stroke within 4.5 hours of symptom onset. Neuroradiological selection is currently based upon non-contrast- brain CT scan (NCCT).

Aims

To verify, in an “expert-opinion setting”, the possible usefulness of CT perfusion (CTP) in decision-making toward i.v. thrombolysis.

Patients and method

One hundred and three consecutive patients with acute ischemic stroke who underwent NCCT and CTP were re-evaluated by an expert in cerebrovascular disease, to verify if adding CTP information would have changed expert’s opinion.

Results

After CTP, a definitive decision was made for 20 more patients, changing the proportion of patients candidate to i.v. tPA from 44% to 51%, and reducing uncertainty from 29% to 10%. CTP results were useful inmilder stroke (p = 0.01).

Conclusions

In a “real world” setting, CT perfusion could be useful for clinical decision, in particular for milder stroke.

     

Stroke Chameleons and Stroke Mimics in the Emergency Department

Purpose of Review

We discuss the frequency of stroke misdiagnosis in the emergency department (ED), identify common diagnostic pitfalls, describe strategies to reduce diagnostic error, and detail ongoing research.

Recent Findings

The National Academy of Medicine has re-defined and highlighted the importance of diagnostic errors for patient safety. Recent rates of stroke under-diagnosis (false-negative cases, “stroke chameleons”) range from 2–26% and 30–43% for stroke over-diagnosis (false-positive cases, “stroke mimics”). Failure to diagnosis stroke can preclude time-sensitive treatments and has been associated with poor outcomes. Strategies have been developed to improve detection of posterior circulation stroke syndromes, but ongoing work is needed to reduce under-diagnosis in other atypical stroke presentations. The published rates of harm associated with stroke over-diagnosis, particularly thrombolysis of stroke mimics, remain low.

Summary

Additional strategies to improve the accuracy of stroke diagnosis should focus on rapid clinical reasoning in the time-sensitive setting of acute ischemic stroke and identifying imperfections in the healthcare system which may contribute to diagnostic error.

     

Management of Spontaneous Intracerebral Hemorrhage

Purpose of Review

We review the current evidence for medical and surgical treatments of spontaneous intracerebral hemorrhage (ICH).

Recent Findings

Therapy with hemostatic agents (e.g. factor VIIa and tranexamic acid) if started early after bleeding onset may reduce hematoma expansion, but their clinical effectiveness has not been shown. Rapid anticoagulation reversal with prothrombin concentrates (PCC) plus vitamin K is the first choice in vitamin K antagonist-related ICH. In ICH related to dabigatran, anticoagulation can be rapidly reversed with idarucizumab. PCC are recommended for ICH related to FXa inhibitors, whereas specific reversal agents are not yet approved. While awaiting ongoing trials studying minimally invasive approaches or hemicraniectomy, the role of surgery in ICH remains to be defined. Therapies targeting downstream molecular cascades in order to prevent secondary neuronal damage are promising, but the complexity and multi-phased nature of ICH pathophysiology is challenging. Finally, in addition to blood pressure control, antithrombotic prevention after ICH has to consider the risk of recurrent bleeding as well as the risk of ischemic events.

Summary

Treatment of acute ICH remains challenging, and many promising interventions for acute ICH await further evidence from trials.

     

Thrombectomy for Acute Ischemic Stroke: Recent Insights and Future Directions

Purpose of Review

Mechanical thrombectomy has become the standard of care for acute ischemic stroke with proximal large vessel occlusions (LVO). This article reviews recent research relating to thrombectomy.

Recent Findings

Thrombectomy for anterior circulation stroke with proximal LVO was first shown to be highly efficacious within 6 h of stroke onset, but “late-window” trials have further demonstrated efficacy until 24-h postonset in select patients with salvageable tissue. However, the concept of “time is brain” remains critical. Thrombectomy trials have further stimulated worldwide efforts to develop systems of care for rapid treatment of eligible patients. Thrombectomy is cost-effective and likely to have long-term efficacy for both disability and mortality outcomes.

Summary

Thrombectomy is a highly efficacious acute stroke therapy. Enduring uncertainties include efficacy in patients with premorbid disability, posterior circulation, or more distal occlusions; use of bridging thrombolysis; and optimal techniques to achieve consistent revascularization and address tandem occlusions or stenoses.

     

Secondary Stroke Prevention in Cryptogenic Stroke and Embolic Stroke of Undetermined Source (ESUS)

Purpose of the Review

The purpose of the study was to review the literature on cryptogenic stroke and embolic stroke of undetermined stroke (ESUS). Cryptogenic stroke according to TOAST criteria is a stroke which is not due to cardiogenic embolism, small vessel disease with lacunes or large vessel disease of brain supplying arteries. In the context of secondary stroke prevention studies, cryptogenic stroke is not operationally defined.

Recent Findings

The new concept of “embolic stroke of undetermined source” (ESUS) provides an operational definition. ESUS is diagnosed as a non-lacunar stroke on cerebral imaging and exclusion of large vessel atherosclerosis by CTA, MRA or ultrasound. Cardiogenic embolism is made less likely by ECG monitoring and echocardiography. At present, aspirin is used for secondary stroke prevention in patients with cryptogenic stroke.

Summary

Based on the construct that ESUS might be caused by undetected atrial fibrillation or other embolic mechanisms, ongoing randomised secondary stroke prevention trials are comparing non-vitamin K oral anticoagulants (NOACs) with aspirin.

     

Closure of Patent Foramen Ovale and Cryptogenic Stroke: Unresolved Issues

Purpose of Review

This review summarises the results of randomised trials comparing closure of patent foramen ovale (PFO) with antithrombotic therapy in patients with cryptogenic stroke.

Recent Findings

Initially, three randomised trials failed to show superiority of PFO closure over antithrombotic therapy in patients with cryptogenic stroke. Three recently performed trials and the prolongation of an earlier trial provided evidence that PFO closure in patients with cryptogenic stroke and an age range of 18–60 years is superior to stroke prevention with antiplatelet therapy. PFO closure was not superior to anticoagulation. Anticoagulation, however, has a higher long-term bleeding risk. PFO closure could result in atrial fibrillation (AF) in a small number of patients. In most patients, AF was transient in duration. Optimal patient selection requires future research.

Summary

In patients with cryptogenic stroke aged <?60 years, PFO closure is superior to antiplatelet therapy in the prevention of recurrent stroke.

     

Serotonin Selective Reuptake Inhibitors (SSRIs) and Stroke

Purpose of Review

The interest in SSRIs after stroke has increased in the past few years, with better knowledge of post-stroke depression and with the demonstrated capacity of some SSRIs to act on the functional recovery of non-depressed subjects.

Recent Findings

Arguments for the action of SSRIs in favour of post-stroke neurological function recovery have improved through new elements: basic science and preclinical data, positive clinical trials and repeated series of stroke patient meta-analysis, and confirmation of favourable safety conditions in post-stroke patients.

Summary

Global coherence is appearing, showing that SSRIs improve stroke recovery in non-depressed patients when given for 3 months after the stroke, with highly favourable safety conditions and a favourable benefit/risk ratio. Large series are still needed.

     

Unresolved Issues in Thrombectomy

Purpose of Review

Trials demonstrating marked benefit of mechanical thrombectomy (MT) for acute stroke caused by large vessel occlusion (LVO) in the anterior circulation have been the most significant advance in acute ischemic stroke in the past 20 years. However, despite this marked advance, there are still many hurdles to improving access to thrombectomy worldwide. Additionally, despite these advances, a substantial portion of patients with LVO still are left disabled.

Recent Findings

The major randomized trials focused on patients within 6 h from symptom onset, with occlusion of the ICA or proximal MCA, small amount of permanently damaged brain, and a moderate to large clinical deficit. We will explore the role of thrombectomy outside of these areas, but also explore larger issues as they pertain to re-organization of stroke systems of care to improve access to this remarkable therapy.

Summary

Now that we have proven, without a shadow of doubt, that rapid revascularization with mechanical thrombectomy improves outcomes in LVO stroke, we must reorganize our systems of care to improve access and assess the role for MT outside of the patients who meet trial criteria.

     

Telemedizinische Voranmeldung in der akuten Schlaganfallversorgung

Objective

The Stroke Angel initiative investigates the implementation of telemedicine for improvement of preclinical communication between emergency medical services (EMS) and stroke units in cases of acute stroke.

Material and methods

Stroke Angel is a technical system for the telemedical prenotification of patients in cases of suspected stroke at a stroke unit by the EMS. Within the framework of an observational study, the team has been investigating the effects of the system on door-to-computed tomography (CT) and door-to-needle times as well as the lysis rate in the neighboring regions of Rhön-Grabfeld and Bad Kissingen since 2005.

Results

The system supports the acute treatment of neurological emergencies and functions as a catalyst for the interlinking of medical institutions in the region as well as for communication between emergency physicians/EMS and hospital physicians. The use of a computer-based data collection enables a continuous improvement process leading to an acceleration of internal clinical procedures and an increase of the lysis rate with the mortality rate staying constant.

Conclusion

Telemedicine is applicable in the preclinical care of acute stroke and, thanks to the computer-based data collection, leads to an increase in process transparency, which helps to improve the internal clinical processes in and around a stroke unit.

     

Asymptomatic Carotid Stenosis: Intervention or Best Medical Therapy?

Purpose of Review

Provide a current overview regarding the optimal strategy for managing patients with asymptomatic carotid artery stenosis.

Recent Findings

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce long-term stroke risk in asymptomatic patients. However, CAS is associated with a higher risk of peri-procedural stroke. Improvements in best medical therapy (BMT) have renewed uncertainty regarding the extent to which results from older randomised controlled trials (RCTs) comparing outcomes following carotid intervention can be generalised to modern medical practise.

Summary

‘Average surgical risk’ patients with an asymptomatic carotid artery stenosis of 60–99% and increased risk of late stroke should be considered for either CEA or CAS. In patients deemed ‘high risk’ for surgery, CAS is indicated. Use of an anti-platelet, anti-hypertensive and statin, with strict glycaemic control, is recommended. Results from ongoing large, multicentre RCTs comparing CEA, CAS and BMT will provide clarity regarding the optimal management of patients with asymptomatic carotid artery stenosis.

     

Sleep Apnea Is a Risk Factor for Stroke and Vascular Dementia

Purpose of Review

In this article, we review the cerebrovascular complications of sleep apnea (SA). SA is the major sleep disorder associated with stroke and vascular dementia.

Recent Findings

Sleep apnea syndrome of moderate to severe intensity affects 17% of 50–70-year-old men and 9% of 50–70-year-old women, making SA a notorious and prevalent disorder. SA increases the risk of hypertension, stroke, myocardial infarction, and atrial fibrillation (AF) and is closely linked to vascular dementia. In addition, SA may worsen the neurologic outcome in acute stroke patients and interferes with rehabilitation after stroke.

Summary

Proper management of SA may decrease the clinical impact of stroke risk factors, improve neurologic outcome after stroke, and lessen the progression of subcortical ischemic vascular disease. In this article, we will cover the most salient pathologies that associate SA and cerebrovascular pathology.

     

Aphasia As a Predictor of Stroke Outcome

Purpose of Review

Aphasia is a common feature of stroke, affecting 21–38% of acute stroke patients and an estimated 1 million stroke survivors. Although stroke, as a syndrome, is the leading cause of disability in the USA, less is known about the independent impact of aphasia on stroke outcomes.

Recent Findings

During the acute stroke period, aphasia has been found to increase length of stay, inpatient complications, overall neurological disability, mortality, and to alter discharge disposition. Outcomes during the sub-acute and chronic stroke periods show that aphasia is associated with lower Functional Independence Measures (FIM) scores, longer stays in rehabilitation settings, poorer function in activities of daily living, and mortality. Factors that complicate the analysis of aphasia on post-stroke outcomes, however, include widely different systems of care across international settings that result in varying admission patterns to acute stroke units, allowable length of stays based on reimbursement, and criteria for rehabilitation placement.

Summary

Aphasia arising from stroke is associated with worse outcomes both in the acute and chronic periods. Future research will have to incorporate disparate patterns in analytic models, and to take into account specific aphasia profiles and evolving methods of post-stroke speech-language therapy.

     

Non-Vitamin K Oral Anticoagulants (NOACs) and Their Reversal

Purpose of Review

An 80-year-old man presents with an acute right hemiparesis and National Institutes of Health Stroke Scale (NIHSS) of 25, 14 h after taking dabigatran. Activated partial thromboplastin time (aPTT) is 42.8 s. Arteriogram demonstrates left internal carotid artery thrombosis. What is the appropriate management of this patient with acute ischemic stroke while on a NOAC?

Recent Findings

Idarucizumab is a reversal agent approved for dabigatran, and two more reversal agents, andexanet alfa and aripazine, are currently in development for NOACs.

Summary

In this article, we review currently available NOACs, their laboratory monitoring, and reversal agents.

     

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis

Background

Chronic pain patients increasingly seek treatment through mindfulness meditation.

Purpose

This study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults.

Method

We conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use.

Results

Thirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life.

Conclusions

While mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

     

Devastating Delayed Leukoencephalopathy Associated with Bath Salt Inhalation

Background

“Bath salts” or synthetic cathinone toxicity remains a potentially deadly clinical condition. We report a delayed leukoencephalopathy with persistent minimally conscious state.

Methods

Case report.

Results

A 36-year-old man presents with delayed encephalopathy, dysautonomia, fulminant hepatic failure, and renal failure from severe rhabdomyolysis after consuming bath salts. MRI showed diffusion restriction in the splenium of the corpus callosum and subcortical white matter.

Conclusions

The combination of acute leukoencephalopathy, rhabdomyolysis and fulminant hepatic failure may point to bath salt inhalation and should be known to neurointensivists.

     

Carotid Artery Stenosis: Medical Therapy,Surgery, and Stenting

Purpose of Review

The purpose of the study was to update the recent information pertaining to carotid artery stenosis risk stratification and treatment.

Recent Findings

Current decision-making related to carotid artery stenosis is based on clinical trials that are outdated. Medical therapy has improved considerably in the past two decades, and this has reduced the stroke rate for both symptomatic and asymptomatic carotid stenoses. In recent community-based studies, the stroke risk with asymptomatic stenosis has been < 1% per year. For asymptomatic carotid stenosis, new trials such as CREST 2 and ECST 2 will determine whether revascularization has any benefit beyond aggressive medical management. For symptomatic patients, carotid endarterectomy is associated with a lower periprocedural stroke rate compared to carotid stenting. Age greater than 70 years is also associated with an increased risk for carotid stenting patients.

Summary

Clinicians should consider a variety of clinical and radiologic variables in reaching treatment decisions for patients with carotid stenosis. Both symptomatic and asymptomatic patients should receive optimal medical therapy.

     

Volume of Plasma Expansion and Functional Outcomes in Stroke

Background

Plasma expansion in acute ischemic stroke has potential to improve cerebral perfusion, but the long-term effects on functional outcome are mixed in prior trials. The goal of this study was to evaluate how the magnitude of plasma expansion affects neurological recovery in acute stroke.

Methods

This was a secondary analysis of data from the Albumin in Acute Stroke Part 2 trial investigating the relationship between the magnitude of overall intravenous volume infusion (crystalloid and colloid) to clinical outcome. The data were inclusive of 841 patients with a mean age of 64 years and a median National Institutes of Health Stroke Scale (NIHSS) of 11. In a multivariable-adjusted logistic regression model, this analysis tested the volume of plasma expansion over the first 48 h of hospitalization as a predictor of favorable outcome, defined as either a modified Rankin Scale score of 0 or 1 or a NIHSS score of 0 or 1 at 90 days. This model included all study patients, irrespective of albumin or isotonic saline treatment.

Results

Patients that received higher volumes of plasma expansion more frequently had large vessel ischemic stroke and higher NIHSS scores. The multivariable-adjusted model revealed that there was decreased odds of a favorable outcome for every 250 ml additional volume plasma expansion over the first 48 h (OR 0.91, 95 % CI, 0.88–0.94).

Conclusions

The present study demonstrates an association between greater volume of plasma expansion and worse neurological recovery.

     

„Mission (im)possible“

Background

Specialized neurological treatment decreases the mortality and morbidity of stroke patients. In many regions of the world an extensive coverage is not available. The cooperation between the Krankenhaus Nordwest (KHNW, Frankfurt, Germany) and the Government of Brunei Darussalam describes the set-up process of a specialized neurological center, including stroke unit, science and rehabilitation center.

Aim

The aim of this project called to teach to treat – to treat to teach was to set up a center of excellence in neurology in Brunei Darussalam over a distance of 12,000?km. Treatment options were elucidated by teaching and taught by case examples.

Material and methods

The construction of the Brunei Neuroscience Stroke and Rehabilitation Center (BNSRC) began in July 2010. To overcome the large distance between the department of neurology and neuroradiology at the KHNW and the BNSRC, a telemedical network was established. We provided daily teleteaching for all professions involved in patient care as well as 24/7 availability of teleneurological services from Germany to support the local team on site.

Results

In the BNSRC unit over 1000 patients with ischemic and hemorrhagic stroke and all the various acute neurological conditions were treated from July 2010 until July 2016 as inpatients and over 5000 were treated as outpatients. Since 2010, a total of 52 patients with stroke were treated by thrombolysis within the thrombolytic window and 81 hemicraniectomies were performed.

Conclusion

The project has shown that it is possible to convey specialized neurological knowledge over large distances to provide significant benefits for patients and caregivers.

     

Albumin-Induced Neuroprotection in Focal Cerebral Ischemia in the ALIAS Trial: Does Severity,Mechanism, and Time of Infusion Matter?

Objective

To determine whether there is any differential benefit of albumin administration within 2 h of onset of ischemia and in settings (severe ischemia with reperfusion in cardioembolic strokes with National Institutes of Health Stroke Scale [NIHSS] ≥15), most representative of experimental models of cerebral ischemia in which albumin was effective in reducing neurological injury.

Background

High-dose intravenous (IV) albumin treatment for acute ischemic stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke patients in contrast to preclinical studies; however, models of preclinical studies were not completely followed.

Methods

A total of 1275 patients combined from ALIAS trials I and II were included in our analysis. We analyzed preclinical studies and selected patients with large ischemic stroke (NIHSS ≥15) related to cardioembolic etiology (n = 189). Outcomes were then studied including time from onset to IV albumin administration.

Results

The odds of excellent outcome (mRS 0–1) at 3 months was not different with high-dose IV albumin infusion (n = 100) compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719–3.708], p value 0.2419). When we further classified these subjects according to time of IV albumin administration, we observed significantly higher odds of excellent outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI 1.040–84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS score, and any therapeutic procedure.

Conclusion

A trend for benefit is noted in ischemic stroke patients with large cardioembolic stroke (NIHSS ≥15) when high-dose albumin was initiated within 2 h, suggesting that certain ischemic stroke subgroups of patients most representative of preclinical settings may benefit from such a treatment. Additional clinical trials maybe needed to stratify subjects and treatment assignments according to NIHSS severity and timely randomization to evaluate this concept further.