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Summary The identification of vulnerable and unstable carotid atherosclerotic lesions is up-to-date an important topic of research, in order to adopt the adequate strategy for preventing cerebrovascular events. Plaque inflammation, presence of adventitial vasa vasorum, intimal angiogenesis and plaque neovascularization have been identified in histological studies as indicators of the instability of the atheroma of carotid arteries in cerebrovascular patients and of coronary arteries in cardiovascular patents. Consequently, the identification “in vivo” of these pathophysiological aspects has been objective for the development of new imaging techniques. Ultrasound of carotid arteries, with ultrasound contrast agents, is not only able to provide an enhanced visualization of the arterial lumen and plaque morphology, but also allows to directly visualize adventitial vasa-vasorum and carotid plaque neovascularization. This technique and its clinical implications in the unstable plaque identification are discussed in the present paper.

A variety of imaging modalities exist for the diagnosis of stroke. Several studies have been carried out to ascertain their contribution to the management of acute stroke and to compare the benefits and limitations of each modality. Diffusion-weighted imaging (DWI) has been described as the optimal imaging technique for diagnosing acute ischemic stroke, yet limited evidence is available on the value of DWI in the management of ischemic stroke with low-field magnetic resonance (MR) systems. Although high-field MR imaging (MRI) is desirable for DWI, low-field scanners provide an acceptable clinical compromise which is of importance to developing countries posed with the challenge of limited availability of high-field units. The purpose of this paper was to systematically review the literature on the usefulness of DWI in acute stroke management with low-field MRI scanners and present the experience in Nigeria.

Evaluation of: Akhondi A, Gevorgyan R, Tseng CH et al.: The Association of patent foramen ovale morphology and stroke size in patients with paradoxical embolism. Circ. Cardiovasc. Interv. 3, 506–510 (2010). This paper evaluated the relationship between the morphological characteristics of the patent foramen ovale using echocardiography compared with cerebral infarct volume identified on MRI.

Oxidative stress has been involved in the pathogenesis of several neurological diseases including acute stroke. The paper describes the main features of the oxygen and nitrogen reactive species, their role in damage caused by stroke, and briefly indicates the effects of antioxidants given in acute brain lesions.

Part 2: Industry Track; International audience; Acute stroke is the leading cause of disabilities and the fourth cause of death worldwide. The treatment of stroke patients often requires fast collaboration between medical experts and fast analysis and sharing of large amounts of medical data, especially image data. In this situation, cloud technologies provide a potentially cost-effective way to optimize management of stroke patients and, consequently, improve patient outcome. This paper presents a cloud-based platform for Medical Distributed Utilization of Services & Applications (MEDUSA). This platform aims at improving current acute care settings by allowing fast medical data exchange, advanced processing of medical image data, automated decision support, and remote collaboration between physicians in a secure and responsive virtual space. We describe a prototype implemented in the MEDUSA platform for supporting the treatment of acute stroke patients. As the initial evaluation illustrates, this prototype improves several aspects of current stroke care and has the potential to play an important role in the care management of acute stroke patients.

This paper presents some findings from a randomised controlled trial in patients with upper-limb weakness in acute stroke services within the UK's National Health Service. Three patients were selected from the robot arm of the trial; one who exhibited a large increase in Fugl-Meyer score (change > 30); one who exhibited a moderate change (10 < change < 20) and a subject who demonstrated no change between baseline and follow-up. The results from robot assistance level and target achievement over the course of the treatment are presented for the three patients, demonstrating the system's ability to automatically alter the assistance level as patients progress.

Objective: To observe the impact on stroke code time metrics after applying a “pit stop” model of bedside nursing for telestroke encounters. Background: Despite the recent push for target treatment times in acute stroke codes, no guidelines exist for optimizing practices specific to stroke care via telemedicine. Effective telestroke is dependent on efficient data gathering by remote staff, and lengthy metrics for real-world telestroke often preclude timely tPA treatment. By co-opting “pit stops” as inspiration, an optimized nursing workflow for telestroke can be created on the following principles: Identification of Shared Goals; Organized Urgency with the Removal of Gatekeepers; Multi-personnel, Non-Sequential Processes; Focus on Defined Staged Roles; and Empowered Engagement/Responsibility. Methods: The QCI-NASCAR protocol was implemented in Oct 2013, and data was collected prospectively on consecutive stroke code activations through Apr 2014 at St. Paul University Hospital (Dallas, TX), a telestroke spoke site. The nurse-driven protocol was reinforced by a paper checklist (i.e. “Driver Sheet”), which doubled as a data collection form. Timestamps were recorded in real time for: door time, MD at bedside, CT arrival, needle time, and/or code cancellation. The primary outcome was Door-to-CT (D2CT) times to reflect the portion of the stroke code most impacted by the nursing protocol. Results: Mean D2CT times were: all cases (n=152, 33.2 min), intervention-eligible cases (n=71, 27.0 min), and thrombolytic-eligible cases (n=57, 22.2 min). A trend for lower D2CT times and standard deviations was noted in comparing the first half of the data (n=76, 38.04 ± 58.1 min) to the second (n=77, 27.8 ± 19.1 min; p Conclusion: QCI-NASCAR demonstrates the feasibility of implementing a nursing-driven protocol for telestroke encounters. A larger, multi-institutional trial will demonstrate if such a protocol can significantly and reproducibly lower stroke code metrics to national guideline parameters.

Objective To conduct a systematic review of studies reporting on the validity of International Classification of Diseases (ICD) codes for identifying stroke in administrative data. Methods MEDLINE and EMBASE were searched (inception to February 2015) for studies: (a) Using administrative data to identify stroke; or (b) Evaluating the validity of stroke codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), or Kappa scores) for stroke, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2015) of original papers. Studies solely evaluating codes for transient ischaemic attack were excluded. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Results Seventy-seven studies published from 1976–2015 were included. The sensitivity of ICD-9 430-438/ICD-10 I60-I69 for any cerebrovascular disease was ≥ 82% in most [≥ 50%] studies, and specificity and NPV were both ≥ 95%. The PPV of these codes for any cerebrovascular disease was ≥ 81% in most studies, while the PPV specifically for acute stroke was ≤ 68%. In at least 50% of studies, PPVs were ≥ 93% for subarachnoid haemorrhage (ICD-9 430/ICD-10 I60), 89% for intracerebral haemorrhage (ICD-9 431/ICD-10 I61), and 82% for ischaemic stroke (ICD-9 434/ICD-10 I63 or ICD-9 434&436). For in-hospital deaths, sensitivity was 55%. For cerebrovascular disease or acute stroke as a cause-of-death on death certificates, sensitivity was ≤ 71% in most studies while PPV was ≥ 87%. Conclusions While most cases of prevalent cerebrovascular disease can be detected using 430-438/I60-I69 collectively, acute stroke must be defined using more specific codes. Most in-hospital deaths and death certificates with stroke as a cause-of-death correspond to true stroke deaths. Linking vital statistics and hospitalization data may improve the ascertainment of fatal stroke.

A paper that changed my practice: which tugboat turned the Queen Mary? My immediate thoughts revolve around such issues as the nature of my practice and any really dramatic changes that have occurred over the nearly 20 years since I became a neurologist. If they have occurred, were they in clinical assessment and diagnostic approaches, general management or treatment? Mmm. To lay my cards on the table: I am an academic neurologist who sees patients every day as inpatients or outpatients, mainly those with an acute stroke, but also patients with general neurological problems. Upon reflection, there is not much doubt that the most dramatic change in my practice pertains to the former group, those who have had an acute stroke. When I first became interested in this aspect of neurology, what mainly appealed was the myriad of clinical presentations and subtypes of stroke and the clinical challenge of determining

Multiscale entropy (MSE) analysis method has been widely used to evaluate the physiologic control mechanisms. However, MSE is vulnerable to trends. Ensemble empirical mode decomposition (EEMD) is a powerful tool to remove the trend from non-stationary physiological signals before MSE analysis. In this paper, trend-extracted MSE (T-MSE) based on adaptive aligned EEMD (AA-EEMD) with early termination scheme is proposed. AA-EEMD not only reduces the computing time, but also considers the frequency meaning of different physiological signals and different subjects. We have applied T-MSE based on AA-EEMD to analyze the acute stroke patients' physiological signals in intensive care unit (ICU). We find that the complexity of electrocardiogram (EKG) is higher in the acute stroke patients with good functional outcome than those with bad functional outcome. For EKG parameter, the p-value is approximately 10−8, which shows significant statistical difference. Moreover, the average number of IMFs in a single member of ensemble is reduced to 74% of the original. The average computing time in a single member of ensemble is reduced to 76%. Also, the average computing time of combining EEMD and MSE is reduced to 72%.

Large hemispheric infarctions have malignant course and constitute a major cause of severe morbidity and mortality after stroke. The medical management is usually not effective in these cases. Decompressive craniectomy is a salvage therapy for medically refractory ICP. This paper discusses the merits and demerits of decompressive craniectomy for large hemispheric infarctions. Hemicraniectomy is a life-saving but non-restorative surgery. Surgery should be done before clinical signs of brain herniation to obtain maximum benefit. The relatives of the patient should be explained clearly about possibility of survival with disability before offering the surgery.

Purpose:This paper presents the initial experience with thrombolysis for acute ischaemic stroke at Hospital de Base do Distrito Federal (HBDF), Brazil, and the difficulties associated with the implementation of this treatment.Method:A retrospective study was performed using the medical records of all patients with acute stroke who were treated with intravenous alteplase in our department, between May 2011 and April 2012.Results:The thrombolytic therapy was administered to 32 patients. The mean time between the ictus and the start of stroke therapy start was 195 (60-270) minutes. Sixteen patients demonstrated a significant clinical improvement (decrease in National Institute Health Stroke Scale [NIHSS] score≥4 points in 24 hours); 6 patients were discharged with an NIHSS score of 0 and 2 demonstrated haemorrhagic transformation.Conclusions:The results of our study are similar to those reported in the literature, although we have been dealing with difficulties, such as the lack of a stroke unit.

The publication of the positive results of the National Institutes of Neurological Disease and Stroke (NINDS)1 trial of alteplase (a recombinant tissue plasminogen activator) for patients with acute stroke in 1995 and its approval by the US Food and Drug Administration as well as by the American Academy of Neurology and American Heart Association2 3 increased the interest and attention of the medical community for acute stroke treatment. However, the implication of this NINDS Stroke Study and other thrombolytic trials in clinical practice remains extremely controversial and debated. Furthermore, the recent publication of the results from the European Cooperative Acute Stroke Study II (ECASS II)4will feed the controversy as ECASS II4 results are disappointing and do not confirm the positive results of the NINDS Stroke Study.1 Consequently, what is the more reasonable position concerning thrombolysis by alteplase, and what seems to work has not been established yet beyond reasonable doubt. Numerous trials devoted to neuroprotection against acute ischaemic stroke have been prematurely stopped because of safety concerns or poor risk:benefit ratios, but some new neuroprotective drugs seem promising and are being tested. The third area of research in progress is the use of antithrombotic drugs in the acute phase of stroke. In this paper, we review selected recent clinical trials focusing on recent advances in acute stroke therapy. The recent publication of the neutral results of the European Cooperative Acute Stroke Study II (ECASS II)4 in October 1998, did not confirm the positive results of the NINDS Stroke Study1 and constitutes a great problem for people who wanted to obtain a rapid licensing of alteplase in Europe as well as the recognition that alteplase was a treatment for acute ischaemic stroke. ECASS II4 was designed to test whether intravenous alteplase (rtPA), …

Those of us in the stroke field have a big job ahead of us. When I started attending this meeting 20 years ago, most of the papers related to acute stroke therapy were laboratory related. Now, of course, we are in the era of clinical trials. But in designing clinical trials, we cannot forget the lessons that need to be learned from laboratory research. And it’s the job of the stroke neurologist to marry these 2 together, and that’s the main focus of what I’d like to talk about in the next few minutes. I’d like to make 4 key points. First, that stroke therapy is difficult. It’s a complex disease, and nobody said it would be easy. There are not going to be any magic bullets for stroke patients. Second, the most critical but ignored lesson from the laboratory is the importance of time. Third, it’s critical to change the role of neurologists in taking care of stroke patients, particularly because of the importance of time. Finally, I’d like to make a few comments about the direction of future stroke research. The bad news for acute stroke therapy is that as far as translating what we’ve done in the laboratory to clinical reality, stroke has been and always will be difficult to treat. We should expect small advances and many failures, and for every 1 positive clinical trial, we will probably have many negative ones; that’s just the nature of stroke disease. But substantial attenuation of damage is possible. I will try to show how the hopes of the laboratory have often been dashed by the reality of translation to human stroke by using an autobiographical approach. The basic principle that acute stroke is a treatable disease was demonstrated to me when I was a fellow at Massachusetts General …

Acute ischemic stroke imaging is one of the leading causes of death and disability worldwide. Neuroimaging plays a crucial role in early diagnosis and yields essential information regarding tissue integrity, a factor that remains a key therapeutic determinant. Given the widespread public health implications of stroke and central role of neuroimaging in overall management, acute stroke imaging remains a heavily debated, extensively researched, and rapidly evolving subject. There has been recent debate in the scientific community due to divided opinions on the use of CT perfusion and access-related limitations of MRI. In this paper we review and summarize recent updates relevant to acute stroke imaging and propose an imaging paradigm based on the recently available evidence.

Glucose derangement is commonly observed among adults admitted to hospital with acute stroke. This paper presents the findings from a descriptive cohort study that investigated the glucose monitoring practices of nurses caring for adults admitted to hospital with stroke or transient ischaemic attack. We found that a history of diabetes mellitus was strongly associated with initiation of glucose monitoring and higher frequency of that monitoring. Glucose monitoring was continued for a significantly longer duration of days for adults with a history of diabetes mellitus, when compared to the remainder of the cohort. As glucose monitoring was not routine practice for adults with no history of diabetes mellitus, the detection and treatment of hyperglycaemia and hypoglycaemia events could be delayed. There was a significant positive association between the admission hospital that is most likely to offer stroke unit care and the opportunity for glucose monitoring. We concluded that adults with acute stroke, irrespective of their diabetes mellitus status prior to admission to hospital, are vulnerable to both hyperglycaemic and hypoglycaemic events. This study suggests that the full potential of nurses in the monitoring of glucose among hospitalised adults with stroke has yet to be realised.

Persistent controversy exists as to whether there are worthwhile beneficial effects of early, rapid lowering of elevated blood pressure (BP) in acute stroke. Elevated BP or ‘hypertension’ (i.e. systolic >140 mmHg) is common in stroke, especially in patients with pre-existing hypertension and large strokes, due to variable ‘autonomic stress’ and raised intracranial pressure. While positive associations between BP levels and poor outcomes are evident across a range of studies, very low BP levels and large reductions in BP have also been shown to predict death and dependence, more so for ischaemic stroke (IS) than intracerebral haemorrhage (ICH). Accumulating evidence indicates that early BP lowering can reduce haematoma expansion in ICH, but there is uncertainty over whether this translates into improved clinical outcomes, particularly since such an effect was not evident from haemostatic therapy in clinical trials. Guidelines generally recommend control of high systolic BP (>180 mmHg), but recent evidence indicates that even more modest elevation (>140 mmHg) increases risks of cerebral oedema and haemorrhagic transformation following thrombolysis in IS. Thus, any potential benefits of rapid BP lowering in acute stroke, particularly in IS, must be balanced against the potential risks of worsening cerebral ischaemia from altered autoregulation/perfusion. This paper explores current knowledge regarding the management of hypertension in acute stroke and introduces ongoing clinical trials aimed at resolving such a critical issue in the care of patients with acute stroke.

Extensive efforts have recently been devoted to developing noninvasive imaging tools capable of delineating brain tissue viability (penumbra) during acute ischemic stroke. These efforts could have profound clinical implications for identifying patients who may benefit from tPA beyond the currently approved therapeutic time window and/or patients undergoing neuroendovascular treatments. To date, the DWI/PWI MRI and perfusion CT have received the most attention for identifying ischemic penumbra. However, their routine use in clinical settings remains limited. Preclinical and clinical PET studies with [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) have consistently revealed a decreased18F-FDG uptake in regions of presumed ischemic core. More importantly, an elevated18F-FDG uptake in the peri-ischemic regions has been reported, potentially reflecting viable tissues. To this end, this paper provides a comprehensive review of the literature on the utilization of14C-2-DG and18F-FDG-PET in experimental as well as human stroke studies. Possible cellular mechanisms and physiological underpinnings attributed to the reported temporal and spatial uptake patterns of18F-FDG are addressed. Given the wide availability of18F-FDG in routine clinical settings,18F-FDG PET may serve as an alternative, non-invasive tool to MRI and CT for the management of acute stroke patients.

Acute stroke is one of the major causes of death and disabilities. Since the 1980s many clinical studies have been conducted to evaluate neuroprotective approaches to treat this important brain vascular event. However, to date the only drug approved (recombinant tissue plasminogen activator [rtPA]) represents a thrombolytic, nonneuroprotective approach. An important neuroprotective strategy is based on erythropoietin (EPO). Exogenously administered EPO exhibits neuroprotective effects in numerous animal models, through the activation of anti-apoptotic, anti-oxidant and anti-inflammatory pathways as well as through the stimulation of angiogenic and neurogenic events. The capability of EPO to cross the blood–brain barrier after systemic administration and its effective therapeutic window are advantages for human acute stroke therapy. However, a multicenter stroke trial where recombinant human EPO (rhEPO) was combined with rtPA had negative outcomes. The present paper reviews the EPO neuroprotective strategy and its mechanisms in ischemic stroke and in other human nervous system diseases.

Julie A Luker1, Julie Bernhardt2,3, Karen A Grimmer-Somers11International Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia; 2School of Physiotherapy, La Trobe University, Melbourne, Victoria, Australia; 3Stroke Division, Florey Neurosciences Institute, Heidelberg Heights, Victoria, AustraliaBackground: We recently indicated that patient age on its own is not a determinant of quality of allied health care received after an acute stroke. It has not been tested whether other non-age variables influence care decisions made by allied health professionals. This paper explores demographic and stroke-related variables that are putatively associated with the quality of care provided to acute stroke patients by allied health professionals.Methods: Data were retrospectively audited from 300 acute stroke patient records regarding allied health care. Compliance with each of 20 indicators of allied health care quality was established. The influence of various demographic and stroke-related variables on each performance indicator was examined. We undertook a series of analyses using univariate logistic regression models to establish the influence of these variables on care quality.Results: Patient age had a significant correlation with only one process indicator (early mobilization). Seven variables, including stroke severity and level of dependence, were associated with patient age. The majority of these age proxies had significant associations with process indicator compliance. Correlations between non-age variables, in particular stroke severity and comorbidity, suggest the potential for complex confounding relationships between non-age variables and quality of allied health care.Conclusion: Compliance with individual indicators of allied health care was significantly associated with variables other than patient age, and included stroke severity, previous independence, comorbidities, day of admission, stroke unit admission, and length of stay. The inter-relationships between these non-age variables suggest that their influence on quality of care is complex.Keywords: predictor variables, stroke severity, allied health care, comorbidity levels

Part I of this discussion of my 65 years since graduating from medical school covered my reasons for being in medicine at all, my explanation for the theatrical terms in the earlier para-scientific document, and finally the effect of World War II on my career.1 Part II will attempt to touch on the privileged life I led in the field of stroke prevention research. In its entirety it is designed as a story or tale about my 50 years in medical practice and does not follow the standard format of a scientific paper. Previously I alluded to the ongoing prejudicial custom of critical attempts to resist new ideas in scientific endeavor. I gave as examples the discordant behavior in Toronto that greeted the discovery of insulin and of less far-reaching consequence my own attempts to convince Canadian and American colleagues that there were 5 distinct causal mechanisms leading to syringomyelia. Surgeons in Cleveland and Boston were adamant that there was but one. Postmortem studies and now routine MR studies prove them wrong. My next contribution of a controversial nature was a description of a group of young patients with stroke whose causes we defined in a study with age and gender-matched controls as being due to emboli associated with mitral valve prolapse and to suggest that this was a clinically overlooked cause of cerebral ischemic events.2 Denials of variable vehemence appeared but the accumulating pathological and surgical data were quite incontrovertible. Ultimately in an Olmstead County prevalence study its occurrence as a cause of stroke was validated.3 Its prevalence is probably less than we suggested in our first report. The difference is probably explained by improvement in the conduct, interpretation and the delineation of newer stroke causes revealed by echocardiography. At times more than one potential cause …

With demographic change, Western populations are becoming older. The prolonged decline in incidence of stroke, already a very costly illness, may soon reverse. This paper briefly review medical treatments of acute stroke that have been popular in the past and finds that they have been generally of little value. The place of naftidrofuryl, a drug with a complex pharmacological profile that includes selective S 2 -receptor blockade, is discussed in greater detail.

Background: The organized stroke alert is critical in quickly evaluating and treating patients with acute stroke. The purpose of this paper was to further understand how this process functions in a moderate sized general hospital by exploring the effects of patient location and time of day on the pace of evaluation and the eventual outcome of evaluation. Methods: Retrospective chart review. Results: The rate of stroke alerts depended on the time of day and patient location. There was a low probability (41%) that the eventual diagnosis was stroke after a stroke alert, but there was no effect of diagnosis on the pace of evaluation. The time between stroke alert and a computed tomography (CT) scan being read was shortest for patients in the emergency room (ER) and longer for patients in the intensive care unit (ICU) or medical/surgical floors. Patients evaluated on medical/surgical floors were less likely to receive tissue plasminogen activator (tPA) than those evaluated in the ER, even though the comorbidities were similar. This may be due to the greater severity of the comorbidities in patients who were already admitted to the hospital. Conclusion: The rate of tPA administration was lower for stroke alerts called from medical/surgical floors than from the ER. Stroke alerts were most frequent in late afternoon.

This paper reports findings related to the transition from hospital to home during the first month after discharge following acute stroke. Qualitative data were obtained from in-depth, semistructured interviews with 51 male stroke survivors and their caregivers. Data were analyzed with the N6 software application, designed to assist with qualitative data analysis. Stroke survivors described experiences related to changes in the temporal order of life, disruptions in sense of self, and strategies used to manage time. Findings indicate that changes in the temporal order of life are related to functional impairments and disruption in the taken-for-granted body. At 1 month post-discharge, survivors are struggling with establishing routines in their day and coping with an increased amount of idle time. In conclusion, strategies for managing increased idle time are "passing time," "waiting on time," and "killing time."

As Bob Dylan has said ‘The times they are a-changin’. Only a decade ago stroke patients in the UK would routinely wait two to three days for their emergency computed tomography (CT) scan following admission. Some thought that this delay was even advantageous as it allowed infarct changes to become well established. For ischaemic strokes, acute treatment was limited to aspirin. Moving forward 10 years, with the introduction of routine intravenous thrombolysis and the advent of interventional neuroradiology, Greater London has undergone a dramatic transformation of acute stroke services. Currently, eight hyper acute stroke units (HASUs) are being established across the capital, providing 116 monitored beds (Fig 1). The aim of this is to offer equitable, around-the-clock access to stroke specialists, investigations, imaging and, if indicated, thrombolysis. Thrombolysis, if given early enough, has been shown to significantly reduce stroke morbidity, with a number needed to treat of 3.1. 1 This has the potential to make serious inroads into a condition that afflicts 110,000 people yearly in the UK. If established infarct changes are seen on a CT brain, stroke physicians now would feel an opportunity had been missed. This paper describes experiences in the North Central London sector, which spans inner city areas to the northern green belt, with University College Hospital (UCLH) as the serving HASU. Transforming stroke services has been taxing at times and some of the key challenges faced and lessons learnt are discussed below.

From October 1994 to June 1997, a multidisciplinary team of scientists and engineers at Lawrence Livermore National Laboratory were funded through LDRD to develop and integrate technologies for diagnosis and treatment of acute stroke. The project was summarized in a Science and Technology Review article `Brain Attack` that appeared in June 1997 and again in the Center for Healthcare Technologies Report (UCRL-LR-124761). This article is the best overview of the project, epidemiology of stroke and technical progress. Most of the technical progress has been documented in conference papers and presentations and refereed journal articles. Additional technical publication can be expected as our remaining patent applications progress through the US Patent and Trademark Office. The purpose of this report is to provide an appropriate introduction and organization to the numerous publications so that interested readers can quickly find information. Because there is no documentation for the history of this project, this report provides a summary. It also provides the final status report for the LDRD funding.

To the Editor: We read with interest the recent paper by Castillo and colleagues evaluating the prognostic relevance of admission blood pressure (BP) values and describing a U-shaped effect in patients with acute ischemic stroke, as well as Boysen’s editorial comment on this issue.1,2 The study’s conclusion was that both high and low admission BP values are associated with poor prognosis regarding early neurological deterioration, infarct volume, and mortality at 3 months. After adjustment for the use of antihypertensive drugs and BP drop >20mm Hg, the authors found that the latter was the most important prognostic factor for poor outcome. Before accepting these important conclusions, we think that some comments are needed. We have also evaluated the prognostic value of admission BP values in an unselected collective of acute stroke patients. Our findings demonstrated that early and late mortality in patients with ischemic stroke as well as in patients with intracerebral hemorrhage followed a U-shaped pattern in relation to systolic and diastolic BP at admission.3 Low admission BP values were associated with heart failure and coronary artery disease, whereas high BP values were associated with history of hypertension and lacunar stroke. Death due to cardiovascular disease was significantly more frequent among patients with admission BP values beneath the U-point of 130 mm Hg, whereas death due to brain edema was significantly more frequent above this U-point.3 We also demonstrated by means of 24-hour BP monitoring that persisting elevated systolic 24-hour BP values during the acute phase of stroke are associated with subsequent brain edema formation in patients not receiving antihypertensive medication during the BP monitoring.4 Investigating the relationship …

SSV model is a useful research tool In their paper (see pp 401),1 Counsell et al compare a “six simple variable” (SSV) model, which they developed for predicting outcome after stroke,2 with two other simple models and with clinical predictions of stroke outcome, and find that their model is at least as good as the other evaluated predictive systems. Predictive models of stroke outcome may be useful in epidemiological studies and clinical trials of stroke to stratify cohorts by baseline severity, and they could also guide patient management. A multitude of predictive models already exists,3 and one might argue that yet another model …

Ensuring the reliability and validity of outcome measures used in clinical trials is essential to the success of the trial. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) is a multicenter clinical trial that is recruiting patients with acute ischemic stroke seen at medical centers across the United States. This paper describes an approach to train physicians to use three clinical measures: the National Institutes of Health (NIH) Stroke Scale, a supplemental motor examination, and the Glasgow Outcome Scale. The program included education, certification, remediation when needed, monitoring, and reliability assessment. The goal was to ensure that interrater assessments were as equivalent to one another as possible. Of the first 95 clinicians who began the certification process, 75 passed during the first evaluation. Eighteen of the other physicians were able to complete the process after remediation. The intraclass correlations of both the NIH Stroke Scale and supplemental motor examination exceeded 0.95. The kappa values for the Glasgow Outcome Scale were 0.61 and 0.62 for the first and second ratings of the videotape, respectively. Our experience suggests that a program that includes educational and certification processes can be performed as part of the design of a multicenter clinical trial. The method of providing educational and testing videotapes to each site so that physicians can be trained and certified is an effective, inexpensive, and practical approach for enhancing and certifying the expertise of the large number of physicians involved in a multicenter study.

Reperfusion and neuroprotection are two present-day therapy strategies for patients with acute stroke. The paper reviews currently available drugs used for neuroprotection in ischemic strokes in the context of evidence-based medicine.

Editor,—Although “passive smoking” may be intuitively harmful, the paper by Bonita and colleagues1on the risk of stroke and environmental tobacco smoke (ETS) exposure suffers from two fundamental defects. The first is the enormously disproportionate effect due to a small exposure, and the second is the lack of allowance for confounding variables, especially diet. Serum cotinine concentrations have recently been determined at the US National Center for Environmental Health using the most sensitive method to date of high resolution gas chromatography with mass spectrometry.2 In 10 000 subjects it was shown that the mean serum cotinine concentration in ETS exposed non-smokers was 0.6 ng/ml compared to 300 ng/ml in active smokers. This represents 1/500th of the dose received by the active smoker. It is difficult to reconcile this degree of exposure with an increased risk of stroke which is one quarter that of the active smoker. A similar disproportionate effect has been claimed for the increased risk of ischaemic heart disease and ETS exposure, but the biological plausibility and mechanisms of effect advanced to support this have been shown to lack credibility.3 4 It is well established that active smokers have other associated risk factors. They are physically less active and have lower intakes of fruit, vegetables, folate, and flavenoids,5 which are all linked to a substantial increased risk for stroke,6-8 and many of these characteristics are shared with non-smokers …

We agree with the comments of Drew Dawson and colleagues. In fact, organized care in an inpatient stroke unit — which includes early mobilization and rehabilitation — is the first key indicator in our paper[1][1] and is effective in improving outcomes after stroke.[1][1],[2][2] We recognize that

Profound changes in the protocols for the management of acute stroke patients irrespective of whether ischaemic or haemorrhagic in origin Although the approval of recombinant tissue plasminogen activator (rtPA) for the treatment of acute ischaemic stroke has been based on the primary imaging technique of conventional cerebral computerised tomography (CT),1 newer and more refined magnetic resonance (MR) techniques are unrelentlessly extending into this particular field of emergency medicine, stimulated by the important hope that these new techniques could help to prolong the therapeutic time window beyond the 3 hour limit in selected patients. Several recent papers have clearly demonstrated that the mismatch concept,2 though leading to diagnostic pitfalls in a small number of cases as well, seems to be helpful in …

To the Editor: We read with interest the work of Missler et al1 and Buttner and colleagues2 and agree with both sets of researchers on the need for reliable, noninvasive markers of neuronal damage following acute stroke. Such markers may allow prognostication of future clinical outcome and may be useful in acute therapy trials as surrogate markers of efficacy. However, neither study cited our publication on serum S-100 protein levels in acute stroke,3 4 a study that examined 81 patients (68 with ischemic stroke and 13 with hemorrhagic stroke) within 48 hours of stroke ictus and compared them with 51 age-, race-, and gender-matched control subjects.3 As with both recent papers in Stroke , we found significantly higher serum S-100 protein levels in the stroke population than in the control group. Furthermore, the highest S-100 protein levels were seen in the hemorrhagic stroke group, and differentiation between the two stroke populations almost reached statistical significance. We also performed a temporal study (24, 48, 72, and 96 hours …

Previous surveys of stroke populations have offered only cursory information on language disturbance, and, conversely, few surveys of aphasic populations have dealth exclusively with stroke or with acute phenomena. This paper describes aphasia in 850 acute stroke patients consecutively registered by the Harlem Regional Stroke Program, of whom 177 (21%) were aphasic; of these, nine were of Broca's type, 24 were of Wernicke's type, 14 were of anomic, ten were conduction, seven were of "isolation" type, and 107 were "mixed." An unexpected finding was a significant over-representation of men among the nonfluent aphasics. During the following four to 12 weeks, 12% of fluent aphasics died, and 12% remained moderately or severely impaired; among survivors, aphasia improved in 74%, and in 44% it cleared completely. During the same period, 32% of nonfluent aphasics died, and 34% remained moderately or severely impaired; among survivors, aphasia improved in 52%, and in only 13% did it clear completely. In both fluent and nonfluent groups, hemiparesis and/or visual field cut were associated with poor prognosis.

In this paper we describe the use of triage to select patients for a trial in which a comparison was made of the effectiveness of a stroke unit and medical units in the rehabilitation of acute stroke. Completing the triage for hospital admission of stroke enabled an estimate to be made of the size of a stroke unit per unit of population.

The present paper reports the third part of an investigation of first-time cerebrovascular strokes occurring in people under the age of 70. The long-term prognosis for 214 patients discharged alive from hospital after the acute phase of the stroke is presented. The clinical and laboratory findings for 114 patients alive at the time of a follow-up examination 32 months after the stroke are discussed. The long-term prognosis could be predicted best by a score, calculated from the neurological findings on admission after the acute stroke. Recurrence of stroke was associated with a very high mortality. Forty-five per cent of the patients who survived the first month had died by the time of follow-up. About 15% were able to return to normal life or go back to work. There was a trend among patients originally severely handicapped to improve their performance ability. Factors influencing the chances for rehabilitation are discussed. Among the survivors there was a strikingly high percentage of patients with overt diabetes or decreased glucose tolerance, of patients with arteriosclerotic heart disease and patients with elevated serum triglyceride levels. These findings are discussed.