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Therapeutic options available for acute stroke management are sparse and inadequate. Therefore, new insights into stroke pathophysiology leading to new therapeutic targets are needed. In order to attain these goals, adequate animal models for cerebral ischemia are needed. In the following paper the authors will review the various animal models for stroke and emphasize their potential strengths and weaknesses.

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.

The publication of the positive results of the National Institute of Neurological Disorders and Stroke (NINDS) trial of alteplase (a recombinant tissue plasminogen activator; rt-PA) for acute stroke patients in 1995 and its approval by the US Food and Drug Administration as well as the American Academy of Neurology and American Heart Association increased the interest and attention of the medical community in acute stroke treatment. However, the implication of this NINDS Stroke Study and other thrombolytic trials in clinical practice remains controversial and debated. Furthermore, the recent publication of the results from the European Cooperative Acute Stroke Study II (ECASS II) and Alteplase Thrombolysis of Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) studies will feed the controversy, since the results of these two studies are disappointing and do not confirm the positive results of the NINDS Stroke Study as expected by clinicians managing patients with acute stroke. The Standard Treatment with Alteplase to Reverse Stroke (STARS) and Cleveland studies, which involved a large number of community hospitals to assess the safety profile and the benefit of rt-PA thrombolysis for acute stroke patients in clinical practice, have shown controversial results. Consequently, the issue arises of which is the more reasonable position concerning thrombolysis by alteplase, which seems to work but has not been proven yet beyond reasonable doubt? The recent publication of the results from the Prolyse in Acute Cerebral Thromboembolism (PROACT II) study has shown that intra-arterial thrombolysis with prourokinase is a benefit treatment in stroke patients with a proven middle cerebral artery occlusion within 6 h of stroke onset. Numerous trials devoted to neuroprotection against acute ischemic 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 in ongoing studies. The third issue under study concerns the use of antithrombotic drugs in the acute phase of stroke, particularly the new potent platelet glycoprotein IIb/IIIa antagonists such as abciximab. In this paper, we have reviewed selected recent clinical trials focusing on recent advances in acute stroke therapy.

Factor analysis of dynamic studies (FADS) is a technique that allows structures with different temporal characteristics to be extracted from dynamic contrast enhanced studies without making any a priori assumptions about physiology. These dynamic structures may correspond to different tissue types or different organs or they may simply be a useful way of characterising the data. This paper describes a method of automatically extracting factor images and curves from contrast enhanced MRI studies of the brain. This method has been applied to 107 studies carried out on patients with acute stroke. The results show that FADS is able to extract factor curves correlated to arterial and venous signal intensity curves and that the corresponding factor images allow a distinction to be made between areas of the brain with normal and abnormal perfusion. The method is robust and can be applied routinely to dynamic studies of the brain. The constraints described are sufficiently general to be applicable to other dynamic MRI contrast enhanced studies where an increase in contrast concentration produces an increase in signal intensity.

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.

This paper looks at improving care and trolley waiting times for acute stroke patients in Accident and Emergency departments.

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.

Tc-99m HMPAO SPECT is more likely to detect a stroke in early stages than CT. However, a conventional HMPAO SPECT study takes at least 30 minutes to complete. This paper compares fast Tc-99m HMPAO SPECT scans and conventional Tc-99m HMPAO SPECT scans with respect to spatial resolution and diagnostic efficacy in vitro and in a small series of patients, respectively. The spatial resolution of fast Tc-99m HMPAO SPECT did not match that of images obtained from conventional SPECT, though the difference proved to be of no clinical significance. Since fast SPECT requires only one-fourth to one-fifth the time necessary for conventional SPECT, it may be more suitable for investigating cases of acute stroke in critical clinical situations.

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 …

This volume represents a complication of papers presented at the International Symposium on Ischemic Cerebrovascular Pathology held by the Societat Catalana de Neurologia in Tarragona, Spain, in 1989. The volume opens, with the only chapter written in English, on selected aspects of human and experimental stroke. Subsequent chapters contain a number of relevant topics related to diagnostic, pathologic, and therapeutic aspects of ischemic cerebrovascular disease. There are interesting contributions on the local and regional strategies regarding care services for patients with acute stroke. Another chapter summarizes a discussion on vascular dementias and brain-heart interactions. The book is well written, easy to read, and most sections are clearly organized and referenced. Although much of the information presented is well known, the chapters serve as useful review. Overall, controversial points are presented in a well-balanced manner. Like many published reports of conference proceedings, this volume suffers from an uneven quality of the

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 …

Approximately 75% of strokes occur to people aged 65 years and over. In this paper data are presented based on the results of a study of stroke disease carried out among people of this age-group in a geographically defined population. In particular, the results are used to provide an estimate of the relative contributions made by home- and hospital-care in the management of such disease in this community.

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.

Hypervolemic hemodilution is being evaluated for use in the treatment of acute ischemic cerebral infarction in a multicenter randomized, controlled study using pentastarch. Pentastarch is a 10% solution of hydroxyethyl starch in normal saline, with an average molecular weight of 264000, an intrinsic colloid oncotic pressure of 55 mm Hg, and a molar substitution of 0.45 (45 hydroxyethyl bonds for each 100 glucose molecules). It brings about a plasma expansion effect of 1.5 times the administered volume on average, with a duration of effect of about 12 h. We compared the acute changes in hemispheric cerebral blood flow associated with pentastarch treatment with the changes observed with standard medical therapy. Other researchers have documented increases in CBF with hemodilution [1–4, 6, 7]. The contribution of this paper is the comparison of two groups selected and managed by the same protocol, except for hypervolemic hemodilution with pentastarch.

Stroke is one of the major contributors towards morbidity and mortality, together with myocardial infarction and Cancer. Clinical data can give prognostic Information, not during the acute phase of the allness, but after weeks of Observation. As published earlier, the SEP can give prognostic information about recovery, even in the acute stage of the disease (1–5). In this paper the correlation between the N20 from the SEP from median nerve Stimulation and the recovery from acute stroke will be described.

Very little time is available for arm and hand training while patients are in hospital after stroke. Therapeutic strategies that use intensive practice in the early days and weeks after stroke may improve the recovery of upper limb function. This paper considers the physiology of the brain in acute stroke and evaluates the evidence for and against early intensive activity of the upper limb as an essential precursor to any decision to invest in increased activity.