J. Rudolf

Early Intravenous Thrombolysis for Acute Ischemic Stroke in a Community-Based Approach

BACKGROUND AND PURPOSEnControlled multicenter studies have demonstrated the efficacy of systemic recombinant tissue-type plasminogen activator (rtPA) treatment in selected cases of acute ischemic stroke. The feasibility of this therapeutic option in clinical practice was assessed in a community-based approach.nnnMETHODSnWe offered rtPA treatment to stroke patients in a prospective open-label monocenter study applying inclusion criteria similar to those of the National Institute of Neurological Disorders, and Stroke study. In order to treat patients within 3 hours of symptom onset, a referral system was used by which eligible patients from all over the city of Cologne, Federal Republic of Germany, were rushed to the Department of Neurology of the University Hospital. We present data on the effectiveness of the referral system and the outcome results of the first 100 consecutive patients treated within an 18-month period.nnnRESULTSnOf 453 consecutive patients with a presumed diagnosis of acute stroke referred to our department between March 1996 and August 1997, 100 patients (22%) were treated with intravenous thrombolysis, 26% of them within 90 minutes of symptom onset. The average time from stroke onset to arrival at our department was 78 minutes, and from arrival to treatment 48 minutes. After 3 months, 53 patients recovered to fully independent function. The rates of total, symptomatic, and fatal intracerebral hemorrhage were 11%, 5%, and 1%, respectively. Overall mortality was 12%.nnnCONCLUSIONSnThrombolysis with rtPA was effectively applied in routine management of stroke patients in a community-based approach with acceptable efforts and without additional costs. Under these circumstances, outcome and complication rates were comparable to those of multicenter trials.

European brain death codes: a comparison of national guidelines.

Abstract The majority of European countries have published recommendations for the diagnosis of brain death as a necessary prerequisite for organ donation. The concept of brain death as defining the death of the individual is accepted in all European countries; however, the guidelines for determining the total and irreversible loss of all brain functions differ somewhat in the various countries. While the clinical examination and documentation of the clinical signs of brain death are very uniform, there are significant differences in the guidelines for using technical confirmatory tests to corroborate the clinical signs. These range from rejecting all technical tests to accepting of multiple neurophysiological tests alone or in combination. The present study examined the similarities and differences in current concepts of brain death in the various European countries and their recommendations for the diagnosis of brain death.The diagnosis of brain death is based on a number of prerequisites, on the clinical diagnosis of deep coma, loss of all brainstem reflexes, and the demonstration of apnea. Neurophysiological tests are recommended by a number of national professional societies as confirmatory tests to confirm the clinical diagnosis of brain death and shorten otherwise necessary waiting periods of 6–12 h. Most brain death codes allow the use of electroencephalography, which must demonstrate electrocortical silence over a certain period. Evoked cerebral potentials can demonstrate the successive loss of activity of various afferent pathways and are accepted in some countries as a confirmatory test. Other neurophysiological tests which demonstrate the loss of cerebral perfusion can be implemented. Brain scintigraphy can confirm the loss of isotope uptake into the brain. Doppler sonography also demonstrates cessation of brain perfusion. Cerebral panangiography may also be used to demonstrate the loss of brain perfusion but is less desirable since it might endanger the patient.

One-year follow-up in acute stroke patients treated with rtPA in clinical routine

BACKGROUND AND PURPOSEnA recent placebo-controlled study provided evidence of a sustained benefit at 1 year from systemic thrombolysis in patients with acute ischemic stroke. The scope of the present study is to determine whether comparable results may be attained in everyday practice if current management guidelines are closely met.nnnMETHODSnBetween March 1996 and July 1998, 150 consecutive patients with acute ischemic stroke were treated with systemic thrombolysis using alteplase, strictly in accordance with American Heart Association (AHA) guidelines. The patients were followed up for 12 months after treatment.nnnRESULTSnBaseline characteristics and complication rates were comparable to those of the National Institute of Neurological Disorders and Stroke (NINDS) study, except for a somewhat younger age (mean 63 years) and lower National Institutes of Health Stroke Scale score (median 11). At 1 year, 41% of our patients showed minimal or no disability (Rankin scale score of 0 or 1), comparable to 41% in the NINDS rtPA group. The overall rate of recurrent stroke was 6.6% and the transient ischemic attack rate 3.3% at 1 year. Six patients (4%) died after the first 3 months, none of them due to recurrent stroke, and 5 had already been severely disabled at 3 months.nnnCONCLUSIONSnThese observations further encourage the routine use of rtPA for the treatment of acute ischemic stroke in strict accordance with the AHA guidelines.

Stroke following internal carotid artery occlusion — a contra-indication for intravenous thrombolysis?

Between March 1996 and December 1997, 15 consecutive patients with carotid artery occlusion diagnosed with duplex sonography were treated with intravenous recombinant tissue plasminogen activator (rt‐PA), following a protocol similar to that of the National Institute of Neurological Disorders and Stroke (NINDS) study. On the basis of ultrasound findings, six of the 15 patients had internal carotid artery dissection (ICD), and the remaining nine had atherothrombotic internal carotid artery (ICA) occlusion. No relevant haemorrhagic complications were observed after rt‐PA treatment of ICA occlusion. Excellent late functional outcome was observed in three of the 15 patients with ICA occlusion, moderate and poor outcome in four patients. Four patients died, and mortality was related to stroke severity upon admission. A good outcome seemed to be more likely in the small group of patients with ICD, than in the patients suffering atherothrombotic ICA occlusion.

Alterations of neuropsychological function and cerebral glucose metabolism after cardiac surgery are not related only to intraoperative microembolic events.

BACKGROUND AND PURPOSEnHigh-intensity transient signals (HITS) during cardiac surgery are capable of causing encephalopathy and cognitive deficits. This study was undertaken to determine whether intraoperative HITS cause alterations of neuropsychological function (NPF) and/or cerebral glucose metabolism (CMRGlc), even in a low-risk patient group, and whether induced changes are interrelated.nnnMETHODSnEighteen patients without signs of cerebrovascular disease underwent elective coronary artery bypass grafting (CABG), and two of these additionally underwent valve replacement in normothermia. Intraoperatively, HITS were recorded by means of transcranial Doppler ultrasonography (TCD). Perioperatively, NPF and CMRGlc were assessed using a standardized complex test battery and positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET), respectively.nnnRESULTSnIntraoperatively, the number of HITS ranged from 90 to 1710 per patient and hemisphere, more on the right side than on the left (P<.05). HITS occurred primarily during cardiopulmonary bypass (71.3%) and, to a lesser extent, during aortic manipulation (22.2%). Changes in global and regional CMRGlc between first (one day preoperatively) and second (8 to 12 days postoperatively) FDG-PET scans were mild. No correlations were found between the number of HITS, age of patient, duration of cardiac ischemia or cardiopulmonary bypass and the changes in CMRGlc. In patients with recorded HITS and a postoperative decrease of regional CMRGlc (n=11), the maximal decrease of rCMR Glc in each hemisphere below the individual global change of CMRGlc correlated with the number of HITS (r= -0.46, P<.05). Limitations in NPF occurred 8 to 12 days postoperatively, resolved within 3 months, and were not found to be correlated to the absolute number of HITS or changes in CMRGlc.nnnCONCLUSIONSnHITS during cardiac surgery can cause alterations of both NPF and CMRGlc, even in a low-risk patient group. However, the number of HITS and changes in NPF and CMRGlc are not necessarily interrelated, which indicates that (1) the location of brain damage related to HITS is more important for the development of NPF than is the absolute number of HITS, and (2) factors in addition to HITS might contribute to surgery-related brain damage.

Hydroxyethyl Starch for Hypervolemic Hemodilution in Patients with Acute Ischemic Stroke: A Randomized, Placebo-Controlled Phase II Safety Study

Background: Hypervolemic hemodilution (HH) with hydroxyethyl starch (HES) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. The objective of this study was to investigate the safety of a 10% solution of HES 130/0.4 versus 0.9% saline solution in acute ischemic stroke by the incidence of adverse events (AEs). Methods: In a controlled, double-blind, randomized, multicenter, phase II, parallel-group study, 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a randomization ratio of 2:1 in favor of HES therapy. Results: There were no significant differences between the groups with regard to the incidence of the specific AEs (cardiovascular events, bleeding complications, allergic reactions) assessed over days 1–30, or mortality over days 1–8. In addition, global tests of efficacy showed a trend towards a better functional outcome with HES therapy; however, the study was not designed to prove efficacy. Conclusions: High-dose HH with HES or NaCl was generally safe and well tolerated. Safety profiles were similar for the two treatment groups, and there was a nonsignificant trend towards a better functional outcome with HES therapy.

Identification by positron emission tomography of neuronal loss in acute vegetative state.

Positron emission tomography with the benzodiazepine receptor ligand carbon-11-labelled flumazenil Identified the extent of neuronal damage in acute vegetative state and predicted the possibility of recovery of consciousness and function.

Evidence of Anaphylaxy After Alteplase Infusion

BACKGROUND AND PURPOSEnAlthough alteplase, a recombinant tissue plasminogen activator (tPA), is structurally identical to endogenous tPA and therefore should not induce allergy, single cases of acute hypersensitivity reactions have been reported. Until now, specific antibodies against alteplase were not detected in blood samples obtained in these patients.nnnCASE DESCRIPTIONnWe report an anaphylactic reaction in a 70-year-old white female who was treated with intravenous alteplase for thrombolysis of acute ischemic stroke 160 minutes after onset of a right-sided hemiparesis. Thirty minutes after infusion of alteplase had been started, the patient suffered acute severe sinus tachycardia and hypotension, followed by cyanosis and loss of consciousness. The alteplase infusion was stopped, and following antiallergic therapy, tachycardia and hypotension resolved within 1 hour. The hemiparesis remained unaltered, but additional harm resulting from the hemodynamic complication was not observed. Serum samples analyzed with a radioimmunoprecipitation assay were negative for total antibodies to alteplase, but in a subsequent ELISA, both samples were positive for IgE antibodies to alteplase.nnnCONCLUSIONSnThe detection of specific IgE antibodies reactive with alteplase in this patient could provide the first evidence of an anaphylactic-type reaction to alteplase in man. Because previous exposure to alteplase can be excluded, the results suggest that this patient had preexisting antibodies that were cross-reactive with one or more epitopes of alteplase and therefore precipitated the anaphylactic-type reaction.

Training as a Prerequisite for Reliable Use of NIH Stroke Scale

To the Editor: nnBefore new therapies for ischemic stroke are established, their safety and effectiveness must be proved. In particular, the numerous multicenter acute stroke trials currently being performed require a valid, efficient, and reliable measure of patient status and outcome after treatment. Interrater variation in the assessment of neurological deficits could imply that important effects of the treatment remain concealed, which in turn may have a misleading influence on therapeutic decisions. A commonly used yardstick for measuring the outcome of neurological deficits in stroke patients is the National Institutes of Health Stroke Scale (NIHSS).1 2 3 Not only experienced neurologists can reliably apply the NIHSS; it can be used as well by nonneurologists or even nonphysicians (eg, study nurses),4 5 6 7 provided the raters are well trained and given detailed instructions. As far as the NINDS study is concerned, the investigators were video trained and required to take an examination.1 nnThe question, however, of whether the NIHSS provides precise and reliable data when applied without an intensive training program has not yet been raised. We therefore investigated the reliability of the NIHSS as used by trained and untrained raters in 22 stroke patients in the Neurological Department at …

Incidence of Space-Occupying Brain Edema following Systemic Thrombolysis of Acute Supratentorial Ischemia

Whether ‘malignant’ brain edema following ischemic stroke is due to or aggravated by reperfusion and therefore more frequent after thrombolytic therapy of stroke is still under debate. From 3/96 to 1/97, we treated 51 patients with acute supratentorial stroke within 3 h after symptom onset with rt-PA following a protocol similar to the NINDS study. The results of thrombolytic therapy were evaluated by repeated clinical examination and computed tomography (CT) during the first week after ictus. The incidence of space-occupying brain edema following intravenous thrombolytic therapy of acute ischemic stroke was lower than the edema frequency after conventional treatment, but mortality from ‘malignant’ edema was higher in the patients with thrombolysis. Thus, space-occupying edema after acute ischemic stroke may be aggravated by thrombolytic treatment. Forced reperfusion of already irreversibly damaged tissue increases edema formation and enlarges developing infarcts with a deleterious increase of intracranial pressure.