Martin Grond

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

BACKGROUND AND PURPOSE Controlled 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. METHODS We 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. RESULTS Of 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%. CONCLUSIONS Thrombolysis 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.

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

BACKGROUND AND PURPOSE A 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. METHODS Between 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. RESULTS Baseline 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. CONCLUSIONS These 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.

Predictive Value of Neurochemical Monitoring in Large Middle Cerebral Artery Infarction

Background and Purpose— Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke. Early identification of patients at risk is necessary to decide on invasive therapies such as decompressive hemicraniectomy or hypothermia. To assess potential predictors of malignant brain edema by measurement of intracranial pressure (ICP) and microdialysis in patients with large hemispheric stroke and different clinical course. Methods— In an ongoing prospective clinical study, an ICP and microdialysis probe were placed into the parenchyma of the ipsilateral frontal lobe of 10 patients. Extracellular concentrations of glutamate, lactate, pyruvate, and glycerol were measured continuously. Repeated cranial CT scans were scrutinized for size of infarction and presence of mass effect. Results— The dynamics of the different substances varied in accordance with the clinical course, size of infarction, and local brain edema: Increase in ICP and in glutamate concentration and lactate-pyruvate ratio was followed by massive edema and large infarcts; generally low and stable ICP and substrate concentrations were found in patients without progressive space-occupying infarcts. Conclusions— In patients with large hemispheric infarction, bedside monitoring with microdialysis is feasible and might be helpful together with ICP recording to follow the development of malignant brain edema.

Acetylsalicylic acid pretreatment, concomitant heparin therapy and the risk of early intracranial hemorrhage following systemic thrombolysis for acute ischemic stroke.

Background: The risk of intracerebral hemorrhage in systemic thrombolysis for acute ischemic stroke after acetylsalicylic acid (ASA) pretreatment or with subsequent heparin is controversially discussed. Methods: 300 consecutive stroke patients were treated with recombinant tissue-type plasminogen activator (rt-PA) in a prospective open study (92 pretreated with ASA, 202 ASA nonusers) with 3 months of follow-up. After thrombolysis, 122 patients received low-dose, 153 patients high-dose heparin. Results: Logistic regression analysis showed no relationship of hemorrhagic complications within the first 48 h to ASA pretreatment (p = 0.15), or heparin application (p = 0.38), but dependency on stroke severity (NIHSS) at baseline (p = 0.01). Conclusion: ASA pretreatment does not increase the risk of symptomatic bleeding after systemic thrombolysis with rt-PA, even if thrombolysis is followed by anticoagulation.

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 PURPOSE Although 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. CASE DESCRIPTION We 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. CONCLUSIONS The 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: Before 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 The 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.

Late Resolution of Diffusion-Weighted MRI Changes in a Patient With Prolonged Reversible Ischemic Neurological Deficit After Thrombolytic Therapy

Background Reduced apparent diffusion coefficients (ADCs) correlate with cerebral ischemia. The combination of ADC with techniques to measure cerebral perfusion may help to assess the effect of treatment. Case Description—The authors describe a patient who experienced an acute stroke with hemianopia, consequently treated with intravenous recombinant tissue plasminogen activator. Positron emission tomographic imaging and MRI, including diffusion-weighted MRI, were performed during and shortly after treatment with recombinant tissue plasminogen activator and 34 to 35 hours later. Cerebral perfusion of the left occipital region was reduced to 74%. Diffusion-weighted MRI detected a territory of restricted water movement in the corresponding area. Further magnetic resonance sequences did not show any pathologies. In follow-up, positron emission tomography demonstrated reperfusion. The volume of diffusion and ADC abnormalities detected by MRI decreased markedly. A few hours later, the patient recovered completely. A third MRI examination 10 days later showed normal findings. Conclusions In a patient with prolonged reversible ischemic neurological deficit, resolution of early diffusion changes corresponded to cerebral reperfusion and to the recovery of clinical symptoms.