Michael Neveling

Nosocomial Pneumonia After Acute Stroke. Implications for Neurological Intensive Care Medicine

Background and Purpose— Pneumonia has been estimated to occur in about one third of patients after acute stroke. Only limited data are available on stroke-associated pneumonia (SAP) in specialized neurological intensive care units (NICUs). Methods— We enrolled 124 patients with acute stroke who were treated at our university hospital NICU in a prospective observational study. Incidence rates and risk factors of SAP and long-term clinical outcome were determined. Results— SAP incidence was 21% with a spectrum of pathogens, which is comparable to previously published data on general ICU patients. Mechanical ventilation, multiple location, and vertebrobasilar stroke, as well as dysphagia and abnormal chest x-ray findings, were identified as risk factors for the disease. SAP patients showed higher mortality rates than nondiseased subjects (acute, 26.9% versus 8.2%; long-term, 35.3% versus 14.3%) and a significantly poorer long-term clinical outcome (Barthel Index, 50.5±42.4 versus 81.5±27.8; Rankin Scale, 3.5±1.7 versus 2.2±1.6). Conclusions— Our data underline the considerable epidemiological and prognostic impact of SAP for the treatment of acute stroke patients in a specialized NICU setting. They demonstrate that the occurrence of SAP deteriorates clinical outcome in these patients. Our results allow us to identify high-risk stroke patients at time of NICU admission in whom the use of preventive treatment strategies is most promising.

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.

Does the Mismatch Match the Penumbra? Magnetic Resonance Imaging and Positron Emission Tomography in Early Ischemic Stroke

Background and Purpose— In ischemic stroke, diffusion-weighted (DW) and perfusion-weighted (PW) magnet resonance imaging (MRI) is used to define the mismatch as the therapeutic target. With positron emission tomography (PET), we characterized the metabolic patterns of tissue compartments identified by MRI and compared the volumes of mismatch to those of PET-defined penumbra. Methods— In 6 acute (median, 5.2 hours) and 7 chronic (median, 10 days) stroke patients in whom a mismatch was defined by PW/DW MRI, PET was performed (median, 120-minute delay). Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF) was determined in the areas of DWI lesion, mismatch, and oligemia. Then, the mismatch volume was compared with the volume of penumbra. Results— DWI lesions showed impaired tissue integrity (low CMRO2 and low OEF). Mismatch areas were viable (normal CMRO2) but showed largely varying OEF. Oligemic areas had metabolic patterns comparable to normal tissue. A mismatch volume was found in all 13 patients. However, only 8 of 13 had a corresponding penumbra volume that covered only a part of the mismatch. Conclusion— Our comparative PET/MRI study confirmed the current pathophysiological hypothesis for the DWI lesion and for the oligemic areas. However, the mismatch area did not reliably detect elevated OEF and overestimated the penumbra defined by PET.

Which time-to-peak threshold best identifies penumbral flow? A comparison of perfusion-weighted magnetic resonance imaging and positron emission tomography in acute ischemic stroke

Background and Purpose— In acute ischemic stroke, the hypoperfused but viable tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP) maps are frequently used to estimate the hemodynamic compromise and to calculate the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral flow by comparison with positron emission tomography (PET). Methods— Magnetic resonance imaging (MRI) and PET were performed in 11 patients with acute ischemic stroke (median 8 hours after stroke onset, 60 minutes between MRI and PET imaging). The volumes defined by increasing TTP thresholds (relative TTP delay of >2, >4, >6, >8, and >10 seconds) were compared with the volume of hypoperfusion (<20 mL/100 g per min) assessed by 15O-water PET. In a volumetric analysis, each threshold’s sensitivity, specificity, and predictive values were calculated. Results— The median hypoperfusion volume was 34.5 cm3. Low TTP thresholds included large parts of the hypoperfused but also large parts of normoperfused tissue (median sensitivity/specificity: 93%/60% for TTP >2) and vice versa (50%/91% for TTP >10). TTP >4 seconds best identifies hypoperfusion (84%/77%). The positive predictive values increased with the size of hypoperfusion. Conclusion— This first comparison of quantitative PET-CBF with TTP maps in acute ischemic human stroke indicates that the TTP threshold is crucial to reliably identify the tissue at risk; TTP >4 seconds best identifies penumbral flow; and TTP maps overestimate the extent of true hemodynamic compromise depending on the size of ischemia. Only if methodological restrictions are kept in mind, relative TTP maps are suitable to estimate the mismatch volume.

Prediction of Malignant Course in MCA Infarction by PET and Microdialysis

BACKGROUND AND PURPOSE To predict malignant course in patients with large middle cerebral artery (MCA) infarction, we combined PET imaging and neuromonitoring, including microdialysis. METHODS Thirty-four patients with stroke of >50% of the MCA territory in early cerebral CT scan were included. Probes for microdialysis and measurement of intracranial pressure and tissue oxygen pressure (Pto2) were placed into the ipsilateral frontal lobe. PET was performed with 11C-flumazenil to assess CBF and irreversible neuronal damage. RESULTS PET measurements within 24 hours after stroke showed larger volumes of ischemic core (mean, 144.5 versus 62.2 cm3) and larger volumes of irreversible neuronal damage (157.9 versus 47.0 cm3) in patients with malignant course (ie, edema formation with midline shift) than in patients with benign course. Mean cerebral blood flow values within the ischemic core were significantly lower and the volume of the ischemic penumbra was smaller in the malignant than in the benign group. In patients with malignant course, cerebral perfusion pressure dropped to <50 to 60 mm Hg 22 to 72 hours (mean, 52.0 hours) after onset of symptoms; subsequently, Pto2 dropped and glutamate increased, indicating secondary ischemia. Maximal changes in the monitored variables reached significant levels for glutamate, aspartate, GABA, glycerol, lactate-to-pyruvate ratio, hypoxanthine, intracranial pressure, cerebral perfusion pressure, and Pto2. CONCLUSIONS PET allowed prediction of malignant MCA infarction within the time window suggested for hemicraniectomy. Neuromonitoring helped to classify the clinical courses by characterizing pathophysiological sequelae of malignant edema formation. In contrast to PET, however, it did not predict fatal outcome early enough for successful implementation of invasive therapies.

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 PURPOSE High-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. METHODS Eighteen 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. RESULTS Intraoperatively, 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. CONCLUSIONS HITS 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.

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.

The cologne stroke experience: safety and outcome in 450 patients treated with intravenous thrombolysis

Background: Predictors of outcome and safety in intravenous thrombolysis within 3 h in clinical routine is a matter of ongoing debate. Available reports contain small patient numbers or summarize heterogeneous multicenter data. Methods: Four hundred and fifty patients received intravenous thrombolysis within 3 h after stroke. Pretreatment NIHSS score and detailed medical history were analyzed. Noncontrast CT was performed before thrombolysis, 24–36 h later and in case of clinical deterioration. Symptomatic intracranial hemorrhage (SICH; any bleeding with an NIHSS increase of ≧4 points) and clinical outcome (modified Rankin Scale, mRS) after 3 months were recorded. Logistic regression identified parameters predictive of independence (mRS 0–2) and SICH. Results: Median onset to admission, door to needle and onset to treatment time was 75, 50 and 135 min, respectively. Direct presentation by emergency service (64%) was the fastest way of referral. Median pretreatment NIHSS was 11 points. Independence (mRS 0–2) was reached by 53%. Mortality was 11% (7% intracerebral, 4% extracerebral complications). Logistic regression identified low NIHSS, low age and absent diabetes as predictors of independence. Overall hemorrhagic complications and SICH were found in 18 and 4% of the patients, respectively. Extracerebral bleeding complications and allergic reactions were found in 3 and 1%, respectively. Conclusion: This largest single center report presents a sample in the range of the 3 h rt-PA cohort of all randomized controlled trials. Outcome was comparable to randomized studies with a higher rate of independence and a lower rate of mortality and SICH.

Extracellular Concentrations of Non–Transmitter Amino Acids in Peri-Infarct Tissue of Patients Predict Malignant Middle Cerebral Artery Infarction

Background and Purpose— Space-occupying brain edema is a life-threatening complication in patients with large middle cerebral artery (MCA) infarction. To determine predictors of this detrimental process, we investigated alterations of extracellular non–transmitter amino acid concentrations in peri-infarct tissue. Methods— Thirty-one patients with infarctions covering >50% of the MCA territory in early cranial CT scans were included in the study. Probes for microdialysis, intracranial pressure, and tissue oxygen pressure were placed into the noninfarcted ipsilateral frontal lobe. Positron emission tomography imaging was performed in 16 of these patients to measure cerebral blood flow in the tissue around the neuromonitoring probes. Results— Fourteen of the 31 patients developed a malignant MCA infarction, and 17 did not. The patients in the malignant group had significantly lower extracellular concentrations of non–transmitter amino acids than those in the benign group in the first 12 hours of neuromonitoring. At this time, CBF values determined in regions of interest around the probes by positron emission tomography and tissue oxygen pressure showed that the monitored tissues were not yet infarcted, and no differences in transmitter amino acids concentrations were found between the 2 groups. Furthermore, extracellular concentrations of non–transmitter amino acids were negatively correlated with size of infarction. Conclusions— We assume that reduction of non–transmitter amino acid concentrations reflects an expansion of the extracellular space by vasogenic edema formation in peri-infarct tissue of patients with malignant MCA infarction. Our findings facilitate early prediction of malignant edema formation and may help to increase knowledge of the pathophysiology of the peri-infarct zone of large MCA infarction.