Hypertension in patients with cerebrovascular accident. To treat or not to treat?
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Antihypertensive Agents↗
Biomedical subjects
W Hacke
Publications and source records attributed to W Hacke.
Secondary hemorrhage after intraventricular fibrinolysis: a cautionary note: a report of two cases.
OBJECTIVE AND IMPORTANCE: To hasten the lysis of intraventricular hemorrhages, intraventricular administration of recombinant tissue plasminogen activator (rt-PA) or urokinase has been advocated as an effective and safe treatment for patients with intraventricular hemorrhage. Until now, cases of secondary hemorrhage after intraventricular fibrinolysis, to our knowledge, have not been reported in the literature. We present a report of two patients with clinically significant bleeding complications associated with intraventricular infusion of rt-PA. CLINICAL PRESENTATION: Both patients, a 42-year-old woman (Patient 1) and a 70-year-old man (Patient 2), suffered from hypertensive left-sided thalamic hemorrhage with ventricular extension and ventricular dilatation. INTERVENTION: Both patients required external ventricular drainage and were treated with intraventricular rt-PA. In Patient 1, a secondary intraventricular hemorrhage occurred 20 minutes after the first instillation of 2 mg of rt-PA and was associated with a sudden loss of consciousness. Treatment with rt-PA was stopped, and the patient needed a permanent shunt. In Patient 2, intraventricular subsequent bleeding was noted 4 hours after the second 4-mg dose of rt-PA, clinically apparent as anisocoria. In Patient 2, rt-PA administration was continued without further complications. In both patients, a second external ventricular drainage was required after secondary hemorrhage. CONCLUSION: Intraventricular lysis is a potentially hazardous therapy. To weigh the potential benefits against the potential risks, a controlled study of this promising new treatment is urgently warranted.
Adult↗
Combination therapy with neuroprotectants and thrombolytics in acute ischaemic stroke.
A reduction in neuronal damage following acute ischaemic stroke can be achieved by two major strategies: restoration of cerebral blood flow through the use of thrombolytics, and inhibition of the pathophysiological cascade that occurs as a result of a decreased cerebral blood flow through the use of neuroprotective agents. Therefore, combination therapy with thrombolytic and neuroprotective agents may provide additional benefits to those that can be achieved using the individual agents alone. Indeed, such benefits have already been demonstrated in several animal studies. However, a number of problems in trial design and statistical methodology need to be overcome. Nevertheless, combination therapy offers the potential of reducing the cost of stroke in terms of both health care and social welfare, and as well as limiting disability.
Brain Ischemia↗
Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke.
BACKGROUND AND PURPOSE: To obtain information on the safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. METHODS: An open, uncontrolled, dose titration study was conducted in 32 patients hospitalized for stroke. Patients received one of four fixed dose regimens of enlimomab. A loading dose of enlimomab administered within 24 h of the onset of stroke symptoms was followed by four daily maintenance doses; total doses ranged from 140 to 480 mg. RESULTS: The pharmacokinetic target levels (enlimomab serum levels of >/=10 microg/ml) were consistently achieved in all patients receiving dose regimens III and IV. Non-serious adverse events thought to be causally related to enlimomab administration included headache, vomiting and extrasystoles. Serious events occurred in 14 patients, including pneumonia, sepsis, cardiac failure and cardiac arrest. The only serious adverse event considered to be related to enlimomab administration was an anaphylactoid reaction, in a patient who received an unfiltered loading dose of antibody; the patient recovered. The overall mortality in the study was 15.6% and the 30-day mortality was 12.5%. There was no increase in the frequency of adverse events with increasing doses of enlimomab. CONCLUSIONS: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days. A loading dose of 160 mg followed by four daily maintenance doses of 40 mg appears to be suitable for further study.
Acute Disease↗
Dichotomized efficacy end points and global end-point analysis applied to the ECASS intention-to-treat data set: post hoc analysis of ECASS I.
BACKGROUND AND PURPOSE: It is not yet known which end points are the most suitable for evaluation of the effects of acute stroke intervention. The European Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The study was powered to detect a 15% improvement of the median of each primary end point. The study failed to show this effect and was negative in the intention-to-treat analysis. The National Institute of Neurological Disorders and Stroke (NINDS) study used 4 dichotomized end points and applied a global end-point analysis. This study was positive and led to FDA approval of thrombolytic therapy for acute ischemic stroke. This study was undertaken to answer the question of whether a different statistical design may have shown a positive results of the ECASS I trial. METHODS: We performed a retrospective analysis of the ECASS I intention-to-treat data set (615 randomized and treated patients, rtPA treatment versus placebo) and post hoc application of the NINDS trial statistical methodology (global end-point analysis). The scores of the modified Rankin Scale (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale (NIHSS) were dichotomized according to the criteria used in the NINDS trial. Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100 on BI, and a score of 0 or 1 on NIHSS. RESULTS: The number of patients reaching favorable outcome were higher in all 3 end points in the rtPA-treated group. The effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The differences are statistically significant for the mRS (P=0.044; odds ratio [OR], 1. 4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS (P=0.001; OR, 1.9; 95% CI, 1.4 to 2.8), while for the BI significance was missed (P=0.102; OR, 1.3; 95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a significant increase (P=0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome in the rtPA-treated patient group. CONCLUSIONS: Using the global end-point analysis, ECASS is positive in the intention-to-treat analysis. This may indicate that the time window for thrombolysis may be as long as 6 hours. Looking at the 3 dichotomized end points, the effect sizes for 2 end points, mRS and BI, are smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial all 3 end points reveal statistically significant results, in ECASS only 2 of the 3 corresponding end points, mRS and NIHSS, were statistically significant. This finding underlines an important difference of a global end-point approach: it may show a positive overall result although one of the end points is not positive.
Cerebrovascular Disorders↗
Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction.
BACKGROUND AND PURPOSE: Animal research and clinical studies in head trauma patients suggest that moderate hypothermia may improve outcome by attenuating the deleterious metabolic processes in neuronal injury. Clinical studies on moderate hypothermia in the treatment of acute ischemic stroke patients are still lacking. METHODS: Moderate hypothermia was induced in 25 patients with severe ischemic stroke in the middle cerebral artery (MCA) territory for therapy of postischemic brain edema. Hypothermia was induced within 14+/-7 hours after stroke onset and achieved by external cooling with cooling blankets, cold infusions, and cold washing. Patients were kept at 33 degreesC body-core temperature for 48 to 72 hours, and intracranial pressure (ICP), cerebral perfusion pressure, and brain temperature were monitored continuously. Outcome at 4 weeks and 3 months after the stroke was analyzed with the Scandinavian Stroke Scale (SSS) and Barthel index. The side effects of induced moderate hypothermia were analyzed. RESULTS: Fourteen patients survived the hemispheric stroke (56%). Neurological outcome according to the SSS score was 29 (range, 25 to 37) 4 weeks after stroke and 38 (range 28 to 48) 3 months after stroke. During hypothermia, elevated ICP values could be significantly reduced. Herniation caused by a secondary rise in ICP after rewarming was the cause of death in all remaining patients. The most frequent complication of moderate hypothermia was pneumonia in 10 of the 25 patients (40%). Other severe side effects of hypothermia could not be detected. CONCLUSIONS: Moderate hypothermia in the treatment of severe cerebral ischemia is not associated with severe side effects. Moderate hypothermia can help to control critically elevated ICP values in severe space-occupying edema after MCA stroke and may improve clinical outcome in these patients.
Adult↗
Role of CT angiography in patient selection for thrombolytic therapy in acute hemispheric stroke.
BACKGROUND AND PURPOSE: It has been shown that thrombolytic therapy can improve clinical outcome in a subgroup of patients with acute cerebral ischemia. This subgroup was characterized by certain clinical and imaging findings (eg, moderate to severe neurological deficit for less than 3 to 6 hours, occlusion of the middle cerebral artery, lack of extended infarct signs on CT, and efficient leptomeningeal collaterals). Although not part of published prospective randomized rtPA trials, information about the status of the brain vessels would be helpful in the selection of patients who may benefit the most. Our purpose was to determine the feasibility of CT angiography (CTA) in patients with acute hemispheric ischemia and to evaluate its relevance for thrombolytic therapy. METHODS: CTA was performed in 40 consecutive patients (11 women and 29 men; age range, 19 to 80 years) with moderate or severe symptoms (National Institutes of Health Stroke Scale score of > or =8) of acute hemispheric ischemia. CTA findings were compared with Doppler ultrasonography (US; n=22) and intra-arterial digital subtraction angiography (DSA; n=7). Twenty patients received thrombolytic therapy, the remaining patients received intravenous heparin. RESULTS: Images and 3-dimensional reconstructions of diagnostic quality could be obtained in all patients. Thirty-four patients had a vessel occlusion. The extent of leptomeningeal collaterals correlated significantly with the outcome after thrombolytic therapy (rs=0.46, P<0.05). The evaluation of diagnostic accuracy showed a high agreement with US (22 of 22) and DSA (6 of 7). CONCLUSIONS: CTA can provide important information for the initiation of therapy in patients with acute hemispheric ischemia. Identification of patients with autolyzed thrombi, occlusion of the internal carotid artery bifurcation, and poor leptomeningeal collaterals is feasible with the use of CTA. These patients may have little potential for benefit from thrombolytic therapy.
Acute Disease↗
Effects of hypertonic saline hydroxyethyl starch solution and mannitol in patients with increased intracranial pressure after stroke.
BACKGROUND AND PURPOSE: The purpose of this study was to prospectively evaluate a protocol with hypertonic saline hydroxyethyl starch (HS-HES) and mannitol in stroke patients with increased intracranial pressure (ICP). METHODS: We studied 30 episodes of ICP crisis in 9 patients. ICP crisis was defined as (1) a rise of ICP of more than 25 mm Hg (n = 22), or (2) pupillary abnormality (n=3), or (3) a combination of both (n=5). Baseline treatment was performed according to a standardized protocol. For initial treatment, the patients were randomly assigned to either infusion of 100 mL HS-HES or 40 g mannitol over 15 minutes. For repeated treatments the 2 substances were alternated. ICP, blood pressure, and cerebral perfusion pressure (CPP) were monitored over 4 hours. Blood gases, hematocrit, blood osmolarity, and sodium were measured before and 15 and 60 minutes after the start of infusion. Treatment was regarded as effective if ICP decreased >10% below baseline value or if the pupillary reaction had normalized. RESULTS: Treatment was effective in all 16 HS-HES-treated and in 10 of 14 mannitol-treated episodes. ICP decreased from baseline values in both groups, P < 0.01. The maximum ICP decrease was 11.4 mm Hg (after 25 minutes) in the HS-HES-treated group and 6.4 mm Hg (after 45 minutes) in the mannitol-treated group. There was no constant effect on CPP in the HS-HES-treated group, whereas CPP rose significantly in the mannitol-treated group. Blood osmolarity rose by 6.2 mmol/L in the mannitol-treated group and by 10.5 mmol/L in the HS-HES-treated group; sodium fell by 3.2 mmol/L in the mannitol and rose by 4.1 mmol/L in the HS-HES-treated group. CONCLUSIONS: Infusion of 40 g mannitol and 100 mL HS-HES decreases increased ICP after stroke. The maximum effect occurs after the end of infusion and is visible over 4 hours. HS-HES seems to lower ICP more effectively but does not increase CPP as much as does mannitol.
Adult↗
Early hemicraniectomy in patients with complete middle cerebral artery infarction.
BACKGROUND AND PURPOSE: Malignant, space-occupying supratentorial ischemic stroke is characterized by a mortality rate of up to 80%. Several reports indicate a beneficial effect of hemicraniectomy in this situation. However, whether and when decompressive surgery is indicated in these patients is still a matter of debate. METHODS: In an open, prospective trial we performed hemicraniectomy in 63 patients with acute complete middle cerebral artery infarction. Initial clinical presentation was assessed by the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Scale (GCS). All survivors were reexamined 3 months after surgical decompression, with the clinical evaluation graded according to the Rankin Scale (RS) and Barthel Index (BI). We analyzed the influence of early decompressive surgery (<24 hours after symptom onset, based on clinical status at admission and initial CT findings) versus late surgery (>24 hours after first reversible signs of herniation) on mortality, functional outcome, and the length of time of critical care therapy was needed. RESULTS: In total, 46 patients (73%) survived. Despite complete hemispheric infarction, no survivor suffered from complete hemiplegia or was permanently wheelchair bound. In patients with speech-dominant hemispheric infarction (n=11), only mild to moderate aphasia was present. The mean BI score was 65, and RS score revealed severe handicap in 13% of the patients. In 31 patients with early decompressive surgery, mortality was 16% and BI score 68.8. Early hemicraniectomy led to a significant reduction in the length of time critical care therapy was needed (7.4 versus 13.3 days, P<0.05). CONCLUSIONS: In general, the outcome of patients treated with craniectomy in severe ischemic hemispheric infarction was surprisingly good. In addition, early decompressive surgery may further improve outcome in these patients.
Adult↗
Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies.
We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.
Adult↗
An integrated approach for a knowledge-based clinical workstation: architecture and experience.
Today, the demand for medical decision support to improve the quality of patient care and to reduce costs in health services is generally recognized. Nevertheless, decision support is not yet established in daily routine within hospital information systems which often show a heterogeneous architecture but offer possibilities of interoperability. Currently, the integration of decision support functions into clinical workstations is the most promising way. Therefore, we first discuss aspects of integrating decision support into clinical workstations including clinical needs, integration of database and knowledge base, knowledge sharing and reuse and the role of standardized terminology. In addition, we draw up functional requirements to support the physician dealing with patient care, medical research and administrative tasks. As a consequence, we propose a general architecture of an integrated knowledge-based clinical workstation. Based on an example application we discuss our experiences concerning clinical applicability and relevance. We show that, although our approach promotes the integration of decision support into hospital information systems, the success of decision support depends above all on an adequate transformation of clinical needs.
Artificial Intelligence↗
Increased fraction of circulating activated platelets in acute and previous cerebrovascular ischemia.
Determination of circulating activated platelets may be helpful to estimate the prognosis and to stratify therapies in arterial vascular disorders including stroke. We used flow cytometry and phase contrast microscopy to study whether the fraction of platelets expressing p-selectin and CD63 and the fraction of platelets with shape change are increased in patients with acute and previous cerebrovascular ischemia. The proportion of platelets expressing activation dependent antigens was higher in patients with acute (n = 24; p-selectin: 8.23 +/- 4.21%; CD63: 3.53 +/- 2.53%) and with previous cerebrovascular ischemia (n = 46; 3.86 +/- 1.98%; 2.80 +/- 1.79%) as compared to age- and sex-matched control subjects (n = 35; 2.17 +/- 0.96%; 1.79 +/- 0.75%; p < or = 0.005, respectively). In patients with previous ischemia, there was no difference between treatment with aspirin (n = 25) or phenprocoumon (n = 21). Hypertension, diabetes mellitus and smoking were not associated with increased antigen expression (analysis of variance). The fraction of discoid platelets and platelet counts were not significantly different between groups. Our results indicate increased expression of platelet neoantigens in acute and to a less degree in previous cerebrovascular ischemia. Ongoing platelet activation after cerebrovascular ischemia despite therapy with aspirin or phenprocoumon indicates that new anti-platelet drugs may be of benefit for these patients. Flow cytometry appears to be a useful tool to assess platelet function in cerebrovascular ischemia.
Aged↗
[Continuing medical education in neurology. Concept of the German Society of Neurology and the Neurology Section of the Professional Society of German Neurologists].
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Curriculum↗
Thrombolytic therapy for acute ischaemic stroke. ECASS Study Group.
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Cerebrovascular Disorders↗
[Thrombolytic therapy in ischemic infarct].
Thrombolytic therapy in acute ischemic stroke is safe and effective in a defined subgroup of stroke patients. Until now, different fibrinolytic substances including urokinase, streptokinase and recombinant tissue plasminogen activator (rt-PA) have been tested regarding safety, efficacy, dosage and economic parameters in patients suffering from both carotid and basilar artery territory strokes. Recently, two large multicenter placebo-controlled intravenous rt-PA studies were published. The results show that thrombolysis of acute carotid territory strokes (European Cooperative Acute Stroke Study) and of strokes with a deficit measurable on the NIH Stroke Scale (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study) improves clinical and economic outcome parameters in patients who were treated within 6 hours of the onset of symptoms and had that no signs of extended early infarction on the initial CT-scan. The occurrence of intracranial hemorrhages is more frequent after thombolytic therapy, but the majority of bleeding complications referred to petechial or more confluent hemorrhage limited to the infarcted tissue, without clinical deterioration. However, the identification of the appropriate patients is difficult and depends on the level of clinical and diagnostic experience. In vertebrobasilar artery territory stroke, local intraarterial thrombolysis with urokinase or streptokinase is performed in most cases. Thrombolytic treatment within twelve hours of the onset of symptoms was associated with significantly better results concerning both survival and neurological recovery.
Brain Ischemia↗
Hemicraniectomy with dural augmentation in medically uncontrollable hemispheric infarction.
Surgical decompression to alleviate raised intracranial pressure has been reported repeatedly in the past decades in small series of patients. Only recently have there been indications from larger trials that surgical decompression may be beneficial in treating space-occupying hemispheric infarction. However, surgical requirements for the procedure to be effective have not yet been defined. Based on theoretical criteria, the authors operated on 43 patients with medically uncontrollable hemispheric infarctions. The craniectomies were planned to be as large as possible and performed in combination with a subtemporal decompression. Postoperative computerized tomography scans were evaluated for these criteria. The mean survival rate for the group of 43 patients was 72.1% and no surviving patient ended up in a vegetative state. The mean area of craniectomy was found to be 84.3 +/- 16.5 cm2 and the mean distance of the inferior craniectomy margin to the middle fossa was 1.8 +/- 1.3 cm. Comparison of survivors and nonsurvivors failed to show a significant difference in the size of craniectomy or the distance to the floor of the middle fossa. Compared with the reported 80% fatality rate for medically treated stroke patients, in this subgroup the outcome (72.1% survival rate) is remarkably good. The authors conclude that decompressive craniectomy is an effective treatment, able to reduce mortality, and to improve neurological outcome in patients with space-occupying cerebral infarction if the size of craniectomy is large enough. Nevertheless, there is a need for further investigation to identify patients who will benefit from surgery and predictors to optimize the timing of surgical intervention.
Journal Article↗
Haematoma evacuation does not improve outcome in spontaneous supratentorial intracerebral haemorrhage: a case-control study.
Surgical intervention in supratentorial intracerebral haemorrhage (ICH) is still controversial. We assessed the value of haematoma evacuation with a case-control study. 145 consecutive patients with supratentorial spontaneous ICH without tumour or vascular abnormalities were analysed. Haematoma evacuation was performed in 24 patients. Age, sex, Glasgow Coma Scale (GCS), level of consciousness, pupillary reaction on admission, localisation, aetiology and volume of the haematoma, presence of ventricular blood, and Glasgow Outcome Scale (GOS) on discharge were analysed. From statistical analysis 40 patients > 80 years and with haematoma volume < 10 ml, who were always treated conservatively, were excluded. Prognostic factors retained from a multiple regression model with the dichotomised GOS scale (GOS 1-3, 4 + 5) as response variable were GCS, haematoma volume and location. The only difference between all medically treated and "operated" patients was haematoma volume, which was larger in the "operated" patients. All 24 evacuated cases could be matched to a medically treated control regarding age, haematoma volume and location, GCS, and pupillary reaction. Significant differences between the two groups could not be detected. Outcome was not different between the two groups. After separating the sample into patients with and without ventricular haemorrhage, there was no different outcome between the two groups either. We conclude that haematoma evacuation did not improve outcome in supratentorial spontaneous ICH. Since haematomas were evacuated mainly in clinically deteriorating patients, our data suggest that the only effect of haematoma evacuation is to stop progressive deterioration rather than to improve overall clinical outcome.
Adult↗
[Neurogenic disorders of heart and lung function in acute cerebral lesions].
Incidence and clinical significance of cardiopulmonary complications of acute cerebral lesions are still unclear. Neurogenic pulmonary edema (NPE) is characterized as an acute, protein-rich lung edema occurring shortly after cerebral lesions associated with an acute rise of intracranial pressure. NPE is infrequently diagnosed, usually in association with head trauma. Pathophysiological mechanisms include a rise of the pulmonary vascular hydrostatic pressure either due to sympathetic innervation with pulmonary vasoconstriction or increased left-atrial pressure following systemic arterial hypertension or an increase in pulmonary capillary permeability. In contrast to NPE, cardiac complications are frequently observed, most consistently in patients with subarachnoid hemorrhage. Typical ECG changes are repolarization abnormalities, similar to those observed in coronary heart disease, and cardiac arrhythmias. The CK-MB may be slightly elevated; echocardiographic findings show a depressed left-ventricular function. Pathological examination reveals myofibrillar necrosis. Cardiac complications are explained with overactivity of the sympathetic innervation and high levels of circulating catecholamines. For adequate treatment, close cardiac monitoring is required in all patients with acute cerebral lesions.
Arrhythmias, Cardiac↗