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This article summarises the recommendations for the management of managing patients with intracerebral haemorrhage published in 2006 by the European Stroke Initiative (EUSI) on behalf of the European Stroke Council (ESC), the European Neurological Society (ENS), and the European Federation of Neurological Societies (EFNS).
Patients suffering a transient ischaemic attack (TIA) or ischaemic stroke (IS) have a high recurrence risk. Secondary prevention aims to prevent not only further strokes but also cardiac events. Important parts of secondary prevention regimens are the modification of vascular risk factors and the inhibition of platelet function or anticoagulation if indicated. The inhibition of platelet function is effective in the reduction of secondary vascular events in patients with TIA or stroke. This is true for acetylsalicylic acid (ASA), clopidogrel, and the combination of ASA plus slow-release dipyridamole. A prediction model which allows to identify patients in whom clopidogrel or dipyridamol plus ASA is superior to ASA for the secondary prevention of stroke is presented.
Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.
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The annual stroke risk for patients with asymptomatic stenoses of the carotid artery is around 1% in case of <70% stenosis (NASCET criteria) and 2-5% in patients with >70% stenosis. The risk of recurrent ischemic events for patients with symptomatic stenoses is much higher, around 15% during the first year. For more than 10 years, the efficacy of carotid surgery has been proven, and there is growing evidence to support surgery in case of asymptomatic stenosis. Patients with severe stenoses, male or elderly patients, and those with bilateral stenoses benefit more from surgery. Carotid artery stenting has not proven its safety or efficacy. Despite this lack of evidence, the method is used in many centers as an alternative to surgery. Especially symptomatic carotid artery stenosis should be used mainly in the setting of a randomized trial such as SPACE.
During recent years, stent-protected angioplasty of the carotid artery (SPAC) has become an alternative to endartectomy (CEA) in many centers. Despite many case reports, case series, and open records, it has not been proven that these therapeutical regimens are comparable regarding complication rates and long-term outcome. Until now, only three randomized trials were published on this theme, two of them only as abstracts. This is not sufficient for answering the question of whether SPAC is a good alternative to CEA. At present, four major, randomized, multicenter trials are being run (EVA3S in France, CREST in the US, ICSS in Great Britain and several other countries, and SPACE in Germany and Austria). About 7,300 patients will be included in these trials. At present, 24 centers are participating in the SPACE trial, recruiting about 350 patients. It has been prospectively agreed that EVA-3S, ICSS, and SPACE will combine their results after completion of initial randomization and follow-up to conduct a combined European meta-analysis of the data. Three to 5 years are needed until these trials' final results will be published. Until then, stent-protected angioplasty should be done only under the consideration that it has not been scientifically evaluated.
OBJECTIVES: to examine the relationship between the degree of extracranial internal carotid artery (ICA) stenosis and changes in the ipsilateral ICA blood flow after carotid endarterectomy (CEA). MATERIALS AND METHODS: in a prospective study we studied 51 patients with unilateral 60-99% ICA stenosis (median degree 84%, asymptomatic stenosis n = 13, symptomatic stenosis n = 38). The degree of ICA diameter stenosis was determined by ex-vivo plastination of the surgically removed atherosclerotic specimen and video-assessed planimetry. Intraoperative transit time ultrasound flow measurements of the carotid arteries were performed before and after CEA. Blood flow changes were assessed by mathematical approximations. Statistics were done by use of the Wilcoxon signed Rank test. RESULTS: common carotid artery (CCA) and ICA median blood flow increased after CEA from 370 and 130 ml/min to 450 and 282 ml/min, respectively (p <.001). The relative increase of ICA blood flow was 5% and 18% for 60-69% and 70-79% ICA stenosis (n.s.) but 70% and 247% for 80-89% and 90-99% stenosis (p <.001 each). Mathematical evaluation (fourth-polynomal function) determined a significant increase of carotid blood flow after CEA in ICA stenosis of > or =82.3%. CONCLUSIONS: in the absence of severe contralateral ICA occlusive disease a significant increase of ipsilateral ICA blood flow by CEA can be expected in patients with an ICA stenosis of > or =82.3% (linear degree of stenosis, ECST criteria).
OBJECTIVE: The purpose of this study was to examine the safety of carotid endarterectomy (CEA) within 6 weeks after a nondisabling carotid-related ischemic stroke. Endpoints were the perioperative stroke or mortality rate and the incidence rate of cerebral bleedings. METHODS: This prospective observational multicenter trial was performed in community and university centers. One hundred sixty-four hospitalized patients with nondisabling carotid-related ischemic stroke were included. The patients were identified clinically with the modified Rankin scale (initial neurologic deficit grade >/= 2, n = 160). Four patients with evidence of ischemic territorial infarction on cerebral computed tomographic (CT) scan but no persisting functional deficit were also included. CEA was performed within 6 weeks after stroke. Neurologic examinations were performed initially, before surgery, 3 days after surgery, and 6 weeks after CEA. Worsening of more than 1 grade on the Rankin scale was considered as a new stroke or stroke extension. Unenhanced CT scans of the brain were performed before and after surgery. CT scans were evaluated blind to clinical patient data. Statistical analysis included univariate and multivariate analysis. RESULTS: The combined stroke or mortality rate within 30 days after CEA was 6.7%. Ten patients had a new ipsilateral stroke or stroke extension, and one patient died after surgery of a myocardial infarction. One patient (0.6%) had parenchymatous cerebral bleeding, and in 10 patients, hemorrhagic transformation within the preexisting ischemic infarction was detected but no infarct extension was observed. In the multivariate analysis, American Society of Anesthesiology (ASA) grades III and IV and decreasing age were significant predictors for an increased perioperative risk. Patients with a higher risk profile (ASA classification grades III and IV) had a high perioperative risk when CEA was performed within the first 3 weeks (14.6% versus 4.8% beyond 3 weeks). Patients without severe concomitant diseases (ASA grades I/II) had a low perioperative risk of 3.4% if CEA was performed within the first 3 weeks. CONCLUSION: Early CEA within 6 weeks after a carotid-related ischemic stroke can be performed with a perioperative stroke or mortality rate comparable with the results reported in the European Carotid Surgery Trial and the North American Symptomatic Carotid Endarterectomy Trial. The risk of parenchymatous bleeding is low. ASA grades III and IV and decreasing age were predictive of an increased perioperative risk, especially if CEA was performed within the first 3 weeks. Patients at low risk can undergo operation safely within the first 3 weeks. Individual patient selection in an interdisciplinary approach between neurologists, anesthesiologists, and vascular surgeons remains mandatory in these patients.
Some stroke patients suffering acute middle cerebral artery (MCA) infarction develop massive brain edema and herniation, a condition known as malignant MCA infarction. Severe swelling increases intracranial pressure (ICP) and leads to progressive brainstem dysfunction. Once ICP reaches critical values (>30 mm Hg) herniation occurs, usually within 2 to 5 days. Patients rarely survive (80% mortality) with standard treatment, and those who do are often severely disabled. Malignant MCA infarction is often missed by neurologists, despite well-defined clinical and neuroimaging (CT scan) diagnostic criteria. After diagnosis, conventional treatments such as osmotherapy, barbiturates, buffers, and hyperventilation center on reducing ICP. The goal of hyperosmolar therapy is to increase the serum osmolarity to approximately 315-320 mOsm/L. Enteric glycerol is used routinely to reduce ICP. In more severe cases and when glycerol fails, mannitol may be administered. Other therapies are also available, including hypertonic saline solution, THAM (Tris-hydroxy-methyl-aminomethane) buffer, and high-dose barbiturates. Hyperventilation also helps reduce ICP. All measures work effectively for a short time only. Other approaches to control elevated ICP, including decompression surgery and hypothermia, have shown promising results. In the Heidelberg decompression surgery trial, mortality in surgically treated patients was significantly lower (32%) than in non-treated patients (76%) despite conventional treatment. Importantly, of the surviving treated patients, 66% were rated independent with only mild to moderate disability. Moderate hypothermia (33-36 degrees C) has recently been shown to be effective in severe MCA infarction. Hypothermia induction within 14 hours of ischemic injury and maintained for 72 hours significantly reduced ICP and mortality (44%).
Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for vascular diseases. There are no data on Lp(a) levels in patients on long-term medication with carbamazepine, phenytoin, phenobarbital, or valproate. To investigate the effects of such treatment on Lp(a) levels and common carotid artery intima media thickness we studied 51 epileptic outpatients on long-term antiepileptic medication and 51 age-and sex-matched controls. Lp(a) levels above 45 mg/dl were found in 11 of 50 patients, but in only 4 of 51 controls (P < 0.05). The mean serum concentration of Lp(a) was 33.0+/-7.0 mg/dl in patients and 16.9+/-2.7 mg/dl in controls (P < 0.05). Epileptic patients also had a thicker intima media of the common carotid artery (0.79+/-0.04 mm) than controls (0.69+/-0.02 mm, P < 0.05) as measured by B-mode ultrasonography. Our results suggest an untoward effect of long-term antiepileptic medication on Lp(a) serum concentrations. Elevated Lp(a) levels might be a risk factor for arteriosclerosis in epileptic patients.
Repeated cranial computerized tomography scan examination in patients with elevated intracranial pressure is time consuming and requires patient transportation. We prospectively evaluated the diagnostic value of transcranial duplex sonography as a bedside tool for detection of the mass effect after space-occupying ischemic stroke and brain haemorrhage and for evaluating the width and dislocation of the ventricular system and the dislocation of brain mid-line structures. We used transcranial duplex sonography in 21 consecutive patients with space-occupying ischemic middle cerebral artery infarction and brain haemorrhage. The transcranial duplex sonography examinations were performed within 2 h before or after corresponding follow-up cranial computerized tomography scans. We measured the third ventricular width as a parameter for infratentorial and the mid-line shift for supratentorial space-occupying effect. In all patients, mid-line structures could be identified by transcranial duplex sonography. Significant third ventricular dilation was found subsequently in most patients with infratentorial mass effect, and mid-line shift occurred in all patients with supratentorial space-occupying lesions, respectively. The mean difference (absolute values) between transcranial duplex sonography and cranial computerized tomography measurements was 0.8 mm for the ventricular width (standard deviation 1 mm) and 1.1 mm for the mid-line shift (standard deviation: 1.46 mm), with a tendency for these parameters to be underestimated at higher values using transcranial duplex sonography. The linear correlation coefficients were R = 0.97 and R = 0.94, respectively. Transcranial duplex sonography appears to be a sufficiently reliable bedside method for evaluating the width and the lateral displacement of the third ventricle, as validated by cranial computerized tomography scan. Thus, it may be suitable for monitoring the space-occupying effect of both supra- and infratentorial strokes during treatment on critical care and stroke units.
OBJECTIVE: To test the practicability of a new double indicator dilution method for bedside monitoring of cerebral blood flow (CBF) and to assess the clinical value of CBF monitoring as a prognostic tool for outcome and in therapy of elevated intracranial pressure (ICP) in patients with acute hemispheric stroke. DESIGN: Prospective study. Clinical evaluation of a new method. SETTING: Neurological intensive care unit of a university hospital. PATIENTS: Ten patients with acute complete middle cerebral artery territory- or hemispheric infarctions. INTERVENTIONS: Two combined fiberoptic thermistor catheters were placed in the right jugular bulb and in the thoracic aorta. Central venous injections of ice-cold indocyanine green dye were performed. CBF was estimated by calculating the mean transit times of the cold bolus and dye. MEASUREMENTS AND MAIN RESULTS: A total of 104 reproducible CBF measurements were obtained. No complications associated with the method were observed. Twelve pairs of measurements were performed within 30 mins with unchanged clinical conditions. The standard deviation of repeated measurements was 2.7 mL/100 g/min; the interrater reliability was between 0.95 and 0.99. The median CBF in patients who died (n = 4) was lower (27 mL/100g/min) than in those who survived (n = 6) (45 mL/100g/ min). Patients who died more frequently had low CBF values of <30 mL/100g/min (22 of 38; 58%) than patients who survived (10 of 54; 19%). A total of 37 CBF measurements were done during ICP elevation of >20 mm Hg. In patients who survived, ICP elevations were only associated with low CBF values in 5 of 26 events; whereas in patients who died, ICP elevations were associated with low CBF values in 8 of 11 events. CONCLUSIONS: The new double indicator dilution technique may be suitable for serial bedside CBF measurement. It is easy to perform and can be rapidly repeated in the ICU environment. Validation of the method by comparison with standard methods is needed. The preliminary data indicate that bedside monitoring of CBF may give prognostic information for outcome and may guide therapy of elevated ICP in patients with malignant hemispheric infarction.
BACKGROUND AND OBJECTIVE: Dissection of extracranial arteries that supply the brain is a common cause of ischemic stroke in youngish persons. Yet this disease, with its warning and early symptoms, is inadequately known among the population as well as doctors. This study was undertaken to demonstrate the incidence, severity and sequelae of this condition, important in both routine general and hospital practice, with particular emphasis on early signs and diagnosis. PATIENTS AND METHODS: The data from 33 patients (20 men, 13 women, average age 42 [21-72] years) who during one year had been treated in the authors' hospital for carotid (n = 23) or vertebral (n = 10) artery dissection were analysed. RESULTS: The admission diagnosis of dissection, based on the history and ultrasound findings was in almost all cases confirmed by magnetic resonance imaging (wall haematoma), magnetic resonance angiograhy, computed tomography-angiography or conventional angiography. Typical warning and early symptoms such as whiplash sensation unilateral pain in the throat, neck and head or Horner's syndrome were elicited in nearly 50% of patients, while known causes such as trauma or connective tissue disease were confirmed in only 27%. Neurological deficits of ischemic infarction, some of them severe, persisted in two-thirds of patients, brain death occurred in one. CONCLUSIONS: Dissection of carotid or vertebral arteries is a statistically and medically relevant cause of stroke in youngish persons that can be diagnosed by attention to typical warning and early symptoms and the performance of noninvasive tests. The often life-threatening sequelae of possible cerebral ischemia can be diagnosed and even averted by early recognition of the cause.
A standardized postacute inpatient rehabilitation program (Anschlussheilbehandlung) after stroke is well established in Germany. Yet the needs of patients being admitted to an Anschlussheilbehandlung (AHB) are not completely known. Therefore sociodemographic data, handicap, impairment and neuropsychologic deficits in 200 stroke patients were evaluated before admission to an AHB with different scores (Barthel, modified Rankin Score, NIHSS, HAWIE-R, Wilde, etc.). About half of the patients were still working prestroke. Most patients suffered from several vascular risk factors, which were insufficiently treated, and about a third of the patients had cerebrovascular disease prior to this stroke. At admission to the rehabilitation program the group of patients with severe neurological deficits was small. In average the disability was rather moderate (Rankin = 2.6). Mainly gait and finger dexterity were handicapped. Functional impairment was outweighed by neuropsychological deficits.
PURPOSE: The feasibility and safety of combining carotid surgery and thrombolysis for occlusions of the internal carotid artery (ICA) and the middle cerebral artery (MCA), either as a simultaneous or as a staged procedure in acute ischemic strokes, was studied. METHODS: A nonrandomized clinical pilot study, which included patients who had severe hemispheric carotid-related ischemic strokes and acute occlusions of the MCA, was performed between January 1994 and January 1998. Exclusion criteria were cerebral coma and major infarction established by means of cerebral computed tomography scan. Clinical outcome was assessed with the modified Rankin scale. RESULTS: Carotid reconstruction and thrombolysis was performed in 14 of 845 patients (1.7%). The ICA was occluded in 11 patients; occlusions of the MCA (mainstem/major branches/distal branch) or the anterior cerebral artery (ACA) were found in 14 patients. In three of the 14 patients, thrombolysis was performed first, followed by carotid enarterectomy (CEA) after clinical improvement (6 to 21 days). In 11 of 14 patients, 0.15 to 1 mIU urokinase was administered intraoperatively, ie, emergency CEA for acute ischemic stroke (n = 5) or surgical reexploration after elective CEA complicated by perioperative intracerebral embolism (n = 6). Thirteen of 14 intracranial embolic occlusions and 10 of 11 ICA occlusions were recanalized successfully (confirmed with angiography or transcranial Doppler studies). Four patients recovered completely (Rankin 0), six patients sustained a minor stroke (Rankin 2/3), two patients had a major stroke (Rankin 4/5), and two patients died. In one patient, hemorrhagic transformation of an ischemic infarction was detectable postoperatively. CONCLUSION: Combining carotid surgery with thrombolysis (simultaneous or staged procedure) offers a new therapeutic approach in the emergency management of an acute carotid-related stroke. Its efficacy should be evaluated in interdisciplinary studies.
PURPOSE: Homocysteine is an experimental convulsant and an established risk factor in atherosclerosis. A nutritional deficiency of vitamin B6, vitamin B12, or folate leads to increased homocysteine plasma concentrations. During treatment with carbamazepine (CBZ), phenytoin, or phenobarbital, a deficiency in these vitamins is common. The objective of the study was to test the hypothesis that antiepileptic drug (AED) treatment is associated with increased homocysteine plasma concentrations. METHODS: A total of 51 consecutive outpatients of our epilepsy clinic receiving stable, individually adjusted AED treatment and 51 sex- and age-matched controls were enrolled in the study. Concentrations of total homocysteine and vitamin B6 were measured in plasma; vitamin B12 and folate were measured in the serum of fasted subjects. RESULTS: Patients and controls differed significantly in concentrations of folate ( 13.5+/-1.0 vs. 17.4+/-0.8 nM and vitamin B6 (39.7+/-3.4 vs. 66.2+/-7.5 nM), whereas serum concentrations of vitamin B12 were similar. The homocysteine plasma concentration was significantly increased to 14.7+/-3.0 microM in patients compared with controls (9.5+/-0.5 microM; p < 0.05, Wilcoxon rank-sum test). The number of patients with concentrations of >15 microM was significantly higher in the patient group than among controls. The same result was obtained if only patients with CBZ monotherapy were included. Patients with increased homocysteine plasma concentrations had lower folate concentrations. CONCLUSIONS: These data support the hypothesis that prolonged AED treatment may increase plasma concentrations of homocysteine, although the alternative explanation that increased homocysteine plasma concentrations are associated with the disease and not the treatment cannot be completely excluded at the moment.
BACKGROUND AND PURPOSE: The hyperdense middle cerebral artery sign (HMCAS) is a marker of thrombus in the middle cerebral artery. The aim of our study was to find out the frequency of the HMCAS, its association with initial neurological severity and early parenchymal ischemic changes on CT, its relevance to clinical outcome, and the efficacy of intravenous recombinant tissue plasminogen activator (rtPA) in patients with the HMCAS. METHODS: Secondary analysis of the data from 620 patients who received either rtPA or placebo in the European Cooperative Acute Stroke Study I (ECASS I), a double-blind, randomized, multicenter trial. The baseline CT scans were obtained within 6 hours from the onset of symptoms. Functional and neurological outcomes were assessed using the modified Rankin Scale and the Scandinavian Stroke Scale at day 90. RESULTS: We found an HMCAS in 107 patients(17.7%). The initial neurological deficit was more severe in patients with the HMCAS than in those lacking this sign (P<0.0001). Early cerebral edema and mass effect were also more common in patients with the HMCAS (P<0.0001). The HMCAS was related to the risk of poor functional outcome (grade of 3 to 6 on the modified Rankin Scale) on univariate analysis: 90 patients (84%) with the HMCAS and 310 patients (62%) lacking this sign were dependent or dead at day 90 (P<0.0001). However, this association was no longer significant in a logistic model accounting for the effect of age, sex, treatment with rtPA, initial severity of neurological deficit and early parenchymal ischemic changes on CT. Patients with the HMCAS who were given rtPA had better neurological recovery than those who received placebo (P=0.0297). CONCLUSIONS: The HMCAS is associated with severe brain ischemia and poor functional outcome. However, it has no significant independent prognostic value when accounting for the effect of initial severity of neurological deficit and of early parenchymal ischemic changes on CT. Patients with the HMCAS may benefit from intravenous rtPA.
Several studies have proven the usefulness of thrombolytic agents in the therapy of ischemic stroke. Data from open and small placebo-controlled trials show a relationship between recanalization and an improved clinical outcome. Three large scaled studies have examine the effect of streptokinase treatment. Because of an increasing mortality the results of these studies were negative, and so streptokinase should not be used to treat acute ischemic stroke. In contrast, three rt-PA studies with together more than 2000 patients showed a significant benefit. Recent meta-analyses including data of all these trials show an odds ratio for death and disability of 0.67 (95 p. 100 CI 0.56; 0.8). The number needed to treat to prevent one death or disability is 11 in a 6 hour time window and 7 in a 3 hour time window. These are impressive numbers that are rarely found in other areas of internal or neurological medicine. The most important risk of thrombolytic therapy is the occurrence of intracerebral hemorrhage, which is reported as between 0-18 p. 100, but which is not associated with increased morbidity or mortality. At present, thrombolytic therapy cannot be recommended for all patients with acute stroke. Careful selection and experiences with this therapy and its risks are necessary.