Impact of intravenous thrombolysis on functional outcome in patients with mild ischemic stroke without large vessel occlusion or rapidly improving symptoms.

BACKGROUND: Optimal treatment strategy in patients with mild ischemic stroke remains uncertain. While functional dependency or death has been reported in up to one-third of non-thrombolyzed mild ischemic stroke patients, intravenous thrombolysis is currently not recommended in this patient group. Emerging evidence suggests two risk factors-rapid early improvement and large vessel occlusion-as main associates of unfavorable outcome in mild ischemic stroke patients not undergoing intravenous thrombolysis. AIMS: To analyze natural course as well as safety and three-month outcome of intravenous thrombolysis in mild ischemic stroke without rapid early improvement or large vessel occlusion. METHODS: Mild ischemic stroke was defined by a National Institute of Health Stroke Scale score ≤6. We used the modified Rankin Scale (mRS) to compare three-month functional outcome in 370 consecutive mild ischemic stroke patients without early rapid improvement and without large vessel occlusion, who either underwent intravenous thrombolysis (n = 108) or received best medical treatment (n = 262). RESULTS: Favorable outcome (mRS ≤ 1) was common in both groups (intravenous thrombolysis: 91%; no intravenous thrombolysis: 90%). Although intravenous thrombolysis use was independently associated with a higher risk of asymptomatic hemorrhagic transformation (OR = 4.62, p = 0.002), intravenous thrombolysis appeared as an independent predictor of mRS = 0 at three months (OR = 3.33, p < 0.0001). CONCLUSIONS: Mild ischemic stroke patients without rapidly improving symptoms and without large vessel occlusion have a high chance of favorable three-month outcome, irrespective of treatment type. Patients receiving intravenous thrombolysis, however, more often achieved complete remission of symptoms, which particularly in mild ischemic stroke may constitute a meaningful endpoint.

Effective surgical treatment of cerebral cavernous malformations: a multicenter study of 79 pediatric patients.

OBJECT: Cerebral cavernous malformations (CCMs) are common vascular lesions in the brain, affecting approximately 0.5% of the population and representing 10%-20% of all cerebral vascular lesions. One-quarter of all CCMs affect pediatric patients, and CCMs are reported as one of the main causes of brain hemorrhage in this age group. Symptoms include epileptic seizures, headache, and focal neurological deficits. Patients with symptomatic CCMs can be treated either conservatively or with resection if lesions cause medically refractory epilepsy or other persistent symptoms. METHODS: The authors retrospectively analyzed 79 pediatric patients (41 boys and 38 girls) from 3 different centers, who were surgically treated for their symptomatic CCMs between 1974 and 2004. The mean age of the children at first manifestation was 9.7 years, and the mean age at operation was 11.3 years. The main goal was to compare the clinical outcomes with respect to the location of the lesion of children who preoperatively suffered from epileptic seizures. RESULTS: Of these patients, 77.3% were seizure free (Engel Class I) after the resection of the CCM. Significant differences in the outcome between children who harbored CCMs at different locations were not found. CONCLUSIONS: Resection seems to be the favorable treatment of symptomatic CCMs not only in adults but also in children.

Impact of obesity on stroke outcome after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Obesity is an established risk factor for stroke and has reached epidemic proportions. However, its impact on intravenous thrombolysis applied for acute ischemic stroke is not well known. We aimed to compare the clinical outcome and safety after intravenous thrombolysis in obese (body mass index ≥30 kg/m²) and nonobese (body mass index <30 kg/m²) patients with ischemic stroke. METHODS: Data of 304 consecutive patients with stroke (251 nonobese and 53 obese) treated with intravenous thrombolysis were studied. We assessed the rate of favorable outcome (modified Rankin Scale score 0 or 1), mortality, and symptomatic intracranial hemorrhage in the 2 groups. RESULTS: Obese patients presented more often with diabetes mellitus (30.2% versus 12.4%, P<0.01) and arterial hypertension (77.4% versus 61.4%, P=0.03) as compared with their nonobese counterparts. At 3 months, the rate of favorable outcome was lower in obese compared with nonobese patients (50.9% versus 68.1%, P=0.02). More obese than nonobese patients died (13.2% versus 4.0%, P=0.01), whereas the rate of symptomatic intracranial hemorrhage was similar in the 2 groups (1.9% versus 1.6%, P=1.0). After multivariable adjustment, obesity still remained an independent predictor of unfavorable outcome (P=0.04) and mortality (P=0.04). CONCLUSIONS: Our data indicate that obesity is an independent predictor of unfavorable clinical outcome and mortality in acute ischemic stroke treated with intravenous thrombolysis.

Outcomes of intravenous thrombolysis in posterior versus anterior circulation stroke.

BACKGROUND AND PURPOSE: Intravenous thrombolysis is an approved treatment for anterior (ACS) and posterior (PCS) circulation stroke. However, no randomized controlled trial has investigated safety and efficacy of intravenous thrombolysis according to stroke territory, although PCS is assumed to differ from ACS in many ways. We aimed to compare the safety and clinical outcome of intravenous thrombolysis applied to patients with PCS and ACS. METHODS: Prospectively collected data of 883 consecutive patients with acute ischemic stroke (788 ACS, 95 PCS) treated with intravenous thrombolysis in 3 Swiss stroke centers were analyzed. Presenting characteristics, symptomatic intracranial hemorrhage, mortality, and favorable outcome (modified Rankin scale 0 or 1) at 3 months were compared between patients with PCS and ACS. RESULTS: As compared with patients with ACS, those with PCS were younger (mean age, 63 versus 67 years, P=0.012) and had a lower mean baseline National Institutes of Health Stroke Scale score (9 versus 12, P<0.001). Patients with PCS less often had symptomatic intracranial hemorrhage (0% versus 5%, P=0.026) and had more often a favorable outcome (66% versus 47%, P<0.001). Mortality was similar in the 2 groups (PCS, 9%; ACS, 13%; P=0.243). After multivariable adjustment, PCS was an independent predictor of lower symptomatic intracranial hemorrhage frequency (P=0.001), whereas stroke territory was not associated either with favorable outcome (P=0.177) or with mortality (P=0.251). CONCLUSIONS: Our study suggests that PCS is associated with a lower risk of symptomatic intracranial hemorrhage after intravenous thrombolysis as compared with ACS, whereas favorable outcome and mortality were similar in the 2 stroke territories.

Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data.

BACKGROUND AND PURPOSE: The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. METHODS: We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. RESULTS: We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. CONCLUSIONS: Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.

CT-based intravenous thrombolysis 3-4.5 hours after acute ischemic stroke in clinical practice.

BACKGROUND: Outcome of stroke patients selected with cerebral computed tomography for intravenous thrombolysis administered in clinical routine from 3 to 4.5 hours after symptoms onset is not well investigated. Aim of this single-center, prospective, observational study was to compare the safety and efficacy of intravenous alteplase given in routine clinical praxis 181-270 minutes (late) and within 180 minutes (early) after stroke onset in patients selected with cerebral computed tomography. METHODS: A total of 454 consecutive patients underwent intravenous thrombolysis within 4.5 hours after stroke onset. Sixty of 454 patients were excluded (inclusion in a controlled-randomized trial, n = 51; stroke mimics, n = 9). Of remaining 394 patients, 100 were included in the late group, and 294 were included in the early group. The outcome parameters of symptomatic intracranial hemorrhage at 24 hours, and mortality and favorable outcome (modified Rankin scale score 0-1) at 3 months, and its predictors were investigated. RESULTS: In the late cohort, median baseline National Institutes of Health Stroke Scale score was lower (9.5, interquartile range (IQR): 5-13; 11.3, IQR: 6-16; P = 0.01), and median time-to-treatment was longer (209, IQR: 190-222 minutes; 142, IQR: 125-170 minutes; P<0.0001) than in the early group. The incidence of symptomatic intracranial hemorrhage (2.0% versus 2.4%; P = 1.0), death (9.0% versus 9.9%; P = 1.0) and favorable outcome (58.0% versus 51.5%; P = 0.3) did not differ between the late and early cohorts. CONCLUSION: These data suggest that intravenous alteplase administered 181-270 minutes after symptoms onset in stroke patients selected with cerebral computed tomography is also beneficial in real-life clinical practice.

Differences in demographic characteristics and risk factors in patients with spontaneous vertebral artery dissections with and without ischemic events.

BACKGROUND AND PURPOSE: Spontaneous vertebral artery dissection (sVADs) mainly cause cerebral ischemia, with or without associated local symptoms and signs (headache, neck pain, or cervical radiculopathy), or with local symptoms and signs only. METHODS: We compared the presenting characteristics of consecutive patients with single sVADs and ischemic events and those with local symptoms and signs only. RESULTS: Of the 186 patients with first-ever unilateral sVAD, 165 (89%) presented with cerebral ischemia, and 21 (11%) presented with local symptoms and signs only. Patients with sVAD and ischemia were more often male (63% vs 29%; P=0.002), older (mean+/-SD age, 43.6+/-9.9 vs 38.6+/-9.0 years; P=0.027), and smokers (14% vs 3%; P=0.010), but less often, they had a history of migraine without aura (17% vs 38%; P=0.025) than did patients without ischemia. The multivariate analysis confirmed independent associations between male sex (P=0.024), increasing age (0.027), and smoking (P=0.012) and sVADs causing cerebral ischemia. CONCLUSIONS: These results suggest that men, older patients, and smokers with sVADs may be at increased risk for ischemic events.

Intravenous thrombolysis in stroke attributable to cervical artery dissection.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Whether this is also true for cervical artery dissection (CAD) is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score

Organized inpatient (stroke unit) care in very old patients.

BACKGROUND AND PURPOSE: It is unclear whether very old patients benefit from organized inpatient (stroke unit) care. The aim of this work was to compare the clinical outcome of patients with first-ever ischemic stroke aged either >or=80 or <80 years who were treated conservatively (without cerebral revascularization) in a university-based stroke unit. PATIENTS AND METHODS: We included 147 (11%) patients >or=80 years and 1241 (89%) patients, <80 years. All patients underwent clinical examination, blood tests, electrocardiography (ECG), brain imaging and cerebrovascular ultrasound. Additional investigations were done at the discretion of the treating physician. The modified Rankin scale (mRS) score was used to assess the 3-month outcome (favorable: mRS, 0-1; poor: mRS, 2-6; death of any cause). RESULTS: Stroke severity did not differ between both groups [median National Institutes of Health Stroke Scale (NIHSS) score, 4]. Younger patients underwent magnetic resonance (MR) imaging of the brain, MR and catheter angiography and echocardiography (p<0.001) more frequently, whereas older patients underwent computed tomography of the brain and 24-hour ECG (p<0.001) more frequently. Stroke prevention included clopidogrel (p<0.001) and heparin (p=0.047) more often in older patients and aspirin (p=0.016) in younger patients. Recurrent ischemic events were similarly frequent in old (7%) and young (5%) patients. Favorable outcome was equally prevalent in old (71%) and young (76%) patients, whereas mortality was higher in older patients (7 and 3%, p=0.007). Admission NIHSS score >or=12 was the only independent predictor of unfavorable outcome (odds ratio, 19.6; 95% confidence interval, 9.7-39.6; p<0.001). CONCLUSION: Our work provides further evidence that also the oldest patients may benefit from conservative stroke unit care.

Alpha-stat versus pH-stat guided ventilation in patients with large ischemic stroke treated by hypothermia.

BACKGROUND: Moderate hypothermia (MH) is a therapeutic approach for ischemic stroke as well as cardiac arrest. Two different technical strategies of ventilation during MH called alpha- and pH-stat dramatically influence cerebral blood flow (CBF). In turn this might influence neuronal damage and intracranial pressure (ICP). Therefore, effects of ventilation on CBF and ICP were measured in patients undergoing MH because of large ischemic stroke to address optimal ventilation management. METHODS: Eight patients (n = 8) with large ischemic stroke in the territory of the middle cerebral artery (MCA) were treated by MH of 33 degrees C within 24 h after symptom onset. MH was applied at least for 72 h. Each day, patients were ventilated repetitively with either alpha-stat or pH-stat for 60 min periods. Alpha-stat was applied between the measurements. ICP, CBF, and mean arterial blood pressure (MABP) were measured. The xenon clearance method was used to assess CBF at the bedside. RESULTS: There were no significant differences between ICP values for alpha-stat or pH-stat during days 1 and 2 after induction of hypothermia. However, ICP was higher in the pH- as compared to the alpha-stat group (P < 0.05) and exceeded a mean of 20 mmHg on day 3. pH-stat led to a significant increase of CBF in all measures (P < 0.05), while MABP was unaffected. CONCLUSIONS: pH-stat implies a better CBF to the injured brain, while it might be dangerous by elevating ICP in more subacute stages.

R2-recanalization of spontaneous carotid artery dissection.

BACKGROUND AND PURPOSE: We set out to investigate the predictors and time course for recanalization of spontaneous dissection of the cervical internal carotid artery (SICAD). METHODS: We prospectively included 249 consecutive patients (mean age, 45+/-11 years) with 268 SICAD. Ultrasound examinations were performed at presentation, during the first month, and then at 3, 6, and 12 months, and clinical follow-ups after 3, 6, and 12 months. RESULTS: Of 268 SICADs, 20 (7.5%) presented with

Comparison of intraarterial and intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign.

BACKGROUND AND PURPOSE: It is unclear whether intraarterial (IAT) or intravenous (IVT) thrombolysis is more effective for ischemic stroke with hyperdense middle cerebral artery sign (HMCAS) on computed tomography (CT). The aim of this study was to compare IAT and IVT in stroke patients with HMCAS. METHODS: Comparison of data from 2 stroke units with similar management of stroke associated with HMCAS, except that 1 unit performed IAT with urokinase and the other IVT with plasminogen activator. Time to treatment was up to 6 hours for IAT and up to 3 hours for IVT. Outcome was measured by mortality and the modified Rankin Scale (mRS), dichotomized at 3 months into favorable (mRS 0 to 2) and unfavorable (mRS 3 to 6). RESULTS: One hundred twelve patients exhibited a HMCAS, 55 of 268 patients treated with IAT and 57 of 249 patients who underwent IVT. Stroke severity at baseline and patient age were similar in both groups. Mean time to treatment was longer in the IAT group (244+/-63 minutes) than in the IVT group (156+/-21 minutes; P=0.0001). However, favorable outcome was more frequent after IAT (n=29, 53%) than after IVT (n=13, 23%; P=0.001), and mortality was lower after IAT (n=4, 7%) than after IVT (n=13, 23%; P=0.022). After multiple regression analysis IAT was associated with a more favorable outcome than IVT (P=0.003) but similar mortality (P=0.192). CONCLUSIONS: In this observational study intraarterial thrombolysis was more beneficial than IVT in the specific group of stroke patients presenting with HMCAS on CT, even though IAT was started later. Our results indicate that a randomized trial comparing both thrombolytic treatments in patients with middle cerebral artery occlusion is warranted.

Ultrasound diagnosis of spontaneous carotid dissection with isolated Horner syndrome.

BACKGROUND AND PURPOSE: Isolated Horner syndrome without associated cranial nerve palsies or ischemic symptoms is an important presentation of spontaneous internal carotid artery dissection (sICAD). Ultrasound is often used as a screening method in these patients because cervical MRI is not always available on an emergency basis. Current knowledge on ultrasound findings in patients with sICAD presenting with isolated Horner syndrome is limited. METHODS: Patients were recruited from prospective cervical artery dissection databases of 3 tertiary care centers. Diagnosis of sICAD was confirmed by cervical MRI and MR angiography or digital subtraction angiography in all patients. Data on Doppler sonography and color duplex sonography examinations performed within 30 days of symptom onset were analyzed. RESULTS: We identified 88 patients with Horner syndrome as the only sign of sICAD. Initial ultrasound examination was performed in 72 patients after a mean time interval from symptom onset to examination of 11 (SD 8) days. The overall frequency of false-negative ultrasound findings was 31% (22 of 72 patients). It showed stenosis >or=80% or occlusion in 34 (47%) patients, and stenosis

Serum cholesterol levels do not influence outcome or recovery in acute ischemic stroke.

OBJECTIVE: To examine the influence of admission serum cholesterol levels (SCL) on severity of initial neurological deficit, neurological outcome at month 3 and neurological recovery in patients with acute first-ever ischemic stroke. METHODS: Prospectively collected data from 889 consecutive patients with first-ever acute ischemic stroke were retrospectively analysed. Patients who suffered a recurrent ischemic stroke (n=22) or died (n=30) during the follow-up period were excluded from this study. Age, gender, arterial hypertension, diabetes mellitus, smoking, stroke etiology, SCL and severity of neurological deficit, using the National Institute of Health Stroke Scale (NIHSS), at presentation (NIHSS0) and after 3 months (NIHSS1), were assessed. Neurological recovery was defined as difference in NIHSS score (Delta(NIHSS)), according to Delta(NIHSS)=NIHSS0 - NIHSS1. RESULTS: Data from 837 patients (66% men, age: 62 +/- 14 years) were analysed. NIHSS1 was 2.3 +/- 1.8 and Delta(NIHSS) was 3.4 +/- 3. Clinically insignificant correlations between SCL and NIHSS0 (r=-0.13, p=0.0002), NIHSS1 (r=-0.09, p=0.001) and Delta(NIHSS) (r=-0.1, p=0.03) were evident. Multivariate binary logistic regression analysis revealed smoking (p=0.008), stroke etiology (p=0.023) and NIHSS0 (p<0.001) but not age, gender, arterial hypertension, diabetes mellitus or SCL as predictors for Delta(NIHSS). CONCLUSION: Our data suggest that SCL in patients with acute ischemic stroke are not associated with neurological deficit on admission, outcome or neurological recovery.

Seizure outcome after resection of supratentorial cavernous malformations: a study of 168 patients.

PURPOSE: The optimal management of cerebral cavernous malformations (CCMs) with epileptic seizures is still a matter of debate. The aim of our study was to examine seizure outcome in the largest published series of surgically treated patients with epilepsy due to a supratentorial CCM, and to define predictors for good surgical outcome. METHODS: We retrospectively studied 168 consecutive patients with a single supratentorial CCM and symptomatic epilepsy in a multicenter study. Pre- and postoperative clinical examinations, age at epilepsy onset, age at operation, type of symptoms due to the CCM (seizures, headache, hemorrhage, focal deficits), type and frequency of epileptic seizures, and the localization and size of the CCM were assessed. Seizure outcome was determined in the first, second, and third postoperative years. RESULTS: The CCM was completely resected in all patients. More than two thirds of the patients were classified as seizure free in the first 3 postoperative years. Predictors for good seizure outcome were age older than 30 years at the time of surgery, mesiotemporal CCM localization, CCM size <1.5 cm, and the absence of secondarily generalized seizures. No mortality occurred in our series, but only mild postoperative neurologic deficits in 12 (7%) patients. CONCLUSIONS: Considering the natural history of CCMs, the favorable neurologic and seizure outcome, surgical resection of CCMs should be considered in all patients with supratentorial CCMs and concomitant epilepsy, irrespective of the presence or absence of predictors for a favorable seizure outcome.

Different degrees of hypothermia after experimental stroke: short- and long-term outcome.

BACKGROUND AND PURPOSE: The neuroprotective role of mild therapeutic hypothermia was established in animal models of cerebral ischemia. Still, several issues, including optimal target temperature, remain unclear. The optimal depth of hypothermia in a rat model of focal cerebral ischemia was investigated. METHODS: Eighty-four male Wistar rats (n=84) were subjected to filament occlusion of the middle cerebral artery for 90 minutes. Sixty animals were equally split into 6 groups kept at core temperatures of 37 degrees C, 36 degrees C, 35 degrees C, 34 degrees C, 33 degrees C, and 32 degrees C over a period of 4 hours starting 90 minutes after middle cerebral artery occlusion. Twenty-four hours later, after performing a neuroscore, animals were killed and brains examined for infarct size, edema, and invasion of leukocytes. In the second part, 24 animals (8 per group) were kept at 33 degrees C, 34 degrees C, and 37 degrees C for 4 hours, allowed to survive for 5 days, and underwent additional investigation of transferase dUTP nick-end labeling. RESULTS: In the first part, one animal in each treatment group and 2 animals in group 37 degrees C died. The infarct size and edema were smaller for 34 degrees C and 33 degrees C compared with all other groups (P<0.05) over 24 hours. These animals also had better functional outcome (P<0.05) with an advantage for 34 degrees C versus 33 degrees C (P<0.05). Leukocyte count was lower for 34 degrees C and 33 degrees C as compared with the 37 degrees C group. Similar results were obtained in the second part of the study with an advantage for 34 degrees C versus 33 degrees C. CONCLUSIONS: Our results suggest that the optimal depth of therapeutic hypothermia in temporary middle cerebral artery occlusion is 34 degrees C.

Spontaneous and endothelial-independent vasodilation are impaired in patients with spontaneous carotid dissection: a case-control study.

BACKGROUND AND PURPOSE: We undertook this case-control study in patients with unilateral spontaneous dissection of the cervical internal carotid artery to investigate spontaneous and endothelium-independent dilation of the nondissected, contralateral carotid arteries and the ipsilateral brachial artery using high-resolution ultrasound. METHODS: Spontaneous and endothelial-independent (nitroglycerin-mediated) absolute and relative dilation were assessed in the internal and common carotid and brachial arteries of 27 patients with unilateral spontaneous dissection of the cervical internal carotid artery and 27 age- and sex-matched healthy controls. RESULTS: Absolute and relative spontaneous and endothelial-independent dilation of the carotid, but not brachial arteries, were significantly lower in patients as compared with controls. CONCLUSIONS: Vasodilation abnormalities may be a predisposing factor for spontaneous dissection of the cervical internal carotid artery.