Alexandra Zangerle

Recanalization after thrombolysis in stroke patients Predictors and prognostic implications

Objective: To estimate rates, predictors, and prognostic importance of recanalization in an unselected series of patients with stroke treated with IV thrombolysis. Methods: We performed a CT angiography or transcranial Doppler (TCD) follow-up examination 24 hours after IV thrombolysis in 64 patients with documented occlusion of the intracranial internal carotid or middle cerebral artery (MCA). Complete recanalization was defined by a rating of 3 on the Thrombolysis in Myocardial Infarction or 4/5 on the Thrombolysis in Brain Ischemia grading scales. Information about risk factors, clinical features, and outcome was prospectively collected by standardized procedures. Results: Complete recanalization was achieved in 36 of the 64 patients (56.3%). There was a nonsignificant trend of recanalization rates to decline with a more proximal site of occlusion: 68.4% (M2 segment of MCA), 53.1% (M1 segment), and 46.2% (carotid T) (p for trend = 0.28). Frequencies of vessel reopening were markedly reduced in subjects with diabetes (9.1% vs 66.0% in nondiabetics, p < 0.001) and less so in subjects with additional extracranial carotid occlusion (p = 0.03). Finally, complete recanalization predicted a favorable stroke outcome at day 90 independently of the information provided by age, NIH Stroke Scale, and onset-to-needle time. Conclusions: We found a high rate of vessel recanalization after IV thrombolysis occlusion. However, recanalization was infrequent in patients with diabetes and extracranial carotid occlusion. Information on recanalization was a powerful, early predictor for clinical outcome.

Functional recovery after ischemic stroke—A matter of age Data from the Austrian Stroke Unit Registry

Objective: To analyze the association between patient age and good functional outcome after ischemic stroke with special focus on young patients who were numerically underrepresented in previous evaluations. Methods: Of 43,163 ischemic stroke patients prospectively enrolled in the Austrian Stroke Unit Registry, 6,084 (14.1%) were ≤55 years old. Functional outcome was available in a representative subsample of 14,256 patients free of prestroke disability, 2,223 of whom were 55 years or younger. Herein we analyzed the effects of age on good functional outcome 3 months after stroke (modified Rankin Scale score ≤2). Results: Good outcome was achieved in 88.2% (unadjusted probability) of young stroke patients (≤55 years). In multivariable analysis, age emerged as a significant predictor of outcome independent of stroke severity, etiology, performance of thrombolysis, sex, risk factors, and stroke complications. When the age stratum 56–65 years was used as a reference, odds ratios (95% confidence interval [95%CI]) of good outcome were 3.4 (1.9–6.4), 2.2 (1.6–3.2), and 1.5 (1.2–1.9) for patients aged 18–35, 36–45, and 46–55 years and 0.70 (0.60–0.81), 0.32 (0.28–0.37), and 0.18 (0.14–0.22) for those aged 66–75, 76–85, and >85 years (p < 0.001). In absolute terms, the regression-adjusted probability of good outcome was highest in the age group 18–35 years and gradually declined by 3.1%–4.2% per decade until age 75 with a steep drop thereafter. Findings applied equally to sexes and patients with and without IV thrombolysis or diabetes. Conclusions: Age emerged as a highly significant inverse predictor of good functional outcome after ischemic stroke independent of stroke severity, characteristics, and complications with the age-outcome association exhibiting a nonlinear scale and extending to young stroke patients. Neurology® 2012;78:279–285

Cardiovascular Risk Factors and Atherosclerosis in Young Women Atherosclerosis Risk Factors in Female Youngsters (ARFY Study)

Background and Purpose— Little research has been conducted into risk factors of atherosclerosis development in young women. Methods— This cross-sectional study enrolled 205 18- to 22-year-old female students from the Educational Centre for Allied Health Professions. A broad array of risk conditions and lifestyle behaviors was carefully assessed. Intima media thickness (IMT) was used as a well-established surrogate for atherosclerosis and a predictor of vascular risk. High IMT was defined as levels exceeding the 90th percentile in the common and/or internal carotid arteries. Results— In multivariable logistic regression analysis, systolic blood pressure, family history for hypertension, lipoprotein(a), homocysteine, T-cell immune reaction against human heat shock protein 60, and exposure to environmental tobacco smoke and exhaust gases emerged as independent predictors of high IMT. Obesity, metabolic syndrome, and classical risk factors other than high blood pressure were rare and unrelated to IMT. Findings were similar once focusing on IMT as a continuous variable. Conclusion— In female youngsters displaying initiating stages of vascular pathology, blood pressure level and numerous nontraditional risk conditions showed a significant relation to high IMT. Our study indicates that (auto)immune processes, high lipoprotein(a), and environmental exposure to tobacco smoke and traffic exhaust may play a role in early atherogenesis.

Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke thrombolysis

Objective: To quantify the risk for bleeding complications after thrombolysis for ischemic stroke in patients on warfarin (international normalized ratio [INR] ≤1.7) and to put these data into perspective with previous studies. Methods: A total of 548 consecutive stroke patients receiving IV recombinant tissue plasminogen activator (rtPA) were prospectively evaluated and details about warfarin pretreatment were carefully recorded. Prothrombin time–based INR values were measured before thrombolysis and 6 and 24 hours thereafter. Intracranial hemorrhage occurring within 72 hours was assessed by CT examinations and defined according to National Institute of Neurological Disorders and Stroke criteria. Main outcome variables were symptomatic intracranial and major systemic bleedings. Results: Of the 548 patients, 33 (6.0%) and 14 (2.6%) experienced symptomatic intracranial and major systemic bleedings, respectively. Patients taking warfarin until the day of or day before admission (n = 15, mean ± SD INR 1.21 ± 0.32 vs 1.01 ± 1.12, p = 0.030) faced an approximately 4-fold risk for intracranial hemorrhage (20.0% vs 5.6%, unadjusted odds ratio [OR] [95% confidence interval (CI)] 4.2 [1.1–15.7], p = 0.033). Findings were similar after adjustment for age, NIH Stroke Scale score, and diabetes (adjusted OR [95% CI] 4.1 [1.0–16.1], p = 0.044) and when focusing on any major bleeding (intracranial or systemic) (unadjusted OR [95% CI] 4.1 [1.3–13.6], p = 0.019). Half of the patients with bleedings showed an INR rise above 1.7 6 hours after thrombolysis. A meta-analysis yielded confirmatory yet heterogeneous results (unadjusted OR [95% CI] derived from a random effects model, 2.31 [1.15–4.62], p = 0.018, I2 = 58% [11%–80%]). Conclusions: Our data suggest a statistically significant and clinically meaningful increase in the risk for symptomatic intracranial and major systemic bleedings among patients with stroke thrombolysis receiving warfarin up to the day of or day before stroke. Neurology® 2012;79:31–38

Basilar Artery Dissection: Series of 12 Consecutive Cases and Review of the Literature

Background: Current knowledge on primary or isolated basilar artery dissection (IBAD) is limited to case vignettes and small patient series. Objective: To delineate the frequency and clinical presentations of IBAD along with short-term outcome, specific prognosis and targeted management. Methods: Data were derived from a series of 12 consecutive patients and a review of 88 cases reported in the literature. In all the cases, the dissection was confined to the basilar artery. Results: Disease incidence was estimated at 0.25 per 100,000 person-years. IBAD accounted for roughly 1.0% of all subarachnoid hemorrhage events and for no less than 10.5 and 4.5% of posterior circulation and brain-supplying artery dissections, respectively. The main clinical presentations were subarachnoid hemorrhage (46%) and posterior circulation brain ischemia (42%). Subarachnoid hemorrhage typically manifested at a higher age than brain ischemia (mean age, 48.9 vs. 41.4 years) and was more prevalent among women. Rebleedings related to pseudoaneurysm formation in patients with subarachnoid hemorrhage and recurrent ischemia in stroke patients were common in the acute phase (26.1 and 33.3%, respectively) but were rare in the long term. The outcome was generally favorable in stroke patients but variable in subarachnoid hemorrhage (case fatality rate, 21.7%). The mainstay of therapy for subarachnoid hemorrhage related to IBAD was endovascular occlusion of the aneurysm pouch whereas stroke patients were usually put on anticoagulants. Conclusions: IBAD is probably an underrecognized disease with heterogeneous clinical presentation and prognosis. It should be considered as a differential diagnosis in peritruncal subarachnoid hemorrhage, classic subarachnoid hemorrhage and posterior circulation stroke, especially in young individuals. Case management is challenging and has to be tailored to each patient.

Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis

Objective: Prominent fibrinogen cleavage by recombinant tissue plasminogen activator and formation of fibrinogen degradation products with anticoagulant properties was proposed to amplify the risk of thrombolysis-related bleeding complications, but supportive evidence mainly derived from studies on myocardial infarction. Methods: This study included 547 consecutive stroke patients treated with recombinant tissue plasminogen activator, who underwent repeated assessment of fibrinogen levels before and 6 hours after thrombolysis. Symptomatic intracranial hemorrhages were ascertained using National Institute of Neurological Disorders and Stroke criteria. Results: Intracranial hemorrhage or systemic bleeding events manifested in 47 patients (8.6%). A decrease ≥200 mg/dL in the fibrinogen level 6 hours after thrombolysis emerged as a significant and independent predictor for bleeding risk (multivariable odds ratio [95% confidence interval] 4.53 [2.39–8.60], p < 0.001). The population-attributable risk was 39.9% (95% confidence interval, 19.0–60.2) for any major bleeding, causality assumed, and surpassed 50% in patients with less severe strokes (NIH Stroke Scale score ≤16). Quantification of fibrinogen depletion after stroke thrombolysis significantly improved routine risk prediction of bleeding complications as indicated by an increase in the C-statistics from 0.712 to 0.798 (p = 0.015) and a net reclassification index of 0.341 (p < 0.001). A prospective bicenter validation sample (n = 148) corroborates the key findings of this study and suggests positive and negative predictive values of fibrinogen depletion for any major bleeding of 29.2% and 93.5%. Conclusion: This study lends strong support to the concept that prominent fibrinogen turnover after IV stroke thrombolysis—a condition termed “early fibrinogen degradation coagulopathy”—is a relevant cause of major bleeding complications. Rigorous testing of more fibrin-specific thrombolytic agents in the setting of acute stroke is warranted.

High dose Erythropoietin increases Brain Tissue Oxygen Tension in Severe Vasospasm after Subarachnoid Hemorrhage

BackgroundVasospasm-related delayed cerebral ischemia (DCI) significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH). Erythropoietin (EPO) may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2).MethodsSeven consecutive poor grade SAH patients with multimodal neuromonitoring (MM) received systemic EPO therapy (30.000 IU per day for 3 consecutive days) for severe cerebral vasospasm. Cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), intracranial pressure (ICP), PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model.ResultsA total of 22 interventions were analyzed. Median age was 47 years (32–68) and 86 % were female. Three patients (38 %) developed DCI. MAP decreased 2 hours after intervention (P < 0.04) without significantly affecting CPP and ICP. PbtO2 significantly increased over time (P < 0.05) to a maximum of 7 ± 4 mmHg increase 16 hours after infusion. Brain metabolic parameters did not change over time.ConclusionsEPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.

Prognostic Relevance of Limb Shaking in Symptomatic Carotid Artery Occlusion

Background: Internal carotid artery (ICA) occlusion, present in up to 15% of stroke patients, may cause low-flow transient ischemic attacks (TIAs) like limb shaking (LS) or retinal claudication (RC). Reliable data on the frequency of these phenomena and their potential prognostic relevance are still sparse. Aims: To provide more data about the frequency of low-flow TIA and investigate their influence on outcome. Material and Methods: Medical records of 260 consecutive patients with symptomatic ICA occlusion were carefully reviewed (survey period: January 2000 to December 2006). Baseline stroke severity and outcome at 90 days and in the long term were assessed. All patients were specifically questioned about symptoms of LS and RC, were exposed to bright light (pupillary testing) and carefully watched during testing of posture/gait and early mobilization. Results: LS, RC or both occurred in 28.6, 9.5 and 2.7%, respectively, of patients eligible for a thorough assessment of low-flow TIAs (n = 147). An adverse outcome was more likely in patients with LS than in those without at day 90 (modified Ranking Scale ≧4, 45.2 vs. 21.9%, p = 0.005) and in the long term (median, 37 months) (52.7 vs. 23.1%, p < 0.001). In a multivariable analysis, prognostic relevance was found to be independent of baseline stroke severity (National Institutes of Health Stroke Scale). There was also a tendency towards higher rates of recurrent stroke and TIA in limb shakers. RC had no prognostic relevance regarding functional outcome and recurrent events. Conclusion: In patients with ICA occlusion, RC and LS are more common than previously assumed. The presence of LS is associated with a worse outcome independent of initial stroke severity and patient characteristics.

[Juvenile stroke--results from the Austrian Stroke Registry].

In recent years, many aspects of juvenile stroke have been addressed in medium-sized case series. We have analyzed stroke severity, etiology, risk factors, and outcome in different age groups in the large dataset of the Austrian Stroke Unit Registry. In the nationwide Austrian Stroke Unit Registry 13,440 men and women with ischemic stroke or transient ischemic attack were recorded between March 2003 and February 2007. A number of important disease characteristics were documented by a stroke specialist upon admission of a patient and at discharge from the stroke unit and during a 3-month follow-up interview. A total of 749 patients (5.6%) were 18 to 45 years old and 1895 (14.1%) 18 to 55 years. Arterial dissection and cardiac/paradoxical embolism were the most common causes of stroke up to an age of 45. With a steeply increasing frequency of standard vascular risk factors, micro- and macroangiopathic causes of stroke substantially gain weight after the fourth decade of life. At 3-month follow-up, good clinical outcome (mRS 0-2) and death were 88.3% and 1.4% in the young (<or=55 years), and 65.3 (9.2%) in subjects aged 56 years and over. In multivariate analysis, young age (<or=55 years) predicted a good clinical outcome (Odds Ratio [95% confidence interval] 3.4 [2.4-5.0]) independently from stroke severity (NIH-SS), concomitant risk factors, stroke etiology, and thrombolytic therapy. Young men experience a significant delay in the onset-to-door time in comparison to other segments of the population. Increasing awareness about the relevance of stroke in the young is a valuable target for future health campaigns.SummaryIn recent years, many aspects of juvenile stroke have been addressed in medium-sized case series. We have analyzed stroke severity, etiology, risk factors, and outcome in different age groups in the large dataset of the Austrian Stroke Unit Registry. In the nationwide Austrian Stroke Unit Registry 13,440 men and women with ischemic stroke or transient ischemic attack were recorded between March 2003 and February 2007. A number of important disease characteristics were documented by a stroke specialist upon admission of a patient and at discharge from the stroke unit and during a 3-month follow-up interview. A total of 749 patients (5.6%) were 18 to 45 years old and 1895 (14.1%) 18 to 55 years. Arterial dissection and cardiac/paradoxical embolism were the most common causes of stroke up to an age of 45. With a steeply increasing frequency of standard vascular risk factors, micro- and macroangiopathic causes of stroke substantially gain weight after the fourth decade of life. At 3-month follow-up, good clinical outcome (mRS 0–2) and death were 88.3% and 1.4% in the young (≤55 years), and 65.3 (9.2%) in subjects aged 56 years and over. In multivariate analysis, young age (≤55 years) predicted a good clinical outcome (Odds Ratio [95% confidence interval] 3.4 [2.4–5.0]) independently from stroke severity (NIH-SS), concomitant risk factors, stroke etiology, and thrombolytic therapy. Young men experience a significant delay in the onset-to-door time in comparison to other segments of the population. Increasing awareness about the relevance of stroke in the young is a valuable target for future health campaigns.ZusammenfassungViele Aspekte des juvenilen Schlaganfalls wurden bereits an kleinen bis mittelgroßen Fallserien beschrieben. Wir analysierten den großen Datensatz des Österreichischen Stroke Unit Registers in Hinblick auf Schweregrad, Ätiologie, Risikofaktoren und Outcome von Schlaganfällen in den verschiedenen Altersgruppen. Im österreichweiten Stroke Unit Register wurden zwischen März 2003 und Februar 2007 13.440 Männer und Frauen mit ischämischem Schlaganfall oder einer transitorisch-ischämischen Attacke jenseits des 18. Lebensjahres registriert. Eine Vielzahl von Parametern wurde bei Aufnahme und Entlassung, sowie in einem 3-Monats-Follow-up erhoben 749 (5,6 %) Patienten waren zwischen 18 und 45 bzw. 1895 (14,1 %) zwischen 18 und 55 Jahre alt. Unter den bekannten Schlaganfallätiologien waren in der jungen Population (18.–45. Lebensjahr) die Dissektion und kardiale paradoxe Embolie die häufigsten. Ab der 4. Lebensdekade nahmen – parallel zum Anstieg der vaskulären Risikofaktoren – die Häufigkeit von arteriosklerotisch bedingter Mikro- und Makroangiopathie zu. Im 3-Monats-Follow-up waren 1.4 % der jungen Schlaganfallpatienten (≤55 Jahre) und 9,2 % der über 55-Jährigen verstorben, eine gutes klinisches Outcome (mRS 0–2) wurde bei 88,3 % bzw. 65,3 % beobachtet. In der multivariaten Analyse war junges Alter (≤55 Jahre) ein signifikanter Prädiktor für Selbständigkeit nach 3 Monaten (Odds Ratio [95 % Konfidenzintervall] 3,4 [2,4–5,0]) unabhängig von Geschlecht, NIH-SS bei Aufnahme, begleitenden Risikofaktoren, erfolgter Lysetherapie und Ätiologie. Bei jungen Männern ist die Zeitspanne zwischen Manifestation des Schlaganfalls und Eintreffen im Krankenhaus signifikant länger als in der restlichen Population, was Anlass zu entsprechenden Aufklärungskampagnen geben sollte.

Juveniler Schlaganfall in Österreich – Daten aus dem Österreichischen Schlaganfallregister

In recent years, many aspects of juvenile stroke have been addressed in medium-sized case series. We have analyzed stroke severity, etiology, risk factors, and outcome in different age groups in the large dataset of the Austrian Stroke Unit Registry. In the nationwide Austrian Stroke Unit Registry 13,440 men and women with ischemic stroke or transient ischemic attack were recorded between March 2003 and February 2007. A number of important disease characteristics were documented by a stroke specialist upon admission of a patient and at discharge from the stroke unit and during a 3-month follow-up interview. A total of 749 patients (5.6%) were 18 to 45 years old and 1895 (14.1%) 18 to 55 years. Arterial dissection and cardiac/paradoxical embolism were the most common causes of stroke up to an age of 45. With a steeply increasing frequency of standard vascular risk factors, micro- and macroangiopathic causes of stroke substantially gain weight after the fourth decade of life. At 3-month follow-up, good clinical outcome (mRS 0-2) and death were 88.3% and 1.4% in the young (<or=55 years), and 65.3 (9.2%) in subjects aged 56 years and over. In multivariate analysis, young age (<or=55 years) predicted a good clinical outcome (Odds Ratio [95% confidence interval] 3.4 [2.4-5.0]) independently from stroke severity (NIH-SS), concomitant risk factors, stroke etiology, and thrombolytic therapy. Young men experience a significant delay in the onset-to-door time in comparison to other segments of the population. Increasing awareness about the relevance of stroke in the young is a valuable target for future health campaigns.SummaryIn recent years, many aspects of juvenile stroke have been addressed in medium-sized case series. We have analyzed stroke severity, etiology, risk factors, and outcome in different age groups in the large dataset of the Austrian Stroke Unit Registry. In the nationwide Austrian Stroke Unit Registry 13,440 men and women with ischemic stroke or transient ischemic attack were recorded between March 2003 and February 2007. A number of important disease characteristics were documented by a stroke specialist upon admission of a patient and at discharge from the stroke unit and during a 3-month follow-up interview. A total of 749 patients (5.6%) were 18 to 45 years old and 1895 (14.1%) 18 to 55 years. Arterial dissection and cardiac/paradoxical embolism were the most common causes of stroke up to an age of 45. With a steeply increasing frequency of standard vascular risk factors, micro- and macroangiopathic causes of stroke substantially gain weight after the fourth decade of life. At 3-month follow-up, good clinical outcome (mRS 0–2) and death were 88.3% and 1.4% in the young (≤55 years), and 65.3 (9.2%) in subjects aged 56 years and over. In multivariate analysis, young age (≤55 years) predicted a good clinical outcome (Odds Ratio [95% confidence interval] 3.4 [2.4–5.0]) independently from stroke severity (NIH-SS), concomitant risk factors, stroke etiology, and thrombolytic therapy. Young men experience a significant delay in the onset-to-door time in comparison to other segments of the population. Increasing awareness about the relevance of stroke in the young is a valuable target for future health campaigns.ZusammenfassungViele Aspekte des juvenilen Schlaganfalls wurden bereits an kleinen bis mittelgroßen Fallserien beschrieben. Wir analysierten den großen Datensatz des Österreichischen Stroke Unit Registers in Hinblick auf Schweregrad, Ätiologie, Risikofaktoren und Outcome von Schlaganfällen in den verschiedenen Altersgruppen. Im österreichweiten Stroke Unit Register wurden zwischen März 2003 und Februar 2007 13.440 Männer und Frauen mit ischämischem Schlaganfall oder einer transitorisch-ischämischen Attacke jenseits des 18. Lebensjahres registriert. Eine Vielzahl von Parametern wurde bei Aufnahme und Entlassung, sowie in einem 3-Monats-Follow-up erhoben 749 (5,6 %) Patienten waren zwischen 18 und 45 bzw. 1895 (14,1 %) zwischen 18 und 55 Jahre alt. Unter den bekannten Schlaganfallätiologien waren in der jungen Population (18.–45. Lebensjahr) die Dissektion und kardiale paradoxe Embolie die häufigsten. Ab der 4. Lebensdekade nahmen – parallel zum Anstieg der vaskulären Risikofaktoren – die Häufigkeit von arteriosklerotisch bedingter Mikro- und Makroangiopathie zu. Im 3-Monats-Follow-up waren 1.4 % der jungen Schlaganfallpatienten (≤55 Jahre) und 9,2 % der über 55-Jährigen verstorben, eine gutes klinisches Outcome (mRS 0–2) wurde bei 88,3 % bzw. 65,3 % beobachtet. In der multivariaten Analyse war junges Alter (≤55 Jahre) ein signifikanter Prädiktor für Selbständigkeit nach 3 Monaten (Odds Ratio [95 % Konfidenzintervall] 3,4 [2,4–5,0]) unabhängig von Geschlecht, NIH-SS bei Aufnahme, begleitenden Risikofaktoren, erfolgter Lysetherapie und Ätiologie. Bei jungen Männern ist die Zeitspanne zwischen Manifestation des Schlaganfalls und Eintreffen im Krankenhaus signifikant länger als in der restlichen Population, was Anlass zu entsprechenden Aufklärungskampagnen geben sollte.