Prediction of infarction development after endovascular stroke therapy with dual-energy computed tomography.

OBJECTIVES: After intraarterial recanalisation (IAR), the haemorrhage and the blood-brain barrier (BBB) disruption can be distinguished using dual-energy computed tomography (DECT). The aim of the present study was to investigate whether future infarction development can be predicted from DECT. METHODS: DECT scans of 20 patients showing 45 BBB disrupted areas after IAR were assessed and compared with follow-up examinations. Receiver operator characteristic (ROC) analyses using densities from the iodine map (IM) and virtual non-contrast (VNC) were performed. RESULTS: Future infarction areas are denser than future non-infarction areas on IM series (23.44 ± 24.86 vs. 5.77 ± 2.77; p < 0.0001) and more hypodense on VNC series (29.71 ± 3.33 vs. 35.33 ± 3.50; p < 0.0001). ROC analyses for the IM series showed an area under the curve (AUC) of 0.99 (cut-off: <9.97 HU; p < 0.05; sensitivity 91.18 %; specificity 100.00 %; accuracy 0.93) for the prediction of future infarctions. The AUC for the prediction of haemorrhagic infarctions was 0.78 (cut-off >17.13 HU; p < 0.05; sensitivity 90.00 %; specificity 62.86 %; accuracy 0.69). The VNC series allowed prediction of infarction volume. CONCLUSIONS: Future infarction development after IAR can be reliably predicted with the IM series. The prediction of haemorrhages and of infarction size is less reliable. KEY POINTS: • The IM series (DECT) can predict future infarction development after IAR. • Later haemorrhages can be predicted using the IM and the BW series. • The volume of definable hypodense areas in VNC correlates with infarction volume.

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.

Non-toxic cadmium concentrations induce vascular inflammation and promote atherosclerosis.

BACKGROUND: Cadmium is a potential new risk factor for early atherosclerosis and cardiovascular diseases in humans, yet pathogenetic mechanisms are still a matter of debate. METHODS AND RESULTS: In-depth histological analysis of 18 sections taken from 6 cadmium-fed ApoE-/- mice and 12 sections from 5 litter-mates not exposed to cadmium by light and scanning electron microscopy was performed. Cadmium-fed mice showed a marked increase in lesion load (plaque area) and severity as classified according to the American Heart Association vascular lesion grading. All inflammatory markers studied (CD68, CD3, CD25, vascular cell adhesion molecule 1 (VCAM-1), and heat shock protein 60 (Hsp60)) yielded a higher expression in cadmium-fed mice. Statistical difference was achieved for VCAM-1 and Hsp60 (P=0.03 and P=0.02). The shoulder region of atherosclerotic plaques in cadmium-fed mice showed a prominent retraction of endothelial cells on electron microscopy. CONCLUSIONS: Our data indicate that cadmium exposure amplifies the development of vessel pathology in atherosclerosis susceptible ApoE-/- mice and suggests upregulation of VCAM-1 and Hsp60 and endothelial leakage as potential pathomechanisms.

Stroke thrombolysis: having more time translates into delayed therapy: data from the Austrian Stroke Unit Registry.

BACKGROUND AND PURPOSE: Efficacy of intravenous thrombolysis in acute ischemic stroke declines with increasing time to treatment initiation. Previous small-scale studies suggested that the earlier patients arrive, the longer it takes to administer recombinant tissue plasminogen activator. METHODS: Of 32 529 patients with stroke prospectively enrolled in the Austrian Stroke Unit Registry (2004 to 2009), 3287 received intravenous thrombolysis and 2663 of them were eligible for the current analysis. RESULTS: Median (interquartile range) onset-to-door and door-to-needle times were 70 (50 to 100) and 50 (35 to 70) minutes. Of note, both time intervals were inversely correlated with each other. After adjustment for multiple stroke characteristics, the door-to-needle time of patients arriving in the hospital within the first hour after stroke onset was 6.9 minutes (P<0.001) and 13.9 minutes (P<0.001) longer than those for patients arriving between 61 to 120 and 121 to 180 minutes. Findings were consistent in subgroups. CONCLUSIONS: Early hospital arrival translates into a significant delay in the application of intravenous thrombolysis among patients with acute stroke. This finding calls for concerted measures to ensure that all patients with stroke are treated with the same urgency irrespective of the time available.

ABCD3-I score and the risk of early or 3-month stroke recurrence in tissue- and time-based definitions of TIA and minor stroke.

Changing definition of TIA from time to a tissue basis questions the validity of the well-established ABCD3-I risk score for recurrent ischemic cerebrovascular events. We analyzed patients with ischemic stroke with mild neurological symptoms arriving < 24 h after symptom onset in a phase where it is unclear, if the event turns out to be a TIA or minor stroke, in the prospective multi-center Austrian Stroke Unit Registry. Patients were retrospectively categorized according to a time-based (symptom duration below/above 24 h) and tissue-based (without/with corresponding brain lesion on CT or MRI) definition of TIA or minor stroke. Outcome parameters were early stroke during stroke unit stay and 3-month ischemic stroke. Of the 5237 TIA and minor stroke patients with prospectively documented ABCD3-I score, 2755 (52.6%) had a TIA by the time-based and 2183 (41.7%) by the tissue-based definition. Of the 2457 (46.9%) patients with complete 3-month followup, corresponding numbers were 1195 (48.3%) for the time- and 971 (39.5%) for the tissue-based definition of TIA. Early and 3-month ischemic stroke occurred in 1.1 and 2.5% of time-based TIA, 3.8 and 5.9% of time-based minor stroke, 1.2 and 2.3% of tissue-based TIA as well as in 3.1 and 5.5% of tissue-based minor stroke patients. Irrespective of the definition of TIA and minor stroke, the risk of early and 3-month ischemic stroke steadily increased with increasing ABCD3-I score points. The ABCD3-I score performs equally in TIA patients in tissue- as well as time-based definition and the same is true for minor stroke patients.

Predictive value of ABCD2 and ABCD3-I scores in TIA and minor stroke in the stroke unit setting.

OBJECTIVE: It is not clear whether risk scores for early stroke recurrence after TIA that have been mainly established in outpatient and emergency department settings are valid on the background of highly specialized stroke unit care. METHODS: ABCD2 and ABCD3-I scores have been prospectively documented in a cohort of patients admitted to Austrian stroke units within 24 hours of symptom onset with TIA or minor stroke (NIH Stroke Scale score <4). RESULTS: A total of 5,237 TIA and minor stroke patients met inclusion criteria, with 3-month follow-up data available on 2,457. Early and 3-month stroke were observed in 2.4% and 4.2% of the study population. The probability of early stroke during the stroke unit stay (median 2 [interquartile range 1-3] days) steadily increased from 0% to 4.8% and 0% to 16.7% with increasing ABCD2 and ABCD3-I score points, respectively. On 3-month follow-up, stroke risk increased from 0% to 8.0% and 0% to 23.8% with increasing ABCD2 and ABCD3-I score points, respectively. Of the individual score components, age, blood pressure, and diabetes were not related to early or 3-month stroke, whereas clinical presentation (C), symptom duration (D), and cerebral as well as carotid imaging (I) were and accounted for the information provided by the full scores. CONCLUSIONS: Standard ABCD2 and ABCD3-I scores are useful instruments to estimate the probability of early and 3-month stroke in TIA and minor stroke patients treated at specialized stroke units, with C, D, and I being the most important score components in this setting.

Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study.

BACKGROUND: Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients. METHODS: In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13). FINDINGS: We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001). INTERPRETATION: During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke. FUNDING: Reformpool of the Tyrolean Health Care Fund.

Recanalization of extracranial internal carotid artery occlusion after i.v. thrombolysis for acute ischemic stroke.

BACKGROUND: Although extracranial internal carotid artery (e-ICA) occlusion is a common pathology in patients undergoing intravenous thrombolysis for treatment of acute ischemic stroke, no data on e-ICA recanalization rate or potential effects on outcome are yet available. METHODS AND RESULTS: This study included 52 consecutive patients with e-ICA occlusion and ischemic stroke undergoing standard intravenous thrombolysis. The rate of e-ICA recanalization was 30.8% [95%CI, 18.2-43.3], documented at 3.5 [2.0-11.8] (median [IQR]) days after stroke, as compared to 8.6% [95%CI, 3.5-13.7] in a series of 116 consecutive patients with symptomatic e-ICA occlusion not undergoing thrombolysis (P<0.001 for difference). Functional outcome three months after stroke did not significantly differ for those with or without e-ICA recanalization following intravenous thrombolysis (modified Rankin scale ≤2: 31.3% vs. 22.2%, odds ratio 1.6 [95%CI, 0.4-5.9], P = 0.506). In patients with e-ICA occlusion of atherothrombotic origin, recanalization resulted in most instances in residual high-grade stenosis (13 of 14). CONCLUSIONS: Recanalization of e-ICA occlusion after stroke thrombolysis occurred in about one third of patients. Although e-ICA recanalization had no significant effect on patient outcome, control sonography in the early days after thrombolysis is recommended for the detection of potential residual e-ICA stenosis.

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.

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, I(2) = 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.

A case of a traumatic trigeminal-cavernous fistula occluded by coil embolization.

BACKGROUND: A trigeminal artery as the most common persisting embryonic carotid-basilar anastomosis is found in up to .2% of adults. In rare instances, trigeminal-cavernous fistulas develop either spontaneously or after a trauma. RESULTS: We present a 16-year-old patient with a traumatic trigeminal-cavernous fistula (Saltzmann type 2), which was successfully treated by interventional occlusion of the persistent trigeminal artery. After intervention, clinical symptoms (chemosis, right-temporal bruits, and sixth nerve palsy) resolved. DISCUSSION: In this case, fistula occlusion was achieved by coil embolization with only 4 coils placed directly at the rupture point of the trigeminal artery but not into the cavernous sinus. Thus, the cavernous sinus was preserved in function and structure. Special anatomy and interventional peculiarities of this unique case are described in detail.

Phenotypical variability of post-partum reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome is recognized increasingly as a complication of the postpartum period. Our series of four cases illustrates its phenotypical variability, summarizes the diagnostic work-up, and outlines potential treatment strategies for this usually benign but sometimes disabling and life-threatening disease.

Progressive leukoencephalopathy caused by primary CNS lymphoma.

Prominent leukoaraiosis is common in the clinical routine setting. In addition to microatheroma and hypertensive small vessel disease (lipohyalinosis), a large number of rare but clinically relevant differential diagnoses have to be considered. A man in his 60s presented with left pontine infarction and subsequent rapidly deteriorating leukoaraiosis associated with dementia. Standard non-invasive examination did not enable the correct diagnosis to be obtained. A brain biopsy sample revealed a combination of diffuse infiltrating and intravascular large B cell central nervous system (CNS) lymphoma, which has not previously been described in literature. Despite immediate treatment with state of the art chemotherapy, the patient died 3 months after the onset of symptoms. Diffuse infiltrating and intravascular primary CNS lymphoma is a rare cause of rapidly progressive leukoencephalopathy and stroke mediated by neoplastic microvessel occlusion and inflammatory tissue damage. This report intends to increase awareness among neurologists and other stroke physicians about this disease in order to accelerate diagnosis and initiation of treatment.

[Implementation of thrombolysis in acute stroke--10-year results of the Innsbruck stroke registry]. / Einsatz der Thrombolyse beim akut ischämischen Schlaganfall : 10-Jahres-Ergebnisse an der Stroke Unit Innsbruck.

BACKGROUND: Randomized controlled trials have yielded evidence for the efficacy and safety of intravenous alteplase in the therapy of acute ischemic stroke. A large patient registry has recently confirmed the safe implementation of this therapy in the clinical routine setting. METHODS: Between January 1998 and December 2007 302 stroke patients were treated with 0.9 mg/kg rt-PA at the stroke unit of the Innsbruck University Hospital. Severity and circumstances of the stroke event, indicators of pre- and intrahospital management as well as safety and outcome at three months were prospectively assessed in the local thrombolysis database. RESULTS: The number of patients receiving intravenous thrombolysis increased continuously from 2 patients in 1998 to 67 in 2007 and 87 patients in 2008. 43% of our patients were females. The median age and NIHSS-score on admission was 67 and 16, respectively. The mean onset-to-needle time decreased from 171 min to 110 min--mainly due to a substantial shortening of the door-to-needle time from 105 min to 45 min. A proportion of 41% of our patients were treated in the main working time while 59% received rt-PA during night and weekend service. A total of 38% of our patients were functionally independent at three months (mRS 0-2). Once considering the high initial stroke severity in our patient series and correcting the NIHSS scores to levels usually seen in randomized control trials and patient registries, 56% of our patients would reach a good outcome (mRS 0-2). The rate of symptomatic intracranial bleedings was low at 6.3%. CONCLUSION: Our data reinforce that intravenous thrombolysis is safe in the treatment of acute ischemic stroke in clinical routine setting. Establishment of modern stroke services and the implementation of structural operating procedures have contributed to an increase in the number of treated patients and a parallel decrease in door-to-needle time at our hospital. Widespread educational programs in the general community, introduction of optimized pre-hospital triage algorithms as well as the potential extension of the 3-hour window to 4.5 hours all are suitable measures to further extend the benefit of i.v. thrombolysis to large proportion of stroke patients.