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Objective: To assess whether connective tissue disorder is evident in patients with spontaneous cervical artery dissection and therefore identify patients at risk of recurrence using a cutting-edge quantitative proteomics approach., Methods: In the ReSect study, all patients with spontaneous cervical artery dissection treated at the Innsbruck University Hospital since 1996 were invited to attend a standardized clinical follow-up examination. Protein abundance in skin punch biopsies (n = 50) was evaluated by a cutting-edge quantitative proteomics approach (liquid chromatography-mass spectrometry) that has hitherto not been applied to such patients., Results: Patients with 1-time single-vessel (n = 19) or multiple-vessel (n = 13) dissections did not differ between each other or compared to healthy controls (n = 12) in protein composition. Patients with recurrent spontaneous cervical artery dissection (n = 6), however, showed significantly different expression of 25 proteins compared to the other groups combined. Literature review and Gene Ontology term annotation check revealed that 13 of the differently expressed proteins play a major role in the structural integrity of connective tissue or are linked to connective tissue disorders. These proteins showed clustering to a collagen/elastin cluster and one consisting of desmosome related proteins., Conclusion: This study unravels an extracellular matrix protein signature of recurrent spontaneous cervical artery dissection. In the long run and after large-scale validation, our findings may well assist in identifying patients at risk of recurrent spontaneous cervical artery dissection and thus guide therapy., (© 2020 American Academy of Neurology.)

Objective: To analyze the frequency of inadequately treated risk factors in a large representative cohort of patients with acute ischemic stroke or TIA and to estimate the proportion of events potentially avertable by guideline-compliant preventive therapy compared to the status quo., Methods: A total of 1,730 patients from the Poststroke Disease Management STROKE-CARD trial (NCT02156778) were recruited between 2014 and 2017. We focused on 8 risk conditions amenable to drug therapy and 3 lifestyle risk behaviors and assessed pre-event risk factor control in retrospect., Results: The proportion of patients with at least 1 inadequately treated risk condition was 79.5% (95% confidence interval [CI] 77.6%-81.4%) and increased to 95.1% (95% CI 94.1%-96.1%) upon consideration of the lifestyle risk behaviors. Risk factor control was worse in patients with recurrent vs first-ever events ( p < 0.001), men vs women ( p = 0.003), and patients ≤75 vs >75 years of age ( p < 0.001). The estimated degree of stroke preventability ranged from 0.4% (95% CI 0.2%-0.6%) to 13.7% (95% CI 12.2%-15.2%) for the individual risk factors. Adequate control of the 5 most relevant risk factors combined (hypertension, hypercholesterolemia, atrial fibrillation, smoking, and overweight) would have averted ≈1 of 2 events or 1 in 4 with a highly conservative computation approach., Conclusions: Our study confirms the existence of a considerable gap between risk factor control recommended by guidelines and real-world stroke prevention. Our study intends to increase awareness among physicians about stroke preventability and provides a quantitative basis for the emerging discussion on how to best tackle this challenge., (© 2019 American Academy of Neurology.)

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., (© 2016 American Academy of Neurology.)

Objective: To determine whether chronic alcohol consumption or acute alcohol intoxication affects the rate of IV thrombolysis (IVT) and associated risk of symptomatic intracranial hemorrhage (SICH) in patients with acute ischemic stroke (IS)., Methods: We analyzed data from the nationwide Austrian Stroke Unit Registry for all patients with IS admitted to one of 35 stroke units between 2004 and 2014. We compared demographic and clinical characteristics for patients with chronic alcohol consumption (>2 drinks/d) or acute intoxication and for patients without these factors and their rates of IVT and associated SICH., Results: We identified 47,422 patients with IS. Of these patients, 3,999 (8.5%) consumed alcohol chronically and 216 (0.5%) presented with acute intoxication. Alcohol abusers were younger, more frequently men, and less often functionally disabled before the index event. Stroke severity was comparable between alcoholic and nonalcoholic IS patients. Nevertheless, patients who abused alcohol were less likely to receive IVT (16.6% vs 18.9%) and this difference remained after accounting for possible confounders. Rates of SICH after IVT were not increased in patients who abused alcohol (2.1% vs 3.7%, p = 0.04). Multivariate analysis including age, NIH Stroke Scale score, and time from symptom onset to IVT treatment showed that alcohol abuse was not an independent risk factor for SICH and was not protective (odds ratio 0.73, 95% confidence interval 0.43-1.25, p = 0.2)., Conclusions: IS patients with chronic alcohol consumption or acute intoxication have decreased likelihood of receiving IVT and are not at an increased risk of associated SICH. This supports current practice guidelines, which do not list chronic alcohol consumption or acute intoxication as an exclusion criterion., (© 2015 American Academy of Neurology.)

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.