A Managed Care System with Telemedicine Support for Neurological Emergencies.

OBJECTIVES: Telemedicine is frequently used to provide remote neurological expertise for acute stroke workup and was associated with better functional outcomes when combined with a stroke unit system-of-care. We investigated whether such system-of-care yields additional benefits when implemented on top of neurological competence already available onsite. METHODS: Quality improvement measures were implemented within a "hub-and-spoke" teleneurology network in 11 hospitals already provided with onsite or telestroke expertise. Measures included dedicated units for neurological emergencies, standardization of procedures, multiprofessional training, and quality-of-care monitoring. Intervention effects were investigated in a controlled study enrolling patients insured at 3 participating statutory health insurances diagnosed with acute stroke or other neurological emergencies. Outcomes during the intervention period between November 2017 and February 2020 were compared with those pre-intervention between October 2014 and March 2017. To control for temporal trends, we compared outcomes of patients with respective diagnoses in 11 hospitals of the same region. Primary outcome was the composite of up-to-90-day death, new disability with the need of ambulatory or nursing home care, expressed by adjusted hazard ratio (aHR). RESULTS: We included 1,418 patients post-implementation (55% female, mean age 76.7 ± 12.8 year) and 2,306 patients pre-implementation (56%, 75.8 ± 13.0 year, respectively). The primary outcome occurred in 479/1,418 (33.8%) patients post-implementation and in 829/2,306 (35.9%) pre-implementation. The aHR for the primary outcome was 0.89 (95% confidence interval [CI]: 0.79-0.99, p = 0.04) with no improvement seen in non-participating hospitals between post- versus pre-implementation periods (aHR 1.04; 95% CI: 0.95-1.15). INTERPRETATION: Implementation of a multicomponent system-of-care was associated with a lower risk of poor outcomes. ANN NEUROL 2023;93:511-521.

Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

Association Between Thrombus Perviousness Assessed on Computed Tomography and Stroke Cause.

BACKGROUND AND PURPOSE: A recent study proposed that thrombus perviousness (TP)-the degree to which contrast agents penetrate the thrombus in an occluded vessel measured on noncontrast computed tomography (NCCT) and CT angiography-may be associated with cardioembolic stroke cause with high specificity. Our aim was to investigate which clinical and laboratory parameters affect measures of TP and to validate its diagnostic accuracy in an independent cohort of patients with acute ischemic stroke. METHODS: Seventy-five patients from a prospectively maintained database with proximal occlusions of the middle cerebral artery (M1) were retrospectively analyzed. Thrombi were segmented on coregistered noncontrast computed tomography and CT angiography to determine the thrombus attenuation increase and void fraction (attenuation increase relative to contralateral side). RESULTS: TP measures were significantly higher in patients with cardioembolic stroke compared to patients with stroke attributed to large artery atherosclerosis (median thrombus attenuation increase [interquartile range], 2.79 [-3.54 to 8.85] versus -5.11 [-11.23 to -1.47]; P=0.001). In linear regression analysis for TP including age, time to scan, prior medication with antiplatelets or anticoagulants, and selected laboratory parameters, only stroke cause was significantly associated with TP. In multivariable binary logistic regression analysis for dichotomized stroke cause (ie, cardioembolic versus noncardioembolic stroke), only thrombus attenuation increase was independently associated with cardioembolic stroke (odds ratio of 1.12 [95% CI, 1.04-1.22]; P=0.004). Receiver operating characteristic analysis indicated that TP can identify cardioembolic stroke with an area under the curve of 0.75 (95% CI, 0.63-0.87) for thrombus attenuation increase. With a cutoff value of 6.23 Hounsfield units, cardioembolic strokes were identified with 100% specificity. Results for void fraction were similar. CONCLUSIONS: The assessment of TP on baseline noncontrast computed tomography/CT angiography in patients with M1 occlusion may aid in determining cardioembolic stroke cause and guide secondary prevention. Selected clinical and laboratory parameters other than stroke cause did not affect TP measures.

Intravenous thrombolysis for suspected ischemic stroke with seizure at onset.

OBJECTIVE: Seizure at onset (SaO) has been considered a relative contraindication for intravenous thrombolysis (IVT) in patients with acute ischemic stroke, although this appraisal is not evidence based. Here, we investigated the prognostic significance of SaO in patients treated with IVT for suspected ischemic stroke. METHODS: In this multicenter, IVT-registry-based study we assessed the association between SaO and symptomatic intracranial hemorrhage (sICH, European Cooperative Acute Stroke Study II definition), 3-month mortality, and 3-month functional outcome on the modified Rankin Scale (mRS) using unadjusted and adjusted logistic regression, coarsened exact matching, and inverse probability weighted analyses. RESULTS: Among 10,074 IVT-treated patients, 146 (1.5%) had SaO. SaO patients had significantly higher National Institutes of Health Stroke Scale score and glucose on admission, and more often female sex, prior stroke, and prior functional dependence than non-SaO patients. In unadjusted analysis, they had generally less favorable outcomes. After controlling for confounders in adjusted, matched, and weighted analyses, all associations between SaO and any of the outcomes disappeared, including sICH (odds ratio [OR]unadjusted = 1.53 [95% confidence interval (CI) = 0.74-3.14], ORadjusted = 0.52 [95% CI = 0.13-2.16], ORmatched = 0.68 [95% CI = 0.15-3.03], ORweighted = 0.95 [95% CI = 0.39-2.32]), mortality (ORunadjusted = 1.49 [95% CI = 1.00-2.24], ORadjusted = 0.98 [95% CI = 0.5-1.92], ORmatched = 1.13 [95% CI = 0.55-2.33], ORweighted = 1.17 [95% CI = 0.73-1.88]), and functional outcome (mRS ≥ 3/ordinal mRS: ORunadjusted = 1.33 [95% CI = 0.96-1.84]/1.35 [95% CI = 1.01-1.81], ORadjusted = 0.78 [95% CI = 0.45-1.32]/0.78 [95% CI = 0.52-1.16], ORmatched = 0.75 [95% CI = 0.43-1.32]/0.45 [95% CI = 0.10-2.06], ORweighted = 0.87 [95% CI = 0.57-1.34]/1.00 [95% CI = 0.66-1.52]). These results were consistent regardless of whether patients had an eventual diagnosis of ischemic stroke (89/146) or stroke mimic (57/146 SaO patients). INTERPRETATION: SaO was not an independent predictor of poor prognosis. Withholding IVT from patients with assumed ischemic stroke presenting with SaO seems unjustified. ANN NEUROL 2019;86:770-779.

Validation of two nurse-based screening tools for delirium in elderly patients in general medical wards.

BACKGROUND: Delirium is an acute disturbance characterized by fluctuating symptoms related to attention, awareness and recognition. Especially for elderly patients, delirium is frequently associated with high hospital costs and resource consumption, worse functional deterioration and increased mortality rates. Early recognition of risk factors and delirium symptoms enables medical staff to prevent or treat negative effects. Most studies examining screening instruments for delirium were conducted in intensive care units and surgical wards, and rarely in general medical wards. The aim of the study is to validate the Nursing Delirium Screening Scale (Nu-DESC) and the Delirium Observation Screening Scale (DOS) in general medical wards in a German tertiary care hospital, considering predisposing delirium risk factors in patients aged 65 and older. METHODS: The prospective observational study including 698 patients was conducted between May and August 2018 in two neurological and one cardiology ward. During their shifts, trained nurses assessed all patients aged 65 or older for delirium symptoms using the Nu-DESC and the DOS. Delirium was diagnosed according to the DSM-5 criteria by neurologists. Patient characteristics and predisposing risk factors were obtained from the digital patient management system. Descriptive and bivariate statistics were computed. RESULTS: The study determined an overall delirium occurrence rate of 9.0%. Regarding the DOS, sensitivity was 0.94, specificity 0.86, PPV 0.40 NPV 0.99 and regarding the Nu-DESC, sensitivity was 0.98, specificity 0.87, PPV 0.43, NPV 1.00. Several predisposing risk factors increased the probability of delirium: pressure ulcer risk OR: 17.3; falls risk OR: 14.0; immobility OR: 12.7; dementia OR: 5.38. CONCLUSIONS: Both screening instruments provided high accuracy for delirium detection in general medical wards. The Nu-DESC proved to be an efficient delirium screening tool that can be integrated into routine patient care. According to the study results, pressure ulcer risk, falls risk, and immobility were risk factors triggering delirium in most cases. Impaired mobility, as common risk factor of the before mentioned risks, is well known to be preventable through physical activity programmes.

Clinical significance of acute and chronic ischaemic lesions in multiple cerebral vascular territories.

OBJECTIVES: To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke. METHODS: We analysed data from the 1000+ study - a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone. RESULTS: Of the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06-1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06-1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10-5.77), malignant disease (aOR=1.99, 95% CI 1.25-3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84-0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27-3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85-0.97) were associated with MTLPa. CONCLUSIONS: An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke. KEY POINTS: • Brain imaging with MRI may help to determine the aetiology of stroke. • Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories. • Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.

Effects of Prehospital Thrombolysis in Stroke Patients With Prestroke Dependency.

BACKGROUND AND PURPOSE: Data on effects of intravenous thrombolysis on outcome of patients with ischemic stroke who are dependent on assistance in activities of daily living prestroke are scarce. Recent registry based analyses in activities of daily -independent patients suggest that earlier start of intravenous thrombolysis in the prehospital setting leads to better outcomes when compared with the treatment start in hospital. We evaluated whether these observations can be corroborated in patients with prestroke dependency. METHODS: This observational, retrospective analysis included all patients with acute ischemic stroke depending on assistance before stroke who received intravenous thrombolysis either on the Stroke Emergency Mobile (STEMO) or through conventional in-hospital care (CC) in a tertiary stroke center (Charité, Campus Benjamin Franklin, Berlin) during routine care. Prespecified outcomes were modified Rankin Scale scores of 0 to 3 and survival at 3 months, as well as symptomatic intracranial hemorrhage. Outcomes were adjusted in multivariable logistic regression. RESULTS: Between February 2011 and March 2015, 122 of 427 patients (28%) treated on STEMO and 142 of 505 patients (28%) treated via CC needed assistance before stroke. Median onset-to-treatment times were 97 (interquartile range, 69-159; STEMO) and 135 (interquartile range, 98-184; CC; P<0.001) minutes. After 3 months, modified Rankin Scale scores of 0 to 3 was observed in 48 STEMO patients (39%) versus 35 CC patients (25%; P=0.01) and 86 (70%, STEMO) versus 85 (60%, CC) patients were alive (P=0.07). After adjustment, STEMO care was favorable with respect to modified Rankin Scale scores of 0 to 3 (odds ratio, 1.99; 95% confidence interval, 1.02-3.87; P=0.042) with a nonsignificant result for survival (odds ratio, 1.73; 95% confidence interval, 0.95-3.16; P=0.07). Symptomatic intracranial hemorrhage occurred in 5 STEMO versus 12 CC patients (4.2% versus 8.5%; P=0.167). CONCLUSIONS: The results of this study suggest that earlier, prehospital (as compared with in-hospital) start of intravenous thrombolysis in acute ischemic stroke may translate into better clinical outcome in patients with prestroke dependency. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02358772.

Intracerebral Hemorrhage and Outcome After Thrombolysis in Stroke Patients Using Selective Serotonin-Reuptake Inhibitors.

BACKGROUND AND PURPOSE: Selective serotonin-reuptake inhibitors (SSRIs) impair platelet function and have been linked to a higher risk of spontaneous intracerebral hemorrhage-an association that may be augmented by oral anticoagulants (OAC). We aimed to assess whether preadmission treatment with SSRIs in patients with acute ischemic stroke is associated with post-thrombolysis symptomatic intracerebral hemorrhage (sICH) and functional outcome. METHODS: A multicenter retrospective analysis was conducted in prospective registries of patients treated by thrombolysis within 4.5 hours of stroke onset. The association between preadmission treatment with SSRIs and sICH (ECASS II definition [European Cooperative Acute Stroke Study]) or unfavorable 3-month outcome (modified Rankin Scale >2) was assessed by logistic regression, taking into account potential interaction with concomitant use of antithrombotics. RESULTS: Six thousand two hundred forty-two patients were included (mean age, 70.1±14.0 years; median National Institutes of Health Stroke Scale, 9 [5-16]). Preadmission treatment with SSRIs was present in 4.3% (n=266) of patients. Overall, SICH rate was 3.9% (95% confidence interval [CI], 3.5%-4.4%; n=244), and SSRI use was not significantly associated with sICH in unadjusted (odds ratio [OR], 1.28; 95% CI, 0.72-2.27) or adjusted (OR, 1.30; 95% CI, 0.71-2.40) analysis. However, there was a significant interaction of concomitant use of OACs (international normalized ratio <1.7) and SSRI for occurrence of sICH (P=0.01). SICH was significantly more frequent in patients taking both OAC and SSRI (23.1%; 95% CI, 8.2%-50.3%) than in patients taking OAC but not SSRI (adjusted OR, 9.04; 95% CI, 1.95-41.89). Preadmission use of SSRI was associated with unfavorable 3-month outcome (unadjusted OR, 1.90; 95% CI, 1.48-2.46; adjusted OR, 1.59; 95% CI, 1.15-2.19). CONCLUSIONS: Preadmission treatment with SSRIs was not significantly associated with an increased risk of post-thrombolysis sICH in this cohort study. However, subgroup analysis suggested an increased risk of sICH in patients taking both SSRI and OAC. Preadmission treatment with SSRIs was associated with unfavorable outcome, which may reflect the prognostic significance of prestroke depression.

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis.

Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.

BACKGROUND: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). METHODS AND RESULTS: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. CONCLUSIONS: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke.

BACKGROUND AND PURPOSE: We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones. METHODS: In a multicenter IVT-register-based cohort study, we compared previously dependent (prestroke modified Rankin Scale score, 3-5) versus independent (prestroke modified Rankin Scale score, 0-2) patients. Outcome measures were poor 3-month outcome (not reaching at least prestroke modified Rankin Scale [dependent patients]; modified Rankin Scale score of 3-6 [independent patients]), death, and symptomatic intracranial hemorrhage. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (OR [95% confidence interval]) were calculated. RESULTS: Among 7430 IVT-treated patients, 489 (6.6%) were dependent and 6941 (93.4%) were independent. Previous stroke, dementia, heart, and bone diseases were the most common causes of preexisting dependency. Dependent patients were more likely to die (ORunadjusted, 4.55 [3.74-5.53]; ORadjusted, 2.19 [1.70-2.84]). Symptomatic intracranial hemorrhage occurred equally frequent (4.8% versus 4.5%). Poor outcome was more frequent in dependent (60.5%) than in independent (39.6%) patients, but the adjusted ORs were similar (ORadjusted, 0.95 [0.75-1.21]). Among survivors, the proportion of patients with poor outcome did not differ (35.7% versus 31.3%). After adjustment for age and stroke severity, the odds of poor outcome were lower in dependent patients (ORadjusted, 0.64 [0.49-0.84]). CONCLUSIONS: IVT-treated stroke patients who were dependent on the daily help of others before stroke carry a higher mortality risk than previously independent patients. The risk of symptomatic intracranial hemorrhage and the likelihood of poor outcome were not independently influenced by previous dependency. Among survivors, poor outcome was avoided at least as effectively in previously dependent patients. Thus, withholding IVT in previously dependent patients might not be justified.

Comparing consultation-liaison psychiatrist's and neurologist's approaches to delirium - A retrospective analysis.

OBJECTIVE: To compare the diagnostic, management, and treatment recommendations made by consultation-liaison psychiatrists (CLP) and neurologists (CLN) for suspected delirium and to investigate factors that may have influenced the choice for a particular consultation service. METHOD: In this retrospective case analysis, we screened the files of 1882 (CLP: 1112, CLN: 770) inpatients seen by CLP and CLN at the Charité - University Medicine, Berlin, Germany, in 2013. This revealed a total of 148 (CLP: 99, CLN: 49) delirium patients. Information found on the consultation form and in the patients' files was used for data collection and subsequently analyzed. RESULTS: Intensive care and surgical units preferably called CLP, while internists consulted more CLN and patients suffering from neurological or psychiatric preconditions were more often seen by the respective specialist. Despite no significant difference between psychomotor activity levels among the groups, CLP recommended significantly more pharmacological interventions (p = 0.000) and CLN ordered significantly more diagnostic procedures (p = 0.000). CONCLUSION: Our results show considerable differences between CLP and CLN treatment recommendations, which may indicate a conflicting approach to delirium work-up, not accountable to unequal patient characteristics. These preliminary results are not conclusive and should be followed up by high evidence level research.

Insular cortex lesions, cardiac troponin, and detection of previously unknown atrial fibrillation in acute ischemic stroke: insights from the troponin elevation in acute ischemic stroke study.

BACKGROUND AND PURPOSE: Detection rates of paroxysmal atrial fibrillation (AF) after acute ischemic stroke increase with duration of ECG monitoring. To date, it is unknown which patient group may benefit most from intensive monitoring strategies. Therefore, we aimed to identify predictors of previously unknown AF during in-hospital ECG monitoring. METHODS: All consecutive patients with imaging-confirmed ischemic stroke admitted to our tertiary care hospital from February 2011 to December 2013 were registered prospectively. Patients received continuous bedside ECG monitoring for at least 24 hours. Detection of previously unknown AF during in-hospital ECG monitoring was obtained from medical records. Patients with AF on admission ECG or known history of AF were excluded from analysis. RESULTS: Among 1228 patients (median age, 73 years; median National Institutes of Health Stroke Scale, 4; 43.4% women), previously unknown AF was detected in 114 (9.3%) during a median time of continuous ECG monitoring of 3 days (interquartile range, 2-4 days). Duration of monitoring (P<0.01), older age (P<0.01), history of hypertension (P=0.03), insular cortex involvement (P<0.01), and higher high-sensitivity cardiac troponin T (P=0.04) on admission were independently associated with subsequent detection of AF in a multiple regression analysis. Addition of high-sensitivity cardiac troponin T, insular cortex stroke, or both to the CHADS2 score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke [2P]) significantly improved c-statistics from 0.63 to 0.68 (P=0.01), 0.70 (P<0.01), and 0.72 (P<0.001), respectively. CONCLUSIONS: Insular cortex involvement, higher admission high-sensitivity cardiac troponin T, older age, hypertension, and longer monitoring are associated with new detection of AF during in-hospital ECG monitoring. Patients with higher high-sensitivity cardiac troponin T or insular cortex involvement may be candidates for prolonged ECG monitoring.

In-hospital stroke recurrence and stroke after transient ischemic attack: frequency and risk factors.

BACKGROUND AND PURPOSE: We aimed to assess the risk of recurrent ischemic events during hospitalization for stroke or transient ischemic attack (TIA) with optimal current management and to identify associated risk factors. METHODS: We performed a retrospective analysis of all patients treated for acute ischemic stroke or TIA in 3 stroke units between 2010 and 2013. Recurrent stroke was defined as new persisting (≥24 hours) neurological deficit occurring >24 hours after the index event and not attributable to other causes of neurological deterioration. Cox proportional hazard regression identified risk factors associated with recurrent stroke. RESULTS: The study included 5106 patients. During a median length of stay of 5 days (interquartile range, 4-8), stroke recurrence (or stroke after TIA) occurred in 40 patients (0.8%) and was independently associated with history of TIA, symptomatic carotid stenosis (≥70%), or other determined etiology. Patients with recurrent stroke and other determined etiology had cervical arterial dissection (n=2), primary angiitis of the central nervous system (n=1), giant cell arteritis (n=1), and lung cancer with nonbacterial thrombotic endocarditis (n=1). In patients with initial TIA or minor stroke (National Institutes of Health Stroke Scale ≤5) recurrence was associated additionally with pneumonia after the inciting ischemic event but before stroke recurrence. Patients with initial stroke and aphasia had a lower stroke recurrence rate and there were no recurrences in patients with lacunar stroke. Recurrence was associated with significantly higher in-hospital mortality (17.5% versus 3.1%; P<0.001). CONCLUSIONS: In-hospital stroke recurrence was low with optimal current management. Patients with a history of TIA, severe symptomatic carotid stenosis, or uncommon causes of stroke were at higher risk. Pneumonia was associated with a higher risk of stroke recurrence in patients with initial TIA or minor stroke but not in the overall population studied. Aphasia may bias the detection rate by concealing new neurological symptoms.

Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are found in a substantial proportion of patients with ischemic stroke eligible for treatment with intravenous thrombolysis. Until now, there is limited data on the impact of multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis. METHODS: Between 2008 and 2013, all patients receiving MRI-based intravenous thrombolysis were identified within our prospective thrombolysis register. Number of CMBs was rated on pretreatment T2*-weighted MRI by a rater blinded to clinical data and follow-up. Outcomes of interest were occurrence of symptomatic ICH (sICH) and parenchymal hemorrhage (PH). RESULTS: Among 326 included patients, 52 patients had a single CMB (16.0%), 19 had 2 to 4 CMBs (5.8%), and 10 had ≥5 CMBs (3.1%). Frequency of sICH/PH was 1.2%/5.7% in patients without CMBs, 3.8%/3.8% in patients with a single CMB, 10.5%/21.1% in patients with 2 to 4 CMBs, and 30.0%/30.0% in patients with ≥5 CMBs, respectively (each P for trend<0.01). The unadjusted odds ratio per additional CMB for sICH was 1.19 (95% confidence interval, 1.07-1.33; P<0.01) and for PH was 1.13 (95% confidence interval, 1.03-1.24; P=0.01). Compared with patients without CMBs, both patients with 2 to 4 CMBs (P=0.02/P=0.02) and patients with ≥5 CMBs (P<0.01/P<0.01) had significantly increased odds ratios for sICH and PH, whereas in patients with a single CMB, odds ratios were not significantly increased (P=0.21/P=0.59). The association of CMB burden with sICH/PH remained significant after adjustment for possible confounders (age, age-related white matter changes score, atrial fibrillation, onset-to-treatment time, prior statin use, and systolic blood pressure on admission). CONCLUSIONS: Our findings indicate a higher risk of sICH and PH after intravenous thrombolysis when multiple CMBs are present, with a graded relationship to increasing baseline CMB number.

Safety of thrombolysis in patients with acute ischemic stroke and cerebral cavernous malformations.

BACKGROUND AND PURPOSE: Data on safety of intravenous thrombolysis with recombinant tissue-type plasminogen activator for acute ischemic stroke in patients with coexisting cerebral cavernous malformations (CCMs) are scarce. We assessed the risk of thrombolysis-associated hemorrhage in these patients. METHODS: We searched our tertiary care hospital thrombolysis register for patients with CCM confirmed by MRI (3 T, Siemens, TimTrio) before thrombolysis for acute ischemic stroke. CCMs were graded into subtypes according to the Zabramski classification on the basis of their MRI appearance. The primary end point was symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study III (ECASS III) criteria. The secondary end point was any parenchymal hemorrhage. RESULTS: In a total of 350 patients (median age, 76 years; interquartile range, 68-84; median National Institutes of Health Stroke Scale score, 8; interquartile range, 5-14; 51.4% women), CCMs were found in 9 patients (2.6%). Seven patients had a single CCM, and 2 patients had multiple CCMs with a total number of 12 CCMs in all patients. The subtype of CCMs was type III in 9 cases and type I in 3 cases. Symptomatic intracerebral hemorrhage occurred in 1 of 9 patients with CCM versus 11 of 341 patients without CCM (P=0.27). Parenchymal hemorrhage occurred in 2 of 9 patients with CCM versus 27 of 341 patients (P=0.17) without CCM. CONCLUSIONS: Given the limitations of our study (mainly low number of patients with CCM), the risk of thrombolysis-associated hemorrhage in patients with CCM remains uncertain. Although our data do not suggest an increased hazard from thrombolysis in patients with CCM, larger studies are necessary to determine definitively the influence of CCMs on parenchymal hemorrhage and symptomatic intracerebral hemorrhage.

Recommendations for the organization of the teleconsultation service in a telestroke network.

Telestroke networks aim to improve acute stroke care within their catchment area. Through a teleconsultation service, the network centers provide support to network hospitals that lack continuous neurological expertise for acute stroke management decisions. Although the importance of telemedical treatment in stroke care is steadily increasing, so far no standards exist for the organization of the teleconsultation service in networks.To ensure a high-level of quality for all processes and measures concerning telemedical stroke treatment, the commission for telemedical stroke care of the German Stroke Society (Deutsche Schlaganfall-Gesellschaft, DSG) created the following recommendations on how to organize a teleconsultation service within a telestroke network. The recommendations are the result of an adjustment process between the authors and include guidance on requirements, qualifications, processes and quality management within the teleconsultation service.