Cerebral Ischemia in Patients on Direct Oral Anticoagulants.

Background and Purpose- In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods- Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50-100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results- Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 [interquartile range, 3-15] versus intermediate: 4 [1-11] versus high: 3 [0-8]; P<0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P<0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 [95% CI, 1.80-8.20]; P=0.001). Conclusions- The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.

Heart Failure in Ischemic Stroke: Relevance for Acute Care and Outcome.

Background and Purpose- Heart failure (HF) in patients with acute ischemic stroke constitutes the source of various detrimental pathophysiologic mechanisms including prothrombotic and proinflammatory states, worsening of cerebral tissue oxygenation, and hemodynamic impairment. In addition, HF might affect the safety and efficacy of the acute recanalization stroke therapies. Methods- Patients treated with intravenous recombinant tissue-type plasminogen activator or mechanical recanalization at a universitary stroke center were included into a prospective registry. Patients received cardiological evaluation, including echocardiography, during acute care. Functional outcome was assessed after 90 days by structured telephone interviews. Safety and efficacy of intravenous thrombolysis and mechanical thrombectomy were investigated among patients with HF and compared with patients with normal cardiac function after propensity score matching. Results- One thousand two hundred nine patients were included. HF was present in 378 patients (31%) and an independent predictor of unfavorable functional outcome. Recanalization rates were equal among patients with HF after intravenous thrombolysis and after mechanical recanalization or combined treatment. The rate of secondary intracranial hemorrhage was not different (7% versus 8%; P=0.909 after thrombolysis and 15% versus 20%, P=0.364 after mechanical recanalization or combined therapy). Early mortality within 48 hours after admission was equal (<1.5% in both groups). Conclusions- In this real-world cohort of patients with stroke, HF was an independent predictor of unfavorable functional long-term outcome, while the safety and efficacy of intravenous thrombolysis and mechanical recanalization appeared unaffected.

Direct Oral Anticoagulant Plasma Levels for the Management of Acute Ischemic Stroke.

INTRODUCTION: The management of acute ischemic stroke in patients on direct oral anticoagulants (DOACs) is challenging. However, the substance-specific plasma level could guide treatment decisions on recanalization therapies. We present a plasma-level-based protocol for emergency treatment of stroke patients on oral anticoagulants. Bleeding complications and clinical outcome for patients on DOACs are reported and compared to patients on vitamin K antagonists (VKAs). METHODS: In patients with acute ischemic stroke and suspected use of DOACs within 48 h prior to hospital admission, plasma levels were measured using the calibrated Xa-activity (apixaban, edoxaban, rivaroxaban) or the Hemoclot®-assay (dabigatran). Levels <50 ng/mL were supportive for thrombolysis, while high values >100 ng/mL excluded patients from recombinant tissue plasminogen activator use. For patients on VKAs, the cutoff was set at international normalized ratio of 1.7. Endovascular thrombectomy of a large vessel occlusion was performed independently from coagulation testing. Consecutive patients were included in an observational registry. RESULTS: Five hundred and twenty-two patients (261 on VKAs and 261 on DOACs) were included. Thirty patients (11.5%) on VKAs and 24 (9.2%) on DOACs received thrombolysis, followed by mechanical thrombectomy in 10 and 14 patients, respectively. Seventeen patients in each group received thrombectomy only. Symptomatic intracranial hemorrhage associated with thrombolysis occurred in 1 patient on VKA (3.3%) and 1 on DOAC (4.2%; p = 0.872). The turnaround time of specific assays did not show a significant delay in comparison to standard coagulation parameters. CONCLUSION: DOAC plasma levels could support decisions on emergency treatment of ischemic stroke. Systemic thrombolysis below suggested thresholds appears preliminary feasible and safe without an excess in bleeding complications.

Endovascular treatment in patients with large vessel occlusion: reduced mortality despite minimal penumbra.

PURPOSE: In patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO), endovascular treatment (EVT) is highly effective for emergency revascularization. However, data on functional outcome are lacking for patients, which show no or minimal mismatch between ischemic core and penumbra. METHODS: Forty-five patients with AIS due to LVO of the anterior circulation were retrospectively analyzed within 6 h since onset when administered to our department. In all patients, there was no relevant penumbra according to CT perfusion (CTP). Functional outcome, defined by the modified Rankin Scale (mRS) at 30 and 90 days, was analyzed according to LVO treatment (EVT versus non-EVT). Confounding was addressed by multivariable regression analyses. RESULTS: mRS values at 30 days (p = 0.002) and 90 days (p = 0.005) after AIS occurrence were significantly lower in patients who had received EVT. There was no significant difference regarding good functional outcome, as measured by mRS of 0-2 at 30 (p = 0.432) and 90 days, respectively (p = 0.186). Mortality was significantly reduced in patients undergoing EVT at 30-day (p < 0.001) and at 90-day follow-up (p = 0.003), respectively. Multivariable regression analyses revealed that EVT was associated with reduced mortality at 30 (OR 0.091; CI (0.013-0.612); p = 0.014) and 90 days (OR 0.134; CI (0.021-0.857); p = 0.034) after AIS. CONCLUSIONS: Despite a small and highly selected patient collective, our study indicates that AIS patients with minimal penumbra in CTP might benefit from EVT in terms of reduced mortality at 30 and 90 days after AIS. However, in this group of patients, we could not prove favorable functional outcome at 30 and 90 days, despite receiving EVT.

Re-evaluation of the stroke prognostication using age and NIH Stroke Scale index (SPAN-100 index) in IVT patients - the-SPAN 10065 index.

BACKGROUND: The SPAN-100 index adds patient age and baseline NIHSS-score and was introduced to predict clinical outcome after acute ischemic stroke (AIS). Even with high NIHSS-scores younger patients cannot reach a SPAN-100-positive status (index ≥100). We aimed to evaluate the SPAN-100 index among a large, contemporary cohort of i.v.-thrombolysed AIS-patients and exclusively among older patients who can at least theoretically achieve SPAN-100-positivity. METHODS: The SPAN-100 index was applied to AIS-patients receiving i.v.-thrombolysis (IVT) in our institution between 01/2006 and 01/2013. Clinical outcome and symptomatic intracerebral hemorrhage rates were compared between SPAN-100-positive and -negative patients. Furthermore we excluded patients < 65 years, without any theoretical chance to achieve SPAN-100-positivity, and re-evaluated the index (SPAN65-100 index). RESULTS: SPAN-100-positive IVT-patients (124/1002) had a 9-fold increased risk for unfavorable outcome compared to SPAN-negative patients (OR 9.39; 95% CI 5.87-15.02; p <  0.001). The odds ratio for mortality was 7.48 (95% CI 4.90-11.43; p <  0.001). No association was found between SPAN-100-positivity and sICH-incidence (OR 0.88; 95% CI 0.31-2.53; p = 0.810). SPAN65-100-positivity (124/741) was associated with an 8-fold increased risk for unfavorable outcome (OR 7.6; 95% CI 4.71-12.22; p <  0.001) but not associated with higher sICH-rates (OR 0.86; 95% CI 0.29-2.53; p <  0.001). CONCLUSIONS: Also for patients ≥65 years the SPAN-100 index can be a fast, easy method to predict clinical outcome of IVT-patients in everyday practice. However, it should not be used to determine the risk of sICH after IVT. Based on a SPAN-positive status IVT should not be withheld from AIS-patients merely because of feared sICH-complications.

Telemedicine in General Neurology: Interrater Reliability of Clinical Neurological Examination Via Audio-Visual Telemedicine.

INTRODUCTION: While there are several studies on reliability of telemedicine in assessing stroke scales, little is known about the validity of a general neurological examination performed via telemedicine. Therefore, we sought to test the agreement between bedside and remote examination in acute patients of the emergency room. METHODS: Acute patients at the emergency room of a 450-bed academic teaching hospital were included in this study. A clinical neurological examination consisting of 22 items was performed at bedside and also remotely via an audio-visual link by a different neurologist; both were experienced clinicians at the consultant level. Kappa statistics were calculated for each item of the examination. RESULTS: Forty three patients completed both examinations (mean age 58.3 years, 56% female). Patients were seen between 8 and 72 min after admission (mean 36.3 min). Total time for remote examination was 12.6 min (8-21 min) and 8.9 min (5-18 min) for bedside examination. K-coefficients ranged from 0.32 (muscle tone) - 0.82 (language) indicating a fair to excellent agreement in most items. CONCLUSIONS: Remote examination via an audio-visual link produces comparable results to bedside performance even in acute patients of the emergency room. Compared to the scarce data available, inter-observer agreement is about the same as that between 2 examiners at bedside. However, more studies on reliability and validity of clinical neurological examination are required.

Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke. METHODS: We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (>⅓MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications. RESULTS: In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2. CONCLUSIONS: No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort.

Dabigatran Plasma Levels in Acute Cerebrovascular Events.

BACKGROUND: Oral anticoagulation with dabigatran was shown to be effective for stroke prevention in patients with nonvalvular atrial fibrillation without the need for laboratory monitoring. However, a recent publication based on data of the Randomized Evaluation of Long-Term Anticoagulation Therapy study reported that ischemic stroke and bleeding outcomes are correlated with dabigatran plasma concentration (DPC). DPC was determined at a prespecified time point and correlated with cardiovascular events at any time during follow-up. Because of the known variability of DPC, among others depending on renal function, this approach might compromise data evaluation. We report on dabigatran plasma levels in acute cerebrovascular events. METHODS: Consecutive patients with acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) while taking dabigatran were retrospectively identified if admission DPC was available. DPC was determined using the diluted thrombin time (Hemoclot (HYPHEN BioMed, Neuville sur Oise, France)). Creatinine clearance (CrCl) was determined by measuring creatinine in plasma and 24-hour urine. RESULTS: Fifteen AIS and 4 ICH patients were included. Median DPC on admission was significantly higher in ICH patients than in AIS patients (135 ng/mL [interquartile range {IQR} 79-218] and 69.1 ng/mL [IQR 20.6-85.0], respectively; P = .035). Increased CrCl (values above published normal range) was correlated with lower median DPC (60 ng/mL [IQR 10-69] versus 100 ng/mL [IQR 79-157] in patients with normal CrCl, P = .01). CONCLUSIONS: Higher DPC was found in ICH patients than in AIS patients in temporal proximity to the event. Both decreased and increased renal functions seem to have an important influence on DPC.

Limited versus Whole-Brain Perfusion for the Indication of Thrombolysis in the Extended Time Window of Acute Cerebral Ischemia.

BACKGROUND: Perfusion computed tomography (PCT) has emerged as alternative to magnetic resonance imaging (MRI) for assessment of patients clinically qualifying for off-label thrombolysis within 4.5 to 9 hours after onset of ischemic stroke. However, disadvantage of PCT is its often limited anatomic coverage with only 2 or 3 slices when using a 4- to 64-section scanner. Our purpose was therefore to evaluate the value of 2- and 3-slice perfusion compared to whole-brain perfusion. METHODS: One hundred twenty-five patients undergoing MRI beyond 4.5 hours after symptom onset with supratentorial perfusion deficit were selected retrospectively. Accordingly to PCT slice positioning, 2 or 3 slices of the whole-brain perfusion weighted imaging data set were depicted. Volumes of infarct (using cerebral blood volume) and penumbra (using time-to-peak and cerebral blood volume) were calculated, and results were compared with 2- and 3-slice-derived volumes, respectively. RESULTS: Whole-brain imaging revealed a mismatch of more than 20% in 68.8% of patients (defined as 100%). Two-slice imaging detected a perfusion deficit in 72% and a mismatch in 48.8% (sensitivity = 70.9%). Three-slice imaging detected a perfusion deficit in 76% and a mismatch in 50.4% (sensitivity = 73.3%). Although there was no significant difference between 2- and 3-slice imaging (P > .23), both techniques revealed significantly less patients with mismatch compared to whole-brain coverage (P < .01). CONCLUSIONS: Two- and 3-slice imaging like obtained with PCT on most installed CT systems to assess perfusion deficits with subsequent mismatch calculation in acute stroke outside the 4.5-hour time window is significantly inferior to whole-brain coverage and, hence, has to be considered as a less-than-ideal solution.

Impaired renal function in stroke patients with atrial fibrillation.

BACKGROUND: Stroke patients with atrial fibrillation (AF) are prone to have comorbidities such as impaired renal function. Because poly-pharmacotherapy is often required in those patients, renal function is important to consider in light of renally cleared medications such as direct oral anticoagulants. In this study, we analyzed frequency and predictors for impaired renal function and its impact on functional outcome in stroke patients with underlying AF. METHODS: We analyzed 272 patients with acute ischemic stroke and AF of our prospective, observational stroke database. Estimated glomerular filtration rate (eGFR) was calculated on admission and during hospitalization from the equation of the Modification Diet for Renal Disease. Outcome measures included mortality and functional outcome at 90 days, assessed as modified Rankin Scale (mRS) score. RESULTS: On admission, impaired renal function was found in 41.5% (n = 113) and was associated with worse 90-day outcome (mRS score ≤ 2: 26.5% versus 45.9%, P = .001) and a higher mortality rate (23.9% versus 14.5%, P = .043). Multivariate logistic regression identified older age and history of myocardial infarction as independent predictors of renal dysfunction on admission (P < .05). Normalization of eGFR during hospitalization was achieved in 55.8%. CONCLUSIONS: In patients with acute ischemic stroke and AF, impaired renal function on admission is frequent and associated with worse outcome. Normalization of eGFR can often be achieved during hospitalization, but in everyday life, fluctuations of renal function because of infection or dehydration have to be considered. Careful monitoring of renal status is indispensable and should influence drug treatment decisions.

Relationship between onset-to-door time and door-to-thrombolysis time: a pooled analysis of 10 dedicated stroke centers.

BACKGROUND AND PURPOSE: Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. METHODS: Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. RESULTS: In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year (P<0.001). Median DNT of 55 minutes was observed in patients with ODT ≤30 minutes, whereas it declined for patients presenting within the last 30 minutes of the 3-hour time window (median, 33 minutes) and of the 4.5-hour time window (20 minutes). For ODT within the first 30 minutes of the extended time window (181-210 minutes), DNT increased to 42 minutes. DNT was stable for ODT for 30 to 150 minutes (40-45 minutes). We found a weak inverse overall correlation between ODT and DNT (R(2)=-0.12; P<0.001), but it was strong in patients treated between 3 and 4.5 hours (R(2)=-0.75; P<0.001). ODT was independently inversely associated with DNT (P<0.001) in regression analysis. Octogenarians and women tended to have longer DNT. CONCLUSIONS: DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE: We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS: In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS: I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation.

BACKGROUND AND PURPOSE: The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. RESULTS: Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). CONCLUSIONS: The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

Neuroendocrine changes in patients with spontaneous supratentorial intracerebral hemorrhage.

BACKGROUND: Neuroendocrine changes have been reported after ischemic stroke, subarachnoid hemorrhage, and brain trauma. As there are no corresponding data in patients with intracerebral hemorrhage (ICH) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH. METHODS: Twenty patients with ICH were prospectively enrolled in the study. Patients were a priori parted into two groups: Ten non-ventilated patients treated on the stroke-unit (hemorrhage volumes <20 ml, "small ICH"), and 10 ventilated patients treated on the neurocritical care unit (hematoma volumes >20 ml with possible additional ventricular involvement ("large ICH"). Neuroendocrine parameters were compared between both groups referring to reference values. The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH: thyrotropin, free thiiodothyronine and thyroxine, human growth hormone, insulin-like growth factor 1, luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, adrenocorticotropic hormone, and cortisol. RESULTS: Small ICH patients were in a median 71 (54-88) years old and had a mean ICH volume of 9.5 ± 6.5 ml, whereas large ICH patients were 65 (47-80) years old and showed a mean volume of 56 ± 30.2 ml. None of the patients revealed pathological alterations for thyrotropin, free thiiodothyronine, thyroxine, human growth hormone, insulin-like growth factor 1, and testosterone. There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients. Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period. Large ICH patients showed a marked increase of prolactin that developed during the course. CONCLUSIONS: Overall, neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage. The clinical significance of increased LH and FSH levels in small ICH is unclear, whereas elevation of prolactin in large ICH was anticipated. Future randomized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome.

A structured reading algorithm improves telemetric detection of atrial fibrillation after acute ischemic stroke.

BACKGROUND AND PURPOSE: Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). METHODS: Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. RESULTS: Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. CONCLUSIONS: Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

Serious cardiac arrhythmias after stroke: incidence, time course, and predictors--a systematic, prospective analysis.

BACKGROUND AND PURPOSE: Patients with acute cerebrovascular events are susceptible to serious cardiac arrhythmias, but data on the time course and the determinants of their onset are scarce. METHODS: The prospective Stroke-Arrhythmia-Monitoring-Database (SAMBA) assessed cardiac arrhythmias with need for urgent evaluation and treatment in 501 acute neurovascular patients during the first 72 hours after admission to a monitored stroke unit. Arrhythmias were systematically detected by structured processing of telemetric data. Time of arrhythmia onset and predisposing factors were investigated. RESULTS: Significant cardiac arrhythmias occurred in 25.1% of all patients. Incidence was highest during the first 24 hours after admission. Serious arrhythmic tachycardia (ventricular or supraventricular>130 beats/min) was more frequent than bradycardic arrhythmia (sinus-node dysfunction, bradyarrhythmia, or atrioventricular block °II and °III). Arrhythmias were independently associated with higher age and severer neurological deficits as measured by the National Institutes of Health Stroke Scale on admission. CONCLUSIONS: The risk for significant cardiac arrhythmia after an acute cerebrovascular event is highest during the first 24 hours of care and declines with time during the first 3 days. Along with established vascular risk factors, the National Institutes of Health Stroke Scale may be considered for a stratified allocation of monitoring capabilities. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

Sonographic monitoring of midline shift predicts outcome after intracerebral hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) and the evolution of subsequent perihemorrhagic edema lead to midline shift (MLS), which can be assessed by transcranial duplex sonography (TDS). In this observational study, we monitored MLS with TDS in patients with supratentorial ICH up to day 14 after the ictus, and then correlated MLS with the outcome 6 months after hospital discharge. METHODS: Sixty-eight patients with spontaneous ICH (volume >20 cm(3)) were admitted during a 1-year period between April 2009 and April 2010. Sixty-one patients fulfilled the inclusion criteria and were eligible for analysis. TDS to measure MLS was performed upon admission and then subsequently, using serial examinations in 24-hour intervals up to day 14. Statistical tests were used to determine cut-off values for functional outcome and mortality after 6 months. RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score upon admission was 21 and the mean hematoma volume was 52 cm(3). NIHSS score, functional outcome, hematoma volume and MLS were correlated in the examined patient cohort. ICH score upon admission, hematoma volume and the extent of MLS on days 1-14 were predictive of functional outcome and death. Values of MLS showed two peaks, the first between day 2 and day 5 and the second between day 12 and day 14, indicating that edema progresses not only during the acute but also during the subacute phase. Depending on the time point, an MLS of 4.5-7.5 mm or greater indicated an impending failure of conservative therapy. An MLS of 12 mm or greater at any time indicated mortality with a sensitivity of 69%, a specificity of 100% and positive and negative predictive values of 100 and 74%, respectively. CONCLUSIONS: MLS seems to be a crucial factor for outcome after ICH. Apart from the hematoma volume itself, edema adds to the intracranial pressure. To monitor MLS in early patient management after ICH, TDS is a useful noninvasive bedside alternative, avoiding increased radiation exposure and repeated transportation of critically ill patients. Cut-off values may help to reliably predict functional outcome and treatment failure in patients undergoing maximal neurointensive therapy.

Standardized antipyretic treatment in stroke: a pilot study.

BACKGROUND: Fever after acute cerebral injury is associated with unfavorable functional outcome and increased mortality, but there is controversy about the optimal antipyretic treatment. This study investigated an institutional standard operating procedure (SOP) for fever treatment in stroke patients including a sequence of pharmacologic and physical interventions. METHODS: A 4-step antipyretic SOP was established for patients with acute cerebral ischemia or hemorrhage and a body temperature ≥37.5°C within the first 6 days after admission. Data on the course of body temperature, duration of fever and achievement of normothermia were recorded. Results were compared to a historic control group that underwent conventional treatment. RESULTS: A total of 77 patients (mean age 70.4 ± 14.2 years) received 331 antipyretic interventions. Sequential administration of paracetamol (n = 219), metamizole (n = 71) and calf packing (n = 24) resulted in a significant drop in body temperature after 60 min in each instance. In 5 of 9 cases which were refractory to previous attempts, normothermia followed the infusion of ice-cooled saline. In more than 90% of cases treated per protocol, normothermia was achieved within 120 min. Compared to conventional treatment, fever burden was significantly lower within the first 4 days after admission (p < 0.001). CONCLUSION: This SOP may help to optimize antipyretic treatment for stroke patients.

Vasospasm in intracerebral hemorrhage with ventricular involvement: a prospective pilot transcranial Doppler sonography study.

BACKGROUND: Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH), but has rarely been reported after intracerebral hemorrhage (ICH) without subarachnoidal bleeding. The underlying pathophysiological mechanism is mainly mediated by circulating heme products within the cerebrospinal fluid, and thus patients with ICH and ventricular involvement (IVH) may also be in danger of developing VSP. The incidence and role of VSP in IVH, however, have not been systematically studied. METHODS: We prospectively enrolled 115 patients with ICH with or without IVH into the study between April 2009 and April 2010. All patients received serial extracranial and transcranial Doppler sonography (TCD) at baseline, on days 3-5 and 7-9 to detect and monitor VSP. In addition, CT scans taken on admission, after 24 h and before discharge were evaluated for the occurrence of delayed cerebral ischemia. RESULTS: Three out of 53 patients (5.7%) with IVH showed a significant elevation of flow velocities over the examined timeframe. One of these patients developed severe VSP resulting in secondary ischemic infarction. None of the ICH patients without IVH showed significantly elevated flow velocities or secondary infarction. CONCLUSIONS: Cerebral VSP with secondary infarction may occur in patients with spontaneous IVH, though far less frequently than in SAH; thus, systematic screening of all patients with IVH may not be warranted. However, serial TCD should be considered in patients with secondary clinical worsening or extensive IVH.