Adherence to positive airway pressure therapy initiated in the early subacute phase of ischemic stroke: a PRESS study follow-up.

BACKGROUND: Sleep-disordered breathing (SDB) is frequent in stroke patients and negatively affects stroke outcomes. Positive airway pressure (PAP) is the standard first-line treatment for patients with moderate-to-severe SDB. Despite a strong link between PAP adherence and therapeutic response, rates of post-stroke PAP adherence remain underexplored. Our study aimed to determine PAP adherence in patients undergoing comprehensive sleep apnea assessment and in-lab PAP titration in the early subacute phase of stroke. METHODS: In-hospital screening pulse oximetry was performed in consecutive patients with imaging-confirmed acute ischemic stroke. Subjects with desaturation index ≥ 15.3/h were selected as PAP candidates, and polysomnography was recommended. In a sleep laboratory setting, subjects underwent a diagnostic night followed by a titration night, and PAP therapy was initiated in subjects with apnea-hypopnea index ≥ 15/h. Adherence to PAP therapy was assessed at a 6-month follow-up visit. RESULTS: Of 225 consecutive patients with acute ischemic stroke, 116 were PAP candidates and 52 were able to undergo polysomnography. PAP therapy was initiated in 35 subjects. At a 6-month follow-up visit, out of 34 stroke survivors, PAP adherence (PAP use of > 4 h per night) was present in 47%. Except for the significantly lower minimal nocturnal O2 saturation determined from the polysomnography (74.6 ± 11.7% vs. 81.8 ± 5.2%, p = 0.025), no other significant difference in characteristics of the groups with PAP adherence and PAP non-adherence was found. CONCLUSIONS: Less than half of the stroke subjects remained adherent to PAP therapy at 6 months post-PAP initiation. Special attention to support adaptation and adherence to PAP treatment is needed in this group of patients.

Temporal Trends of Functional Outcome in Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis.

BACKGROUND: Intravenous thrombolysis improves functional outcome in patients with acute stroke and frequencies of r-tPA (recombinant tissue-type plasminogen activator) treatment have been increasing over time. We aimed to assess whether functional outcome in r-tPA-treated patients improved over time and to investigate the influence of clinical variables on functional outcome. METHODS: We analyzed data of r-tPA-treated patients in the Austrian Stroke Unit Registry from 2006 to 2019. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 2. Frequencies of modified Rankin Scale score of 0 to 2 were assessed for the overall population and in prespecified subgroups; multivariable logistic regression analysis was performed to assess associations of baseline characteristics including clinically relevant interactions, and outcome. RESULTS: Overall, 4865 out of 9409 r-tPA-treated patients (51.7%) achieved favorable functional outcome 3 months post stroke. Between 2006 and 2019, frequencies of favorable functional outcome increased from 45.9% to 56.8%. In multivariable logistic regression analysis, year of treatment (adjusted odds ratio [adjOR], 1.08 [95% CI, 1.01-1.15]) was associated with favorable functional outcome. Stroke severity (National Institutes of Health Stroke Scale, adjOR, 0.86 [95% CI, 0.85-0.87]), age (61-70 years: adjOR, 0.67 [95% CI, 0.55-0.80], 71-80 years: adjOR, 0.42 [95% CI, 0.35-0.50], >80 years: adjOR, 0.16 [95% CI, 0.13-0.20]), female sex (adjOR, 0.89 [95% CI, 0.79-0.99]), and various comorbidities (eg, atrial fibrillation, prior stroke, diabetes) were negatively associated. Inclusion of interaction terms into the multivariable logistic regression model suggests a positive effect of year of treatment and endovascular treatment by increasing stroke severity on functional outcome (interaction between year of treatment and National Institutes of Health Stroke Scale: adjOR, 1.01 [95% CI, 1.00-1.02], interaction between National Institutes of Health Stroke Scale and endovascular treatment: adjOR, 1.02 [95% CI, 1.01-1.03]). CONCLUSIONS: Frequencies of favorable functional outcome in r-tPA-treated patients have been increasing over time, likely driven by improved outcome in patients with more severe strokes receiving endovascular treatment. However, some subgroups are still less likely to achieve functional independency and deserve particular attention.

Pre-hospital and intrahospital workflow optimization for patients with suspected ischemic stroke due to large vessel occlusion - findings from a tertiary care facility.

BACKGROUND: The efficacy of recanalization treatment in patients with ischemic stroke due to large vessel occlusion (LVO) is highly time dependent. We aimed to investigate the effects of an optimization of prehospital and intrahospital pathways on time metrics and efficacy of endovascular treatment in ischemic stroke due to LVO. METHODS: Patients treated with mechanical thrombectomy (MT) at the Hospital of St. John of God Vienna, Austria, between 2013 and 2020 were extracted from the Austrian Stroke Unit Registry. Study endpoints including time metrics, early neurological improvement and functional outcome measured by modified Rankin Scale (mRS) at 3 months were compared before and after optimization of prehospital and intrahospital pathways. RESULTS: Two hundred ninety-nine patients were treated with MT during the study period, 94 before and 205 after the workflow optimization. Workflow optimization was significantly associated with time metrics improvement (door to groin puncture time 45 versus 31 min; p < 0.001), rates of neurological improvement (NIHSS ≥ 8: 30 (35%) vs. 70 (47%), p = 0.04) and radiological outcome (TICI ≥ 2b: 71 (75%) versus 153 (87%); p = 0.013). Functional outcome (mRS 0-2: 17 (18%) versus 57 (28%); p = 0.067) and mortality (34 (37%) versus 54 (32%); p = 0.450) at 3 months showed a non-significant trend in the later time period group. CONCLUSION: The implementation of workflow optimization was associated a significant reduction of intrahospital time delays and improvement of neurological and radiological outcomes.

Prehospital triage optimization of patients with large vessel occlusion by Austrian Prehospital Stroke Scale.

OBJECTIVES: The Austrian Prehospital Stroke Scale (APSS) score was developed to predict large vessel occlusion (LVO) and improve prehospital transportation triage. Its accuracy has been previously analyzed retrospectively. We now aimed to investigate the accuracy, as well as the impact of the implementation of a triage strategy using this score on treatment times and outcome in a prospective study. MATHERIAL & METHODS: Prospective diagnostic test accuracy and before-after interventional study. EMS prospectively evaluated APSS in patients suspected of stroke. Accuracy was compared with other LVO scores. Patients with APSS ≥4 points were brought directly to the comprehensive stroke center. Treatment time frames, neurological, and radiological outcome before and after the APSS implementation were compared. RESULTS: A total of 307 patients with suspected stroke were included from October 2018 to February 2020. Treatable LVO was present in 79 (26%). Sensitivity of APSS to detect those was 90%, specificity 79%, positive predictive value 66%, negative predictive value 95%, and area under the curve 0.87 (95% CI 0.83-0.91). This was similar to in-hospital NIHSS (AUC 0.89 95% CI 0.89-0.92, p = .06) and superior to CPSS (AUC 0.83 95% CI 0.78-0.87, p = .01). Implementation of APSS triage increased direct transportation rate for LVO patients (21% before vs. 52% after; p < .001) with a significant time benefit (alert to groin puncture time benefit: 51 min (95% CI 28-74; p < .001). Neurological and radiological outcome did not differ significantly. CONCLUSIONS: Austrian Prehospital Stroke Scale triage showed an accuracy comparable with in-hospital NIHSS, and lead to a significant optimization of prehospital workflows in patients with potential LVO.

Thrombolytic therapy for wake-up stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake-up stroke [WUS]), which renders patients ineligible for IV tPA administered via time-based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta-analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging-based treatment algorithms. METHODS: We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single-arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)- or computed tomography (CT)-based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects. RESULTS: We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI-based (five studies) or CT-based (10 studies) imaging selection, and one study used a combination of modalities. Sixty-one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%-70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01-1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%-4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85-5.61, seven studies). CONCLUSIONS: This systematic review and meta-analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.

Design and Derivation of the Austrian Prehospital Stroke Scale (APSS) to Predict Severe Stroke with Large Vessel Occlusion.

Objectives: Prediction of large vessel occlusion (LVO) is highly relevant for accurate prehospital transportation triage. The Austrian Prehospital Stroke Scale (APSS) score for LVO prediction was developed using critical synthesis of previously published LVO-scores. The aim of this study was to investigate the accuracy of the APSS and compare it to other LVO-scores. Methods: APSS consists of 5 items: "facial palsy," "motor arm," "language," "motor leg" and "gaze deviation." The score ranges from 0 to 9 points. Data from 741 consecutive stroke patients with acute vessel imaging admitted to an independent comprehensive stroke center was used to test the predictive performance of the APSS in context of other LVO-scores (CPSS, FAST-ED, G-FAST, sNIHSS-EMS and RACE). Results: In the prediction of treatable LVO the APSS showed the highest area under the curve (0.834) with significant difference to CPSS (p = 0.010) and G-FAST (p = 0.006) and showed highest sensitivity (69%) as compared to other LVO scores. Specificity (85%), positive predictive value (75%), negative predictive value (81%) and accuracy (79%) were comparable to other LVO scores. Receiver operating curve analysis revealed an optimal cutoff for LVO prediction at APSS equal to 4 points. Conclusions: The easy assessable 5-item APSS score tended to outperform other LVO scores. Real-life prospective evaluation in prehospital setting is ongoing.

Intravenous thrombolysis and mechanical thrombectomy in patients with minor or rapidly improving neurological deficits.

PURPOSE OF REVIEW: A substantial proportion of patients with ischemic stroke present with mild neurological deficits ('Stroke with mild symptoms,' SMS). Treating these patients with thrombolysis or with thrombectomy is controversial and clinical practice is different. We will highlight the importance of these treatment decisions by reviewing the recent advances in this area. RECENT FINDINGS: Intravenous thrombolysis with recombinant tissue plasminogen activator in patients with SMS showed a significant reduction in functional disability after 3 months. Treatment with tenecteplase seems to be a pharmacologically superior and possibly safer thrombolytic agent making it ideal for use in this patient group. Imaging criteria to select the profiting patients are evolving. Thrombectomy in patients with a large vessel occlusion and minor deficits are showing promising results in cohort studies so far, however, randomized controlled trials are lacking. SUMMARY: Patients with acute ischemic stroke and minor or rapidly improving symptoms should be carefully treated the same way as more severe strokes are treated as neurological deterioration is not infrequent. Nevertheless, treatment decisions should be individualized dependent on clinical and radiological features.

Modified DWI-FLAIR mismatch guided thrombolysis in unknown onset stroke.

DWI-FLAIR mismatch has been recently proven to identify patients with unknown onset stroke (UOS) eligible for thrombolysis. However, this concept may exclude patients from thrombolysis who may eventually benefit as well. We aimed to examine the feasibility, safety and potential efficacy of thrombolysis in wake-up stroke (WUS) and UOS patients using a modified DWI-FLAIR mismatch allowing for partial FLAIR positivity. WUS/UOS patients fulfilling the modified DWI-FLAIR mismatch and treated with intravenous thrombolysis (IVT) were compared to propensity score matched WUS/UOS patients excluded from IVT due to FLAIR positivity. The primary endpoint was a symptomatic intracranial hemorrhage (SICH), the secondary endpoints were improvement of ≥ 4 in NIHSS score and mRS score at 3 months. 64 IVT-treated patients (median NIHSS 9) and 64 controls (median NIHSS 8) entered the analysis (p = 0.2). No significant difference in SICH was found between the IVT group and the controls (3.1% vs. 1.6%, p = 0.9). An improvement of ≥ 4 NIHSS points was more frequent in IVT patients as compared to controls (40.6% vs. 18.8%, p = 0.01). 23.4% of IVT patients achieved a mRS score of 0-1 at 3 months as compared to 18.8% of the controls (p = 0.8). SICH, improvement of NIHSS ≥ 4 and mRS 0-1 at 3 months were comparable in thrombolyzed patients with negative FLAIR images versus those thrombolyzed with partial positive FLAIR images (3% vs. 3%, p = 0.9; 40% vs. 41%, p = 0.9; 19% vs. 22%, p = 0.8). Our study signalizes that thrombolysis may be feasible in selected WUS/UOS patients with partial FLAIR signal positivity.

Baroreflex Impairment After Subarachnoid Hemorrhage Is Associated With Unfavorable Outcome.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. METHODS: The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving ß-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. RESULTS: Forty-eight patients were included. Median age was 58 years old (36-76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS (P=0.007), sedation (P=0.001), World Federation of Neurosurgery score (P=0.001), Glasgow score (P=0.002), Fisher score (P=0.022), and heart rate (P=0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048-1.818; P=0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171-0.706; P=0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. CONCLUSIONS: In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study.

Climatic and Seasonal Circumstances of Hypertensive Intracerebral Hemorrhage in a Worldwide Cohort.

BACKGROUND AND PURPOSE: Numerous studies have investigated the influence of meteorologic factors and seasons on the incidence of spontaneous intracerebral hemorrhage (ICH) with ambiguous results. In the present study, data from a large, international multicenter trial in patients with ICH were used to identify seasonal and meteorologic determinants for hypertensive-ICH with greater applicability. METHODS: Patients were grouped according to the presumptive ICH cause, that is, hypertensive when located in the basal ganglia brain stem as well as cerebellum and nonhypertensive when located lobar. Both groups were compared with regard to air temperature and air pressure and their occurrence during the year. A regression analysis was performed to identify independent predictors of hypertensive-ICH. RESULTS: Only hypertensive-ICH showed a seasonal pattern and occurred with higher air pressure values and at younger age. Independent predictors of hypertensive-ICH were increased air pressure on the actual day of the event and younger age as well as higher temperature. CONCLUSIONS: In the present study with an international cohort, besides age air pressure, more than temperature, had an influence on the occurrence of hypertensive-ICH, only.

Association of lipoprotein subfractions with endothelial function and arterial stiffness in acute ischemic stroke.

Hypercholesterolemia represents a risk factor for the development of atherosclerosis. Lipoprotein research has recently been focused on the phenomenon of atherogenic and non-atherogenic lipoproteins. The aim of this study was to explore the association of lipoprotein subfractions with a measure for endothelial function (represented by reactive hyperemia index [RHI]) and arterial stiffness (represented by augmentation index [AI]) in patients with acute ischemic stroke. We enrolled 51 patients with acute ischemic stroke. Blood samples were obtained within 24 h after the stroke onset in a fasting condition. Electrophoresis method on polyacrylamide gel was used for the analysis of plasma lipoproteins. RHI and AI was measured by peripheral arterial tonometry (EndoPAT2000 device). We failed to find any significant correlation between RHI and baseline characteristics of the population. Significant correlation was found between AI and age, hypertension, low density lipoprotein cholesterol (LDL) 1, LDL 3-7, score for anti-atherogenic risk and atherogenic profile. Age (beta = .362, p = .006) and LDL1 (beta = -0.283, p = .031) were the only independent variables significantly associated with AI in regression analysis. Significantly higher AI was found in an atherogenic lipoprotein profile compared to a non-atherogenic profile population (median 25% vs. median 11.5%, p = .043). In conclusion, our results suggest significant inverse correlation between levels of LDL 1 subfraction and measures of AI in patients with acute ischemic stroke. Significantly higher values of AI were observed in the population with an atherogenic lipoprotein profile.

The Association Between Leukoaraiosis and Poor Outcome in Intracerebral Hemorrhage Is Not Mediated by Hematoma Growth.

BACKGROUND: The significance of white matter lesions (WMLs) in intracerebral hemorrhage (ICH) remains unclear. We investigated the effects of WML on initial hematoma volume, hematoma growth, intraventricular extension, and clinical outcome in patients with spontaneous ICH. METHODS: Computed tomography scans of 262 patients included in a placebo arm of a prospective, multicenter trial were used for a semi-quantitative analysis of white matter changes. A logistic regression analysis was used to explore the effects on hematoma volume, volume changes, intraventricular hemorrhage, and clinical outcome after 90 days. RESULTS: The degree of WML was not associated with initial hematoma volume, absolute and relative hematoma growth, hematoma growth >33% or >6 mL, or with intraventricular extension. WML significantly increased the odds for poor outcome after 90 days (adjusted OR 1.4, 95% CI 1.1-1.8, P = .02). CONCLUSIONS: WMLs were not associated with initial hematoma volume, hematoma growth, or intraventricular extension. WMLs were associated with poor outcome independently.

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study.

OBJECTIVES: Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. DESIGN: Retrospective analysis of a prospective database. SETTING: Neurocritical care unit in a university hospital. SUBJECTS: Sedated patients with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p < 0.001) were individually associated with mortality, independently of age, admission Glasgow Coma Scale, intracranial pressure, pressure reactivity index, or cerebral perfusion pressure. Baroreflex sensitivity showed no correlation with intracranial pressure or cerebral perfusion pressure; the correlation with pressure reactivity index was strong in older patients (age, > 60 yr). The relative power of high frequency correlated significantly with intracranial pressure and cerebral perfusion pressure, but not with pressure reactivity index. The relative power of low frequency correlated significantly with pressure reactivity index. CONCLUSIONS: Autonomic impairment, as measured by heart rate variability and baroreflex sensitivity, is significantly associated with increased mortality after traumatic brain injury. These effects, though partially interlinked, seem to be independent of age, trauma severity, intracranial pressure, or autoregulatory status, and thus represent a discrete phenomenon in the pathophysiology of traumatic brain injury. Continuous measurements of heart rate variability and baroreflex sensitivity in the neuromonitoring setting of severe traumatic brain injury may carry novel pathophysiological and predictive information.

ß-Blockers, Pneumonia, and Outcome After Ischemic Stroke: Evidence From Virtual International Stroke Trials Archive.

BACKGROUND AND PURPOSE: Increased sympathetic drive after stroke is involved in the pathophysiology of several complications including poststroke immunudepression. ß-Blocker (BB) therapy has been suggested to have neuroprotective properties and to decrease infectious complications after stroke. We aimed to examine the effects of random pre- and on-stroke BB exposure on mortality, functional outcome, and occurrence of pneumonia after ischemic stroke. METHODS: Data including standard demographic and clinical variables as well as prestroke and on-stroke antihypertensive medication, incidence of pneumonia, functional outcome defined using modified Rankin Scale and mortality at 3 months were extracted from the Virtual International Stroke Trials Archive. For statistical analysis multivariable Poisson regression was used. RESULTS: In total, 5212 patients were analyzed. A total of 1155 (22.2%) patients were treated with BB before stroke onset and 244 (4.7%) patients were newly started with BB in the acute phase of stroke. Mortality was 17.5%, favorable outcome (defined as modified Rankin Scale, 0-2) occurred in 58.2% and pneumonia in 8.2% of patients. Prestroke BB showed no association with mortality. On-stroke BB was associated with reduced mortality (adjusted risk ratio, 0.63; 95% confidence interval, 0.42-0.96). Neither prestroke BB nor on-stroke BB showed an association with functional outcome. Both prestroke and on-stroke BB were associated with reduced frequency of pneumonia (adjusted risk ratio, 0.77; 95% confidence interval, 0.6-0.98 and risk ratio, 0.49; 95% confidence interval, 0.25-0.95). CONCLUSIONS: In this large nonrandomized comparison, on-stroke BB was associated with reduced mortality. Prestroke and on-stroke BB were inversely associated with incidence of nosocomial pneumonia. Randomized trials investigating the potential of ß-blockade in acute stroke may be warranted.

Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series.

INTRODUCTION: Current guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored. METHODS: Intracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher's exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range. RESULTS: An overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months. CONCLUSIONS: Failure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.

Rapid Induction of COOLing in Stroke Patients (iCOOL1): a randomised pilot study comparing cold infusions with nasopharyngeal cooling.

INTRODUCTION: Induction methods for therapeutic cooling are under investigated. We compared the effectiveness and safety of cold infusions (CI) and nasopharyngeal cooling (NPC) for cooling induction in stroke patients. METHODS: A prospective, open-label, randomised (1:1), single-centre pilot trial with partially blinded safety endpoint assessment was conducted at the neurointensive care unit of Heidelberg University. Intubated stroke patients with an indication for therapeutic cooling and an intracranial pressure (ICP)/temperature brain probe were randomly assigned to CI (4°C, 2L at 4L/h) or NPC (60L/min for 1 h). Previous data suggested a maximum decrease of tympanic temperature for CI (2.1L within 35 min) after 52 min. Therefore the study period was 1 hour (15 min subperiods I-IV). The brain temperature course was the primary endpoint. Secondary measures included continuous monitoring of neurovital parameters and extracerebral temperatures. Statistical analysis based on repeated-measures analysis of variance. RESULTS: Of 221 patients screened, 20 were randomized within 5 months. Infusion time of 2L CI was 33 ± 4 min in 10 patients and 10 patients received NPC for 60 min. During active treatment (first 30 min), brain temperature decreased faster with CI than during NPC (I: -0.31 ± 0.2 versus -0.12 ± 0.1°C, P = 0.008; II: -1.0 ± 0.3 versus -0.49 ± 0.3°C, P = 0.001). In the CI-group, after the infusion was finished, the intervention no longer decreased brain temperature, which increased after 3.5 ± 3.3 min. Oesophageal temperature correlated best with brain temperature during CI and NPC. Tympanic temperature reacted similarly to relative changes of brain temperature during CI, but absolute values slightly differed. CI provoked three severe adverse events during subperiods II-IV (two systolic arterial pressure (SAP), one shivering) compared with four in the NPC-group, all during subperiod I (three SAP, one ICP). Classified as possibly intervention-related, two cases of ventilator failure occurred during NPC. CONCLUSIONS: In intubated stroke patients, brain cooling is faster during CI than during NPC. Importantly, contrary to previous expectations, brain cooling stopped soon after CI cessation. Oesophageal but neither bladder nor rectal temperature is suited as surrogate for brain temperature during CI and NPC. Several severe adverse events in CI and in NPC demand further studying of safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT01573117. Registered 31 March 2012.

Safety evaluation of nasopharyngeal cooling (RhinoChill®) in stroke patients: an observational study.

INTRODUCTION: New technologies for therapeutic cooling have become available. The objective of our study was to investigate the safety of nasopharyngeal cooling with the RhinoChill(®) device in stroke patients, focusing on systemic and neurovital parameters. METHODS: In this prospective observational study, consecutive patients with severe ischemic or hemorrhagic stroke who underwent intracranial pressure (ICP) and brain temperature monitoring have been enrolled. Ten patients who were treated with the RhinoChill(®) device were analyzed. Brain and bladder temperature and systemic and neurovital parameters were monitored continuously. Additional evaluations of safety included bleeding complications and otolaryngological examinations. RESULTS: Baseline brain temperature of 36.7 °C (SD 0.9) decreased by an average of 1.21 °C (SD 0.46) within 1 h, the effect of brain temperature decrease ranged from a maximum of 2 °C (patients 3 and 7) to a minimum of 0.6 °C (patient 4). Within the first several minutes after initiating RhinoChill(®) treatment, 3 of 10 patients experienced an increase in systolic arterial pressure by 30, 30, and 53 mmHg, respectively. Heart rate rose as well (mean 3 bpm, SD 2.9). ICP and oxygen saturation were unaffected by the treatment. We observed 1 bleeding complication in the control CT scan of patient 10. Rhinoscopical findings 3 days after nasopharyngeal cooling and at the follow-up (>6 months) and a 16-item smell test were normal. CONCLUSION: The RhinoChill(®) system cools the brain efficiently. However, steep increases in blood pressure raise serious concerns regarding the safety of its use in stroke patients.

Predictors of impaired endothelial function in obstructive sleep apnea syndrome.

OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is associated with increased cardiovascular morbidity and mortality. Endothelial dysfunction (ED), accelerated atherosclerosis and autonomic dysfunction might be the key players responsible for development of vascular diseases in patients with OSA. In a population with suspected OSA and low burden of cardiovascular risk factors, we therefore aimed to investigate the association between potential cardiovascular risk factors including OSA-specific indices, ED and autonomic activity. METHODS: ED was investigated using reperfusion hyperaemia index (RHI). OSA was assessed using standard polysomnography, autonomic activity was assessed using baroreflex sensitivity (BRS). RESULTS: We enrolled 31 patients (42.1±11.7 years) with OSA. Significant inverse correlation was found between RHI and apnea-hypopnea index (AHI) (r=-0.550, p=0.001) and between RHI desaturation index (r=-0.533, p=0.002). Positive correlation was found between RHI and minimal nocturnal oxygen saturation (r=0.394, p=0.028). In a multiple regression model AHI was the only significant variable to predict RHI (ß=-0.522, p=0.003). We found no correlation between RHI and BRS. RHI in the population with severe OSA (AHI above 30) was significantly lower than RHI in the rest of the population (p=0.012). CONCLUSION: AHI was the only significant independent predictor of impaired endothelial function as expressed by RHI. RHI showed no association with BRS in patients with OSA.

Risk of stroke in patients with prior VKA or DOAC: A population-based real-world registry analysis.

INTRODUCTION: To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation. PATIENTS AND METHODS: Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists. RESULTS: In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p = 0.003). DISCUSSION AND CONCLUSIONS: One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential.