Autotitrating Bilevel Positive Airway Pressure in Large Vessel Steno-Occlusive Stroke Patients With Suspected Sleep Apnea: A Multicenter Randomized Controlled Study.

Background: We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke. Methods: In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0-2], stroke recurrence, and mortality at 90 days were assessed. Results: Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, n = 14; control, n = 10): median baseline NIHSS 13 (5.5-18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients (p = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: -2.0, IQR = 7 points vs. -0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, p = 0.67), stroke recurrence (0 vs. 20%, p = 0.16), and death (14 vs. 20%, p = 1.0). No safety concerns were identified. Conclusions: In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01812993.

Baroreflex sensitivity is associated with post-stroke infections. An open, prospective study.

BACKGROUND AND PURPOSE: Autonomic nervous system (ANS) seems to play an important role in the post-stroke immunosuppression syndrome with increased susceptibility to infections. The aim of this study was to investigate if ANS activity measured at admission is associated with post-stroke infections. METHODS: We prospectively analyzed patients with acute ischemic stroke. ANS was measured using the cross-correlational baroreflex sensitivity (BRS) at admission. The occurrence and cause of in-hospital infections was assessed based on the clinical and laboratory examination. Demographic and clinical variables including initial stroke severity, dysphagia, procedures as nasogastric tubes, central venous and urinary catheters and mechanical ventilation were included in the analysis. RESULTS: We included 161 patients with ischemic stroke, of those 49 (30.4%) developed a nosocomial infection during the first 7 days of hospital stay. Patients with infections had significantly lower BRS (median 3 vs 5 ms/mmHg, p < .001) higher initial NIHSS (median 15 vs 5, p < .001), had more often non-lacunar etiology and underwent more invasive procedures. In the multivariable regression model decreased BRS (adjusted OR 1.21, 95% CI 1.03-1.41, p = .02), admission NIHSS (adjusted OR 1.10, 95% CI 1.02-1.19, p = .02) and invasive procedures (adjusted OR 1.46, 95% CI 1.03-2.06, p = .03) were independently associated with infection after ischemic stroke. CONCLUSIONS: Decreased BRS was independently associated with infections after ischemic stroke. Autonomic shift may play an important role in increased susceptibility to infections after stroke. The possible diagnostic and therapeutic relevance of this finding deserves further research.

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.

Heart rate variability is associated with outcome in spontaneous intracerebral hemorrhage.

PURPOSE: Autonomic imbalance as measured by heart rate variability (HRV) has been associated with poor outcome after stroke. Observations on HRV changes in intracerebral hemorrhage (ICH) are scarce. Here, we aimed to investigate HRV in ICH as compared to a control group and to explore associations with stroke severity, hemorrhage volume and outcome after ICH. METHODS: We examined the autonomic modulation using frequency domain analysis of HRV during the acute phase of the ICH and in a healthy age- and hypertension-matched control group. Hematoma volume, intraventricular extension, initial stroke severity and baseline demographic, clinical parameters as well as mortality and functional outcome were included in the analysis. RESULTS: 47 patients with ICH and 47 age- and hypertension matched controls were analyzed. ICH patients showed significantly lower total high frequency band (HF) and low frequency band (LF) powers (p = 0.01, p < 0.001), higher normalized HF power (p = 0.03), and lower LF/HF ratio (p < 0.001) as compared to the controls. Autonomic parameters showed associations with stroke severity (p = 0.004) and intraventricular involvement (p = 0.01) and predicted poor outcome independently (p = 0.02). CONCLUSIONS: Autonomic changes seems to be present in acute ICH and are associated with poor outcome independently. This may have future monitoring and therapeutic implications.

Intravenous Thrombolysis in Patients with Acute Ischemic Stroke after a Reversal of Dabigatran Anticoagulation with Idarucizumab: A Real-World Clinical Experience.

BACKGROUND: Intravenous thrombolysis (IVT) is contraindicated in patients with acute ischemic stroke (AIS) using oral anticoagulants. A specific human monoclonal antibody was introduced to reverse immediately the anticoagulation effect of the direct inhibitor of thrombin, dabigatran. Until now, mostly individual cases presenting with successful IVT after a reversal of dabigatran anticoagulation in patients with AIS were published. Thus, we aimed to report real-world data from clinical practice. METHODS: Patients with AIS on dabigatran treated with IVT after antidote reversal were enrolled in the retrospective nationwide study. Neurological deficit was scored using the National Institutes of Health Stroke Scale (NIHSS) and 90-day clinical outcome using modified Rankin scale (mRS) with a score 0-2 for a good outcome. Intracerebral hemorrhage (ICH) was defined as a presence of any sign of bleeding on control imaging after IVT, and symptomatic intracerebral hemorrhage (SICH) was assessed according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. RESULTS: In total, 13 patients (7 men, mean age 70.0 ± 9.1 years) with a median NIHSS admission score of 7 points were analyzed. Of these patients, 61.5% used 2 × 150 mg of dabigatran daily. Antidote was administrated 427 ± 235 minutes after the last intake of dabigatran, with a mean activated prothrombin time of 38.1 ± 27.8 seconds and a mean thrombin time of 72.2 ± 56.1 seconds. Of the 13 patients, 2 had ICH and 1 had SICH, and no other bleeding complications were observed after IVT. Of the total number of patients, 76.9% had a good 3-month clinical outcome and 3 patients (23.1%) died. Recurrent ischemic stroke occurred in 2 patients (15.4%). CONCLUSION: The data presented in the study support the safety and efficacy of IVT after the reversal of the anticoagulation effect of dabigatran with antidote in a real-world clinical practice.