Early REperfusion Therapy with Intravenous Alteplase for Recovery of VISION in Acute Central Retinal Artery Occlusion (REVISION): Study Protocol of a Phase III Trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data is lacking to address this question. AIMS: REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO. METHODS: Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

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.

IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke.

BACKGROUND OBJECTIVES: It is unclear whether IV thrombolysis (IVT) outperforms early dual antiplatelet therapy (DAPT) in the acute setting of mild ischemic stroke. The aim of this study was to compare the early safety and efficacy of IVT with that of DAPT. METHODS: Data of mild noncardioembolic stroke patients with admission NIH Stroke Scale (NIHSS) score ≤3 who received IVT or early DAPT in the period 2018-2021 were extracted from a nationwide, prospective stroke unit registry. Study endpoints included symptomatic intracerebral hemorrhage (sICH), early neurologic deterioration ≥4 NIHSS points (END), and 3-month functional outcome by modified Rankin scale (mRS). RESULTS: A total of 1,195 mild stroke patients treated with IVT and 2,625 patients treated with DAPT were included. IVT patients were younger (68.1 vs 70.8 years), had less hypertension (72.8% vs 83.5%), diabetes (19% vs 28.8%), and a history of myocardial infarction (7.6% vs 9.2%), and slightly higher admission NIHSS scores (median 2 vs median 1) when compared with DAPT patients. After propensity score matching and multivariable adjustment, IVT was associated with sICH (4 [1.2%] vs 0) and END (adjusted odds ratio [aOR] 2.8, 95% CI 1.1-7.5), and there was no difference in mRS 0-1 at 3 months (aOR 1.3, 95% CI 0.7-2.6). DISCUSSION: This analysis from a prospective nationwide stroke unit network indicates that IVT is not superior to DAPT in the setting of mild noncardioembolic stroke and may eventually be associated with harm. Further research focusing on acute therapy of mild stroke is highly warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT is not superior to DAPT in patients with acute mild (NIHSS score ≤3) noncardioembolic stroke. The study lacks the statistical precision to exclude clinically important superiority of either therapy.

Endovascular stroke therapy outside core working hours in a nationwide stroke system.

BACKGROUND: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours. METHODS: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications. RESULTS: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications. CONCLUSIONS: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings.

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.

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.

CT- versus MRI-Based Imaging for Thrombolysis and Mechanical Thrombectomy in Ischemic Stroke: Analysis from the Austrian Stroke Registry.

BACKGROUND AND PURPOSE: It is unclear whether a particular stroke imaging modality offers an advantage for the acute stroke treatment. The aim of this study was to compare procedure times, efficacy and safety of thrombolysis and/or thrombectomy based on computed tomography (CT) versus magnetic resonance imaging (MRI) acute stroke imaging. METHODS: Data of stroke patients who received intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were extracted from a nationwide, prospective stroke unit registry and categorized according to initial imaging modality. Study endpoints included procedure times, symptomatic intracerebral hemorrhage (sICH), early neurological improvement, 3-month functional outcome by modified Rankin Scale (mRS) and mortality. RESULTS: Stroke patients (n=16,799) treated with IVT and 2,248 treated with MT were included. MRI-guided patients (n=2,599) were younger, had less comorbidities and higher rates of strokes with unknown onset as compared to CT-guided patients. In patients treated with IVT, no differences were observed regarding the rates of functional outcome by mRS 0-1 (adjusted odds ratio [OR], 0.87; 95% confidence interval [CI], 0.71 to 1.05), sICH (adjusted OR, 0.82; 95% CI, 0.61 to 1.08), and mortality (adjusted OR, 0.88; 95% CI, 0.63 to 1.22). Patients undergoing MT selected by MRI as compared to CT showed equal rates of functional outcome by mRS 0-2 (adjusted OR, 0.87; 95% CI, 0.65 to 1.16), sICH (adjusted OR, 0.9; 95% CI, 0.51 to 1.69), and mortality (adjusted OR, 0.62; 95% CI, 0.35 to 1.09). MRI-guided patients showed a significant intrahospital delay of about 20 minutes in both the IVT and the MT group. CONCLUSIONS: This large non-randomized comparison study indicates that CT- and MRI-guided patient selection for IVT/MT may perform equally well in terms of functional outcome and safety.

Mechanical Thrombectomy in Acute Stroke Patients with Moderate to Severe Pre-Stroke Disability.

BACKGROUND AND PURPOSE: Studies on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with preexisting disability are limited. We aimed to compare the outcomes of MT versus best medical treatment (BMT) in these patients. METHODS: In the nationwide Austrian registry and Swiss monocentric registry, we identified 462 AIS patients with pre-stroke disability (modified Rankin Scale [mRS] score ≥3) and acute large vessel occlusion. The primary outcome was returning to pre-stroke mRS or better at 3 months. Secondary outcomes were early neurological improvement (National Institutes of Health Stroke Scale score improvement ≥8 at 24 to 48 hours), 3-month mortality, and symptomatic intracerebral hemorrhage (sICH). Multivariable regression models and propensity score matching (PSM) were used for statistical analyses. RESULTS: Compared with the BMT group (n=175), the MT group (n=175) had younger age, more severe strokes, and lower pre-stroke mRS, but similar proportion of receiving intravenous thrombolysis. MT was associated with higher odds of returning to baseline mRS or better at 3 months (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 1.39 to 4.47), early neurological improvement (aOR, 2.62; 95% CI, 1.41 to 4.88), and lower risk of 3-month mortality (aOR, 0.29; 95% CI, 0.18 to 0.49). PSM analysis showed similar findings. MT was not associated with an increased risk of sICH (4.0% vs. 2.1% in all patients; 4.2% vs. 2.4% in the PSM cohort). CONCLUSIONS: MT in patients with pre-stroke mRS ≥3 might improve the 3-month outcomes and short-term neurological impairment, suggesting that pre-stroke disability alone should not be a reason to withhold MT, but that individual case-by-case decisions may be more appropriate.

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.

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.

Time trends in stroke severity in the years 2005 to 2020: results from the Austrian Stroke Unit Registry.

BACKGROUND AND PURPOSE: With aging population, there is an increase of atrial fibrillation (AF) and other vascular risk factors. We investigated trends in stroke severity at hospital admission with respect to AF and other risk factors in a prospective national stroke registry from 2005 to 2020. METHODS: Data from the prospective Austrian Stroke Unit Registry were used to study demographic and clinical factors associated with the change in admission stroke severity over years. Time trends in admission stroke severity of patients with pre-stroke modified Rankin Score ≤ 3 were investigated with respect to clinical variables and predefined age groups 18-54, 55-64, 65-74, 75-84 and ≥ 85 years. Time trends were studied using robust generalized linear models assuming normal distribution with a log link. Stroke severity on admission was assessed according to the National Institutes of Health Stroke Scale Score (NIHSS). RESULTS: In total, 140,312 patients with acute ischemic stroke were included in the analysis. Within the study period, mean patients' age increased from 70 to 72 years (p < 0.001) and median NIHSS at admission decreased from 4 to 3 (p < 0.001). The frequency of AF increased from 25 to 32% (p < 0.001). The decrease in median admission NIHSS was evident in all relevant subgroups but more pronounced in patients with risk factors including AF, diabetes, hypercholesterolemia, smoking, elderly patients and those with pre-stroke disability. CONCLUSION: Despite an aging population and generally increasing AF frequency, we observed a consistent trend towards less disabling strokes on admission.

Thrombectomy in basilar artery occlusion.

BACKGROUND AND PURPOSE: The benefit of thrombectomy (TE) for acute ischemic stroke (AIS) in patients suffering basilar artery occlusion (BAO) is still unclear. Our aim was to analyze functional outcome after 3 months in BAO compared to anterior circulation large vessel occlusion (ACLVO) in a nationwide registry. METHODS: Patients enrolled into the Austrian Endostroke Registry from 2013 to 2018 were analyzed. We used propensity score matching to control for imbalances and to compare patients with BAO and ACLVO. The primary outcome was favorable functional outcome after 3 months measured by the modified Rankin Scale (mRS) (0-2). Multivariate models were applied to estimate the effect of localization (BAO vs ACLVO). RESULTS: In total, 2288 patients underwent TE for AIS with proximal vessel occlusion, of these 267 with BAO. Two hundred and sixty-four patients with BAO were matched to 264 patients with ACLVO. Baseline characteristics were well-balanced. The 90-day mortality did not significantly differ between patients with BAO and ACLVO. In a multivariate logistic regression model, we did not detect a significant difference in functional outcome between BAO and ACLVO (odds ratio for favorable outcome defined as mRS = 0-2: 1.19; 95% confidence interval (CI) = 0.78-1.81; p = 0.42). In patients with an onset-to-door-time ⩾270 min, TE of BAO was associated with poor functional outcome defined as mRS 3-6 (odds ratio (OR) = 3.97; 95% CI = 1.32-11.94; p = 0.01) as compared to ACLVO. CONCLUSION: In this study, functional outcome did not differ after TE in patients with BAO and ACLVO overall; however, we detected an association of BAO with poor outcome in patients arriving late.

Intravenous thrombolysis in stroke with admission NIHSS score 0 or 1.

BACKGROUND: Up to 30% of stroke patients initially presenting with non-disabling or mild deficits may experience poor functional outcome. Despite, intravenous thrombolysis remains controversial in this subgroup of stroke patients due to its uncertain risk benefit ratio. AIM: We aimed to analyze the real-world experience with intravenous thrombolysis in stroke patients presenting with very low NIHSS. METHODS: Data of stroke patients presenting with mild initial stroke severity (NIHSS 0-5) including vascular risk factors, stroke syndrome and etiology, early neurological deterioration, symptomatic intracerebral haemorrhage (sICH), and functional outcome by modified Rankin Scale were extracted from a large nationwide stroke registry and analysed. Patients were categorized and compared according to admission severity NIHSS 0-1 versus NIHSS 2-5 and intravenous thrombolysis use. RESULTS: Seven hundred and three (2%) of 35,113 patients presenting with NIHSS 0-1 and 6316 (13.9%) of 45,521 of patients presenting with NIHSS 2-5 underwent intravenous thrombolysis. In the NIHSS 0-1 group, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 8.84, CI 6.61-11.83), sICH (adjusted OR 9.32, CI 4.53-19.15) and lower rate of excellent outcome (mRS 0-1) at three months (adjusted OR 0.67, CI 0.5-0.9). In stroke patients with NIHSS 2-5, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 1.7, 1.47-1.98), sICH (adjusted OR 5.75, CI 4.45-7.45), and higher rate of excellent outcome (mRS 0-1) at three months (adjusted OR 1.21, CI 1.08-1.34). CONCLUSIONS: Among patients with NIHSS 0-1, intravenous thrombolysis did not increase the likelihood of excellent outcome. Moreover, potential signals of harm were observed. Further research seems to be warranted.

Acute Ischemic Stroke With Mild Symptoms-To Thrombolyse or Not to Thrombolyse?

Management of stroke with minor symptoms may represent a therapeutical dilemma as the hemorrhage risk of acute thrombolytic therapy may eventually outweigh the stroke severity. However, around 30% of patients presenting with minor stroke symptoms are ultimately left with disability. The objective of this review is to evaluate the current literature and evidence regarding the management of minor stroke, with a particular emphasis on the role of IV thrombolysis. Definition of minor stroke, pre-hospital recognition of minor stroke and stroke of unknown onset are discussed together with neuroimaging aspects and existing evidence for IV thrombolysis in minor strokes. Though current guidelines advise against the use of thrombolysis in those without clearly disabling symptoms due to a paucity of evidence, advanced imaging techniques may be able to identify those likely to benefit. Further research on this topic is ongoing.

Heart rate variability as a biomarker of functional outcomes in persons with acquired brain injury: Systematic review and meta-analysis.

This review aimed to quantify correlations between heart rate variability (HRV) and functional outcomes after acquired brain injury (ABI). We conducted a literature search from inception to January 2020 via electronic databases, using search terms with HRV, ABI, and functional outcomes. Meta-analyses included 16 studies with 906 persons with ABI. Results demonstrated significant associations: Low frequency (LF) (r = -0.28) and SDNN (r = -0.33) with neurological function; LF (r = -0.33), High frequency (HF) (r = -0.22), SDNN (r = -0.22), and RMSSD (r = -0.23) with emotional function; and LF (r = 0.34), HF (r = 0.41 to 0.43), SDNN (r = 0.43 to 0.51), and RMSSD (r = 0.46) with behavioral function. Results indicate that higher HRV is related to better neurological, emotional, and behavioral functions after ABI. In addition, persons with stroke showed lower HF (SMD = -0.50) and SDNN (SMD = -0.75) than healthy controls. The findings support the use of HRV as a biomarker to facilitate precise monitoring of post-ABI functions.

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.

Autonomic Nervous System Activity during Refractory Rise in Intracranial Pressure.

Refractory intracranial hypertension (RIH) is a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment. Recent reports suggest that the autonomic nervous system (ANS) activity may be altered during changes in ICP. Our study aimed to assess ANS activity during RIH and the causal relationship between rising in ICP and autonomic activity. We reviewed retrospectively 24 multicenter (Cambridge, Tromso, Berlin) patients in whom RIH developed as a pre-terminal event after acute brain injury (ABI). They were monitored with ICP, arterial blood pressure (ABP), and electrocardiography (ECG) using ICM+ software. Parameters reflecting autonomic activity were computed in time and frequency domain through the measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS). Our results demonstrated that a rise in ICP was associated to a significant rise in HRV and BRS with a higher significance level in the high-frequency HRV (p < 0.001). This increase was followed by a significant decrease in HRV and BRS above the upper-breakpoint of ICP where ICP pulse-amplitude starts to decrease whereas the mean ICP continues to rise. Temporality measured with a Granger test suggests a causal relationship from ICP to ANS. The above results suggest that a rise in ICP interacts with ANS activity, mainly interfacing with the parasympathetic-system. The ANS seems to react to the rise in ICP with a response possibly focused on maintaining the cerebrovascular homeostasis. This happens until the critical threshold of ICP is reached above which the ANS variables collapse, probably because of low perfusion of the brain and the central autonomic network.

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH. Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal. Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50-67). WFNS scale was 2 (1-4) and the modified Fisher scale was 3 (1-3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (R p = -0.42; p < 0.001). Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

Sleep apnea prediction in acute ischemic stroke (SLAPS score): a derivation study.

BACKGROUND: Despite its high prevalence and negative impact, sleep-disordered breathing (SDB) remain commonly underdiagnosed and undertreated in stroke subjects. Multiple stroke comorbidities and risk factors, including obesity, hypertension, diabetes mellitus, ischemic heart disease, atrial fibrillation, and heart failure (H.F.) have been associated with SDB. This study aimed to examine associations of clinical and demographic characteristics with moderate-to-severe SDB (msSDB) in stroke patients and to develop a predictive score. METHODS: Consecutive patients with ischemic stroke were enrolled in an open, prospective study. SDB was assessed using standard polysomnography. Clinical and demographic characteristics, as well as findings from echocardiography, entered the analysis. Multivariate logistic regression models were used to examine the associations with msSDB. Based on the results, an original score to predict msSDB was proposed and tested. RESULTS: 120 patients with acute ischemic stroke (mean age: 64.0 ± 12.2 years, median NIHSS: 4) were included. Body-mass index (BMI), wake-up stroke onset (WUS), and diastolic dysfunction were independently associated with msSDB. A score allocating 1 point for BMI≥25 kg/m2 and <30 kg/m2, 2 points for BMI≥30 kg/m2, 1 point for WUS and 1 point for diastolic dysfunction resulted in an area under the curve of 0.81 (95% CI 0.71-0.90, p<0.001), sensitivity 82.9%, specificity 71.9% to identify stroke patients with msSDB. CONCLUSIONS: BMI, WUS, and diastolic dysfunction were associated with msSDB. A simple score might help to identify acute stroke patients with msSDB, who are usual candidates for positive airway pressure therapy.