Multimodal hyperscanning reveals that synchrony of body and mind are distinct in mother-child dyads

Hyperscanning studies have begun to unravel the brain mechanisms underlying social interaction, indicating a functional role for interpersonal neural synchronization (INS), yet the mechanisms that drive INS are poorly understood. The current study, thus, addresses whether INS is functionally-distinct from synchrony in other systems – specifically the autonomic nervous system and motor behavior. To test this, we used concurrent functional near-infrared spectroscopy - electrocardiography recordings, while N = 34 mother-child and stranger-child dyads engaged in cooperative and competitive tasks. Only in the neural domain was a higher synchrony for mother-child compared to stranger-child dyads observed. Further, autonomic nervous system and neural synchrony were positively related during competition but not during cooperation. These results suggest that synchrony in different behavioral and biological systems may reflect distinct processes. Furthermore, they show that increased mother-child INS is unlikely to be explained solely by shared arousal and behavioral similarities, supporting recent theories that postulate that INS is higher in close relationships

Stroke with unknown time of symptom onset: baseline clinical and magnetic resonance imaging data of the first thousand patients in WAKE-UP (efficacy and safety of mri-based thrombolysis in wake-up stroke: a randomized, doubleblind, placebo-controlled trial)

Background and Purpose—We describe clinical and magnetic resonance imaging (MRI) characteristics of stroke patients with unknown time of symptom onset potentially eligible for thrombolysis from a large prospective cohort. Methods—We analyzed baseline data from WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke: A Randomized, Doubleblind, Placebo-Controlled Trial), an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset. MRI judgment included assessment of the mismatch between visibility of the acute ischemic lesion on diffusion-weighted imaging and fluid-attenuated inversion recovery. Results—Of 1005 patients included, diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch was present in 479 patients (48.0%). Patients with daytime-unwitnessed stroke (n=138, 13.7%) had a shorter delay between symptom recognition and hospital arrival (1.5 versus 1.8 hours; P=0.002), a higher National Institutes of Stroke Scale score on admission (8 versus 6; P<0.001), and more often aphasia (72.5% versus 34.0%; P<0.001) when compared with stroke patients waking up from nighttime sleep. Frequency of diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch was comparable between both groups (43.7% versus 48.7%; P=0.30). Conclusions—Almost half of the patients with unknown time of symptom onset stroke otherwise eligible for thrombolysis had MRI findings making them likely to be within a time window for safe and effective thrombolysis. Patients with daytime onset unwitnessed stroke differ from wake-up stroke patients with regards to clinical characteristics but are comparable in terms of MRI characteristics of lesion age. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01525290. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-005906-32

Clinical characteristics of unknown symptom onset stroke patients with and without diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch

Background: Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch was suggested to identify stroke patients with unknown time of symptom onset likely to be within the time window for thrombolysis. Aims: We aimed to study clinical characteristics associated with DWI-FLAIR mismatch in patients with unknown onset stroke. Methods: We analyzed baseline MRI and clinical data from patients with acute ischemic stroke proven by DWI from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset. Clinical characteristics were compared between patients with and without DWI-FLAIR mismatch. Results: Of 699 patients included, 418 (59.8%) presented with DWI-FLAIR mismatch. A shorter delay between last seen well and symptom recognition (p = 0.0063), a shorter delay between symptom recognition and arrival at hospital (p = 0.0025), and history of atrial fibrillation (p = 0.19) were predictors of DWI-FLAIR mismatch in multivariate analysis. All other characteristics were comparable between groups. Conclusions: There are only minor differences in measured clinical characteristics between unknown symptom onset stroke patients with and without DWI-FLAIR mismatch. DWI-FLAIR mismatch as an indicator of stroke onset within 4.5 h shows no relevant association with commonly collected clinical characteristics of stroke patients

Effect of informed consent on patient characteristics in a stroke thrombolysis trial

Objective: To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials. Methods: We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups. Results: In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years, p < 0.0001) and had a higher frequency of arterial hypertension (58.2% vs 43.4%, p < 0.0001). They showed higher scores on the NIH Stroke Scale (median 11 vs 5, p < 0.0001) and more frequently aphasia (73.7% vs 20.0%, p < 0.0001). The rate of proxy consent varied among countries (p < 0.0001), ranging from 77.1% in Spain to 1.2% in Denmark. Conclusions: Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results. Clinicaltrials.gov and Clinicaltrialsregister.eu identifiers: NCT01525290 (clinicaltrials.gov); 2011-005906-32 (clinicaltrialsregister.eu)

Current smoking does not modify the treatment effect of intravenous thrombolysis in acute ischemic stroke patients—a post-hoc analysis of the WAKE-UP trial

Background: The “smoking paradox” indicates that patients with acute ischemic stroke (AIS) who smoke at the time of their stroke may have a better prognosis after intravenous thrombolysis than non-smokers. However, findings are inconsistent and data analyzing the effect of smoking on treatment efficacy of intravenous thrombolysis are scarce. Methods: We performed a pre-specified post-hoc subgroup analysis of the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial that randomized AIS patients with unknown time of symptom onset who had diffusion-weighted imaging-fluid attenuation inversion recovery (DWI-FLAIR) mismatch to either alteplase or placebo. Patients were categorized as current smokers or non-smokers (including former smokers and never-smokers). Baseline demographic and clinical characteristics, as well as clinical and imaging follow-up data were analyzed according to smoking status. Results: Four hundred and eighty six patients were included in the analysis. Current smokers (133, 27.4%) were younger (60.1 ± 13.0 vs. 67.2 ± 10.3 years; p < 0.001) and less often had arterial hypertension (45.0% vs. 56.8%; p = 0.02) or atrial fibrillation (3.8% vs. 15.3%; p < 0.001). The acute stroke presentation was more often due to large vessel occlusion among current smokers (27.1 vs. 16.2%; p = 0.01), and smokers had a trend towards more severe strokes (National Institutes of Health Stroke Scale score>10 in 27.1% vs. 19.5%; p = 0.08). The treatment effect of alteplase, quantified as odds ratio for a favorable outcome (modified Rankin Scale [mRS] score at 90 days of 0 or 1), did not differ between current smokers and non-smokers (p-value for interaction: 0.59). After adjustment for age and stroke severity, neither the proportion of patients with favorable outcome, nor the median mRS score at 90 days differed between current smokers and non-smokers. When additional potential confounders were included in the model, the median mRS score was higher in current smokers than in non-smokers (cOR of better outcome for current smokers vs. non-smokers: 0.664 [0.451–0.978], p = 0.04). Conclusions: In patients with mild to moderate MRI-proven AIS and unknown time of symptom onset with DWI-FLAIR mismatch, current smokers had worse functional outcome as compared to non-smokers. Current smoking did not modify the treatment effect of alteplase. Clinical Trial registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012

Total mismatch in diffusion negative patients in the WAKE-UP trial

No abstract available

Predictors of Early Neurological Improvement and Its Relationship to Thrombolysis Treatment and Long-Term Outcome in the WAKE-UP Study

Introduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score >= 4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of >= 8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0-1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. Results: ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p = 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p <= 0.001), and less often large-vessel occlusion on initial MRI (7/93 [12.1%] versus 40/291 [29.9%], p = 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval [CI] 0.954-1.100), lower baseline stroke volume (OR 0.965, 95% CI: 0.932-0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI: 0.989-0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p <= 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9-96%) of the treatment effect. Conclusion: Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h

Extent of FLAIR Hyperintense Vessels May Modify Treatment Effect of Thrombolysis: A Post hoc Analysis of the WAKE-UP Trial

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusion patients (n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p-value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012