Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site.

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (Pinteraction=0.312) but did with functional independence (Pinteraction=0.010), with a similar trend on excellent outcome (Pinteraction=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (Pinteraction=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (Pinteraction=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Psychosocial conditions during school-age as determinants of long-term labour market attachment: a study of the Northern Swedish Cohort from the 1980s to the 2020s.

BACKGROUND: This study, conducted on a Swedish population cohort, explores how internalized (depressive and functional somatic) and externalized (smoking, drinking, truancy, vandalism, delinquency) mental health symptoms, as well as close interpersonal relations (family climate and school connectedness) reported during adolescence, influence the work-life course up to late midlife. METHODS: We examined repeated measurements of labour market status from age 16 to 56 using sequence analyses. We identified five different labour market attachment (LMA16-56) trajectories, namely 'strong,' 'early intermediate,' 'early weak,' 'late weak,' and 'constantly weak.' Multinomial logistic regressions were employed to relate each of the nine determinants to the identified trajectories. RESULTS: When compared to the risk of 'strong' LMA16-56, adversity in all conditions, except for vandalism, entailed a higher risk of the 'constantly weak' trajectory. Moreover, all conditions, except for functional somatic symptoms, entailed a higher risk of the 'late weak' LMA16-56. The risk of the 'early intermediate' LMA16-56 was non-significant across all the conditions. CONCLUSIONS: This study contributes to existing knowledge through its novel exploration of labour market attachment and the revelation of the significance of proximal interpersonal relationships in attachment outcomes. Additionally, the study reaffirms the importance of externalizing behaviour, while suggesting that internalized symptoms in adolescence might have a less influential, though not negligible, role. These results underscore the importance of addressing acting out behaviour and nurturing human relationships during compulsory basic education, when the entire age group is still within reach. This approach aims not only to reduce frictions in the school-to-work transition but also to prevent midlife labour market attachment problems that may arise with delayed intervention.

How do labour market conditions explain the development of mental health over the life-course? a conceptual integration of the ecological model with life-course epidemiology in an integrative review of results from the Northern Swedish Cohort.

BACKGROUND: The aim of this study was to contribute to the theoretical development within the field of labour market effects on mental health during life by integrating Bronfenbrenner's ecological model with mainly earlier theoretical work on life-course theory. METHODS: An integrative review was performed of all 52 publications about labour market conditions in relation to mental health from the longitudinal Northern Swedish Cohort study. Inductive and deductive qualitative content analysis were performed in relation to Bronfenbrenner's ecological framework combined with life-course theories. RESULTS: The following nine themes were identified: 1. Macroeconomic recession impairs mental health among young people. 2. The mental health effects on individuals of youth unemployment seem rather insensitive to recession. 3. Small but consistent negative effect of neighbourhood unemployment and other work-related disadvantaged on individuals' mental health over life. 4. Youth unemployment becomes embodied as scars of mental ill-health over life. 5. Weak labour market attachment impairs mental health over life. 6. Bidirectional relations between health and weak labour market attachment over life. 7. Macrolevel structures are of importance for how labour market position cause poor health. 8. Unequal gender relations at work impacts negatively on mental health. 9. The agency to improve health over life in dyadic relations. Unemployment in society permeates from the macrolevel into the exolevel, defined by Bronfenbrenner as for example the labour market of parents or partners or the neighbourhood into the settings closest to the individual (the micro- and mesolevel) and affects the relations between the work, family, and leisure spheres of the individual. Neighbourhood unemployment leads to poor health among those who live there, independent of their employment status. Individuals' exposure to unemployment and temporary employment leads to poorer mental health over the life-course. Temporal dimensions were identified and combined with Bronfenbrenner levels into a contextual life-course model CONCLUSION: Combining the ecosocial theory with life-course theories provides a framework for understanding the embodiment of work-related mental health over life. The labour market conditions surrounding the individual are of crucial importance for the embodiment of mental health over life, at the same time as individual agency can be health promoting. Mental health can be improved by societal efforts in regulations of the labour market.

Endovascular Versus Medical Management of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study.

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Effects of rehabilitative psychotherapy on labour market success: Evaluation of a nationwide programme.

AIMS: Psychotherapy is a widely used treatment for mental disorders, but whether it also improves employment and other labour market outcomes remains inconclusive. This study examined the effectiveness of a nationwide subsidized psychotherapy programme using extensive register-based data. METHODS: The sample consisted of individuals who applied for rehabilitative psychotherapy in Finland in 2009-2012 (n = 35,083). Prior to 2011, some applications were rejected due to the limited budget that the central government provided for the programme. From 2011, all eligible applicants were granted rehabilitation. We used propensity score matching to create balanced samples of those who received a negative decision in 2009-2010 (n = 2047) and those who were granted rehabilitative psychotherapy in 2011-2012 (n = 12,046) in terms of their sociodemographic background characteristics, prior labour market attachment and health status. RESULTS: We found that compared to the applicants who were not accepted to the programme, the granted applicants with similar background characteristics had, on average, a six-percentage-point higher employment rate, €2100 higher annual earnings and a six-percentage-point lower probability of becoming a disability benefit recipient five years after their first application. Further sensitivity analyses confirmed that these results were not biased, for example, by differences in macroeconomic conditions during the follow-up. CONCLUSIONS: Quasi-experimental research design showed that rehabilitative psychotherapy was significantly associated with better labour market outcomes. Although several relevant background factors were included in the matching analysis, it is possible that some unobserved factors explain both access to psychotherapy and subsequent labour market outcomes.

Why does youth unemployment lead to scarring of depressive symptoms in adulthood? The importance of early adulthood drinking.

AIM: The aim of the paper is to analyse if alcohol consumption could explain the scarring effect of youth unemployment on later depressive symptoms. METHODS: The analyses are based on the 24-year follow-up of school leavers in a municipality in Northern Sweden (the Northern Swedish Cohort). Four-way decomposition analyses were performed to analyse if alcohol use at age 30 years could mediate and/or moderate the effect of youth unemployment (ages 18/21 years) on depressive symptoms in later adulthood (age 43 years). RESULTS: Excessive alcohol use at early adulthood (age 30 years) mediates 18% of the scarring effect of youth unemployment on depressive symptoms in later adulthood. The scarring effect was seen among both those with and without excessive alcohol use. CONCLUSIONS: Youth unemployment leads to poor mental health later in life and part of these relations are explained by excessive alcohol consumption in early adulthood. Policy interventions should target the prevention of youth unemployment for reaching a lower alcohol consumption and better mental health.

Impact of white matter hypodensities on outcome after intracerebral hemorrhage.

OBJECTIVES: White matter hypodensities (WMH), a surrogate of small vessel disease, associate with cognitive decline and stroke risk. The impact of WMH on functional outcome after intracerebral hemorrhage (ICH) has differed between studies. We aimed to examine factors associated with the severity of WMH in ICH, and whether there is an independent association between the extent of WMH and outcome. MATERIALS AND METHODS: This was a prospective study of consented patients with non-traumatic primary ICH, admitted to the Helsinki University Hospital between May 2014 and December 2018. To evaluate the extent of the WMH, modified van Swieten score of the side contralateral to the ICH was obtained. Patients were grouped into 3 categories of the scores. We performed univariate and multivariable analyses to find out factors associated with the severity of WMH, and whether WMH associate with functional outcome and mortality up to 12 months, adjusted for the known major outcome predictors. RESULTS: In our cohort of 417 ICH patients, WMH severity associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT. We found an independent association between WMH severity and poor functional outcome at 3 months (OR 1.72, 95% CI 1.27-2.33), and 1 year (OR 2.16, 95% CI 1.57-2.95), and mortality at 1 year (OR 1.91, 95% CI 1.29-2.85). CONCLUSIONS: In our ICH patients, vascular comorbidities and older age associated with the presence of WMH, which, in turn, strongly associated with poor functional outcome.

Contribution of astrocytes to familial risk and clinical manifestation of schizophrenia.

Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)-derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron-astrocyte co-cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ.

Comparison of large vessel occlusion scales using prehospital patient reports.

BACKGROUND: Prehospital identification of large vessel occlusion (LVO) holds significant potential to decrease the onset-to-treatment time. Several prehospital scales have been developed to identify LVO but data on their comparison has been limited. The aim of this study was to review the currently available prehospital LVO scales and compare their performance using prehospital data. METHODS: All patients transported by ambulance using stroke code on a six-month period were enrolled into the study. The prehospital patient reports were retrospectively evaluated by two investigators using sixteen LVO scales identified by literature search and expert opinion. After the evaluation, the computed tomography angiography results were reviewed by a neuroradiologist to confirm or exclude LVO. RESULTS: Sixteen different LVO scales met the predetermined study criteria and were selected for further comparison. Using them, a total of 610 evaluations were registered. The sensitivity of the scales varied between 8%-73%, specificity between 71%-97% and overall accuracy between 71%-87%. The areas under curve (AUC) varied between 0.61-0.80 for the whole scale range and 0.53%-0.74 for the scales' binary cut-offs. The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) was the only scale with AUC > 0.8. Regarding scales' binary cut-offs, The FAST-ED (0.70), Gaze - Face Arm Speech Time (G-FAST) (0.74) and Emergency Medical Stroke Assessment (EMSA) (0.72) were the only scales with AUC > 0.7. CONCLUSIONS: In a comparison of 16 different LVO scales, the FAST-ED, G-FAST and EMSA achieved the highest overall performance.

Is infarct core growth linear? Infarct volume estimation by computed tomography perfusion imaging.

OBJECTIVES: Current guidelines for recanalization treatment are based on the time elapsed between symptom onset and treatment and visualization of existing penumbra in computed tomography perfusion (CTP) imaging. The time window for treatment options relies on linear growth of infarction although individual infarct growth rate may vary. We aimed to test how accurately the estimated follow-up infarct volume (eFIV) can be approximated by using a linear growth model based on CTP baseline imaging. If eFIV did not fall within the margins of +/- 19% of the follow-up infarct volume (FIV) measured at 24 h from non-enhanced computed tomography images, the results would imply that the infarct growth is not linear. MATERIALS AND METHODS: All consecutive endovascularly treated (EVT) patients from 11/2015 to 9/2019 at the Helsinki University Hospital with large vessel occlusion (LVO), CTP imaging, and known time of symptom onset were included. Infarct growth rate was assumed to be linear and calculated by dividing the ischemic core volume (CTPcore ) by the time from symptom onset to baseline imaging. eFIV was calculated by multiplying the infarct growth rate with the time from baseline imaging to recanalization or in case of futile recanalization to follow-up imaging at 24 h, limited to the penumbra. Collateral flow was estimated by calculating hypoperfusion intensity ratio (HIR). RESULTS: Of 5234 patients, 48 had LVO, EVT, CTP imaging, and known time of symptom onset. In 40/48 patients (87%), infarct growth was not linear. HIR did not differ between patients with linear and nonlinear growth (p > .05). As expected, in over half of the patients with successful recanalization eFIV exceeded FIV. CONCLUSIONS: Infarct growth was not linear in most patients and thus time elapsed from symptom onset and CTPcore appear to be insufficient parameters for clinical decision-making in EVT candidates.

Risk factors in adolescence as predictors of trajectories of somatic symptoms over 27 years.

BACKGROUND: Somatic symptoms among adolescents are common, yet little is known about long-term trajectories of somatic symptoms and the factors in adolescence that shape them. We examined individual, family and school-based factors at age 16 as predictors of trajectories of somatic symptoms over 27 years. METHODS: Participants from the Northern Swedish Cohort (n = 1001) responded to questions about individual factors (e.g. health behaviours), family factors (e.g. contact with parents, social and material adversity) and school satisfaction at age 16; as well as 10 somatic symptoms at ages 16, 18, 21, 30 and 43. Teacher assessments at age 16 included overall ability at school and peer relations. Age 16 predictors of somatic symptom trajectory group membership were analysed using multinomial logistic regression. RESULTS: Poor contact with mother and poor school satisfaction were significant predictors of adverse symptom trajectories among both men and women. Low birth weight and low parental academic involvement were contributing factors for women, while smoking and social adversity were more relevant factors for men. CONCLUSIONS: Our findings emphasize the importance of a holistic approach that considers the unique contributions of individual, family and school-based factors in the development of trajectories of somatic symptoms from adolescence to middle age.

Clinical frailty and outcome after mechanical thrombectomy for stroke in patients aged ≥ 80 years.

OBJECTIVES: Data concerning the results of endovascular thrombectomy (EVT) in old patients is still limited. We aimed to investigate the outcomes in thrombectomy-treated ischemic stroke patients aged ≥ 80 years, focusing on frailty as a contributing factor. PATIENTS AND METHODS: We performed a single-centre retrospective cohort study with 159 consecutive patients aged ≥ 80 years and treated with EVT for acute ischemic stroke between January 1st 2016 and December 31st 2019. Pre-admission frailty was assessed with the Clinical Frailty Scale (CFS). Patients with CFS ≥ 5 were defined as frail. The main outcome was very poor outcome defined as mRS 4-6 at three months after EVT. Secondary outcomes were recanalization status, symptomatic intracerebral haemorrhage (sICH), and one-year survival. Finally, we recorded if the patient returned home within 12 months. RESULTS: Very poor outcome was observed in 57.9% of all patients (52.4% in non-frail and 79.4% in frail patients). Rates of recanalization and sICH were comparable in frail and non-frail patients. Of all patients, 46.5% were able to live at home within 1 year after stroke. One-year survival was 59.1% (65.6% in non-frail and 35.3% in frail patients). In logistic regression analysis higher admission NIHSS, not performing thrombolysis, lack of recanalization and higher frailty status were all independently associated with very poor three-month outcome. Factors associated with one-year mortality were male gender, not performing thrombolysis, sICH, and higher frailty status. CONCLUSION: Almost 60% of studied patients had very poor outcome. Frailty significantly increases the likelihood of very poor outcome and death after EVT-treated stroke.

Thrombectomy in Acute Ischemic Stroke in the Extended Time Window: Real-Life Experience in a High-Volume Center.

OBJECTIVES: Selected patients with acute ischemic stroke (AIS) caused by proximal middle cerebral artery (MCA) or internal carotid artery occlusion benefit from endovascular thrombectomy (EVT) in extended time window (6-24 h from last seen well) based on two landmark randomized controlled trials (RCTs) DAWN and DEFUSE-3. We evaluated patients' outcome in the real-life with the focus on adherence to protocol of the two RCTs. MATERIALS AND METHODS: We included consecutive patients with AIS (excluding basilar artery occlusions) referred to EVT in our stroke center in the extended time window between January 2018 and December 2019 and compared the outcome of patients who fulfilled criteria of the RCTs with those who did not. RESULTS: Of the total of 100 patients, 23 complied with RCT's criteria and 18 presented with minor non-adherence (lower NIHSS score or longer treatment delay), whereas 22 patients had large baseline ischemia (>1/3 MCA), 28 presented with M2 and more distal occlusions, and 9 patients did not undergo perfusion imaging prior to EVT. Good 3-month outcome (modified Rankin Scale 0-2) was observed in 54% of those who either met the RCT criteria or presented with lower NIHSS score or longer treatment delay, but only in 30% of M2 occlusions, and in none of the patients with large baseline ischemia. CONCLUSIONS: Our findings highlight the impact of mostly large baseline ischemia but also vessel status when selecting patients for EVT in the extended time window and emphasize the need for further data in these patient subgroups.

Neurobiological roots of psychopathy.

Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general population, and 10-30% among incarcerated criminal offenders. Although the heritability of severe antisocial behavior is up to 50%, the genetic background is unclear. The underlying molecular mechanisms have remained unknown but several previous studies suggest that abnormal glucose metabolism and opioidergic neurotransmission contribute to violent offending and psychopathy. Here we show using iPSC-derived cortical neurons and astrocytes from six incarcerated extremely antisocial and violent offenders, three nonpsychopathic individuals with substance abuse, and six healthy controls that there are robust alterations in the expression of several genes and immune response-related molecular pathways which were specific for psychopathy. In neurons, psychopathy was associated with marked upregulation of RPL10P9 and ZNF132, and downregulation of CDH5 and OPRD1. In astrocytes, RPL10P9 and MT-RNR2 were upregulated. Expression of aforementioned genes explained 30-92% of the variance of psychopathic symptoms. The gene expression findings were confirmed with qPCR. These genes may be relevant to the lack of empathy and emotional callousness seen in psychopathy, since several studies have linked these genes to autism and social interaction.

Correction: Neurobiological roots of psychopathy.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Outcomes and long-term mortality after basilar artery occlusion-A cohort with up to 20 years' follow-up.

BACKGROUND: The data on long-term outcome after basilar artery occlusion (BAO) are scarce. Little is known about BAO survivors´ outcome over decades. AIM: We set out to investigate long-term survival and causes of death in BAO patients with up to two decades of follow-up. We also evaluated differences in outcome trends. METHODS: Two hundred and seven BAO patients treated with intravenous thrombolysis (IVT) at the Department of Neurology, Helsinki University Hospital, between 1995 and 2016, were analyzed. Short-term outcome was assessed by modified Rankin Scale (mRS) at 3 months. Long-term cumulative survival rate was analyzed using Kaplan-Meier analysis. Factors associated with mortality were analyzed with Cox regression. RESULTS: Moderate outcome (mRS 0-3) was achieved in 41.1% and good outcome (mRS 0-2) in 30.4% of patients at 3 months. Three-month mortality was 39.6%, of which 89% died within the first month. The median follow-up time in 3-month survivors was 8.9 years (maximum 21.8 years). Total mortality during follow-up was 52.2%. Cumulative mortality rate was 25.7%. Older age, coronary artery disease and more extensive ischemic changes on admission brain imaging were independently associated with long-term mortality. After the acute phase, the rate of other vascular causes of death increased in relation to stroke. CONCLUSIONS: The described evolution of a large, single-center BAO cohort shows a trend towards a higher rate of good and/or moderate outcome during later years in IVT-treated patients. Survivors showed relative longevity, and the rate of cardiac and other vascular causes of death increased in relation to stroke sequelae over the long term.

Prehospital identification of large vessel occlusion using the FAST-ED score.

OBJECTIVES: The prehospital identification of stroke patients with large vessel occlusion (LVO) enables appropriate hospital selection and reduces the onset-to-treatment time. The aim of this study was to investigate whether the Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale could be reconstructed from existing prehospital patient reports and to compare its performance with neurologist's clinical judgement using the same prehospital data. MATERIALS & METHODS: All patients transported by ambulance using stroke code on a six-month period were registered for the study. The prehospital patient reports were retrospectively evaluated using the FAST-ED scale by two investigators. The performance of FAST-ED score (≥4 points) in LVO identification was compared to neurologist's clinical judgement ('LVO or not'). The presence of LVO was verified using computed tomography angiography imaging. RESULTS: A total of 610 FAST-ED scores were obtained. The FAST-ED had a sensitivity of 57.8%, specificity of 87.2%, positive predictive value (PPV) of 37.3%, negative predictive value (NPV) of 93.4% and area under curve (AUC) of 0.724. Interclass correlation coefficient for both raters over the entire range of FAST-ED was 0.92 (0.88-0.94). The neurologist's clinical judgement raised sensitivity to 79.4%, NPV to 97.1% and PPV to 45.0% with an AUC of 0.837 (p < .05). CONCLUSIONS: The existing patient report data could be feasibly used to reconstruct FAST-ED scores to identify LVO. The binary FAST-ED score had a moderate sensitivity and good specificity for prehospital LVO identification. However, the FAST-ED was surpassed by neurologist's clinical judgement which further increased the sensitivity of identification.

Occipital intracerebral hemorrhage-clinical characteristics, outcome, and post-ICH epilepsy.

OBJECTIVES: Posterior location affects the clinical presentation and outcome of ischemic stroke, but little is known about occipital intracerebral hemorrhage (ICH). We studied non-traumatic occipital ICH phenotype, outcome, and post-ICH epilepsy. MATERIALS AND METHODS: Occipital ICH patients were retrospectively identified from the Helsinki ICH Study registry of 1013 consecutive ICH patients treated in our tertiary center in 2005-2010. They were compared to non-occipital ICH patients to evaluate the effect of location on functional outcome at discharge (dichotomized modified Rankin Scale, mRS), 3- and 12-month mortality, and incidence of epilepsy. RESULTS: We found 19 occipital ICH patients (5.3% of lobar and 1.9% of all ICH). Compared to non-occipital lobar ICHs, they were younger (median age 63 vs 71 years, P = .007) and had lower National Institutes of Health Stroke Scale on admission (1 vs 8, P < .001), smaller hematoma volume (6.3 vs 17.7 ML, P = .008), and more frequently structural etiology underlying the ICH (26% vs 7%, P = .01). Mortality at both 3 and 12 months was 6%, whereas 84% reached favorable outcome (mRS 0-2) at discharge. Occipital location was associated with favorable outcome at discharge in lobar ICH (OR 11.02, 95% CI 1.55-78.20). Incidence of post-ICH epilepsy (median follow-up 2.7 years) was 18%, equaling to that of non-occipital lobar ICH. CONCLUSIONS: Occipital ICH patients are younger, have less severe clinical presentation, smaller hematoma volume, more often structural etiology, and better outcome than other ICH patients. They exhibit a similar risk of epilepsy as non-occipital ICHs.