Altered amygdalar emotion space in borderline personality disorder normalizes following dialectical behaviour therapy.

BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

Mental health problems during the COVID-19 pandemic among residents of Jimma town: a cross-sectional study.

The COVID-19 pandemic presents an unprecedented challenge to community wellbeing and mental health. However, quantifiable information on the extent of mental health problems and associated factors due to the pandemic is still lacking in low-income countries. Thus, this study aimed to investigate the levels of depression, anxiety, and stress and their association with risk and resilience factors among residents of Jimma town in Southwestern Ethiopia. A community-based cross-sectional study was conducted between October 2021 and November 2021. Data were collected from 1196 adult Jimma town residents selected through multi-stage sampling. The following scales were used for the cross-sectional assessment of depressions, anxiety and stress and their associations: depression, anxiety, and stress-21(DASS-21), World Health Organization (WHO) wellbeing, University of California, Los Angeles Loneliness Scale (UCLA), Childhood trauma questionnaire, and brief resilience scales. A pre-tested, interviewer-completed questionnaire was used for data collection. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated with depression, anxiety, and stress. Odds ratios consistent with 95% CI were used to report the presence of an association between risk and resilience factors and the outcome variable at a P-value < 0.05. Overall, 963 (80.53%) respondents had divergent DASS-21 score findings. Specifically, 27.68%, 31.52% and 21.32% experienced depression, anxiety, and stress respectively. Higher DASS-21 scores were associated with the presence of one or more COVID-19 risk factors for anyone close to the participants (AOR = 1.53, 95% CI 1.03-2.27), feelings of stress/burden (ß = 1.09, 95% CI 1.07-1.12), positive coping (ß = 1.044, 95% CI 1.01-1.07), loneliness (ß = 1.063, 95% CI 1.04-1.08), and childhood trauma (ß = 1.03, 95% CI 1.01-1.04). In contrast, lower DASS-21 scores were associated with beliefs about the necessity of solidarity-based behavior (ß = 0.94, 95% CI 0.90-0.98), resilience (ß = 0.92, 95% CI 0.87-0.97) and wellbeing (ß = 0.90, 95% CI 0.87-0.94). In the course of the COVID-19 pandemic in 2021, symptoms of depression, anxiety, and stress in the study community were prevalent, and associated with numerous risk and resilience factors. Although causality cannot be inferred, these findings underscore the importance of strengthening mental health services and may guide COVID-19 prevention and treatment strategies.

[Inpatient psychotherapy of depressive disorders: options and challenges]. / Stationäre Psychotherapie depressiver Störungen: Möglichkeiten und Herausforderungen.

BACKGROUND: The psychotherapy of depressive disorders has become established as a central component of inpatient treatment in psychiatric and psychosomatic hospitals and furthermore constitutes an important component of the residency training in Germany; however, the number of studies examining the effectiveness and efficacy is limited. METHODS: This narrative review summarizes the current state of research on inpatient psychotherapy for depressive disorders. The results of meta-analyses as well as practice-based observational studies from routine treatment in Germany, disorder-specific special programs, and side effects of inpatient psychotherapy are summarized. RESULTS: The number of studies on the efficacy of inpatient psychotherapy of depressive disorders is overall low. The main finding of the largest recent meta-analysis indicates that psychotherapy in clinics and other facilities has a significant effect on depressive symptoms, with small to moderate effect sizes in randomized controlled studies. The effects are mostly maintained even after 9-15 months follow-up. An observational study from routine treatment with a very large sample size reported large pre-post and pre-follow-up effect sizes. It additionally revealed factors that appear to be difficult to change during inpatient psychotherapy, negatively affect treatment success and could be specifically addressed in future trials. Special programs, such as inpatient Interpersonal Psychotherapy (IPT) and the inpatient Cognitive Behavioral Analysis System of Psychotherapy (CBASP) indicate acceptance and efficacy/effectiveness in an initial randomized controlled (IPT) study and in observational (CBASP) studies. Side effects of inpatient psychotherapy were reported by 60-94% of patients with depressive disorders, whereby a perceived dependence on the therapist or the therapeutic setting was identified as a frequent side effect. CONCLUSION: Overall, the results of the narrative review reveal that inpatient psychotherapy appears to be meaningful and effective for many patients with depressive disorders. Specific side effects, cost-effectiveness, and the question of differential indications (what works for whom?) should be further investigated.

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001-2017.

The International Classification of Diseases (10th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin-norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD-patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting.

Loneliness in Personality Disorders.

PURPOSE OF REVIEW: Loneliness is a common experience in patients with personality disorders (PDs) that are characterized by impairment in self (identity, self-direction) and interpersonal functioning (empathy, intimacy). Here, we review studies assessing the association of loneliness with PD or PD traits including DSM-5's Alternative Model of PD (AMPD). RECENT FINDINGS: The number of loneliness studies varied greatly among different PDs with most studies conducted in borderline PD. Across PDs, loneliness was associated with the severity of psychopathological symptoms and with several AMPD trait domains. Consequently, loneliness may contribute to PD severity and further impair personality functioning. Loneliness and PD share intra- and interpersonal factors (i.e., increased rejection sensitivity, information processing biases, social withdrawal) and common origins in childhood maltreatment that may explain their close association. Future research needs to investigate mechanisms on how loneliness and core characteristics of PD mutually reinforce each other in order to therapeutically address loneliness in PD.

Differential psychological response to the COVID-19 pandemic in psychiatric inpatients compared to a non-clinical population from Germany.

The COVID-19 pandemic is an inherently stressful situation, which may lead to adverse psychosocial outcomes in various populations. Yet, individuals may not be affected equally by stressors posed by the pandemic and those with pre-existing mental disorders could be particularly vulnerable. To test this hypothesis, we assessed the psychological response to the pandemic in a case-control design. We used an age-, sex- and employment status-matched case-control sample (n = 216) of psychiatric inpatients, recruited from the LMU Psychiatry Biobank Munich study and non-clinical individuals from the general population. Participants completed validated self-report measures on stress, anxiety, depression, paranoia, rumination, loneliness, well-being, resilience, and a newly developed index of stressors associated with the COVID-19 pandemic. Multiple linear regression analyses were conducted to assess the effects of group, COVID-19-specific stressors, and their interaction on the different psychosocial outcomes. While psychiatric inpatients reported larger mental health difficulties overall, the impact of COVID-19-specific stressors was lower in patients and not associated with worse psychological functioning compared to non-clinical individuals. In contrast, depressive symptoms, rumination, loneliness, and well-being were more strongly associated with COVID-19-specific stressors in non-clinical individuals and similar to the severity of inpatients for those who experienced the greatest COVID-19-specific stressor impact Contrary to expectations, the psychological response to the pandemic may not be worse in psychiatric inpatients compared to non-clinical individuals. Yet, individuals from the general population, who were hit hardest by the pandemic, should be monitored and may be in need of mental health prevention and treatment efforts.

Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017.

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001-2003) with the last time period (2015-2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12-1.19), especially mirtazapine (RR 1.16; 95% CI 1.12-1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35-1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03-1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83-0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86-0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81-0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015-2017 than in 2001-2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

Seasonal patterns and associations in the incidence of acute ischemic stroke requiring mechanical thrombectomy.

BACKGROUND: In order to identify risk periods with an increased demand in technical and human resources, we tried to determine patterns and associations in the incidence of acute ischemic stroke due to embolic large vessel occlusions (eLVO) requiring mechanical thrombectomy (MT). METHODS: We conducted a time series analysis over a 9-year period (2010-2018) based on observational data in order to detect seasonal patterns in the incidence of MT due to eLVO (n = 2628 patients). In a series of sequential negative binominal regression models, we aimed to detect further associations (e.g., temperature, atmospheric pressure, air pollution). RESULTS: There was a 6-month seasonal pattern in the incidence of MT due to eLVO (p = 0.024) peaking in March and September. Colder overall temperature was associated with an increase in MT due to eLVO (average marginal effect [AME], [95% CI]: -0.15 [-0.30-0.0001]; p = 0.05; per °C). A current increase in the average monthly temperature was associated with a higher incidence of MT due to eLVO (0.34 [0.11-0.56]; p = 0.003). Atmospheric pressure was positively correlated with MT due to eLVO (0.38 [0.13-0.64]; p = 0.003; per hectopascal [hPa]). We could detect no causal correlation between air pollutants and MT due to eLVO. CONCLUSIONS: Our data suggest a 6-month seasonal pattern in the incidence of MT due to eLVO peaking in spring and early autumn. This might be attributed to two different factors: (1) a current temperature rise (comparing the average monthly temperature in consecutive months) and (2) colder overall temperature. These results could help to identify risk periods requiring an adaptation in local infrastructure.

Cerebral Autoregulation and Neurovascular Coupling after Craniospinal Irradiation in Long-Term Survivors of Malignant Pediatric Brain Tumors of the Posterior Fossa.

INTRODUCTION: Long-term survivors of craniospinal irradiation have an increased risk for stroke which increases with radiation dose and follow-up time. Radiotherapy induces structural changes of the cerebral vasculature, affecting both, large, and small vessels. It is unknown how these structural changes affect functional mechanisms of cerebral blood flow regulation such as cerebral autoregulation and neurovascular coupling. METHODS: Using the transcranial Doppler, we compared dynamic cerebral autoregulation and neurovascular coupling of 12 patients after long-term survival of craniospinal irradiation due to a malignant pediatric brain tumor of the posterior fossa and 12 age- and sex-matched healthy patients. Mean arterial blood pressure and cerebral blood flow velocities in the middle and posterior cerebral artery were recorded at rest during normal breathing to assess cerebral autoregulation (transfer function parameters phase and gain, as well as the correlation coefficient indices Mx, Sx, and Dx), and during 10 cycles of a visual task to assess neurovascular coupling (parameters time delay, natural frequency, gain, attenuation, and rate time). RESULTS: Parameters of cerebral autoregulation showed a consistent trend toward reduced cerebral autoregulation in patients that did not reach statistical significance. Neurovascular coupling was not altered after craniospinal irradiation. CONCLUSION: In this pilot study, we demonstrated a trend toward reduced cerebral autoregulation, and no alteration of neurovascular coupling after irradiation in long-term survivors of malignant pediatric brain tumors of the posterior fossa.

Pharmacotherapy of 1,044 inpatients with posttraumatic stress disorder: current status and trends in German-speaking countries.

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder with limited approved pharmacological treatment options and high symptom burden. Therefore, real-life prescription patterns may differ from guideline recommendations, especially in psychiatric inpatient settings. The European Drug Safety Program in Psychiatry ("Arzneimittelsicherheit in der Psychiatrie", AMSP) collects inpatients' prescription rates cross-sectionally twice a year in German-speaking psychiatric hospitals. For this study, the AMSP database was screened for psychiatric inpatients with a primary diagnosis of PTSD between 2001 and 2017. N = 1,044 patients with a primary diagnosis of PTSD were identified with 89.9% taking psychotropics. The average prescription rate was 2.4 (standard deviation: 1.5) psychotropics per patient with high rates of antidepressant drugs (72.0%), antipsychotics drugs (58.4%) and tranquilizing drugs (29.3%). The presence of psychiatric comorbidities was associated with higher rates of psychotropic drug use. The most often prescribed substances were quetiapine (24.1% of all patients), lorazepam (18.1%) and mirtazapine (15.0%). The use of drugs approved for PTSD was low (sertraline 11.1%; paroxetine 3.7%). Prescription rates of second-generation antipsychotic drugs increased, while the use of tranquilizing drugs declined over the years. High prescription rates and extensive use of sedative medication suggest a symptom-driven prescription (e.g., hyperarousal, insomnia) that can only be explained to a minor extent by existing comorbidities. The observed discrepancy with existing guidelines underlines the need for effective pharmacological and psychological treatment options in psychiatric inpatient settings.

The COVID-19 Pandemic Mental Health Questionnaire (CoPaQ): psychometric evaluation and compliance with countermeasures in psychiatric inpatients and non-clinical individuals.

BACKGROUND: The COVID-19 pandemic has greatly impacted people's lives across a broad spectrum of psychosocial domains. We report the development and psychometric evaluation of the self-report COVID-19 Pandemic Mental Health Questionnaire (CoPaQ), which assesses COVID-19 contamination anxiety, countermeasure necessity and compliance, mental health impact, stressor impact, social media usage, interpersonal conflicts, paranoid ideations, institutional & political trust, conspiracy beliefs, and social cohesion. Further, we illustrate the questionnaire's utility in an applied example investigating if higher SARS-Cov-2 infection rates in psychiatric patients could be explained by reduced compliance with preventive countermeasures. METHODS: A group of 511 non-clinical individuals completed an initial pool of 111 CoPaQ items (Open Science Framework: https://osf.io/3evn9/ ) and additional scales measuring psychological distress, well-being, and paranoia to assess construct validity and lifetime mental health diagnosis for criterion validity. Factor structure was determined by exploratory factor analyses and validated by conducting confirmatory factor analysis in the accompanying longitudinal sample (n = 318) and an independent psychiatric inpatient sample primarily admitted for major depressive-, substance abuse-, personality-, and anxiety disorders (n = 113). Internal consistency was assessed by Cronbach's Alpha and McDonald's Omega. For the applied research example, Welch t-tests and correlational analyses were conducted. RESULTS: Twelve out of 16 extracted subscales were retained in the final questionnaire version, which provided preliminary evidence for adequate psychometric properties in terms of factor structure, internal consistency, and construct and criterion validity. Our applied research example showed that patients exhibited greater support for COVID-19 countermeasures than non-clinical individuals. However, this requires replication in future studies. CONCLUSIONS: We demonstrate that the CoPaQ is a comprehensive and valid measure of the psychosocial impact of the pandemic and could allow to a degree to disentangle the complex psychosocial phenomena of the pandemic as exemplified by our applied analyses.

[Psychosocial support during the COVID-19 pandemic: interdisciplinary concept of care at a university hospital]. / Psychosoziale Unterstützung während der COVID-19-Pandemie: interdisziplinäres Versorgungskonzept an einem Universitätsklinikum.

BACKGROUND: Since the beginning of the outbreak, the COVID-19 pandemic has caused an increased demand for psychosocial support for patients, their family members, and healthcare workers. Concurrently, possibilities to provide this support have been hindered. Quarantine, social isolation, and SARS-CoV­2 infections represent new and severe stressors that have to be addressed with innovative psychosocial care. OBJECTIVE AND METHOD: This article describes the COVID-19 psychosocial first aid concept at the University Hospital Munich (LMU Klinikum) developed by an interdisciplinary team of psychiatric, psychological, spiritual care, psycho-oncological, and palliative care specialists. RESULTS: A new psychosocial first aid model has been implemented for COVID-19 inpatients, family members, and hospital staff consisting of five elements. CONCLUSION: The concept integrates innovative and sustainable ideas, e.g. telemedicine-based approaches and highlights the importance of multidisciplinary collaboration to cope with challenges in the healthcare system.

The Tourniquet Ischemia Test in the Diagnosis of Complex Regional Pain Syndrome.

BACKGROUND: The tourniquet ischemia test (IT) is a hitherto rarely used tool for the diagnostic work-up of patients with suspected complex regional pain syndrome (CRPS). This analysis aims to determine the sensitivity and specificity of this test, and elucidate factors that can influence the test result. METHODS: Consecutive data on clinical presentation, results of the IT and other diagnostic tests, and clinical characteristics were analyzed from patients presenting at our autonomic laboratory between 2000 and 2011. IT results were compared with the final clinical diagnosis at discharge, and statistical analysis was performed to determine specificity, sensitivity, and positive and negative predictive values of the IT. RESULTS: A total of 78 patients were assessed. IT results were positive (≥50% reduction in pain during ischemia) in 26 cases and negative in 52 cases. CRPS was the final diagnosis in 45 cases, and in 33 cases, a different diagnosis was made. This results in a test sensitivity of 49% and a specificity of 88%, with a positive predictive value of 85% and a negative predictive value of 56%. Age, sex, the type and stage of CRPS, and the affected extremity did not influence the test result in a statistically significant manner. Specificity worsened to 76% if any pain reduction was rated as a positive test result. CONCLUSIONS: A positive tourniquet IT has a high positive predictive value for the diagnosis of CRPS. It is thus useful as a confirmatory assay in patients with suspected CRPS. Low sensitivity rules out its use as a screening test. SIGNIFICANCE: This study retrospectively analyzed the clinical significance of the tourniquet IT that was routinely used in patients with suspected CRPS. It showed that a positive IT result is useful as a confirmatory assay in patients fulfilling the clinical criteria.

The vicious circle of social exclusion and psychopathology: a systematic review of experimental ostracism research in psychiatric disorders.

Social exclusion (ostracism) is a major psychosocial factor contributing to the development and persistence of psychiatric disorders and is also related to their social stigma. However, its specific role in different disorders is not evident, and comprehensive social psychology research on ostracism has rather focused on healthy individuals and less on psychiatric patients. Here, we systematically review experimental studies investigating psychological and physiological reactions to ostracism in different responses of psychiatric disorders. Moreover, we propose a theoretical model of the interplay between psychiatric symptoms and ostracism. A systematic MEDLINE and PsycINFO search was conducted including 52 relevant studies in various disorders (some of which evaluated more than one disorder): borderline personality disorder (21 studies); major depressive disorder (11 studies); anxiety (7 studies); autism spectrum disorder (6 studies); schizophrenia (6 studies); substance use disorders (4 studies); and eating disorders (2 studies). Psychological and physiological effects of ostracism were assessed with various experimental paradigms: e.g., virtual real-time interactions (Cyberball), social feedback and imagined scenarios. We critically review the main results of these studies and propose the overall concept of a vicious cycle where psychiatric symptoms increase the chance of being ostracized, and ostracism consolidates or even aggravates psychopathology. However, the specificity and stability of reactions to ostracism, their neurobiological underpinnings, determinants, and moderators (e.g., attachment style, childhood trauma, and rejection sensitivity) remain elusive.

QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors.

Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.

BACKGROUND: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). METHODS AND RESULTS: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. CONCLUSIONS: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Early Vasospasm after Aneurysmal Subarachnoid Hemorrhage Predicts the Occurrence and Severity of Symptomatic Vasospasm and Delayed Cerebral Ischemia.

BACKGROUND: Cerebral vasospasm usually develops several days after subarachnoid hemorrhage (SAH) and is generally acknowledged as a strong outcome predictor. In contrast, much less is known about the nature and eventual consequences of early angiographic vasospasm (EAVS) seen on admission digital subtraction angiography (DSA). Therefore, we aimed at identifying the risk factors and clinical impact of EAVS after SAH. METHODS: Five hundred and thirty-one SAH patients with admission DSA performed within 72 h after the bleeding event were selected from a comprehensive database containing all consecutive SAH patients treated at our institution between January 2005 and December 2012. Predictors of EAVS, as well as associations between EAVS and delayed vasospasm-related complications, and unfavorable outcome (defined as modified Rankin scale >3) were evaluated in univariate and multivariate analyses. RESULTS: EAVS was seen on 60 DSAs (11.3%) and was independently correlated with delayed symptomatic vasospasm requiring intra-arterial spasmolysis (OR 5.24, p < 0.0001), angioplasty (OR 2.56, p = 0.015) and repetitive endovascular treatment (OR 4.71, p < 0.0001). EAVS also increased the risk for multiple versus single territorial infarction on the follow-up CT scan(s) (OR 2.04, p = 0.047) and independently predicted unfavorable outcome (OR 2.93, p = 0.008). The presence of radiographic signs suspicious for fibromuscular dysplasia were independently associated with the occurrence of EAVS (OR 2.98, p = 0.026) and the need for repetitive endovascular vasospasm treatment (OR 3.95, p = 0.019). CONCLUSIONS: In view of the strong correlation with delayed symptomatic vasospasm and its ischemic complications, EAVS can be considered an alerting signal for severe symptomatic vasospasm. Therefore, more attention should be paid to the presence of EAVS on admission DSA.

Cerebral Arterial Time Constant Recorded from the MCA and PICA in Normal Subjects.

Cerebral arterial time constant (τ) estimates how quickly the cerebral arterial bed distal to the point of insonation is filled with arterial blood following a cardiac contraction. It is not known how τ behaves in different vascular territories in the brain. We therefore investigated the differences in τ of two cerebral arteries: the posterior inferior cerebellar artery (PICA) and the middle cerebral artery (MCA).Transcranial Doppler cerebral blood flow velocity (CBFV) in the PICA and left MCA along with Finapres arterial blood pressure (ABP) were simultaneously recorded in 35 young healthy volunteers. τ was estimated using mathematical transformations of pulse waveforms of ABP and the CBFV of the MCA and the PICA. Since τ is independent from the vessel radius, its comparison in different cerebral arteries was feasible. Mean ABP was 76.1 ± 9.6 mmHg. The CBFV of the MCA was higher than that of the PICA (59.7 ± 7.7 vs. 41.0 ± 4.5 cm/s; p < 0.000001). τ of the PICA was shorter than that of the MCA (0.15 ± 0.03 vs. 0.18 ± 0.03 s; p < 0.000001). The MCA-supplied vascular bed has a longer distal average length, measured from the place of insonation up to the small arterioles, than the PICA-supplied vascular bed. Therefore, a longer time is needed to fill it with arterial blood volume. This study thus confirms the physiological validity of the τ concept.

Autoregulation monitoring and outcome prediction in neurocritical care patients: Does one index fit all?

Indexes PRx and Mx have been formerly introduced to assess cerebral autoregulation and have been shown to be associated with 3-month clinical outcome. In a mixed cohort of neurocritical care patients, we retrospectively investigated the impact of selected clinical characteristics on this association. Forty-one patients (18-77 years) with severe traumatic (TBI, N = 20) and non-traumatic (N = 21) brain injuries were studied. Cerebral blood flow velocity, arterial blood pressure and intracranial pressure were repeatedly recorded during 1-h periods. Calculated PRx and Mx were correlated with 3-month clinical outcome score of modified Rankin Scale (mRS) in different subgroups with specific clinical characteristics. Both PRx and Mx correlated significantly with outcome (PRx: r = 0.38, p < 0.05; AUC = 0.64, n.s./Mx: r = 0.48, p < 0.005; AUC = 0.80, p < 0.005) in the overall group, and in patients with hemicraniectomy (N = 17; PRx: r = 0.73, p < 0.001; AUC = 0.89, p < 0.01/Mx: r = 0.69, p < 0.005; AUC = 0.87, p < 0.05). Mx, not PRx, correlated significantly with mRS in patients with heart failure (N = 17; r = 0.69, p < 0.005; AUC = 0.92, p < 0.005), and in non-traumatic patients (r = 0.49, p < 0.05; AUC = 0.79, p < 0.05). PRx, not Mx, correlated significantly with mRS in TBI patients (r = 0.63, p < 0.01; AUC = 0.89, p < 0.01). Both indexes did not correlate with mRS in diabetes patients (N = 15), PRx failed in hypocapnic patients (N = 26). Both PRx and Mx were significantly associated with 3-month clinical outcome, even in patients with hemicraniectomy. PRx was more appropriate for TBI patients, while Mx was better suited for non-traumatic patients and patients with heart failure. Prognostic values of indexes were affected by diabetes (both Mx and PRx) and hypocapnia (PRx only).

Endovascular Treatment versus Sonothrombolysis for Acute Ischemic Stroke.

BACKGROUND: Currently, there are 2 strategies to increase the effect of systemic thrombolysis with alteplase (rtPA) in acute major stroke: endovascular treatment via stent retrieval and ultrasound enhancement (sonothrombolysis). This study compares these 2 approaches in patients with proximal intracranial occlusion of the anterior circulation. METHODS: Consecutive data on the treatment outcome of acute middle cerebral artery (M1) or carotid T occlusion were collected from 2 stroke centers: one center used rtPA plus endovascular stent retrieval as standard treatment and the other rtPA plus ultrasound (sonothrombolysis). The primary outcome was functional independence (modified Rankin scale (mRS) 0-2) after neurorehabilitation. RESULTS: A total of 132 patients were assessed (n = 73 endovascular, n = 59 sonothrombolysis). The rate of functional independence was higher for endovascular treatment (adjusted OR 3.89 (95% CI 1.36-12.58)). Additionally, ordinal mRS analysis favored the endovascular strategy (adjusted common OR 1.70 (95% CI 0.88-3.31)). Subgroup analysis showed that endovascular treatment was superior for carotid T occlusion (adjusted common OR 5.61 (95% CI 1.60-20.93)), but not for middle cerebral artery occlusion (adjusted common OR 1.07 (95% CI 0.47-2.43)). Symptomatic intracerebral hemorrhage occurred in 3 patients from the endovascular group. CONCLUSIONS: This observational study suggests that endovascular treatment of acute major anterior circulation stroke is superior to sonothrombolysis in terms of functional outcome. This benefit seems to pertain primarily to patients with carotid T occlusion, whereas patients with M1 occlusion seem to profit in a similar way from both methods. ( CLINICAL TRIAL REGISTRATION: URL: http://www.germanctr.de. Unique identifier: DRKS0000x200B;5305.).