A practical prediction model for early hematoma expansion in spontaneous deep ganglionic intracerebral hemorrhage

Objective

Early hematoma expansion is a known cause of morbidity and mortality in patients with intracerebral hemorrhage (ICH). The goal of this study was to identify clinical predictors of ICH growth in the acute stage.

Materials and methods

We studied 201 patients with acute (<6 h) deep ganglionic ICH. Patients underwent CT scan at baseline and hematoma expansion (>33% or >12.5 ml increase) was determined on the second scan performed within 24 h. Fourteen clinical and neuroimaging variables (age, gender, GCS at admission, hypertension, diabetes mellitus, kidney disease, stroke, hemorrhagic, antiplatelet use, anticoagulant use, hematoma density heterogeneity, hematoma shape irregularity, hematoma volume and presence of IVH) were registered. Additionally, blood pressure was registered at initial systolic BP (i-SBP) and systolic BP 1.5 h after admission (1.5 h-SBP). The discriminant value of the hematoma volume and 1.5 h-SBP for hematoma expansion were determined by the receiver operating characteristic (ROC) curves. Factors associated with hematoma expansion were analyzed with multiple logistic regression.

Results

Early hematoma expansion occurred in 15 patients (7.0%). The cut-off value of hematoma volume and 1.5 h-SBP were determined to be 16 ml and 160 mmHg, respectively. Hematoma volume above 16 ml (HV > 16) ([OR] = 5.05, 95% CI 1.32–21.36, p = 0.018), hematoma heterogeneity (HH) ([OR] = 7.81, 95% CI 1.91–40.23, p = 0.004) and 1.5 h-SBP above 160 mmHg (1.5 h-SBP > 160) ([OR] = 8.77, 95% CI 2.33–44.56, p = 0.001) independently predicted ICH expansion. If those three factors were present, the probability was estimated to be 59%.

Conclusions

The presented model (HV > 16, HH, 1.5 h-SBP > 160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome.     

Astrocyte‐mediated infantile‐onset leukoencephalopathy mouse model

Astrocytes have recently been shown to provide physiological support for various brain functions, although little is known about their involvement in white matter integrity. Several inherited infantile‐onset leukoencephalopathies, such as Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts (MLC), implicate astrocytic involvement in the formation of white matter. Several mouse models of MLC had been generated by knocking out the Mlc1 gene; however, none of those models was reported to show myelin abnormalities prior to formation of the myelin sheath. Here we generated a new Mlc1 knockout mouse and a Mlc1 overexpressing mouse, and demonstrate that astrocyte‐specific Mlc1 overexpression causes infantile‐onset abnormalities of the white matter in which astrocytic swelling followed by myelin membrane splitting are present, whereas knocking out Mlc1 does not, and only shows myelin abnormalities after 12 months of age. Biochemical analyses demonstrated that MLC1 interacts with the Na⁺/K⁺ ATPase and that overexpression of Mlc1 results in decreased activity of the astrocytic Na⁺/K⁺ pump. In contrast, no changes in Na⁺/K⁺ pump activity were observed in Mlc1 KO mice, suggesting that the reduction in Na⁺/K⁺ pump activity resulting from Mlc1 overexpression causes astrocytic swelling. Our infantile‐onset leukoencephalopathy model based on Mlc1 overexpression may provide an opportunity to further explore the roles of astrocytes in white matter development and structural integrity. We established a novel mouse model for infantile‐onset leukoencephalopathy by the overexpression of Mlc1. Mlc1 overexpression reduced activity of the astrocytic sodium pump, which may underlie white matter edema followed by myelin membrane splitting. GLIA 2016 GLIA 2017;65:150–168     

Anxiety disorder

We reviewed recent advances in biological studies of anxiety disorders. The most important achievement was the discovery of the neural circuits of fear in the 1990s by using an animal model in which conditioned fear was induced. In the 2000s, this discovery led to further elucidation of neurotransmitters involved in fear and the precise neuronal mechanism of fear conditioning, thereby improving the understanding of neuroimaging findings of patients with anxiety disorders. The amygdala is a central region that is associated with the generation of fear, and its inactivation diminishes fear. In humans, amygdala activation has been consistently reported in anxiety disorders, indicating that hyperactivation of the amygdala is involved in the pathogenesis of anxiety disorders. Serotonin plays a key role in the treatment of anxiety disorders, and selective serotonin reuptake inhibitors (SSRIs) are currently regarded the first-line drugs used as anxiolytics. From animal studies, the mechanism underlying the anxiolytic effect of SSRIs is hypothesized as follows: SSRIs inhibit the neuronal activities of the amygdala, and this inhibition decreases the level of fear and anxiety. Animal studies of fear conditioning have proposed new treatment strategies for anxiety disorders: D-cycloserine, propranolol, and reactivation-extinction procedure. Among them, D-cycloserine, which is used as an adjunct to psychotherapy to facilitate extinction of fear, has been investigated in several randomized controlled trials, and its efficacies for several anxiety disorders have been established.     

Heterosynaptic enhancement of the excitability of hippocampal mossy fibers by long-range spill-over of glutamate

Several classes of ionotropic receptors have been reported to depolarize the axonal membrane of hippocampal mossy fibers. Both kainate receptors and GABA(A) receptors are localized on axons and/or presynaptic terminals, and these receptors have been known to be activated by synaptically released glutamate and GABA which spill out from the synaptic clefts. However the relative contribution of these two receptors in modulating the excitability of mossy fiber axon was not reported so far. In this study, we revealed that glutamate spilled out from commissural/associational synapses evoked the facilitation of antidromic population spikes of mossy fibers. Increase in amplitude and decrease in latency of population spikes suggest that the number of recruited mossy fibers increases by depolarization of axonal membrane. Application of non-NMDA receptor antagonist CNQX (10 μM) almost abolished this effect. TBOA (30 μM), an inhibitor of glutamate transporter, prolonged the duration of heterosynaptic facilitation. These results suggest that glutamate released from distant commissural/associational synapses spills out from synaptic cleft and activates the kainate receptors on the mossy fibers of CA3 region, and plays a major role in modulating presynaptic excitability than GABA.     

Sex differences in risk factors for suicidality among Japanese substance use disorder patients: Association with age, types of abused substances, and depression

Aim: The aim of this study was to identify risk factors for suicide in Japanese substance use disorder (SUD) patients, adjusting for age and sex, and to examine sex differences in suicide risk among these patients. Methods: A self-reporting questionnaire on age, sex, types of abused substances, current depression, and suicidality was administered to 1420 SUD patients who consecutively visited seven hospitals specializing in SUD treatment during the month of December 2009. Unadjusted/adjusted odds ratios of factors associated with suicidality were calculated for each sex. Results: The multivariate analysis using the total sample identified younger age, female sex, and current depression as risk factors for severe suicidality in SUD patients. The multivariate analysis by each sex demonstrated that younger age and current depression were associated with severe suicidality in male SUD patients. Only current depression was associated with severe suicidality in female patients. Conclusion: Current depression is a risk factor for suicide in SUD patients common in both Western countries and Japan, although in Japanese SUD patients both younger age and female sex were more closely associated with severe suicidality than aspects of SUD. Additionally, young male SUD patients are speculated to have psychosocial features associated with suicidality in common with female SUD patients.     

Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07–41.66) was indicated, too few events (0–2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.     

Low Free Triiodothyronine Predicts 3-Month Poor Outcome After Acute Stroke

Background and Purpose

The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke.

Japanese and North American Alzheimer's Disease Neuroimaging Initiative studies: Harmonization for international trials

Introduction

We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America.

Reinforcement learning for a biped robot based on a CPG-actor-critic method.

Animals' rhythmic movements, such as locomotion, are considered to be controlled by neural circuits called central pattern generators (CPGs), which generate oscillatory signals. Motivated by this biological mechanism, studies have been conducted on the rhythmic movements controlled by CPG. As an autonomous learning framework for a CPG controller, we propose in this article a reinforcement learning method we call the "CPG-actor-critic" method. This method introduces a new architecture to the actor, and its training is roughly based on a stochastic policy gradient algorithm presented recently. We apply this method to an automatic acquisition problem of control for a biped robot. Computer simulations show that training of the CPG can be successfully performed by our method, thus allowing the biped robot to not only walk stably but also adapt to environmental changes.