A direct estrogenic involvement in the expression of human hypocretin.

Hypocretin is synthesized exclusively in the hypothalamus and distributes inputs to several areas of the brain, which may play an important role in depression. Our previous study showed that hypocretin-1 was increased in the lateral hypothalamus in female patients with depression compared to female controls. Estrogen acts through estrogen receptor (ER)α and ERß. We studied the possibility of a direct action of estrogen receptors on the expression of human hypocretin. We found that hypocretin-1 plasma levels were significantly higher in female patients with depression than in female controls. Female depression estrogen receptors and hypocretin are colocalized in the human lateral hypothalamus, PC12, and SK-N-SH cells. The estrogen receptor response elements (ERE) that exist in the hypocretin promoter region may directly regulate the gene expression of hypocretin. The synchronicity of change of hypocretin and estradiol both in hypothalamus and plasma was verified in female rats. In the presence of estradiol, specific binding occurs between the recombinant human ER and hypocretin-ERE. Expression of ER combined with estradiol repressed hypocretin promoter activity via the ERE. In conclusion, we found that estradiol may directly affect hypocretin neurons in the human hypothalamus via ER binding to the hypocretin-ERE, which may lead to the sex-specific pathogenesis of depression.

MSA-YOLOv5: Multi-scale attention-based YOLOv5 for automatic detection of acute ischemic stroke from multi-modality MRI images.

BACKGROUND AND OBJECTIVE: Acute ischemic stroke (AIS) is a common neurological disorder characterized by the sudden onset of cerebral ischemia, leading to functional impairments. Swift and precise detection of AIS lesions is crucial for stroke diagnosis and treatment but poses a significant challenge. This study aims to leverage multimodal fusion technology to combine complementary information from various modalities, thereby enhancing the detection performance of AIS target detection models. METHODS: In this retrospective study of AIS, we collected data from 316 AIS patients and created a multi-modality magnetic resonance imaging (MRI) dataset. We propose a Multi-Scale Attention-based YOLOv5 (MSA-YOLOv5), targeting challenges such as small lesion size and blurred borders at low resolutions. Specifically, we augment YOLOv5 with a prediction head to detect objects at various scales. Next, we replace the original prediction head with a Multi-Scale Swin Transformer Prediction Head (MS-STPH), which reduces computational complexity to linear levels and enhances the ability to detect small lesions. We incorporate a Second-Order channel attention (SOCA) module to adaptively rescale channel features by employing second-order feature statistics for more discriminative representations. Finally, we further validate the effectiveness of our method using the ISLES 2022 dataset. RESULTS: On our in-house AIS dataset, MSA-YOLOv5 achieves a 79.0% mAP0.5, substantially surpassing other single-stage models. Compared to two-stage models, it maintains a comparable performance level while significantly reducing the number of parameters and resolution. On the ISLES 2022 dataset, MSA-YOLOv5 attains an 80.0% mAP0.5, outperforming other network models by a considerable margin. MS-STPH and SOCA modules can significantly increase mAP0.5 by 2.7% and 1.9%, respectively. Visualization interpretability results show that the proposed MSA-YOLOv5 restricts high attention in the small regions of AIS lesions. CONCLUSIONS: The proposed MSA-YOLOv5 is capable of automatically and effectively detecting acute ischemic stroke lesions in multimodal images, particularly for small lesions and artifacts. Our enhanced model reduces the number of parameters while improving detection accuracy. This model can potentially assist radiologists in providing more accurate diagnosis, and enable clinicians to develop better treatment plans.

Low (0-5) Alberta Stroke Program Early Computed Tomography Score on admission predictive of worse functional outcome after mechanical thrombectomy for anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: We examined functional outcomes of mechanical thrombectomy (MT) procedures following anterior circulation large vessel occlusion (ACLVO)-related acute ischemic strokes (AIS). Results were based on admission non-contrast computed tomography (NCCT) studies, using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as standard metric. METHODS: Qualifying subjects were consecutive patients (N = 343) at a single center undergoing MT for ACLVO-related AIS. Each was grouped according to ASPECTS status on admission, determined from NCCT images by two physicians. Primary clinical endpoint was functional independence, assessed via modified Rankin Scale (mRS) at 90 days. Secondary endpoints were vessel recanalization (i.e., modified Thrombolysis in Cerebral Infarction [mTICI] score), symptomatic intracranial hemorrhage (sICH), and mortality. RESULTS: In this study population (mean age, 63.6 ± 12.6 years; women, 30.3%; median baseline National Institute of Health Stroke Scale [NIHSS] score, 15.2 ± 4.5), patients were stratified by ASPECTS tier at presentation, either 0-5 (n = 50) or 6-10 (n = 293). Multivariate logistic regression showed a relation between ASPECTS values ≤ 5 and lesser chance of 90-day functional improvement (OR = 2.309, 95% confidence interval [CI] 1.012-5.271; p = 0.047), once adjusted for age, baseline NIHSS score, diabetes mellitus, HbA1c concentration, D-dimer level, occlusive location, numbers of device passes, and successful recanalization. CONCLUSIONS: ASPECTS values ≤ 5 correspond with worse long-term functional improvement (mRS scores > 2) in patients undergoing MT for ACLVO-related AIS. Other independent determinants of functional outcomes after MT are age, baseline NIHSS score, HbA1c concentration, and successful recanalization.

Automatic detection of stroke lesion from diffusion-weighted imaging via the improved YOLOv5.

BACKGROUND AND OBJECTIVE: Stroke is the second most deadly disease globally and seriously endangers people's lives and health. The automatic detection of stroke lesions from diffusion-weighted imaging (DWI) can improve the diagnosis. Recently, automatic detection methods based on YOLOv5 have been utilized in medical images. However, most of them barely capture the stroke lesions because of their small size and fuzzy boundaries. METHODS: To address this problem, a novel method for tracing the edge of the stroke lesion based on YOLOv5 (TE-YOLOv5) is proposed. Specifically, we constantly update the high-level features of the lesion using an aggregate pool (AP) module. Conversely, we feed the extracted feature into the reverse attention (RA) module to trace the edge relationship promptly. Overall, 1681 DWI images of 319 stroke patients have been collected, and experienced radiologists have marked the lesions. DWI images were randomly split into the training and test set at a ratio of 8:2. TE-YOLOv5 has been compared with the related models, and a detailed ablation analysis has been conducted to clarify the role of the RA and AP modules. RESULTS: TE-YOLOv5 outperforms its counterparts and achieves competitive performance with a precision of 81.5%, a recall of 75.8%, and a mAP@0.5 of 80.7% (mean average precision while the intersection over union is 0.5) under the same backbone. At the patient level, the positive finding rate can reach 98.51%, while the confidence is set at 80.0%. After ablating RA, the mAP@0.5 decreases to 79.6%; after ablating RA and AP, the mAP@0.5 decreases to 78.1%. CONCLUSIONS: The proposed TE-YOLOv5 can automatically and effectively detect stroke lesions from DWI images, especially for those with an extremely small size and blurred boundaries. AP and RA modules can aggregate multi-layer high-level features and concurrently track the edge relationship of stroke lesions. These detection methods might help radiologists improve stroke diagnosis and have great application potential in clinical practice.

Susceptibility-weighted imaging of cerebral fat embolism: A case report.

RATIONALE: Cerebral fat embolism (CFE) is a rare but critical disease in a clinical setting. Considering that manifestations and CT findings of CFE tend to be atypical, this condition is very difficult to diagnose. The purpose of this article was to assess the value of susceptibility-weighted imaging (SWI) in the diagnosis of CFE. PATIENT CONCERNS: Our patient was an 80-year-old woman who developed hypoxemia, quadriplegia, and progressive confusion after fracture of the right femoral neck and right superior ramus of pubis within 24 hours. DIAGNOSIS: T2-weighted magnetic resonance imaging (T2 W MRI), fluid-attenuated inversion recovery sequences, and diffusion-weighted imaging showed numerous hyperintense foci in the subcortex and white matter of both cerebral hemispheres, some of which were confluent and SWI showed multiple symmetrical punctate microhemorrhages in both hemispheres. Base on the history and MRI findings, the patient was diagnosed with CFE. INTERVENTIONS: The patient received anticoagulation and lipid-lowering therapy. OUTCOMES: The patient regained consciousness, and her muscle strength in the limbs gradually recovered. One year after discharge, the patient could independently walk on her own. LESSION: This case report shows the characteristics of CFE on SWI, which can help clinicians in diagnosing which can help clinicians in diagnosing CFE.

Thrombo-Inflammation and Immunological Response in Ischemic Stroke: Focusing on Platelet-Tregs Interaction.

Strokes are mainly caused by thromboembolic obstruction of a major cerebral artery. Major clinical manifestations include paralysis hemiplegia, aphasia, memory, and learning disorders. In the case of ischemic stroke (IS), hyperactive platelets contribute to advancing an acute thrombotic event progression. Therefore, the principal goal of treatment is to recanalize the occluded vessel and restore cerebral blood flow by thrombolysis or mechanical thrombectomy. However, antiplatelets or thrombolytic therapy may increase the risk of bleeding. Beyond the involvement in thrombosis, platelets also contribute to the inflammatory process induced by cerebral ischemia. Platelet-mediated thrombosis and inflammation in IS lie primarily in the interaction of platelet receptors with endothelial cells and immune cells, including T-cells, monocytes/macrophages, and neutrophils. Following revascularization, intervention with conventional antiplatelet medicines such as aspirin or clopidogrel does not substantially diminish infarct development, most likely due to the limited effects on the thrombo-inflammation process. Emerging evidence has shown that T cells, especially regulatory T cells (Tregs), maintain immune homeostasis and suppress immune responses, playing a critical immunomodulatory role in ischemia-reperfusion injury. Hence, considering the deleterious effects of inflammatory and immune responses, there is an urgent need for more targeted agents to limit the thrombotic-inflammatory activity of platelets and minimize the risk of a cerebral hemorrhage. This review highlights the involvement of platelets in neuroinflammation and the evolving role of Tregs and platelets in IS. In response to all issues, preclinical and clinical strategies should generate more viable therapeutics for preventing and managing IS with immunotherapy targeting platelets and Tregs.

Disrupted Causal Connectivity Anchored on the Right Anterior Insula in Drug-Naive First-Episode Patients With Depressive Disorder.

Object: Major depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks. However, few studies examined information flow in the salience network (SN). This study examined abnormalities in the causal connectivity between the SN and whole brain in drug-naive first-episode patients with MDD in the resting state. Methods: Based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, 23 drug-naive first-episode MDD patients and 20 matched healthy individuals were recruited and underwent a resting-state magnetic resonance scan. The acquired functional image data were preprocessed using resting-state functional magnetic resonance imaging (rs-fMRI) data analysis toolkit plus (RESTplus). Then, using the data processing & analysis for brain imaging (DPABI) software and a coefficient-based general component analysis method with the right anterior insula (rAI) as the region of interest (ROI), the causal connectivity of the SN with the whole brain and its correlation with cognitive and mental performance were examined in the resting state. Results: (1) The MDD group showed a significantly higher Hamilton Depression Rating Scale total score and significantly higher scores for anxiety, cognitive disturbance, and block factors compared with normal controls. (2) Compared with control: from whole brain to the rAI, the MDD group showed a lower causal connectivity in the left inferior frontal gyrus; from the rAI to the whole brain, the MDD group showed a lower causal connectivity in the right cingulate gyrus, the right precuneus, and extending to paracentral lobule but higher causal connectivity in the left inferior and middle frontal gyrus. (3) In the MDD group, from rAI to the whole brain, the causal connectivity values for the right cingulate gyrus/precuneus were negatively correlated with the score of Stroop Color-Word Test A, B, and C as well as interference times. Conclusion: Our results indicated disrupted causal connectivity among the default mode network (DMN), the central executive network (CEN), and SN in drug-naive first-episode MDD patients. Especially, our results suggest a unique role for rAI in the ordered or hierarchical information processing, presumed to include bottom-up and top-down reciprocal influences among the three networks in MDD.

Risk Factors of Impaired Perfusion in Patients With Symptomatic Internal Carotid Artery Steno-Occlusive Disease.

Objective: To quantitatively evaluate the impaired perfusion status of patients with symptomatic internal carotid artery (ICA) steno-occlusive disease and to explore the risk factors of impaired perfusion with computed tomography perfusion (CTP). Methods: The clinical and imaging data of 187 patients with ICA steno-occlusive disease were retrospectively analyzed. The ICA stenosis rate was divided into Grades I-IV (70-79%; 80-89%; 90-99%; 100%), and the circle of Willis was classified as four types (types I-IV). According to the literature, the value of cerebral blood flow/cerebral blood volume (CBF/CBV) of 7.55/min was used as cut-off to predict symptomatic patients. All patients were categorized into two groups: those with impaired perfusion [n = 99 (52.9%)] and those without impaired perfusion [n = 88 (47.1%)]. Symmetrical bilateral internal watershed areas were selected as the regions of interest (ROIs). Statistical analysis was made on the status of impaired perfusion and the risk factors of impaired perfusion. Results: Univariate analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), types of the circle of Willis, and clinical features at admission differed between the two groups (patients with or without impaired perfusion) (p < 0.05). Multiple logistic stepwise regression analysis showed that MAP [odds ratio (OR) = 0.946, 95% confidential interval (CI) = 0.917-0.974, p < 0.001] and type IV (type I vs. IV: OR = 4.987, 95% CI = 1.955-12.723, p = 0.001) at admission were independently associated with impaired perfusion in the internal watershed areas. Conclusion: MAP and the type of circle of Willis at admission are independent risk factors associated with the impaired perfusion in patients with ICA steno-occlusive disease.

Inhalation Aromatherapy via Brain-Targeted Nasal Delivery: Natural Volatiles or Essential Oils on Mood Disorders.

Mood disorders, also often referred to as affective disorders, are a group of psychiatric illnesses that severely impact mood and its related functions. The high medical expenditures have placed a significant financial burden on patients and their families. Aromatherapy is an alternative and complementary treatment that utilizes essential oils (EOs) or volatile oils (VOs) to achieve major therapeutic goals. In general, EOs are volatile chemicals that enter the body primarily through skin absorption and/or nasal inhalation. In addition, they can work through oral administration. Inhalation aromatherapy has shown unique advantages for treating mood disorders, especially depression, anxiety and mental disorders such as sleep disorder, which have been validated over the last decade through clinical and animal studies. Accumulating evidence has shown that EOs or VOs can bypass the blood-brain barrier to target brain tissue through the nasal-brain pathway. Subsequently, they act on the cerebral cortex, thalamus, and limbic system in the brain to improve symptoms of anxiety, depression and improve sleep quality. Here, we review the natural aromatic plants' volatiles or essential oils used commonly as adjuncts to manage mood disorders and illustrate the mechanisms of inhalation aromatherapy, and mainly summarized the application of transnasal inhalation aromatherapy in depression, anxiety, and sleep disorders. We conclude that aromatherapy does not cause side-effects, which is vastly different from commonly used psychotropic drugs. Inhalation aromatherapy via brain-targeted nasal delivery offers potentially efficacious treatment for mental disorders and merits further study.

Hyperdense middle cerebral artery sign predicts favorable outcome after decompressive craniectomy in patients with malignant middle cerebral artery infarction.

BACKGROUND: Malignant middle cerebral artery infarction (MMI) is a life-threatening cerebral vascular event. Early decompressive craniectomy (DC) has proven to be an effective treatment strategy. However, the ideal candidate for DC continues to be debated. PURPOSE: To investigate whether a hyperdense middle cerebral artery sign (HMCAS) provides prognostic value after DC in patients with MMI. MATERIAL AND METHODS: We reviewed clinical information and radiological parameters on computed tomography of 42 patients with MMI who underwent DC. Functional outcome was assessed according to the modified Rankin scale (mRS) at three months as follows: favorable outcome (mRS ≤ 4) versus unfavorable outcome (mRS > 4). Logistic regression analysis was used to identify predictors of functional outcome after DC in patients with MMI. RESULTS: Age (odds ratio [OR] = 0.87; 95% confidence interval [CI] = 0.78-0.97; P = 0.014) and HMCAS (OR = 7.40; 95% CI = 1.35-40.48; P = 0.021) were associated with functional outcome. The area under the receiver operating characteristic curve for predicting favorable outcome using the combination of age and HMCAS was 0.882, and the sensitivity and specificity were 0.947 and 0.696, respectively. CONCLUSION: Patients with MMI with HMCAS, as well as younger patients, often showed a favorable outcome after DC in this study.

White Matter Characteristics of Cognitive Impairment in Tap-Test Positive Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Tract-Based Spatial Study.

The present study was designed to systemically evaluate changes in the diffusion tensor imaging (DTI)-derived parameters of iNPH (idiopathic normal pressure hydrocephalus) patients with different responses to the tap test (TT), and to correlate cognitive impairment with white matter (WM) degeneration. This study included 22 iNPH patients and 14 healthy controls with structural magnetic resonance imaging (MRI) and DTI scanning. DTI was used to explore the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for all participants. DTI parameters were evaluated using an ROI (region of interest)-based and tract-based spatial statistics (TBSS) approach. Neuropsychological assessments and the idiopathic normal pressure hydrocephalus grading scoring scale (iNPHGS) were performed. Compared to the TT non-responders, the TT responders group had significantly lower FA values in the corpus callosum, cingulum cingulate gyrus, superior longitudinal fasciculus, and lower AD values in the right cingulum cingulate gyrus and the left posterior thalamic radiation. Besides, the MD values were significantly increased in the corpus callosum, left anterior corona radiata, and the RD values in the corpus callosum and cingulum cingulate gyrus. In addition, the cognitive improvement was negatively correlated with FA of the corpus callosum, cingulum cingulate gyrus, and MD values of the genu of corpus callosum. While, the cognitive improvement was positively related to the AD of the cingulum cingulate gyrus, superior longitudinal, and RD values of the corpus callosum, cingulum cingulate gyrus and uncinate fasciculus. The ROI specific WM lesions in iNPH patients are the underlying basis for cognitive impairment.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Abnormal causal connectivity of left superior temporal gyrus in drug-naïve first- episode adolescent-onset schizophrenia: A resting-state fMRI study.

This study aimed to investigate the alterations of causal connectivity between the brain regions in Adolescent-onset schizophrenia (AOS) patients. Thirty-two first-episode drug-naïve AOS patients and 27 healthy controls (HC) were recruited for resting-state functional MRI scanning. The brain region with the between-group difference in regional homogeneity (ReHo) values was chosen as a seed to perform the Granger causality analysis (GCA) and further detect the alterations of causal connectivity in AOS. AOS patients exhibited increased ReHo values in left superior temporal gyrus (STG) compared with HCs. Significantly decreased values of outgoing Granger causality from left STG to right superior frontal gyrus and right angular gyrus were observed in GC mapping for AOS. Significantly stronger causal outflow from left STG to right insula and stronger causal inflow from right middle occipital gyrus (MOG) to left STG were also observed in AOS patients. Based on assessments of the two strengthened causal connectivity of the left STG with insula and MOG, a discriminant model could identify all patients from controls with 94.9% accuracy. This study indicated that alterations of directional connections in left STG may play an important role in the pathogenesis of AOS and serve as potential biomarkers for the disease.

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain.

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

IL-6, IL-8 and IL-10 polymorphisms may impact predisposition of Alzheimer's disease: a meta-analysis.

Gene polymorphisms in interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) may affect the predisposition of Alzheimer's disease (AD), but the results of the so far published studies remain controversial. The authors conducted this meta-analysis to assess relationships between IL-6/IL-8/IL-10 polymorphisms and predisposition of AD by pooling the findings of so far published studies. A comprehensive search of Pubmed, Embase, Web of Science, and CNKI was endorsed by the authors to identify the already published studies. Forty-five studies were found to be eligible for meta-analyses. The pooled meta-analyses results showed that genotypic frequencies of IL-6 - 174 G/C, IL-6 - 572 G/C and IL-10 - 1082 A/G polymorphisms among patients with AD and controls differed significantly. Moreover, genotypic frequencies of IL-6 - 174 G/C, IL-6 - 572 G/C, and IL-8 - 251 A/T polymorphisms among patients with AD and controls in Asians also differed significantly. But no such genotypic frequencies' differences were observed for IL-10 - 819 C/T and 592 C/A polymorphisms. This meta-analysis suggests that IL-6 - 174 G/C, IL-6 - 572 G/C, and IL-10 - 1082 A/G polymorphisms may affect the predisposition of AD in overall population. Moreover, IL-6 - 174 G/C, IL-6 - 572 G/C, and IL-8 - 251 A/T polymorphisms may affect the predisposition of AD in Asians.

Neuronavigation-Guided rTMS for the Treatment of Depressive Patients With Suicidal Ideation: A Double-Blind, Randomized, Sham-Controlled Trial.

During the last decade, the problem of suicide has become more serious in individuals with depression. Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). This study aims to investigate the efficacy of magnetic resonance imaging (MRI)-based neuronavigation-guided daily high-dose rTMS for rapidly improving suicidal ideation in treatment-naive patients with MDD. In the present 1-week double-blind study, 42 treatment-naive patients with MDD with suicidal ideation were randomly assigned to the treatment of escitalopram oxalate tablets (10 mg/d) in combination with either active (n = 21) or sham (n = 21) rTMS. The TMS coil was positioned over a specified target location (-44, 40, and 29) in left dorsolateral prefrontal cortex based on MRI data. The severity of suicidal ideation was measured by the Beck Scale for Suicide Ideation (BSI). The 24-item Hamilton Depression Rating Scale (HAMD-24) and Montgomery-Åsberg Depression Rating Scale (MADRS) were utilized to assess the severity of depression. The Wisconsin Card Sorting Test, Continuous Performance Test, and Stroop Color-Word Test were adopted to assess executive function. In contrast to the sham group, the active rTMS group showed a significantly greater BSI score reduction at the third day and the seventh day (P < 0.001). Moreover, the active rTMS group showed a significantly greater HAMD (P < 0.001) and MADRS (P < 0.001) score reduction at the seventh day in comparison to the sham group. The present findings suggested that the neuronavigation-guided high-dose rTMS may be a novel method to rapidly reduce suicidal ideation and mitigate depressive symptoms.

Acute visual impairment as a main presenting symptom of non-convulsive status epilepticus: a case report.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a state of ongoing seizure activity without convulsions. The heterogeneous and subtle clinical features of NCSE make diagnosis and treatment challenging. Here, we report a patient with NCSE who showed a main presenting symptom of acute visual impairment, which is a rare and atypical clinical symptom of NCSE. CASE PRESENTATION: A 62-year-old man was admitted to the neurology department after complaining of an inability to see in the right eye for 2 days and progressive headache. He had a history of poststroke epilepsy and vascular dementia. Physical examination revealed right visual field hemianopia, visual neglect and cognitive impairment. T2 and diffusion-weighted magnetic resonance imaging showed high signal intensity in the left temporal, parietal and occipital lobes. Electroencephalography monitoring was performed, which found continuous sharp wave discharges, especially in the regions of the left temporal, parietal and occipital lobes. These findings were most consistent with the diagnosis of NCSE. Thus, a treatment of intravenous pumping of diazepam and an oral antiepileptic drug was added immediately. After that, the visual loss in the patient recovered quickly, and electroencephalography did not find epileptiform waves. On day 11, a follow-up MRI was performed, which showed that the abnormal signals of the left temporal, parietal and occipital lobes were markedly attenuated, and the patient returned to his premorbid state with a modified Rankin Scale score of 3. CONCLUSIONS: Acute visual impairment can be seen in NCSE, and it can be reversed by administering effective antiepileptic treatment. Meanwhile, transient peri-ictal MRI abnormalities can be observed in NCSE.

Comorbid Bipolar Disorder and Migraine: From Mechanisms to Treatment.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent episodes of manic/hypomanic or depressive symptoms and euthymic periods, with some patients suffering a gradual deterioration of illness and consequent cognitive deficits during the late stage. Migraine is a disease generally without abnormal medical examinations, neurological examinations or laboratory studies, and the diagnosis is made based on the retrospective demonstration of headache features and groupings of disease-associated symptoms. The epidemiology of comorbid BD and migraine is high and it is obligatory to find effective treatments to improve the prognosis. Recent investigations demonstrated that the close relationship between BD and migraine significantly increased the rapid cycling rates of both BD and migraine in patients. Although the detailed mechanism is complex and largely unclear in comorbid BD and migrain, genetic factors, neurotransmitters, altered signaling pathways, disturbances of inflammatory cytokines, and mitochondrial dysfunction are risk factors of BD and migraine. Particularly these two diseases share some overlapping mechanisms according to previous studies. To this end, we call for further investigations of the potential mechanisms, and more efforts are underway to improve the treatment of people with comorbid BD and migraine. In this review, we provide an overview of the potential mechanisms in patients with BD or migraine and we further discuss the treatment strategies for comorbid BD and migraine and it is obligatory to find effective treatments to improve the prognosis. This work will provide insights for us to know more about the mechanisms of comorbid BD and migraine, provides new therapeutic targets for the treatment and give clinicians some guidance for more appropriate and beneficial treatment.

The association between serum growth differentiation factor-15 and 3-month depression after acute ischemic stroke.

OBJECTIVE: The aim of this study was to assess the association between serum growth differentiation factor-15(GDF-15) and 3-month depression after acute ischemic stroke. METHODS: In this single-center prospective study, patients with first-ever acute ischemic stroke between March 2017 and November 2018 were included. Neurological and neuropsychological evaluations were conducted during the 3-month follow-up. The predictive value of GDF-15 to predict the post-stroke depression (PSD) within 3 months, was compared with other known predictors. RESULTS: The median level of GDF-15 in 310 stroke patients was 1285(IQR, 846-1934) ng/l. During the 3-month follow-up, 76 patients were defined as depression (24.5%; 95% confidence interval [CI]: 17.9%-29.3%), and GDF-15 levels in those patients were nearly more than 1 time greater as compared with patients who were free of depression (P < 0.001). Using the ROC curves, GDF-15 serum level at 1660 ng/l predicted the PSD with the highest sensitivity and specificity [67.1% and 77.4%, respectively; AUC=0.78, 95%CI: 0.72-0.84; P < 0.001]. Interestingly, When GDF-15 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.81(0.029) to 0.88(0.020). A significant difference in the AUC between the established risk factors alone and the addition of GDF-15 was observed (difference, 0.07[0.009]; P = 0.001). In a multivariate model using the elevated levels of GDF-15 (≥cut-off=1660 ng/l) vs. normal (