Effectiveness analysis of three-drug combination therapies for refractory focal epilepsy.

Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann-Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini-Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n â€‹= â€‹95). At the last clinical visit, 14.9% (n â€‹= â€‹48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17-0.85; adjusted P â€‹< â€‹0.001) and 0.63 (IQR, 0.21-1.04; adjusted P â€‹< â€‹0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR â€‹= â€‹0.67; adjusted P â€‹= â€‹0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.

Adenosine kinase gene modified mesenchymal stem cell transplantation retards seizure severity and associated cognitive impairment in a temporal lobe epilepsy rat model.

PURPOSE: Temporal lobe epilepsy (TLE) has a high risk of developing drug resistant and cognitive comorbidities. Adenosine has potential anticonvulsant effects as an inhibitory neurotransmitter, but drugs targeting its receptors and metabolic enzyme has inevitable side effects. Therefore, we investigated adenosine augmentation therapy for seizure control and cognitive comorbidities in TLE animals. METHODS: Using lentiviral vectors coexpressing miRNA inhibiting the expression of adenosine kinase (ADK), we produced ADK--rMSC (ADK knockdown rat mesenchymal stem cell). ADK--rMSC and LV-con-rMSC (rMSC transduced by randomized scrambled control sequence) were transplanted into the hippocampus of TLE rat respectively. ADK-+DPCPX group was transplanted with ADK--rMSC and intraperitoneally injected with DPCPX (adenosine A1 receptor antagonist). Seizure behavior, EEG, CA1 pyramidal neuron apoptosis, and behavior in Morris water maze and novel object recognition test were studied RESULTS: Adenosine concentration in the supernatants of 105 ADK--rMSCs was 13.8 ng/ml but not detectable in LV-con-rMSCs. ADK--rMSC (n = 11) transplantation decreased spontaneous recurrent seizure (SRS) duration compared to LV-con-rMSC (n = 11, P < 0.05). CA1 neuron apoptosis was decreased in ADK--rMSC (n = 3, P < 0.05). ADK--rMSC (n = 11) improved the Morris water maze performance of TLE rats compared to LV-con-rMSC (n = 11, escape latency, P < 0.01; entries in target quadrant, P < 0.05). The effect of ADK--rMSC on neuron apoptosis and spatial memory were counteracted by DPCPX. However, ADK--rMSC didn't improve the performance in novel object recognition test. CONCLUSION: Adenosine augmentation-based ADK--rMSC transplantation is a promising therapeutic candidate for TLE and related cognitive comorbidities.

Direct bilirubin: A predictor of hematoma expansion after intracerebral hemorrhage.

BACKGROUND: Previous evidence demonstrated that several biomarkers involved in the pathological process of coagulation/hemostasis dysfunction, impairment of brain vascular integrity and inflammation are associated with hematoma expansion (HE) after intracerebral hemorrhage (ICH). We aimed to explore whether there were unreported laboratory biomarkers associated with HE that were readily and commonly available in clinical practice. METHODS: We retrospectively analyzed consecutive acute ICH patients from 2012 to 2020 with admission laboratory tests and baseline and follow-up computed tomography (CT) scans. Univariate and multivariate regression analyses were used to evaluate associations between conventional laboratory indicators and HE. The results were verified in a prospective validation cohort. The relationship of candidate biomarker and 3-month outcomes was also investigated and mediation analysis was undertaken to determine causal associations among candidate biomarker, HE and outcome. RESULTS: Of 734 ICH patients, 163 (22.2%) presented HE. Among the included laboratory indicators, higher direct bilirubin (DBil) was associated with HE (adjusted odds ratio [OR] of per 1.0 µmol/L change 1.082; 95% confidence interval [CI] 1.011-1.158). DBil >5.65 µmol/L was a predictor of HE in validation cohort. Higher DBil was also associated with poor 3-month outcomes. The mediation analysis indicated that the association of higher DBil and poor outcomes was partially mediated by HE. CONCLUSIONS: DBil is a predictor of HE and poor 3-month outcomes after ICH. DBil's metabolic process and involvement in the pathological mechanism of HE are likely to contribute to the association between DBil and HE. Interventions targeting DBil to improve post-ICH prognosis may be meaningful and worthy of further exploration.

External validation and comparison of clinical scores for predicting late seizures after intracerebral hemorrhage in Chinese patients.

PURPOSE: Clinical scores have been established to predict the probability of late seizures following intracerebral hemorrhage (ICH) for individual patients, including the CAVE, CAVS and LANE scores. The purpose of this study was to compare these prediction scores in the Chinese population and undertake an independent external validation on them. METHODS: At one tertiary hospital in China, we retrospectively recruited consecutive inpatients who had been diagnosed with ICH. Medical records and tele interviews with a modified standardized questionnaire were used to identify late seizures. All the predictors of the prediction scores were collected from patient charts and databases by a standardized data collection protocol. The external validation of the prediction scores was quantified by the area under the curve (AUC), sensitivity, specificity, Youden index (YI), positive predictive value (PPV), and negative predictive value (NPV). RESULTS: 69 (5.4%) of 1276 patients experienced late seizures after ICH. There was no significant difference in the CAVE, CAVS, and LANE scores, which had AUCs of 0.75 (95% CI = 0.70-0.81), 0.74 (95% CI = 0.68-0.80), and 0.76 (95% CI = 0.70-0.82), respectively. At the optimal cutoff score, the LANE score had a lower sensitivity but a higher specificity than the CAVE and CAVS scores. Among the three prediction scores, the LANE score had a higher PPV than the others (0.145 vs. 0.088, 0.083), while the NPV was similar among the three prediction scores (0.989, 0.989, and 0.972). CONCLUSION: Our study showed that the CAVE, CAVS and LANE scores had similar AUCs for the occurrence of late seizures, but the LANE score had a relatively high PPV at the optimal cutoff score. Due to low evidence for using prophylactic antiseizure medications (ASM) in patients with ICH and poor availability of specialist stroke care in China, the LANE score with a cutoff score of 3 could be an applicable prediction tool in Chinese patients with ICH.

Depressive symptom dimensions predict the treatment effect of repetitive transcranial magnetic stimulation for post-stroke depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has attracted considerable attention because of its non-invasiveness, minimal side effects, and treatment efficacy. Despite an adequate duration of rTMS treatment, some patients with post-stroke depression (PSD) do not achieve full symptom response or remission. METHODS: This was a prospective randomized controlled trial. Participants receiving rTMS were randomly assigned to the ventromedial prefrontal cortex (VMPFC), left dorsolateral prefrontal cortex (DLPFC), or contralateral motor area (M1) groups in a ratio of 1:1:1. Enrollment assessments and data collection were performed in weeks 0, 2, 4, and 8. The impact of depressive symptom dimensions on treatment outcomes were tested using a linear mixed-effects model fitted with maximum likelihood. Univariate analysis of variance (ANOVA) and back-testing were used to analyze the differences between the groups. RESULTS: In total, 276 patients were included in the analysis. Comparisons across groups showed that 17-item Hamilton Rating Scale for Depression (HAMD-17) scores of the DLPFC group significantly differed from those of the VMPFC and M1 groups at 2, 4, and 8 weeks after treatment (p < 0.05). A higher observed mood score (ß = -0.44, 95% confidence interval [CI]: -0.85-0.04, p = 0.030) could predict a greater improvement in depressive symptoms in the DLPFC group. Higher neurovegetative scores (ß = 0.60, 95% CI: 0.25-0.96, p = 0.001) could predict less improvement of depressive symptoms in the DLPFC group. CONCLUSION: Stimulation of the left DLPFC by high-frequency rTMS (HF-rTMS) could significantly improve depressive symptoms in the subacute period of subcortical ischemic stroke, and the dimension of depressive symptoms at admission might predict the treatment effect.

The asymmetry of glymphatic system dysfunction in patients with temporal lobe epilepsy: A DTI-ALPS study.

BACKGROUND AND PURPOSE: While the occurrence of glymphatic system dysfunction has been observed in temporal lobe epilepsy (TLE), the potential asymmetry of this system has yet to be investigated in the TLE context. We aimed to investigate the glymphatic system function in both hemispheres and to analyze asymmetric features of the glymphatic system in TLE patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. MATERIALS AND METHODS: 43 patients (left TLE (LTLE), n = 20; right TLE (RTLE), n = 23) and 39 healthy controls (HC) were enrolled in this study. The DTI-ALPS index was calculated for the left (left ALPS index) and right (right ALPS index) hemispheres respectively. An asymmetry index (AI) was calculated by AI = (Right - Left)/ [(Right + Left)/2] to represent the asymmetric pattern. Independent two sample t-test, two-sample paired t-test or one-way ANOVA with Bonferroni correction were conducted to compare the differences in ALPS indices and AI among the groups. RESULTS: Both left ALPS index (p = 0.040) and right ALPS index (p = 0.001) of RTLE patients were significantly decreased, while only left ALPS index of LTLE patients (p = 0.005) was reduced. Compared to contralateral ALPS index, the ipsilateral ALPS index was significantly decreased in TLE (p = 0.008) and RTLE (p = 0.009) patients. Leftward asymmetry of the glymphatic system was found in HC (p = 0.045) and RTLE (p = 0.009) patients. The LTLE patients presented reduced asymmetric traits when compared to RTLE patients (p = 0.029). CONCLUSION: The TLE patients exhibited altered ALPS indices, which could be triggered by glymphatic system dysfunction. Altered ALPS indices were more severe in ipsilateral than in the contralateral hemisphere. Moreover, LTLE and RTLE patients exhibited different change patterns of the glymphatic system. In addition, glymphatic system function presented asymmetric patterns in both normal adult brain and RTLE patients.

Incremental Value of Stroke-Induced Structural Disconnection in Predicting Global Cognitive Impairment After Stroke.

BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.

Effects of a online brief modified mindfulness-based stress reduction therapy for anxiety among Chinese adults: A randomized clinical trial.

The COVID-19 pandemic has exacerbated anxiety and related symptoms among the general population. In order to cope with the mental health burden, we developed an online brief modified mindfulness-based stress reduction (mMBSR) therapy. We performed a parallel-group randomized controlled trial to evaluate the efficacy of the mMBSR for adult anxiety with cognitive-behavioral therapy (CBT) as an active control. Participants were randomized to mMBSR, CBT or waitlist group. Those in the intervention arms performed each therapy for 6 sections in 3 weeks. Measurements were conducted at baseline, post-treatment and 6 months post-treatment by Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Patient Health Questionnaire-15, reverse scored Cohen Perceived Stress scale, Insomnia Severity Index, and Snaith-Hamilton Pleasure Scale. 150 participants with anxiety symptoms were randomized to mMBSR, CBT or waitlist group. Post intervention assessments showed that mMBSR improved the scores of all the six mental problem dimensions (anxiety, depression, somatization, stress, insomnia, and the experience of pleasure) significantly compared to the waitlist group. During 6-month post treatment assessment, the scores of all six mental problem dimensions in the mMBSR group still showed improvement compared to baseline and showed no significant difference with the CBT group. Our results provide positive evidence for the efficacy and feasibility of an online brief modified MBSR program to alleviate anxiety and related symptoms of individuals from the general population, and the therapeutic benefits of mMBSR persisted for up to six months. This low resource-consuming intervention could facilitate the challenges of supplying psychological health therapy to large scale of population.

Catatonia in adult anti-NMDAR encephalitis: an observational cohort study.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent autoimmune encephalitis and is closely related to catatonia. This study aimed to investigate the clinical features and disease outcomes of adult catatonic anti-NMDAR encephalitis patients. METHODS: Adult patients diagnosed with anti-NMDAR encephalitis between January 2013 and October 2021 were retrospectively enrolled in this study. According to the Bush Francis Catatonia screening instrument (BFCSI), patients were divided into two groups: those with catatonia and those without catatonia. The modified Rankin scale (mRS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), Neuropsychiatric Inventory (NPI), Patient Health Questionnaire-9 (PHQ-9) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) scores were assessed at follow-up. The Mann-Whitney U test (nonparametric), Student's t test (parametric), and chi-squared test were used to analyse the differences between the two groups. RESULTS: Eighty-four patients were recruited, including twenty-five catatonic patients and fifty-nine noncatatonic patients. Among them, 28 had positive antibody only in cerebrospinal fluid (CSF), 4 had positive antibody only in serum and 52 had positive antibody both in CSF and serum. Catatonic patients experienced more disturbance of consciousness (p = 0.01), aggression (p = 0.046) and affective disorders (p = 0.043) than noncatatonic patients. The mRS scores of the catatonia group assessed at admission (p = 0.045) were worse than those of the non-catatonia group. Catatonic patients were more inclined to develop deep vein thrombosis (p = 0.003), decubitus (p = 0.046), pneumonia (p = 0.025), and to be admitted to the intensive care unit (ICU) (p = 0.011) than noncatatonic patients. All patients in the catatonia group received first-line immunotherapy. At the 24-month follow-up, 2 patients in the catatonia group did not achieve good outcomes. At the last follow-up, the catatonia group had more relapses (p = 0.014) and more neuropsychiatric problems (p = 0.035). CONCLUSIONS: Adult anti-NMDAR encephalitis patients with catatonia present distinct clinical features in disease course and are prone to experience more relapses and long-term neuropsychiatric problems than those without catatonia.

Development and validation of a novel radiomics-clinical model for predicting post-stroke epilepsy after first-ever intracerebral haemorrhage.

OBJECTIVES: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). METHODS: Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. RESULTS: A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7 days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). CONCLUSIONS: The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. KEY POINTS: • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability.

Psychopathological network for early-onset post-stroke depression symptoms.

BACKGROUND: Post-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD. METHODS: A total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data were collected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity. RESULTS: Depressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region. CONCLUSIONS: There are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDS severity. TRIAL REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx ; Unique identifier: ChiCTR-ROC-17013993.

A 6-month prognostic nomogram incorporating hemoglobin level for intracerebral hemorrhage in younger adults.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. METHODS: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. RESULTS: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram. CONCLUSION: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.

Comparative study on acute management of intracerebral haematoma using local thrombolysis in moyamoya and non-moyamoya patients: a single institution experience.

PURPOSE: Spontaneous intracerebral haemorrhage (ICH) is the main presentation in adults with moyamoya disease (MMD), an unusual clinical entity with a poor prognosis. However, optimal management in the acute stage of ICH in patients with MMD remains a challenge. Since minimally invasive surgery (MIS) plus local thrombolysis has emerged as a promising strategy for ICH, we aimed to describe our experience of performing this procedure in this special population in the acute phase, while focusing on its efficacy and safety. MATERIALS AND METHODS: The medical data of patients with ICH treated with MIS and local thrombolysis between November 2013 and December 2017 were retrospectively reviewed at our institution. MMD was identified based on the angiographic images. The primary outcome was postoperative intracranial rebleeding. The secondary outcomes were 30-day mortality and 6-month outcome graded using the modified Rankin scale (mRS). Logistic regression was applied to explore independent risk factors for the above outcomes. RESULTS: A cohort of consecutive 337 ICH patients was analysed, of whom 14 (4.15%) were diagnosed with MMD. In total, 36 (11.46%) patients experienced postoperative intracranial rehaemorrhage, of which one patient had MMD. No significant difference was found between the patients with and without MMD regarding postoperative rebleeding (9.09% vs. 11.55%, p = 1.000). Additionally, the 30-day mortality of patients with MMD was 21.42% (3/14), which was not significantly different from that of non-MMD patients (10.83%; p = 0.201). Moreover, 53.8% of patients had poor outcomes at the 6-month follow-up among MMD patients, similar to 43.9% of patients without MMD (p = 0.573). The coexistence of MMD failed to show a significant association with postoperative intracranial rebleeding (p = 0.348), 30-day mortality (p = 0.211), or poor outcome at the 6-month follow-up (p = 0.450). CONCLUSION: Our findings suggest that coexistent MMD is not associated with an increased risk of postoperative rebleeding or poor outcome after local thrombolysis for ICH.

Piezo1 Mediates Inflammation in Balloon-inflated Rat Brain and its Bidirectional Mechanosensitivity.

BACKGROUND: Brain injury after intracerebral hemorrhage is extremely complicated, and the exact mechanism remains puzzling. Piezo1, a novel mammalian mechanosensitive ion channel, has been identified to play important roles in several pathologic and physiologic procedures that involve cellular mechanotransduction. However, the role of Piezo1 in hematoma compression after intracerebral hemorrhage is still unclear. MATERIALS AND METHODS: In the present study, we established a balloon-inflated brain model based on an adult male rat mimicking the pure mechanical compression of a hematoma. Then the behavioral assessment (Garcia Scale) was taken to observe the syndrome after "hematoma". Western blotting and immunofluorescence were applied to detect Piezo1 expression around lesions in rat brains. ELISA was used for quantitative analysis of inflammation factors. A statistical significance was confirmed as P value<0.05. RESULTS: Balloon compression lesions were detected in the basal ganglia region of the brain, resulting in abnormal behaviors and a significant increase in the expression of Piezo1 and proinflammatory cytokines. GsMTx4, an antagonist of Piezo1, reversed these effects. Additionally, the balloon deflation time affected behavioral function and the levels of Piezo1 and proinflammatory cytokines. CONCLUSION: These results establish the first in vivo evidence for the role of Piezo1 in blood-brain neuroinflammation after hematoma compression. Piezo1 showed "bidirectional mechanosensitivity" and therefore is a potential therapeutic target for the treatment of intracerebral hemorrhage.

Explore the influencing factors and construct random forest models of post-stroke depression at 3 months in males and females.

BACKGROUND: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. The occurrence, development and prognosis of PSD have long been different between males and females. The main purpose of this study was to explore the influencing factors of PSD at 3 months in males and females, and construct random forest (RF) models to rank the influencing factors. METHODS: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Stroke patients hospitalized in the department of Neurology of three hospitals in Wuhan were enrolled from May 2018 to August 2019. Scale assessments were performed 24 hours after admission and 3 months after stroke onset. Binary logistic regression analysis was used for univariate and multivariate (stepwise backward method) analysis, when p was less than 0.05, the difference between groups was considered statistically significant. Lastly, the RF models were constructed according to the results of multivariate regression analysis. RESULTS: This study found that several baseline variables were associated with PSD at 3 months in males and females. RF model ranked them as stroke severity (OR [odds ratio] =1.17, p < 0.001, 95%CI [confidence interval]:1.11-1.24), neuroticism dimension (OR = 1.06, p = 0.002, 95%CI:1.02-1.10), physical exercise (OR = 0.62, p = 0.007, 95%CI:0.44-0.88), sleeping time < 5 h (OR = 1.91, p = 0.006, 95% CI:1.20-3.04) and atrial fibrillation (OR = 4.18, p = 0.012, 95%CI:1.38-12.68) in males. In females, RF model ranked them as psychological resilience (OR = 0.98, p = 0.015, 95%CI:0.96-1.00), ability of daily living (OR = 0.98, p = 0.001, 95%CI:0.97-0.99), neuroticism dimension (OR = 1.11, p = 0.002, 95%CI:1.04-1.18) and subjective support (OR = 1.11, p < 0.001, 95%CI:1.05-1.78). CONCLUSION: The study found influencing factors of PSD at 3 months were different in males and females, and construct RF models to rank them according to their importance. This suggests that clinicians should focus their interventions on sex-specific influencing factors in order to improve the prognosis of PSD patients. TRIAL REGISTRATION: ChiCTR-ROC-17013993.

Apolipoprotein E ɛ2 Is Associated with the White Matter Hyperintensity Multispot Pattern in Spontaneous Intracerebral Hemorrhage.

The white matter hyperintensity (WMH) multispot pattern, as multiple punctate subcortical foci, could differentiate cerebral amyloid angiopathy (CAA) from hypertensive arteriolopathy. Nevertheless, the pathophysiology underlying the multispot sign is still inexplicit. We aimed to explore risk factors for multispot patterns in cerebral small vessel disease (CSVD)-related intracerebral hemorrhage (ICH). Between June 2018 and January 2020, we retrospectively rated the WMH multispot pattern while blinded to our prospective spontaneous ICH cohort's clinical data. Demographic, genetic, and neuroimaging characteristics were applied in establishing the multispot pattern models via multiple logistic regression. In total, 268 participants were selected from our cohort. The possession of apolipoprotein E (APOE) ε2 (P = 0.051) was associated with multispot WMH in univariate analysis. Multispot WMHs were accompanied by multiple CAA features, such as centrum semiovale (CSO)-perivascular space (PVS) predominance (P = 0.032) and severe CSO-PVS (P < 0.001). After adjusting for confounding factors, APOE ε2 possession (OR 2.99, 95% CI [1.07, 8.40]; P = 0.037), severe CSO-PVS (OR 2.39, 95% CI [1.09, 5.26]; P = 0.031), and large posterior subcortical patches (P = 0.001) were independently correlated with the multispot pattern in multivariate analysis. Moreover, APOE ε2 possession (OR 4.34, 95% CI [1.20, 15.62]; P = 0.025) and severe CSO-PVS (OR 3.39, 95% CI [1.23, 9.34]; P = 0.018) remained statistically significant among the participants older than 55 years of age and with categorizable CSVD. APOE ε2 and severe CSO-PVS contribute to the presence of WMH multispot patterns. Because the multispot pattern is a potential diagnostic biomarker in CAA, genetics-driven effects shed light on its underlying vasculopathy. Clinical Trial Registration: URL- http://www.chictr.org.cn . Unique identifier: ChiCTR-ROC-2000039365. Registration date 2020/10/24 (retrospectively registered).

Structural disconnection-based prediction of poststroke depression.

Poststroke depression (PSD) is a common complication of stroke. Brain network disruptions caused by stroke are potential biological determinants of PSD but their conclusive roles are unavailable. Our study aimed to identify the strategic structural disconnection (SDC) pattern for PSD at three months poststroke and assess the predictive value of SDC information. Our prospective cohort of 697 first-ever acute ischemic stroke patients were recruited from three hospitals in central China. Sociodemographic, clinical, psychological and neuroimaging data were collected at baseline and depression status was assessed at three months poststroke. Voxel-based disconnection-symptom mapping found that SDCs involving bilateral temporal white matter and posterior corpus callosum, as well as white matter next to bilateral prefrontal cortex and posterior parietal cortex, were associated with PSD. This PSD-specific SDC pattern was used to derive SDC scores for all participants. SDC score was an independent predictor of PSD after adjusting for all imaging and clinical-sociodemographic-psychological covariates (odds ratio, 1.25; 95% confidence interval, 1.07, 1.48; P = 0.006). Split-half replication showed the stability and generalizability of above results. When added to the clinical-sociodemographic-psychological prediction model, SDC score significantly improved the model performance and ranked the highest in terms of predictor importance. In conclusion, a strategic SDC pattern involving multiple lobes bilaterally is identified for PSD at 3 months poststroke. The SDC score is an independent predictor of PSD and may improve the predictive performance of the clinical-sociodemographic-psychological prediction model, providing new evidence for the brain-behavior mechanism and biopsychosocial theory of PSD.

Association between minimally invasive surgery and late seizures in patients with intracerebral hemorrhage: A propensity score matching study.

Purpose: The association between minimally invasive surgery (MIS) for hematoma evacuation and late seizures after intracerebral hemorrhage (ICH) remains uncertain. We aimed to investigate whether MIS increases the risk of late seizures after ICH and identify the risk factors for late seizures in this patient subgroup. Methods: We retrospectively included consecutive inpatients diagnosed with ICH at two tertiary hospitals in China. The subjects were divided into the MIS group (ICH patients who received MIS including hematoma aspiration and thrombolysis) and conservative treatment group (ICH patients who received conservative medication). Propensity score matching was performed to balance possible risk factors for late seizures between the MIS and conservative treatment groups. Before and after matching, between-group comparisons of the incidence of late seizures were performed between the MIS and conservative treatment groups. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for late seizures in MIS-treated patients. Results: A total of 241 and 1,689 patients were eligible for the MIS and conservative treatment groups, respectively. After matching, 161 ICH patients from the MIS group were successfully matched with 161 ICH patients from the conservative treatment group (1:1). Significant differences (p < 0.001) were found between the MIS group (31/241, 12.9%) and conservative treatment group (69/1689, 4.1%) in the incidence of late seizures before matching. However, after matching, no significant differences (p = 0.854) were found between the MIS group (17/161, 10.6%) and conservative treatment group (16/161, 9.9%). Multivariate logistic regression analysis revealed that cortical involvement (OR = 2.547; 95% CI = 1.137-5.705; p value = 0.023) and higher National Institutes of Health Stroke Scale (NIHSS) scores (OR = 1.050; 95% CI = 1.008-1.094; p value = 0.019) were independent risk factors for late seizures. Conclusion: Our study revealed that receiving MIS did not increase the incidence of late seizures after ICH. Additionally, cortical involvement and NIHSS scores were independent risk factors for late seizures in MIS-treated patients.