Effect of stress‐induced hyperglycemia after non‐traumatic non‐aneurysmal subarachnoid hemorrhage on clinical complications and functional outcomes

BackgroundDespite having an overall benign course, non‐traumatic non‐aneurysmal subarachnoid hemorrhage (naSAH) is still accompanied by a risk of clinical complications and poor outcomes. Risk factors and mechanisms of complications and poor outcomes after naSAH remain unknown. Our aim was to explore the effect of stress‐induced hyperglycemia (SIH) on complication rates and functional outcomes in naSAH patients.MethodsWe retrospectively reviewed patients with naSAH admitted to our institution between 2013 and 2018. SIH was identified according to previous criterion. Symptomatic vasospasm, delayed cerebral infarction, and hydrocephalus were identified as main complications. Outcomes were reviewed using a modified Rankin Scale (mRS) at discharge, 3 months, and 12 months. A statistical analysis was conducted to reveal the associations of SIH with complications and outcomes.ResultsA total of 244 naSAH patients were included in the cohort with 74 (30.3%) SIH. After adjusting for age, gender, hypertension, Hunt and Hess (HH) grade, modified Fisher Scale (mFS), intraventricular hemorrhage (IVH), and subarachnoid blood distribution, SIH was significantly associated with symptomatic vasospasm (p < 0.001, 12.176 [4.904–30.231]), delayed cerebral infarction (p < 0.001, 12.434 [3.850–40.161]), hydrocephalus (p = 0.008, 5.771 [1.570–21.222]), and poor outcome at 12 months (p = 0.006, 5.506 [1.632–18.581]), whereas the correlation between SIH and poor outcome at discharge (p = 0.064, 2.409 [0.951–6.100]) or 3 months (p = 0.110, 2.029 [0.852–4.833]) was not significant. Incorporation of SIH increased the area under curve (AUC) of ROC in the combined model for predicting symptomatic vasospasm (p = 0.002), delayed cerebral infarction (p = 0.024), hydrocephalus (p = 0.037), and 12‐month poor outcome (p = 0.087).ConclusionsSIH is a significant and independent risk factor for symptomatic vasospasm, delayed cerebral infarction, hydrocephalus, and long‐term poor outcome in naSAH patients. Identifying SIH early after naSAH is important for decision‐making and treatment planning.     

Increasing nodal vulnerability and nodal efficiency implied recovery time prolonging in patients with supplementary motor area syndrome

Supplementary motor area (SMA) syndrome is a surgery‐related complication that commonly occurs after removing SMA glioma, and needs weeks to recover. However, susceptible factors of patients suffering from SMA syndrome remain unknown. Graphic theory was applied to reveal topological properties of sensorimotor network (SMN) by processing resting‐state functional magnetic resonance images in 66 patients with SMA gliomas. Patients were classified into SMA and non‐SMA groups based on whether they suffered from SMA syndrome. We collected recovery time and used causal mediation analysis to find association between topological properties and recovery time. Compared with the non‐SMA group, higher vulnerability (left: p = .0018; right: p = .0033) and lower fault tolerance (left: p = .0022; right: p = .0248) of the whole SMN were found in the SMA group. Moreover, higher nodal properties of lesional‐hemispheric cingulate cortex (nodal efficiency: left, p = .0389; right, p = .0169; nodal vulnerability: left, p = .0185; right, p = .0085) and upper limb region of primary motor cortex (PMC; nodal efficiency: left, p = .0132; right, p = .0001; nodal vulnerability: left, p = .0091; right, p = .0209) were found in the SMA group. Nodal efficiency and nodal vulnerability of cingulate cortex and upper limb region of PMC were important predictors for SMA syndrome occurring and recovery time prolonging. Neurosurgeons should carefully deal with upper limb region of PMC and cingulate cortex, and protect them if these two region were unnecessary to damage during SMA glioma resection.     

Loss of long‐term benefit from VIM‐DBS in essential tremor: A secondary analysis of repeated measurements

AimsDeep brain stimulation (DBS) in the ventral intermediate nucleus (Vim‐DBS) is the preferred surgical therapy for essential tremor (ET). Tolerance and disease progression are considered to be the two main reasons underlying the loss of long‐term efficacy of Vim‐DBS. This study aimed to explore whether Vim‐DBS shows long‐term loss of efficacy and to evaluate the reasons for this diminished efficacy from different aspects.MethodsIn a repeated‐measures meta‐analysis of 533 patients from 18 studies, Vim‐DBS efficacy was evaluated at ≤6 months, 7–12 months, 1–3 years, and ≥4 years. The primary outcomes were the score changes in different components of the Fahn‐Tolosa‐Marin Tremor Rating Scale (TRS; total score, motor score, hand‐function score, and activities of daily living [ADL] score). Secondary outcomes were the long‐term predictive factors.ResultsThe TRS total, motor, and ADL scores showed significant deterioration with disease progression (p = 0.002, p = 0.047, and p < 0.001, respectively), while the TRS total (p < 0.001), hand‐function (p = 0.036), and ADL (p = 0.004) scores indicated a significant long‐term reduction in DBS efficacy, although the motor subscore indicated no loss of efficacy. Hand‐function (p < 0.001) and ADL (p = 0.028) scores indicated DBS tolerance, while the TRS total and motor scores did not. Stimulation frequency and preoperative score were predictive factors for long‐term results.ConclusionThis study provides level 3a evidence that long‐term Vim‐DBS is effective in controlling motor symptoms without waning benefits. The efficacy reduction for hand function was caused by DBS tolerance, while that for ADL was caused by DBS tolerance and disease progression. More attention should be given to actual functional recovery rather than changes in motor scores in patients with ET.     

Urinary albumin creatinine ratio associated with postoperative delirium in elderly patients undergoing elective non‐cardiac surgery: A prospective observational study

IntroductionThe blood‐brain barrier (BBB) disruption contributes to postoperative delirium, but cost‐effective and non‐invasive assessment of its permeability is not practicable in the clinical settings. Urine albumin to creatinine ratio (UACR), reflecting systemic vascular endothelial dysfunction, may be a prognostic and predictive factor associated with postoperative delirium. The aim was to analyze the relationship between UACR and postoperative delirium in elderly patients undergoing elective non‐cardiac surgery.Materials and methodsThrough stratified random sampling, a cohort of 408 individuals aged 60 years and older scheduled for elective non‐cardiac surgery were included between February and August 2019 in the single‐center, prospective, observational study. The presence of delirium was assessed using the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM‐ICU) on the day of surgery, at 2 h after the surgery ending time and on the first 3 consecutive days with repeated twice‐daily, with at least 6‐h intervals between assessments. Urine samples were collected on one day before surgery, and 1st day and 3rd day after surgery. The primary outcome was the presence of postoperative delirium, and association of the level of UACR with postoperative delirium was evaluated with unadjusted/adjusted analyses and multivariable logistic regression.ResultsPostoperative delirium was observed in 26.75% (107 of 400) of patients within 3 days post‐surgery. UACR‐Pre (OR, 1.30; 95% CI, 1.14–1.49, p < 0.001), UACR‐POD1 (OR, 1.20; 95% CI, 1.13–1.27, p < 0.001), and UACR‐POD3 (OR, 1.14; 95% CI, 1.08–1.20, p < 0.001) between the delirium and non‐delirium groups show a significant difference, even after adjusting for age, education levels, and other factors.ConclusionAs the marker of endothelial dysfunction, the high perioperative UACR value may be linked to the postoperative delirium in elderly patients undergoing elective non‐cardiac surgery.     

Predictive value of different bilirubin subtypes for clinical outcomes in patients with acute ischemic stroke receiving thrombolysis therapy

AimsTo explore the association of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels with, as well as the incremental predictive value of different bilirubin subtypes for, poor outcomes in acute ischemic stroke patients after thrombolysis.MethodsWe analyzed 588 individuals out of 718 AIS participants, and all patients were followed up at 3 months after thrombolysis. The primary outcome was 3‐month death and major disability (modified Rankin Scale (mRS) score of 3–6). The secondary outcomes were 3‐month mortality (mRS score of 6), moderate‐severe cerebral edema, and symptomatic intracranial hemorrhage (sICH), respectively.ResultsElevated DBIL pre‐thrombolysis was associated with an increased risk of primary outcome (OR 3.228; 95% CI 1.595–6.535; p for trend = 0.014) after fully adjustment. Elevated TBIL pre‐thrombolysis showed the similar results (OR 2.185; 95% CI 1.111–4.298; p for trend = 0.047), while IBIL pre‐thrombolysis was not significantly associated with primary outcome (OR 1.895; 95% CI 0.974–3.687; p for trend = 0.090). Multivariable‐adjusted spline regression model showed a positive linear dose‐response relationship between DBIL pre‐thrombolysis and risk of primary outcome (p for linearity = 0.004). Adding DBIL pre‐thrombolysis into conventional model had greater incremental predictive value for primary outcome, with net reclassification improvement (NRI) 95% CI = 0.275 (0.084–0.466) and integrated discrimination improvement (IDI) 95% CI = 0.011 (0.001–0.024). Increased DBIL post‐thrombolysis had an association with primary outcome (OR 2.416; 95%CI 1.184–4.930; p for trend = 0.039), and it also elevated the incremental predictive value for primary outcome, with NRI (95% CI) = 0.259 (0.066–0.453) and IDI (95% CI) = 0.025 (0.008–0.043).ConclusionIncreased DBIL pre‐thrombolysis had a stronger association with, as well as greater incremental predictive value for, poor outcomes than TBIL and IBIL did in AIS patients after thrombolysis, which should be understood in the context of retrospective design. The effect of DBIL on targeted populations should be investigated in further researches.     

Pre‐ and post‐conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta‐analysis

BackgroundToll‐like receptor (TLR) agonist polyinosinic–polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear.MethodsWe evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion.ResultsPoly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre‐ and post‐conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor‐κB (NF‐κB) [SMD = −1.78; CIs (−2.67, −0.88); p = 0.0)], and tumor necrosis factor alpha (TNF‐α) [SMD = −16.83; CIs (−22.63, −11.02); p = 0.00].ConclusionWe showed that poly I:C is neuroprotective and acts via the TLR3/NF‐κB/TNF‐α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.     

Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice

BackgroundVasogenic cerebral edema resulting from blood–brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β‐catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β‐catenin signaling.MethodsWe evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV‐induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β‐catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124.ResultsLithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm³ vs. 19.97 ± 3.20 mm³ in vehicle controls, p = 0.0016) and improved the neurological outcomes of mice following ICH. Importantly, lithium significantly increased the BBB integrity, as evidenced by reductions in the levels of brain edema (p = 0.0312), Evans blue leakage (p = 0.0261), and blood IgG extravasation (p = 0.0009) into brain tissue around the hematoma. Mechanistically, lithium upregulated the activity of endothelial Wnt/β‐catenin signaling in mice and increased the levels of tight junction proteins (occludin, claudin‐5 and ZO‐1). Furthermore, the protective effect of lithium on cerebral damage and BBB integrity was abolished in endothelial Gpr124 knockout mice, suggesting that its protective effect on BBB function was mainly dependent on Gpr124‐mediated endothelial Wnt/β‐catenin signaling.ConclusionOur findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.     

Long‐term functional prognosis and related factors of spinal cord stimulation in patients with disorders of consciousness

IntroductionThe treatment of patients with disorders of consciousness (DoC) remains a challenging issue, and spinal cord stimulation (SCS) has been reported to be a promising treatment for DoC in some studies.AimsThis study explores the efficiency of SCS in treating patients with DoC at different consciousness levels, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS) and summarizes and analyzes the long‐term effect and related factors of SCS in patients with DoC.ResultsAn overall positive outcome was reached in 35 of 110 patients (31.8%). Among patients with positive outcomes, the MCS group improved 45.53% more than VS/UWS group, and this difference was statistically significant. In terms of the recommendation standard, positive outcomes occurred in 33 patients (94.3%) in the highly recommended group and 2 patients (5.7%) in the weakly recommended group (p < 0.001). After adjustment for potential covariables, young age (age ≤ 19 years old) (p = 0.045) and MCS (p < 0.001) were significantly correlated with positive outcome. A nomogram based on age, state of consciousness, and pathogeny showed good predictive performance, with a c‐index of 0.794. The Hosmer–Lemeshow goodness‐of‐fit test showed that the model was well calibrated (χ ² = 3.846, p = 0.871).ConclusionsSCS is one of the most feasible treatments for patients with DoC, especially for patients with MCS. Younger age is significantly associated with better outcomes and could therefore serve as a basis for preoperative screening. However, more evidence‐based randomized controlled trials are needed to confirm the efficacy of the treatment.     

New‐onset and persistent neurological and psychiatric sequelae of COVID‐19 compared to influenza: A retrospective cohort study in a large New York City healthcare network

ObjectivesNeurological and neuropsychiatric manifestations of post‐acute SARS‐CoV‐2 infection (neuro‐PASC) are common among COVID‐19 survivors, but it is unknown how neuro‐PASC differs from influenza‐related neuro‐sequelae. This study investigated the clinical characteristics of COVID‐19 patients with and without new‐onset neuro‐PASC, and of flu patients with similar symptoms.MethodsWe retrospectively screened 18,811 COVID‐19 patients and 5772 flu patients between January 2020 and June 2021 for the presence of new‐onset neuro‐sequelae that persisted at least 2 weeks past the date of COVID‐19 or flu diagnosis.ResultsWe observed 388 COVID‐19 patients with neuro‐PASC versus 149 flu patients with neuro‐sequelae. Common neuro‐PASC symptoms were anxiety (30%), depression (27%), dizziness (22%), altered mental status (17%), chronic headaches (17%), and nausea (11%). The average time to neuro‐PASC onset was 138 days, with hospitalized patients reporting earlier onset than non‐hospitalized patients. Neuro‐PASC was associated with female sex and older age (p < 0.05), but not race, ethnicity, most comorbidities, or COVID‐19 disease severity (p > 0.05). Compared to flu patients, COVID‐19 patients were older, exhibited higher incidence of altered mental status, developed symptoms more quickly, and were prescribed psychiatric drugs more often (p < 0.05).ConclusionsThis study provides additional insights into neuro‐PASC risk factors and differentiates between post‐COVID‐19 and post‐flu neuro‐sequelae.     

Selective cutoff reporting in studies of the accuracy of the Patient Health Questionnaire‐9 and Edinburgh Postnatal Depression Scale: Comparison of results based on published cutoffs versus all cutoffs using individual participant data meta‐analysis

ObjectivesSelectively reported results from only well‐performing cutoffs in diagnostic accuracy studies may bias estimates in meta‐analyses. We investigated cutoff reporting patterns for the Patient Health Questionnaire‐9 (PHQ‐9; standard cutoff 10) and Edinburgh Postnatal Depression Scale (EPDS; no standard cutoff, commonly used 10–13) and compared accuracy estimates based on published cutoffs versus all cutoffs.MethodsWe conducted bivariate random effects meta‐analyses using individual participant data to compare accuracy from published versus all cutoffs.ResultsFor the PHQ‐9 (30 studies, N = 11,773), published results underestimated sensitivity for cutoffs below 10 (median difference: −0.06) and overestimated for cutoffs above 10 (median difference: 0.07). EPDS (19 studies, N = 3637) sensitivity estimates from published results were similar for cutoffs below 10 (median difference: 0.00) but higher for cutoffs above 13 (median difference: 0.14). Specificity estimates from published and all cutoffs were similar for both tools. The mean cutoff of all reported cutoffs in PHQ‐9 studies with optimal cutoff below 10 was 8.8 compared to 11.8 for those with optimal cutoffs above 10. Mean for EPDS studies with optimal cutoffs below 10 was 9.9 compared to 11.8 for those with optimal cutoffs greater than 10.ConclusionSelective cutoff reporting was more pronounced for the PHQ‐9 than EPDS.     

Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

BackgroundIndividuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.Methods“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.ResultsNinety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).ConclusionsThere is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.     

The effect of a game training intervention on cognitive functioning and depression symptoms in the elderly with mild cognitive impairment: A randomized controlled trial

ObjectivesThis study aimed to explore whether game training could improve cognitive functioning and depression symptoms in the elderly affected by mild cognitive impairment (MCI).MethodsA non‐blinded randomized controlled trial was conducted. Participants were 72 patients with MCI and depression from a nursing home in Wuhan. Participants were randomized to either the intervention group or the control group (n = 36 each). The intervention group received regular nursing care plus game training for 50 min, three times per week for 8 weeks, whereas the control group received only regular nursing care during the same research period. Cognitive functioning and depression symptoms were tested in both groups at baseline and at the end of the 8‐week intervention. We used the Montreal Cognitive Assessment and the 15‐item Geriatric Depression Scale to assess cognitive functioning and depression symptoms, respectively.ResultsThe 8‐week game training intervention significantly improved the cognitive and depression scores when compared with the control group and baseline scores (p < 0.05). No significant difference was observed in the control group (p > 0.05).ConclusionsOur results suggest that the implementation of game training can improve the cognitive functioning and depression symptoms of the elderly with MCI, indicated that can be widely used.     

Measuring changes in alcohol use in Finland and Norway during the COVID‐19 pandemic: Comparison between data sources

ObjectivesTo examine (1) how a rapid data collection using a convenience sample fares in estimating change in alcohol consumption when compared to more conventional data sources, and (2) how alcohol consumption changed in Finland and Norway during the first months of the COVID‐19 pandemic.MethodsThree different types of data sources were used for the 2nd quarter of 2020 and 2019: sales statistics combined with data on unrecorded consumption; the rapid European Alcohol Use and COVID‐19 (ESAC) survey (Finland: n = 3800, Norway: n = 17,092); and conventional population surveys (Finland: n = 2345, Norway: n1 = 1328, n2 = 2189, n3 = 25,708). Survey measures of change were retrospective self‐reports.ResultsThe statistics indicate that alcohol consumption decreased in Finland by 9%, while little change was observed in Norway. In all surveys, reporting a decrease in alcohol use was more common than reporting an increase (ratios 2–2.6 in Finland, 1.3–2 in Norway). Compared to conventional surveys, in the ESAC survey fewer respondents reported no change and past‐year alcohol consumption was higher.ConclusionThe rapid survey using convenience sampling gave similar results on change in drinking as conventional surveys but higher past‐year drinking, suggesting self‐selection effects. Aspects of the pandemic driving alcohol consumption down were equally strong or stronger than those driving it up.     

Cortical N‐acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper‐extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper‐extremity motor impairment was indexed with the Fugl‐Meyer (FM) scale. N‐acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right‐handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper‐extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke‐related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper‐extremity outcomes in chronic stroke.     

Mutation‐related magnetization‐transfer,not axon density,drives white matter differences in premanifest Huntington disease: Evidence from in vivo ultra‐strong gradient MRI

White matter (WM) alterations have been observed in Huntington disease (HD) but their role in the disease‐pathophysiology remains unknown. We assessed WM changes in premanifest HD by exploiting ultra‐strong‐gradient magnetic resonance imaging (MRI). This allowed to separately quantify magnetization transfer ratio (MTR) and hindered and restricted diffusion‐weighted signal fractions, and assess how they drove WM microstructure differences between patients and controls. We used tractometry to investigate region‐specific alterations across callosal segments with well‐characterized early‐ and late‐myelinating axon populations, while brain‐wise differences were explored with tract‐based cluster analysis (TBCA). Behavioral measures were included to explore disease‐associated brain‐function relationships. We detected lower MTR in patients'' callosal rostrum (tractometry: p = .03; TBCA: p = .03), but higher MTR in their splenium (tractometry: p = .02). Importantly, patients'' mutation‐size and MTR were positively correlated (all p‐values < .01), indicating that MTR alterations may directly result from the mutation. Further, MTR was higher in younger, but lower in older patients relative to controls (p = .003), suggesting that MTR increases are detrimental later in the disease. Finally, patients showed higher restricted diffusion signal fraction (FR) from the composite hindered and restricted model of diffusion (CHARMED) in the cortico‐spinal tract (p = .03), which correlated positively with MTR in the posterior callosum (p = .033), potentially reflecting compensatory mechanisms. In summary, this first comprehensive, ultra‐strong gradient MRI study in HD provides novel evidence of mutation‐driven MTR alterations at the premanifest disease stage which may reflect neurodevelopmental changes in iron, myelin, or a combination of these.     

Mixed‐effects multilevel analysis followed by canonical correlation analysis is an effective fMRI tool for the investigation of idiosyncrasies

We report that regions‐of‐interest (ROIs) associated with idiosyncratic individual behavior can be identified from functional magnetic resonance imaging (fMRI) data using statistical approaches that explicitly model individual variability in neuronal activations, such as mixed‐effects multilevel analysis (MEMA). We also show that the relationship between neuronal activation in fMRI and behavioral data can be modeled using canonical correlation analysis (CCA). A real‐world dataset for the neuronal response to nicotine use was acquired using a custom‐made MRI‐compatible apparatus for the smoking of electronic cigarettes (e‐cigarettes). Nineteen participants smoked e‐cigarettes in an MRI scanner using the apparatus with two experimental conditions: e‐cigarettes with nicotine (ECIG) and sham e‐cigarettes without nicotine (SCIG) and subjective ratings were collected. The right insula was identified in the ECIG condition from the χ ²‐test of the MEMA but not from the t‐test, and the corresponding activations were significantly associated with the similarity scores (r = −.52, p = .041, confidence interval [CI] = [−0.78, −0.17]) and the urge‐to‐smoke scores (r = .73, p <.001, CI = [0.52, 0.88]). From the contrast between the two conditions (i.e., ECIG > SCIG), the right orbitofrontal cortex was identified from the χ ²‐tests, and the corresponding neuronal activations showed a statistically meaningful association with similarity (r = −.58, p = .01, CI = [−0.84, −0.17]) and the urge to smoke (r = .34, p = .15, CI = [0.09, 0.56]). The validity of our analysis pipeline (i.e., MEMA followed by CCA) was further evaluated using the fMRI and behavioral data acquired from the working memory and gambling tasks available from the Human Connectome Project.     

Identification of embolic stroke in patients with large vessel occlusion: The Chinese embolic stroke score,CHESS

AimsThe aim of the study was to develop a simple and objective score using clinical variables and quantified perfusion measures to identify embolic stroke with large vessel occlusions.MethodsEligible patients from five centers participating in the International Stroke Perfusion Imaging Registry were included in this study. Patients were split into a derivation cohort (n = 213) and a validation cohort (n = 116). A score was developed according to the coefficients of independent predictors of embolic stroke from stepwise logistic regression model in the derivation cohort. The performance of the score was validated by assessing its discrimination and calibration.ResultsThe independent predictors of embolic stroke made up the Chinese Embolic Stroke Score (CHESS). There were: history of atrial fibrillation (3 points), non‐hypertension history (2 points), and delay time>6 s volume/delay time>3 s volume on perfusion imaging ≥0.23 (2 points). The AUC of CHESS in the derivation cohort and validation cohort were 0.87 and 0.79, respectively. Patients with a CHESS of 0 could be identified as low‐risk of embolic stroke, with a CHESS of 2–4 could be identified as medium‐risk and with a CHESS of 5–7 could be regarded as high‐risk. The observed rate of embolic stroke of each risk group was well‐calibrated with the predicted rate.ConclusionCHESS could reliably and independently identify embolic stroke as the cause of large vessel occlusion.     

Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes.     

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis

BackgroundTo determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP).MethodsA multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I² test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies.ResultsOne hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49–58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27–36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found.ConclusionsHalf of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.     

Higher serum occludin after successful reperfusion Is associated with early neurological deterioration

AimsEarly neurological deterioration (END) is an important factor that affects prognosis in patients with acute ischemic stroke. We explored the relationship between serum occludin levels after successful reperfusion and END in patients treated with endovascular thrombectomy (EVT).MethodsWe prospectively enrolled 120 stroke patients who underwent EVT with successful reperfusion. Enzyme‐linked immunosorbent assay was used to detect the serum occludin levels on admission and within 1 h after successful reperfusion. Receiver operating characteristic curves (ROC) and regression analysis were used to compare the relationship between serum occludin and END after thrombectomy.ResultsAmong the 120 patients, 36 (30%) experienced END. The END group had higher serum occludin levels than the non‐END group after successful reperfusion [4.31 (3.71–5.38) vs 6.32 (5.88–6.99), p < 0.001]. The ROC curve showed that postoperative serum occludin levels had a significant prediction value for END (AUC: 0.86, p < 0.001). Regression analysis showed that serum occludin was an independent risk factor for END in EVT patients (adjusted odds ratio: 4.46, 95% confidence interval: 1.92–10.32; p < 0.001).ConclusionsThe higher serum occludin levels were strongly related to END after successful reperfusion. Serum occludin may be an independent risk factor for END in EVT patients.