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.     

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.     

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.     

Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation

BackgroundQuestions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.MethodsUsing data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.ResultsExternalizing was heritable (h² = 0.46, p = 1 × 10⁻⁶), but not anxious-misery (h² = 0.09, p = 0.183), fear (h² = 0.04, p = 0.337), psychosis-spectrum (h² = 0.00, p = 0.494), or general psychopathology (h² = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρ_g = −0.412, p = 0.004), verbal reasoning (ρ_g = −0.485, p = 0.001), spatial reasoning (ρ_g = −0.426, p = 0.010), motor speed (ρ_g = 0.659, p = 1x10⁻⁴), verbal knowledge (ρ_g = −0.314, p = 0.002), and general cognitive ability (g)(ρ_g = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γ_g = −0.146, p = 0.004) and increasing environmental variance (γ_e = 0.059, p = 0.009) on externalizing.ConclusionsCognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.     

Influence of hemodynamics on enlarged perivascular spaces in atherosclerotic large vessel disease

ABSTRACT

Objectives: Enlarged perivascular spaces (EPVS) are often observed in small vessel disease on T2-weighted images. However, their role in ischemic conditions caused by cerebral large vessel disease remains unclear. We evaluated EPVS in patients with hemodynamic compromise associated with atherosclerotic large vessel disease and aimed to identify the pathophysiology of EPVS.

Methods: We examined 28 adults with atherosclerotic large vessel disease. EPVS numbers in the basal ganglia and the centrum semiovale were assessed. For each affected hemisphere, the total numbers of EPVS were compared with those on the unaffected side. EPVS in the impaired hemodynamics group were compared with those in the unimpaired hemodynamics group. Moreover, EPVS were compared in the presence/absence of large stroke.

Results: The number of EPVS was significantly increased on the affected side in the centrum semiovale (p = 0.023), particularly in the impaired hemodynamics group (p = 0.006). Moreover, in the small stroke subgroup of the impaired hemodynamics group, the number of EPVS was significantly increased on the affected side (p = 0.002), although this number was insignificant in the large ischemic stroke subgroup.

Conclusions: The number of EPVS was increased in patients with atherosclerotic large vessel disease with hemodynamic compromise and decreased in the presence of a large stroke. EPVS might act as fluid absorbers in a hemodynamically compromised state until the occurrence of an ischemic stroke.     

Adolescent Idiopathic Scoliosis Treatment by a Korean Neurosurgeon: The Changing Role for Neurosurgeons

ObjectiveThe purpose of this study was to evaluate radiographic/clinical outcomes of adolescent idiopathic scoliosis (AIS) patients treated by a Korean neurosurgeon.MethodsTen AIS patients were treated by a single neurosurgeon between January 2011 and September 2013 utilizing segmental instrumentation with pedicle screws. Basic demographic information, curve pattern by Lenke classification, number of levels treated, amount of correction achieved, radiographic/clinical outcomes [by Scolisis Resarch Society (SRS-22r) questionnaire] and complications were evaluated to determine the surgical results. Pulmonary function test was utilized to assess forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) before and after surgery.ResultsThe average percentage of correction of the major structural curve was 73.6% (ranged from 64% to 81.5%). Preoperative and final postoperative absolute FVC averaged 3.03 L and 3.76 L (0.73 L increase, p=0.046), and absolute FEV1 averaged 2.63 L and 3.49 L (0.86 L increase, p=0.021). Preoperative and final postoperative average self-image and function scores of SRS-22r were, 2.6±0.5, 3.3±0.1, 4.0±0.5, and 4.6±0.0, respectively. There was a significant improvement of the self-image and function scores of SRS-22r questionnaires before and after surgery (p<0.05). There was no case of neurological deficit, infection and revision for screw malposition. One patient underwent a fusion extension surgery for shoulder asymmetry.ConclusionRadiographic/clinical outcomes of AIS patients treated by a Korean neurosurgeon were acceptable. Fundamental understanding of pediatric spinal deformity is essential for the practice of AIS surgery.     

Usefulness of Simple Rod Rotation to Correct Curve of Adolescent Idiopathic Scoliosis

ObjectiveTo correct apical vertebral rotation for adolescent idiopathic scoliosis (AIS), direct vertebral derotation (DVD) or simple rod rotation (SRR) might be considered. The aim of the present study is to introduce the surgical experiences of AIS by a Korean neurosurgeon and to evaluate the effectiveness of SRR for apical vertebral rotation.MethodsA total of 9 patients (1 male and 8 females) underwent scoliosis surgery by a neurosurgeon of our hospital. The Lenke classifications of the patients were 1 of 1B, 2 of 1C, 1 of 2A, 1 of 2C, 3 of 5C and 1 of 6C. Surgery was done by manner of simple rod rotation on the concave side and in situ coronal bending. Coronal Cobb''s angles, vertebral rotation angles and SRS-22 were measured on a plain standing X-ray and CT before and after surgery.ResultsThe mean follow up period was 25.7 months (range : 5–52). The mean number of screw positioning level was nine (6–12). The mean age was 16.4 years (range : 13–25) at surgery. The mean Risser grade was 3.7±0.9. The apical vertebral rotation measured from the CT scans was 25.8±8.5° vs. 9.3±6.7° (p<0.001) and the Coronal Cobb''s angle was 53.7±10.4° vs. 15.4±6.5° (p<0.001) preoperatively and postoperative, respectively. The SRS-22 improved from 71.9 preoperatively to 90.3 postoperatively. There were no complications related with the operations.ConclusionSRR with pedicle screw instrumentation could be corrected successfully by axial rotation without complications. SRR might serve as a good option to correct AIS deformed curves of AIS.     

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.     

Comparison between Anterior Cervical Decompression with Fusion and Posterior Cervical Fusion with Wide Facetectomy for Treatment of Severe Bony Foraminal Stenosis

ObjectiveTo compare the anterior cervical discectomy and fusion (ACDF) and posterior cervical fusion (PCF) with wide facetectomy in the treatment of parallel-shaped bony foraminal stenosis (FS). MethodsThirty-six patients underwent surgery due to one-or-two levels of parallel-shaped cervical FS. ACDF was performed in 16 patients, and PCF using CPS was performed in 20 patients. All patients were followed up at 1, 3, 6, and 12 months postoperatively. Standardized outcome measures such as Numeric rating scale (NRS) score for arm/neck pain and Neck disability index (NDI) were evaluated. Cervical radiographs were used to compare the C2–7 Cobb’s angle, segmental angle, and fusion rates. ResultsThere was an improvement in NRS scores after both approaches for radicular arm pain (mean change -6.78 vs. -8.14, p=0.012), neck pain (mean change -1.67 vs. -4.36, p=0.038), and NDI score (-19.69 vs. -18.15, p=0.794). The segmental angle improvement was greater in the ACDF group than in the posterior group (9.4°±2.7° vs. 3.3°±5.1°, p=0.004). However, there was no significant difference in C2–7 Cobb angle between groups (16.2°±7.9° vs. 14.8°±8.5°, p=0.142). As a complication, dysphagia was observed in one case of the ACDF group. ConclusionIn the treatment of parallel-shaped bony FS up to two surgical levels, segmental angle improvement was more favorable in patients who underwent ACDF. However, PCF with wide facetectomy using CPS should be considered as an alternative treatment option in cases where the anterior approach is burdensome.     

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.     

Higher ambulatory systolic blood pressure independently associated with enlarged perivascular spaces in basal ganglia

Backgrounds: Enlarged perivascular spaces (EPVS) have been identified as a marker of cerebral small vessel diseases (CSVD). Ambulatory blood pressure (ABP) is the strongest predictor of hypertension-related brain damage. However, the relationship between ABP levels and EPVS is unclear.

Objectives: This study aimed to investigate the association between ABP levels and EPVS by 24-hour ambulatory blood pressure monitoring (ABPM).

Methods: We prospectively recruited inpatients for physical examinations in our hospital from May 2013 to Jun 2016. 24-hour ABPM data and cranial magnetic resonance imaging information were collected. EPVS in basal ganglia (BG) and centrum semiovale (CSO) were identified and classified into three categories by the severity. White matter hyperintensities were scored by Fazekas scale. Spearman correlation analysis and multiple logistic regression analysis were used to determine the relationship between ABP levels and EPVS.

Results: A total of 573 subjects were enrolled in this study. 24-hour, day and night systolic blood pressure (SBP) levels were positively related to higher numbers of EPVS in BG (24-hour SBP: r = 0.23, p < 0.01; day SBP: r = 0.25, p < 0.01; night SBP: r = 0.30, p < 0.01). The association was unchanged after controlling for confounders by multiple logistic regression analysis. 24-hour and day diastolic blood pressure (DBP) levels increased with an increasing degree of EPVS in CSO (p = 0.04 and 0.049, respectively). But the association disappeared after adjusting for confounders. Spearman correlation analysis indicated that ABP levels were not associated with higher numbers of EPVS in CSO (p > 0.05). DBP levels were not independently associated with the severity of EPVS in BG and CSO.

Conclusion: Higher SBP levels were independently associated with EPVS in BG, but not in CSO, which supported EPVS in BG to be a marker of CSVD. Pathogenesis of EPVS in BG and CSO might be different.     

Decreased 18F-Fluorodeoxyglucose Uptake in Lumbar Vertebrae of Stroke Patients

Background and PurposeWe investigated ¹⁸F-fluorodeoxyglucose (FDG) uptake levels in the lumbar vertebrae, liver, and spleen of stroke patients with carotid atherosclerosis.MethodsThis study analyzed acute ischemic stroke patients with carotid atherosclerosis who underwent whole-body FDG positron-emission tomography between October 2015 and January 2017. FDG uptake in the lumbar vertebrae, liver, and spleen was measured and compared between stroke patients and control subjects without stroke history. Multivariate linear regression analysis was performed to identify independent factors related to FDG uptake in the proximal internal carotid artery (ICA).ResultsTwenty stroke patients aged 75.1±9.0 years (mean±standard deviation; 10 females) and 20 control subjects aged 62.9±10.7 years (6 females) were included. In comparison with the control group, the stroke group showed significantly higher FDG uptake in the proximal ICA (1.16±0.26 vs. 0.87±0.19, p<0.01), but significantly lower FDG uptake in the lumbar vertebrae (1.09±0.26 vs. 1.38±0.38, p=0.007) and liver (1.71±0.30 vs. 2.01±0.34, p=0.005). Multivariate linear regression analysis showed that the lumbar FDG uptake was negatively correlated with FDG uptake in the proximal ICA (standardized coefficient=-0.367, p=0.013) after adjusting for age and hypertension.ConclusionsStroke patients showed decreased FDG uptake in the lumbar vertebrae. Further studies are warranted to evaluate the pathophysiological link between cerebral atherosclerosis and bone.     

Adjuvant High-Flow Normobaric Oxygen After Mechanical Thrombectomy for Anterior Circulation Stroke: a Randomized Clinical Trial

Adjuvant neuroprotective therapies for acute ischemic stroke (AIS) have demonstrated benefit in animal studies, albeit without human translation. We investigated the safety and efficacy of high-flow normobaric oxygen (NBO) after endovascular recanalization in anterior circulation stroke. This is a prospective randomized controlled study. Eligible patients were randomized to receive high-flow NBO by a Venturi mask (FiO₂ 50%, flow 15 L/min) or routine low-flow oxygen supplementation by nasal cannula (flow 3 L/min) after vessel recanalization for 6 h. Patient demographics, procedural metrics, complications, functional outcomes, symptomatic intracranial hemorrhage (sICH), and infarct volume were assessed. A total of 91 patients were treated with high-flow NBO. NBO treatment revealed a common odds ratio of 2.2 (95% CI, 1.26 to 3.87) favoring the distribution of global disability scores on the mRS at 90 days. The mortality at 90 days was significantly lower in the NBO group than in the control group, with an absolute difference of 13.86% (rate ratio, 0.35; 95% CI, 0.13–0.93). A significant reduction of infarct volume as determined by MRI was noted in the NBO group. The median infarct volume was 9.4 ml versus 20.5 ml in the control group (beta coefficient, − 20.24; 95% CI, − 35.93 to − 4.55). No significant differences were seen in the rate of sICH, pneumonia, urinary infection, and seizures between the 2 groups. This study suggests that high-flow NBO therapy after endovascular recanalization is safe and effective in improving functional outcomes, decreasing mortality, and reducing infarct volumes in anterior circulation stroke patients within 6 h from stroke onset.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00979-3.Key Words: Oxygen supplement, neuroprotection, endovascular recanalization, large vessel occlusion, functional prognosis.     

Association between Serum Insulin-Like Growth Factor-1 and Neurological Severity in Acute Ischemic Stroke

Background and PurposeSerum insulin-like growth factor-1 (IGF-1) is known to have a neuroprotective effect. This study aimed to determine the effects of serum IGF-1 on the severity and clinical outcome of acute ischemic stroke (AIS).MethodsThis study included 446 patients with AIS who were admitted to Hallym University Sacred Heart Hospital within 7 days of stroke onset from February 2014 to June 2017. Serum IGF-1 levels were measured within 24 hours of admission. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the functional outcome at 3 months after symptom onset was assessed using the modified Rankin Scale score. The effects of serum IGF-1 levels on stroke severity and 3-month functional outcomes were analyzed using multivariate logistic regression analysis.ResultsThis study evaluated 379 patients with AIS (age 67.2±12.6 years, mean±standard deviation; 59.9% males) after excluding 67 patients who had a history of previous stroke (n=25) or were lost to follow-up at 3 months (n=42). After adjusting for clinically relevant covariates, a higher serum IGF-1 level was associated with a lower NIHSS score at admission (adjusted odds ratio=0.44, 95% confidence interval=0.24–0.80, p=0.01), while there was no significant association at 3 months.ConclusionsThis study showed that a higher serum IGF-1 level is associated with a lower NIHSS score at admission but not at 3 months. Further studies are required to clarify the usefulness of the serum IGF-1 level as a prognostic marker for ischemic stroke.     

Examining the association between exposome score for schizophrenia and functioning in schizophrenia,siblings, and healthy controls: Results from the EUGEI study

BackgroundA cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.MethodsThis cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.ResultsES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.ConclusionsOur findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.     

Relapse and frequency of injection of monthly paliperidone palmitate—A retrospective case–control study

BackgroundOutcomes with long-acting injections (LAIs) are generally better than with oral antipsychotic therapy. However, the use of LAIs does not assure compliance with treatment and in clinical practice patients often miss injections or receive their injections later than intended.MethodWe conducted a case–control study to identify demographic and treatment associations with relapse (cases) on paliperidone 1-monthly injection (PP1M) compared with age-, gender-, and ethnicity-matched controls.ResultsWe identified 16 cases and matched 43 controls. Baseline variables did not differ except that cases had received significantly more antipsychotic drugs before initiation with PP1M (3.94 vs. 2.12; p < 0.001). Cases had fewer PP1M injections administered compared with the control group (9.69 vs. 11.37; p < 0.001) and this group had a longer interval between injections than the control group (37 vs. 33 days; p < 0.001).ConclusionsRelapse on PP1M is associated with reduced frequency of injection and a longer interval between doses.     

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.     

Cardiac and Echocardiographic Markers in Cryptogenic Stroke with Incidental Patent Foramen Ovale

ObjectiveSome cardiac abnormalities could be a substrate for potential embolic source in cryptogenic stroke (CS). We evaluated whether cardiac and echocardiographic markers were associated with CS in patients with incidental patent foramen ovale (PFO) as defined using the Risk of Paradoxical Embolism (RoPE) score.Materials and methodsAmong 677 patients enrolled in a multicenter observational CS registry, 300 patients (44%) had PFOs detected by transesophageal echocardiography. They were classified into probable PFO-related stroke (RoPE score>6, n = 32) and stroke with incidental PFO (RoPE score≤6, n = 268) groups, and clinical characteristics, laboratory findings, cardiac and echocardiographic markers (i.e. brain natriuretic peptide, left atrial [LA] diameter, ejection fraction, early transmitral flow velocity/early diastolic tissue Doppler imaging velocity [E/e’], LA appendage flow velocity, spontaneous echo contrast, atrial septal aneurysm, substantial PFO, and aortic arch plaques), stroke recurrence, and excellent outcome (modified Rankin scale score <2) at discharge were compared. Risk factors for low RoPE scores were determined using multiple logistic regression analysis.ResultsHigher brain natriuretic peptide levels (p = 0.032), LA enlargement (p < 0.001), higher E/e’ (p = 0.001), lower LA appendage flow velocity (p < 0.001), non-substantial PFO (p = 0.021), and aortic arch plaques (p = 0.002) were associated with the low RoPE score group. Patients with high RoPE scores had excellent outcomes (58% versus 78%, p = 0.035). LA enlargement (age- and sex-adjusted odds ratio, 1.15; 95 % confidence interval, 1.00–1.32; p = 0.039) was an independent predictor of low RoPE scores.ConclusionsAbnormal cardiac substrate could be associated with CS occurrence in a subset of patients with PFO. Patients with CS who had incidental PFO may be at risk of cardioembolism.     

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.