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Background: Patent foramen ovale (PFO) is causally associated with stroke in some patients younger than 60 years, especially when it is large or associated with an atrial septal aneurysm (ASA). After 60 years of age, this association is less well understood. We assessed the relationships between detailed atrial septal anatomy and the cryptogenic nature of stroke in this population., Methods and Results: We reviewed all patients aged 60 to 80 years admitted to our stroke center for ischemic stroke who underwent contrast echocardiography between 2016 and 2021. The atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection (ASCOD) classification was used to reevaluate the etiological workup. Associations between cryptogenic stroke and (1) PFO presence or (2) categories of PFO anatomy (nonlarge PFO without ASA, nonlarge PFO with ASA, large PFO without ASA, and large PFO with ASA) were assessed using logistic regression. Among 533 patients (median National Institutes of Health Stroke Scale score=1), PFO was present in 152 (prevalence, 28.5% [95% CI, 24.9-32.5]). Compared with noncryptogenic stroke, cryptogenic stroke (n=218) was associated with PFO presence (44.5% versus 17.5%; P <0.0001). Among patients with a PFO, septal anatomy categories were associated with cryptogenic stroke ( P =0.02), with a strong association for patients with both large PFO and ASA (38.1% versus 14.5%, P =0.002)., Conclusions: PFO presence remains strongly associated with cryptogenic stroke between 60 and 80 years of age. Large PFO, ASA, and their association were strongly associated with cryptogenic stroke in this age group. Our results support performing contrast echocardiography even after 60 years of age, although the optimal secondary prevention therapy in this population remains to be determined in randomized trials.

Introduction: Seclusion or restraint (S/R) are last-resort measures used in psychiatry to ensure the safety of the patient and the staff. However, they have harmful physical and psychological effects on patients, and efforts to limit their use are needed. We describe the characteristics and correlates of S/R events in four Parisian psychiatric centers., Methods: Within a 3-month period, November 5, 2018 to February 3, 2019, we recorded data for patients experiencing an S/R measure as well as characteristics of the measures. We studied the mean duration of a S/R event, the time between hospital admission and the occurrence of the event, as well as correlates of these durations. We also examined factors associated with use of a restraint versus a seclusion measure., Results: For the 233 patients included, we recorded 217 seclusion measures and 64 mechanical restraints. Seclusion measures mostly occurred after the patient's transfer from the emergency department. The duration of a seclusion measure was about 10 days. Patients considered resistant to psychotropic treatments more frequently had a longer seclusion duration than others. The mean duration of a mechanical restraint measure was 4 days. Male sex and younger age were associated with experiencing mechanical restraint., Discussion: S/R measures mostly occur among patients perceived as resistant to psychotropic drugs who are arriving from the emergency department. Developing specific emergency department protocols might be useful in limiting the use of coercive measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dauriac-Le Masson, El-Khoury Lesueur, Lahaye, Launay, Christodoulou, Boiteux, Maman, Bonnemaison, Perquier and Vacheron.)

Background: Clinical remission is a step towards functional remission for subjects with schizophrenia. While recovery is both a subjective personal journey and a clinical outcome to be targeted, data on patient self-rated outcomes are scarce., Objectives: (i) To determine the extent to which the association between clinical and functional remission is mediated by the subjective experience of recovery as reported by patients versus their relatives or their psychiatrist and (ii) to assess differences according to treatment, specifically with oral antipsychotics only versus long-acting injectable antipsychotics (LAIs)., Design: Clinical observational study., Methods: Community-dwelling participants with schizophrenia enrolled in the EGOFORS cohort ( N  = 198) were included. Clinical symptoms and remission were assessed using the Positive and Negative Syndrome Scale. Functional remission was assessed with the Functional Remission of General Schizophrenia Scale. Awareness of recovery was assessed with one question 'What percentage of recovery do you think you have now (from 0% - no recovery - to 100% - full recovery)?', asked of the patient, also of the patient's close relative, and the psychiatrist. We used mediation analyses, taking into account the type of pharmacological treatment., Results: Remission criteria and perceived remission measures were significantly correlated, both within and between groups ( r  > 0.330). The patient's awareness of recovery mediated the relationship between clinical remission and level of functional remission, while the level of recovery according to psychiatrists or close relatives did not. The direct effect of clinical remission on the level of functional remission became non-significant when taking into account the mediator (patients' awareness of recovery) in the group of patients with LAI ( t  = 1.5, p  = 0.150) but not in the group of patients with other treatments ( t  = 3.1, p  = 0.003)., Conclusion: Patients with LAIs may be more efficient in reporting their level of functional remission. Higher patient awareness could be an interesting candidate to explain this. However, as the study was cross-sectional, such a proposal should be tested with a more specifically designed protocol, such as a long-term cohort., Competing Interests: PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Angelini, EISI, Janssen, Lundbeck, Otsuka, Pileje and Merk. The other authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s), 2024.)

Schizophrenia (SZ) is a heterogeneous and debilitating psychiatric disorder with a strong genetic component. To elucidate functional networks perturbed in schizophrenia, we analysed a large dataset of whole-genome studies that identified SNVs, CNVs, and a multi-stage schizophrenia genome-wide association study. Our analysis identified three subclusters that are interrelated and with small overlaps: GO:0007017~Microtubule-Based Process, GO:00015629~Actin Cytoskeleton, and GO:0007268~SynapticTransmission. We next analysed three distinct trio cohorts of 75 SZ Algerian, 45 SZ French, and 61 SZ Japanese patients. We performed Illumina HiSeq whole-exome sequencing and identified de novo mutations using a Bayesian approach. We validated 88 de novo mutations by Sanger sequencing: 35 in French, 21 in Algerian, and 32 in Japanese SZ patients. These 88 de novo mutations exhibited an enrichment in genes encoding proteins related to GO:0051015~actin filament binding ( p = 0.0011) using David, and enrichments in GO: 0003774~transport ( p = 0.019) and GO:0003729~mRNA binding ( p = 0.010) using Amigo. One of these de novo variant was found in CORO1C coding sequence. We studied Coro1c haploinsufficiency in a Coro1c +/- mouse and found defects in the corpus callosum. These results could motivate future studies of the mechanisms surrounding genes encoding proteins involved in transport and the cytoskeleton, with the goal of developing therapeutic intervention strategies for a subset of SZ cases.

Purpose: User-friendly robotic assistance and image-guided tools have been developed in the past decades for intraparenchymal brain lesion biopsy. These two methods are gradually becoming well accepted and are performed at the discretion of the neurosurgical teams. However, only a few data comparing their effectiveness and safety are available., Methods: Population-based parallel cohorts were followed from two French university hospitals with different surgical methods and defined geographical catchment regions (September 2019 to September 2022). In center A, frameless robot-assisted stereotactic intraparenchymal brain lesion biopsies were performed, while image-guided intraparenchymal brain lesion biopsies were performed in center B. Pre-and postoperative clinical, radiological, and histomolecular features were retrospectively collected and compared., Results: Two hundred fifty patients were included: 131 frameless robot-assisted stereotactic intraparenchymal brain lesion biopsies in center A and 119 image-guided biopsies in center B. The clinical, radiological, and histomolecular features were comparable between the two groups. The diagnostic yield (96.2% and 95.8% respectively; p = 1.000) and the overall postoperative complications rates (13% and 14%, respectively; p = 0.880) did not differ between the two groups. The mean duration of the surgical procedure was longer in the robot-assisted group (61.9 ± 25.3 min, range 23-150) than in the image-guided group (47.4 ± 11.8 min, range 25-81, p < 0.001). In the subgroup of patients with anticoagulant and/or antiplatelet therapy administered preoperatively, the intracerebral hemorrhage > 10 mm on postoperative CT scan was higher in the image-guided group (36.8%) than in the robot-assisted group (5%, p < 0.001)., Conclusion: In our bicentric comparative study, robot-assisted stereotactic and image-guided biopsies have two main differences (shorter time but more frequent postoperative hematoma for image-guided biopsies); however, both techniques are demonstrated to be safe and efficient., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Constipation is more common in patients with mental disorders than in the general population. However, its frequency in hospitalized patients, its association with drugs and how teams become aware of it and take care of it are not fully identified., Method: The retrospective study included 141 male and 127 female new patients admitted for routine treatment at France's largest psychiatric hospital between November 15 and December 11, 2017. A physician reviewed electronic medical records to diagnose constipation and record variables of interest: socio-demographic factors, diagnosis, drugs prescribed and taken. We calculated an anticholinergic impregnation score (AIS) for each patient by using a validated French scale. Patients were then classified into two groups by state of constipation defined by the physician. Univariate and multivariate analyses were used to study the frequency of constipation, factors associated with it and its management., Results: The prevalence of constipation was 38% (95% CI 32-44). Associated factors were taking antipsychotics and the burden of anticholinergic treatment. On multiple regression analysis, the only remaining factor was anticholinergic treatment: AIS≥5 was associated with constipation (odds ratio 1.80 [95% CI 1.07-3.14], P=0.027). Only 44.0% of patients were prescribed a preventive laxative, systematically in half of the cases. Above all, only 11.2% were administered this laxative (i.e., 25% of that prescribed). Digestive transit was poorly recorded in the table of constants (34.7%). We found one case of sub-occlusion as a severe case., Conclusion: Constipation is common in psychiatric inpatients. The more the patient is prescribed drugs with a pronounced anticholinergic effect, the greater the risk. Alongside the preventive measures common to all psychiatric patients which must be promoted (concerning diet, physical activity, etc.), polymedication with this type of anticholinergic must be better monitored to prevent complications: prescription and administration of a preventive laxative, monitoring transit in the table of constants. Thus, a better knowledge of the subject and specific training are essential., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Purpose of Review: In this review, we summarize current evidence regarding potential benefits and limitations of using perfusion imaging to estimate presence and extent of irreversibly injured ischemic brain tissue ('core') and severely ischemic yet salvageable tissue ('penumbra') in acute stroke patients with large vessel occlusion (LVO)., Recent Findings: Core and penumbra volumes are strong prognostic biomarkers in LVO patients. Greater benefits of both intravenous thrombolysis and endovascular therapy (EVT) are observed in patients with small core and large penumbra volumes. However, some current definitions of clinically relevant penumbra may be too restrictive and exclude patients who may benefit from reperfusion therapies. Alongside other clinical and radiological factors, penumbral imaging may enhance the discussion regarding the benefit/risk ratio of EVT in common clinical situations, such as patients with large core - for whom EVT's benefit is established but associated with a high rate of severe disability -, or patients with mild symptoms or medium vessel occlusions - for whom EVT's benefit is currently unknown. Beyond penumbral evaluation, perfusion imaging is clinically relevant for optimizing patient's selection for neuroprotection trials., Summary: In an emerging era of precision medicine, perfusion imaging is a valuable tool in LVO-related acute stroke., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Circulating cell-free DNA (cfDNA) holds promise as a rapid and convenient biomarker for identifying individuals with eating disorders. To investigate this hypothesis, we measured plasma cfDNA in patients with different eating disorders., Methods: In this study, 110 participants (98 patients with eating disorders divided into 30 patients with bulimia nervosa, 33 patients with anorexia nervosa (AN) Restricting subtype, 35 patients with AN Binge-eating/purging subtype and 12 controls) were enrolled. We measured both cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) from plasma using two specific droplet digital PCR assays each, referring to two amplicon sizes., Results: Levels of plasma cf-nDNA and cf-mtDNA showed no significant differences between control participants and those with eating disorders. However, we observed a higher proportion of long cf-nDNA fragments in patients with eating disorders, suggesting its potential as a biomarker for eating disorders., Conclusion: This is the first study of cfDNA in patients with eating disorders. Our findings highlight the potential for qualitative exploration of cfDNA, although not of quantitative interest. Full characterization of cfDNA may serve as a valuable biomarker for eating disorders and provide some insights into the hidden mechanisms underlying the chronic development of these conditions. Future studies are needed to confirm or refute this hypothesis., Competing Interests: Declaration of Competing Interest All authors do not report any conflict of interest related to this manuscript. The sources of support did not have any role in the study design, analysis, draft of the manuscript, or the decision to submit for publication., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The 2021 WHO classification of CNS tumors has refined the definition of adult-type diffuse gliomas without 1p19q codeletion. Nevertheless, the aggressiveness of gliomas is based exclusively on histomolecular criteria performed on a limited sample of the tumor. The authors aimed to assess whether the spontaneous radiographic tumor growth rate is associated with tumor aggressiveness and allows preoperative identification of malignancy grade of adult-type diffuse gliomas without 1p19q codeletion., Methods: The authors retrospectively reviewed the records of adult patients harboring a newly diagnosed supratentorial diffuse glioma without 1p19q codeletion, with available preoperative MRI follow-up between January 2008 and April 2022. The spontaneous radiographic tumor growth rate was quantified by tumor volume segmentation and regression of the evolution of the mean tumor diameter over time and was compared with clinical, imaging, histomolecular, and survival data., Results: Ninety-six patients were included. The spontaneous radiographic tumor growth rates (mean 17.8 ± 38.8 mm/year, range 0-243.5 mm/year) significantly varied according to IDH1/2 mutation (p < 0.001), grade of malignancy (p < 0.001), and presence of microvascular proliferation (p < 0.001). The spontaneous radiographic tumor growth rate allowed preoperative identification of high-grade cases: 100% of grade 3 and 4 IDH-mutant diffuse astrocytomas had a spontaneous radiographic tumor growth rate ≥ 8.0 mm/year, and 100% of IDH-wild-type glioblastomas had a spontaneous radiographic tumor growth rate ≥ 42.0 mm/year. A spontaneous radiographic growth rate ≥ 8.0 mm/year was an independent predictor of shorter progression-free (p = 0.014) and overall (p = 0.007) survival. A mitotic count threshold ≥ 4 mitoses was the optimal threshold for identifying aggressive IDH-mutant astrocytomas based on spontaneous radiographic tumor growth., Conclusions: The spontaneous radiographic tumor growth rates could be used as an additional tool to preoperatively screen tumor aggressiveness of adult-type diffuse gliomas without 1p19q codeletion.

KCNQ2 mutations are a common cause of early-onset epileptic syndromes. They are associated with heterogeneous developmental profiles, from mild to severe cognitive and social impairments that need better characterization. We report a case of an inherited KCNQ2 mutation due to a deletion c.402delC in a heterozygous state, in the exon 3 of the KCNQ2 gene. A 5-year-old boy presented a cluster of sudden-onset generalized tonic-clonic seizures at three months of age, after an unremarkable postnatal period. Multiplex ligation-dependent probe amplification identified a familial mutation after an investigation in the family revealed that this mutation was present on the father's side. The patient was diagnosed with autism and intellectual deficiency in a context of KCNQ2 -encephalopathy. We describe his clinical features in light of current literature. This report highlights the importance of appropriate genetic counseling and psychiatric assessment in planning the medical and social follow-up of a disorder with complex socio-behavioral features., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To analyse the performance of arterial spin labelling (ASL) in predicting surgical bleeding in a paediatric cohort of optic pathway glioma (OPG)., Materials and Methods: Preoperative ASL data were obtained for 51 OPG in 40 patients, aged from 9 months to 16 years. The relative cerebral blood flow (rCBF) in the tumour areas with the highest CBF (maximum rCBF) was measured and then correlated with qualitative local bleeding (graded no, moderate, and major by the neurosurgeon) and quantitative global surgical bleeding (assessed in millilitres using haematocrit data)., Results: Intratumoural maximum rCBF was significantly higher when qualitative local bleeding was high (median value in the no, moderate, and major bleeding groups equal to 0.81, 1.39 and 4.22, respectively, p=0.004), but there was no difference in global quantitative bleeding (p=0.7 for the total blood loss). The maximum tumour rCBF cut-off value of 1.1 yielded a sensitivity of 73%, a specificity of 78%, and an accuracy of 76% (39/51 tumours) in detecting haemorrhagic OPG. Choosing a maximum tumour rCBF cut-off value > 1.7 improved the specificity in diagnosing tumours with high bleeding risk with a specificity of 94%, a sensitivity of 53%, and an accuracy of 82% (42/51 tumours)., Conclusion: ASL tumoural rCBF is a useful and simple diagnostic tool to help predict high intraoperative tumoural bleeding risk in paediatric OPG., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: Co-occurrence of Anorexia Nervosa (AN) and borderline personality disorder (BPD) is frequent (8%-40%) and associated with specificities that impact the treatment process. Lifetime history of suicide attempt (HAS), substance use disorder (SUD) and the binge-purging subtype (B-P) might be good markers of such comorbidity. We made the hypothesis that in patients with AN, the presence of HAS, SUD and B-P have sufficient predictive power to efficiently detect an associated BPD comorbidity., Methods: After a case report analysis on a pilot sample of 119 patients with AN, we performed a cross-sectional analysis on a confirmatory sample of 84 patients with AN in a single center specialized in eating disorders systematically assessing HAS, SUD, B-P and BPD using the Mini International Neuropsychiatric Interview for DSM-5 and the Diagnostic Interview for Borderline (DIB-R)., Results: B-P had a 100% negative predictive value, and the combination of SUD plus HAS had a 100% positive predictive value. On a quantitative level, B-P, HAS and SUD were independent explanatory factors of the DIB-R total score., Conclusions: The main limitations were the low number of patients, the single center analyses, the potential overlapping of assessments and the fact that data were exclusively declarative. In this study, every patient with B-P, SUD and HAS had been diagnosed with BPD., (Copyright © 2022 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: The present study aimed to describe the clinical and ultrasound (US) long-term follow-up of patients with transient perivascular inflammation of the carotid artery (TIPIC) syndrome and the risk of recurrence., Methods: We enrolled patients with a definitive diagnosis of TIPIC syndrome who were included in a retrospective multicenter study. These patients were recontacted at least six months after the first TIPIC episode for a clinical and imaging follow-up. Each patient underwent a clinical evaluation through a tailored questionnaire as well as US imaging., Results: Twenty-eight patients were enrolled with a median follow-up of 58.7 months (interquartile range = 8-121). Nineteen out of the 28 patients (67.8%) had residual pain, eight (28.6%) had experienced a clinical recurrence and 12 (42.9%) had a thickening of the carotid wall on US. No patients had neurological complication or other associated diseases., Conclusions: Patients with TIPIC syndrome have often residual pain and recurrence in about one quarter of cases but the long-term follow-up is in favor a benign self-limited pathology. Trial registration: ClinicalTrials.gov (identifier NCT03804112)., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Context: The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization., Methods: We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression., Results: Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians., Conclusion: VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy., Competing Interests: MZ reports a relationship with LivaNova PLC that includes: travel reimbursement. RC reports a relationship with LivaNova PLC that includes: speaking and lecture fees and travel reimbursement. PDo reports a relationship with LivaNova PLC that includes: speaking and lecture fees and travel reimbursement. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aboubakr, Domenech, Heurtebise, Gaillard, Guy-Rubin, Carron, Duriez, Gorwood, Vinckier, Pallud and Zanello.)

Erythroblastic sarcoma (ES) (previously called chloroma or granulocytic sarcoma) are rare hematological neoplams characterized by the proliferation of myeloid blasts at extramedullary sites, and primarily involve the skin and soft tissue of middle-aged adults. ES may be concomitant with or secondary to myeloid neoplasms (mostly acute myeloid leukemia (AML)) or in isolated cases (de novo) without infiltration of the bone marrow by blasts. ES share cytogenetic and molecular abnormalities with AML, including RUNX1T1 fusions. Some of these alterations seem to be correlated with particular sites of involvement. Herein, we report an isolated erythroblastic sarcoma with NFIA::RUNX1T1 located in the central nervous system (CNS) of a 3-year-old boy. Recently, two pediatric cases of CNS MS with complete molecular characterization have been documented. Like the current case, they concerned infants (2 and 3 years-old) presenting a brain tumor (pineal involvement) with leptomeningeal dissemination. Both cases also harbored a NFIA::RUNX1T3 fusion. ES constitutes a diagnostic challenge for neuropathologists because it does not express differentiation markers such as CD45, and may express CD99 which could be confused with CNS Ewing sarcoma. CD43 is the earliest pan-hematopoietic marker and CD45 is not expressed by erythroid lineage cells. E-cadherin (also a marker of erythroid precursors) and CD117 (expressed on the surface of erythroid lineage cells) constitute other immunhistochemical hallmarks of ES. The prognosis of patients with ES is similar to that of other patients with AML but de novo forms seem to have a poorer prognosis, like the current case. To conclude, pediatric ES with NFIA::RUNX1T1/3 fusions seem to have a tropism for the CNS and thus constitute a potential pitfall for neuropathologists. Due to the absence of circulating blasts and a DNA-methylation signature, the diagnosis must currently be made by highlighting the translocation and expression of erythroid markers., (© 2023. The Author(s).)

Pilocytic astrocytomas (PA) typically exhibit distinct clinical, radiological, histopathological, and genetic features. DNA-methylation profiling distinguishes PA according to their location (infratentorial, midline, hemispheric, or spinal). In the hemispheric location, distinguishing PA from glioneuronal tumors remains a common diagnostic challenge for neuropathologists. Furthermore, the current version of the DKFZ classifier seems to have difficulty separating them from gangliogliomas. In this study, after central radiological review, we identified a histopathologically defined set of PA (histPA, n = 11) and a cohort of DNA-methylation defined PA (mcPA, n = 11). Nine out of the 11 histPA matched the methylation class of hemispheric PA, whereas 2 cases were classified at the end of the study as dysembryoplastic neuroepithelial tumors. Similarly, the mcPA cohort contained tumors mainly classified as PA (7/11), but 4 cases were classified as glioneuronal. The analysis of the 16 tumors with an integrated diagnosis of PA revealed that they affect mainly children with a wide spectrum of radiological, histopathological (i.e. a predominantly diffuse growth pattern), and genetic characteristics (large range of mitogen-activated protein kinase alterations). Based on these results, we consider hemispheric PA to be different from their counterparts in other locations and to overlap with other glioneuronal tumors, reinforcing the necessity of interpreting all data to obtain an accurate diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An abundant literature reports on 'sequential effects' observed when humans make predictions on the basis of stochastic sequences of stimuli. Such sequential effects represent departures from an optimal, Bayesian process. A prominent explanation posits that humans are adapted to changing environments, and erroneously assume non-stationarity of the environment, even if the latter is static. As a result, their predictions fluctuate over time. We propose a different explanation in which sub-optimal and fluctuating predictions result from cognitive constraints (or costs), under which humans however behave rationally. We devise a framework of costly inference, in which we develop two classes of models that differ by the nature of the constraints at play: in one case the precision of beliefs comes at a cost, resulting in an exponential forgetting of past observations, while in the other beliefs with high predictive power are favored. To compare model predictions to human behavior, we carry out a prediction task that uses binary random stimuli, with probabilities ranging from 0.05 to 0.95. Although in this task the environment is static and the Bayesian belief converges, subjects' predictions fluctuate and are biased toward the recent stimulus history. Both classes of models capture this 'attractive effect', but they depart in their characterization of higher-order effects. Only the precision-cost model reproduces a 'repulsive effect', observed in the data, in which predictions are biased away from stimuli presented in more distant trials. Our experimental results reveal systematic modulations in sequential effects, which our theoretical approach accounts for in terms of rationality under cognitive constraints., Competing Interests: AP, FM, RA No competing interests declared, (© 2024, Prat-Carrabin et al.)

Background and Objectives: Cerebral venous sinus thrombosis (CVST) after supratentorial craniotomy is a poorly studied complication, for which there are no management guidelines. This study assessed the incidence, associated risk factors, and management of postoperative CVST after awake craniotomy., Methods: This is an observational, retrospective, monocentric analysis of patients who underwent a supratentorial awake craniotomy. Postoperative CVST was defined as a flow defect on the postoperative contrast-enhanced 3D T1-weighted sequence and/or as a T2* hypointensity within the sinus., Results: In 401 supratentorial awake craniotomies (87.3% of diffuse glioma), the incidence of postoperative CVST was 4.0% (95% CI 2.5-6.4): 14/16 thromboses located in the superior sagittal sinus and 12/16 located in the transverse sinus. A venous sinus was exposed during craniotomy in 45.4% of cases, and no intraoperative injury to a cerebral venous sinus was reported. All thromboses were asymptomatic, and only two cases were diagnosed at the time of the first postoperative imaging (0.5%). Postoperative complications, early postoperative Karnofsky Performance Status score, and duration of hospital stay did not significantly differ between patients with and without postoperative CVST. Adjusted independent risk factors of postoperative CVST were female sex (adjusted Odds Ratio 4.00, 95% CI 1.24-12.91, P = .021) and a lesion ≤1 cm to a venous sinus (adjusted Odds Ratio 10.58, 95% CI 2.93-38.20, P < .001). All patients received standard prophylactic-dose anticoagulant therapy, and none received treatment-dose anticoagulant therapy. No thrombosis-related adverse event was reported. All thromboses presented spontaneous sinus recanalization radiologically at a mean of 89 ± 41 days (range, 7-171)., Conclusion: CVST after supratentorial awake craniotomy is a rare event with satisfactory clinical outcomes and spontaneous sinus recanalization under conservative management without treatment-dose anticoagulant therapy. These findings are comforting to neurosurgeons confronted with postoperative MRI reports suggesting CVST., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults., Methods: We performed an observational, retrospective, single-center cohort study at a tertiary surgical neuro-oncological center between January 2006 and December 2021., Results: One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142)., Conclusion: In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited., Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window., Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset)., Data Sources and Methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs)., Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01-1.36; I 2  = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94-1.17; I 2  = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92-1.40; I 2  = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70-4.00; I 2  = 0%), any ICH (RR = 1.08; 95% CI = 0.90-1.29; I 2  = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81-1.49; I 2  = 0%) were similar between the groups., Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported., Trial Registration: PROSPERO registration ID: CRD42023448707., (© The Author(s), 2024.)

Background: Borderline personality disorder is often associated with self-injurious behaviors that cause personal suffering, family distress, and substantial medical costs. Mental health hotlines exist in many countries and have been shown to be effective in some contexts, but none have been specifically designed for borderline patients. The aim of the present study is to evaluate the impact of a 24/7 hotline dedicated to patients with borderline personality disorder on suicide attempts and self-injurious behaviors., Methods: We conducted a single-blind, multicenter (9 French centers) clinical trial with stratified randomization (by age, sex and center). Patients ( N  = 315) with a diagnosis of borderline personality disorder (according to the SIDP-IV) were randomized into two groups with or without access to the hotline in addition to treatment as usual. The number of suicide attempts and self-injurious behaviors in each group within 12 month were analyzed in the "per protocol" population (Student's t -tests, 5% significance threshold), adjusting for possible confounders in a multivariate analysis (using Poisson regression). The percentage of patients with suicide attempts and with self-injurious behaviors (and other percentages) were analyzed in the per protocol population (χ 2 -tests or exact Fischer tests, 5% significance threshold)., Results: The mean number of suicide attempts was 3 times lower in the hotline group (0.41 vs. 1.18, p  = 0.005) and the mean number of self-injurious behaviors was 9 times lower (0.90 vs. 9.5, p  = 0.006). Multivariate analysis confirmed the effectiveness of the hotline in reducing suicide attempts and self-harm., Conclusion: This study supports the effectiveness of hotlines in reducing self-aggressive behavior in patients with borderline personality disorder. Such support is easy to use, cheap and flexible, and therefore easy to implement on a large scale., Competing Interests: PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Angelini, EISAI, Janssen, Lundbeck, Otsuka, Richter, Merk and Viatris. AP-S received during the last 5 years fees for presentations at congresses or participation in scientific boards from Gilead and Abbvie. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Buronfosse, Robin, Speranza, Duriez, Silva, Corcos, Perdereau, Younes, Cailhol, Gorwood and Pham-Scottez.)

Cardioembolic stroke is a major cause of morbidity, with a high risk of recurrence, and anticoagulation represents the mainstay of secondary stroke prevention in most patients. The implementation of endovascular treatment in routine clinical practice complicates the decision to initiate anticoagulation, especially in patients with early hemorrhagic transformation who are considered at higher risk of hematoma expansion. Late hemorrhagic transformation in the days and weeks following stroke remains a potentially serious complication for which we still do not have any established clinical or radiological prediction tools. The optimal time to initiate therapy is challenging to define since delaying effective secondary prevention treatment exposes patients to the risk of recurrent embolism. Consequently, there is clinical equipoise to define and individualize the optimal timepoint to initiate anticoagulation combining the lowest risk of hemorrhagic transformation and ischemic recurrence in cardioembolic stroke patients. In this narrative review, we will highlight and critically outline recent observational and randomized relevant evidence in different subtypes of cardioembolic stroke with a special focus on anticoagulation initiation following endovascular treatment. We will refer mainly to the commonest cause of cardioembolism, non-valvular atrial fibrillation, and examine the possible risk and benefit of anticoagulation before, during, and shortly after the acute phase of stroke. Other indications of anticoagulation after ischemic stroke will be briefly discussed. We provide a synthesis of available data to help clinicians individualize the timing of initiation of oral anticoagulation based on the presence and extent of hemorrhagic transformation as well as stroke severity.

We report a 20-year-old female patient (76 Kg/164 cm) with an extra-cardiac Fontan circulation who was referred to our institution for exertional dyspnoea and desaturation. The patient was diagnosed with a large calcified thrombus at the level of the Fontan fenestration, protruding inside the lumen of the conduit and reducing the diameter by half with a 3 mmHg pressure gradient. Transcatheter stent expansion of the obstructed extra-cardiac conduit was done with a 48 mm long XXL PTFE-covered Optimus-CVS® under temporary cerebral embolic protection with a TriGUARD-3™ deflection filter device (Keystone Heart). There was no procedural complication and the 3 months clinical outcomes are good.

Introduction and Methods: We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers., Results: These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers' data are close to physicians' data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age, and age at first words., Discussion: Each of the two datasets provides complementary knowledge. We confirmed that symptoms are similar to those in the literature and provides more details on feeding difficulties. Caregivers considered that the symptom attention-deficit/hyperactivity disorder were most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention-deficit/hyperactivity disorder, anxiety, and sleep disorders need to be treated., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs., Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion., Methods and Design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial., Study Outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted., Sample Size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation., Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia., Trial Registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The reported incidence of persistent hypoperfusion despite complete recanalization as surrogate for impaired microvascular reperfusion (IMR) has varied widely among clinical studies, possibly due to differences in i) definition of complete recanalization, with only recent Thrombolysis in Cerebral Infarction (TICI) grading schemes allowing distinction between complete (TICI3) and partial recanalization with distal occlusions (TICI2c); ii) operational definition of IMR; and iii) consideration of potential alternative causes for hypoperfusion, notably carotid stenosis, re-occlusion and post-thrombectomy hemorrhage. We performed a systematic review to identify clinical studies that carried out brain perfusion imaging within 72 hrs post-thrombectomy for anterior circulation stroke and reported hypoperfusion rates separately for TICI3 and TICI2c grades. Authors were contacted if this data was missing. We identified eight eligible articles, altogether reporting 636 patients. The incidence of IMR after complete recanalization (i.e., TICI3) tended to decrease with the number of considered alternative causes of hypoperfusion: range 12.5-42.9%, 0-31.6% and 0-9.1% in articles that considered none, two or all three causes, respectively. No study reported the impact of IMR on functional outcome separately for TICI-3 patients. Based on this systematic review, IMR in true complete recanalization appears relatively rare, and reported incidence highly depends on definition used and consideration of confounding factors., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients' anxiety on intensive care unit (ICU) admission is associated with subsequent deterioration., Objective: To assess whether patients' fears/anxiety are predictive of new organ failure within 7 days of ICU admission., Methods: In a prospective 3-center cohort study of non-comatose patients without delirium or invasive mechanical ventilation, 9 specific fears were evaluated through yes/no questions. Illness severity was assessed using the Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA). Intensity of acute and chronic anxiety was assessed with the state and trait components of the State-Trait Anxiety Inventory (STAI). Patients were followed up for 7 days., Results: From April 2014 to December 2017, 373 patients (median [IQR] age, 63 [48-74] years; 152 [40.8%] women; median (IQR) SAPS II, 27 [19-37]) were included. Feelings of vulnerability and fear of dying were reported by 203 (54.4%) and 172 (46.1%) patients, respectively. The STAI-State score was 40 or greater in 192 patients (51.5%). Ninety-four patients (25.2%) had new organ failure. Feelings of vulnerability (odds ratio, 1.96 [95% CI, 1.12-3.43]; P=.02) and absence of fear of dying (odds ratio, 2.38 [95% CI, 1.37-4.17]; P=.002) were associated with new organ failure after adjustment for STAI-State score (≥40), SAPS II, and SOFA score., Conclusion: Absence of fear of dying is associated with new organ failure within the first 7 days after ICU admission. Fear of dying may protect against subsequent deterioration by mobilizing patients' homeostatic resources. ClinicalTrials.gov Identifier: NCT02355626., (©2024 American Association of Critical-Care Nurses.)

Aim: Social and role functioning impairments characterize patients along the schizophrenia spectrum, but the existing evaluations tools do not specifically address younger population issues. The Global Functioning Social (GF:S) and Global Functioning Role (GF:R) scales have been specifically designed for that purpose. The aim of this study is to establish the reliability and concurrent validity of the French version of GF:S and GF:R scales., Methods: The two scales GF: Social (GF:S) and Role (GF:R) have first been translated into French and independently back translated and validated by the original authors. Between March 2021 and March 2022, we enrolled 51 participants (20.3 ± 3.7 years old; female = 22/51) amongst help-seekers referring to two different early mental health services in the Île-de-France. In an ecological design, participants met different diagnoses, 7 (13.7%) met the criteria for Ultra-High Risk of psychosis (UHR) using CAARMS criteria., Results: Inter-rater reliability was excellent for scores related to the past month and to the higher levels of functioning over the past year. Both scales showed good to excellent concurrent validity as measured by correlation with the Social and Occupational Functioning Assessment Scale (SOFAS) and the Personal and Social Performance Scale (PSP)., Conclusion: Overall, this study confirms the reliability and validity of the French version of the GF:S and GF:R scales. The use of these scales may improve the evaluation of social and occupational functioning in French-speaking young help-seekers, in a transdiagnostic approach, both in clinical and research settings., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors., Methods: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay., Results: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses., Conclusion: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Diffuse midline gliomas (DMG) H3 K27-altered are incurable grade 4 gliomas and represent a major challenge in neuro-oncology. This tumour type is now classified in four subtypes by the 2021 edition of the WHO Classification of the Central Nervous System (CNS) tumours. However, the H3.3-K27M subgroup still appears clinically and molecularly heterogeneous. Recent publications reported that rare patients presenting a co-occurrence of H3.3K27M with BRAF or FGFR1 alterations tended to have a better prognosis. To better study the role of these co-driver alterations, we assembled a large paediatric and adult cohort of 29 tumours H3K27-altered with co-occurring activating mutation in BRAF or FGFR1 as well as 31 previous cases from the literature. We performed a comprehensive histological, radiological, genomic, transcriptomic and DNA methylation analysis. Interestingly, unsupervised t-distributed Stochastic Neighbour Embedding (tSNE) analysis of DNA methylation profiles regrouped BRAF V600E and all but one FGFR1 MUT DMG in a unique methylation cluster, distinct from the other DMG subgroups and also from ganglioglioma (GG) or high-grade astrocytoma with piloid features (HGAP). This new DMG subtype harbours atypical radiological and histopathological profiles with calcification and/or a solid tumour component both for BRAF V600E and FGFR1 MUT cases. The analyses of a H3.3-K27M BRAF V600E tumour at diagnosis and corresponding in vitro cellular model showed that mutation in H3-3A was the first event in the oncogenesis. Contrary to other DMG, these tumours occur more frequently in the thalamus (70% for BRAF V600E and 58% for FGFR1 MUT ) and patients have a longer overall survival with a median above three years. In conclusion, DMG, H3 K27 and BRAF/FGFR1 co-altered represent a new subtype of DMG with distinct genotype/phenotype characteristics, which deserve further attention with respect to trial interpretation and patient management., (© 2023. The Author(s).)

In response to repulsive cues, axonal growth cones can quickly retract. This requires the prompt activity of contractile actomyosin, which is formed by the non-muscle myosin II (NMII) bound to actin filaments. NMII is a molecular motor that provides the necessary mechanical force at the expense of ATP. Here, we report that this process is energetically coupled to glycolysis and is independent of cellular ATP levels. Induction of axonal retraction requires simultaneous generation of ATP by glycolysis, as shown by chemical inhibition and genetic knock-down of GAPDH. Co-immunoprecipitation and proximal-ligation assay showed that actomyosin associates with ATP-generating glycolytic enzymes and that this association is strongly enhanced during retraction. Using microfluidics, we confirmed that the energetic coupling between glycolysis and actomyosin necessary for axonal retraction is localized to the growth cone and near axonal shaft. These results indicate a tight coupling between on-demand energy production by glycolysis and energy consumption by actomyosin contraction suggesting a function of glycolysis in axonal guidance., (© 2023 Santos et al.)

Background: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability., Methods: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) before each esketamine administration. Latent class analyses were used to define trajectories of response., Results: In the original sample (N = 50), we identified two classes whose trajectories depicted response and non-response, respectively. The model was validated in the confirmatory sample (N = 55). Class membership was influenced by a few baseline characteristics such as concomitant benzodiazepine medication, number of depressive episodes or polarity. On the other hand, after only two esketamine administrations, the MADRS score predicted the 90-day trajectory of response with an accuracy of 80 %., Limitations: This observational study is not placebo-controlled. Therefore, its results and their generalizability need to be confirmed in experimental settings., Conclusions: After the first administrations of esketamine, the MADRS score has a good capacity to predict the most plausible trajectory of response. While thresholds and their predictive values need to be confirmed, this finding suggests that clinicians could base on MADRS scores their decision to discontinue treatment because of poor remaining chances of treatment response., Competing Interests: Declaration of competing interest PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Angelini, Janssen, Lundbeck, Otsuka and Viatris. ACP and PM received fees for presentations and congress participation from Janssen. RP has been invited by Janssen to a congress. LM has received honoraria or consulting fees from Bristol-Meyers-Squibb, Janssen, Servier, Lilly and Otsuka. RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche, SOBI, and Takeda, has served as a consultant and/or speaker for AstraZeneca, Boehringer Ingelheim, Pierre Fabre, Lilly, Lundbeck, LVMH, MAPREG, Novartis, Otsuka, Pileje, SANOFI, and Servier and received compensation. He has also received research support from Servier. FV has been invited to scientific meetings, consulted and/or served as a speaker, and received compensation from Lundbeck, Servier, Recordati, Janssen, Otsuka, LivaNova, Chiesi, and Rovi. He has received research support from LivaNova and Lundbeck. Other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD., Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system., Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD., Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)., Competing Interests: Dr. Choi has received an honorarium from Depression and Anxiety for service as Deputy Editor. Dr. Raffield has served as a consultant for the TOPMed Administrative Coordinating Center (through Westat). Dr. Andreassen has received speaking honoraria from Janssen, Lundbeck, and Sunovion, and he has served as a consultant for Cortechs.ai and HealthLytix. Dr. Frey has received research support from MediPharm and Janssen. Dr. Grigoriadis has received royalties from the Canadian Pharmacists Association, Norton, and UpToDate. Dr. Jones has received grant funding from Takeda and Akrivia health. Dr. Kennedy has served as a scientific advisory board member for Myriad Neuroscience. Dr. McIntosh has served as a speaker for Illumina and Janssen. Dr. Munk-Olsen has served as a speaker for Lundbeck. Dr. Rubinow has received research funding from the Buszucki Foundation, NIH, and Sage Therapeutics; he serves on scientific advisory boards for the Foundation of Hope, Sage Therapeutics, and Sensorium Therapeutics and on clinical advisory boards for EmbarkNeuro and Felicity Pharma; he has served as a consultant for Aldeyra Therapeutics, Arrivo Bioventures, Brii Biosciences, and GH Research–Ireland; and he has stock options from Sage Therapeutics and Sensorium Therapeutics. Dr. Skalkidou has served as a consultant for Biogen; she receives compensation for lectures and organization of courses in reproductive endocrinology; and she is a shareholder and serves on the board of Svensk Telepsykiatri. Dr. Smoller has served on a scientific advisory board for Sensorium Therapeutics; he has received grant support from Biogen; and he is principal investigator of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe, for which 23andMe provides analysis time as in-kind support but no payments. Dr. Stein has received personal fees from Discovery Vitality, Johnson & Johnson, Kanna, L'Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. Dr. Stowe has served on scientific advisory boards for Sage Therapeutics and Reunion Neuroscience. Dr. Taylor has given a lecture for AbbVie. Dr. Vigod has received royalties from UpToDate. Dr. Zar has received funding from the Bill and Melinda Gates Foundation. Dr. Meltzer-Brody has received sponsored research grant funding from Sage Therapeutics; she has served as a consultant for EmbarkNeuro and the Neuroscience Education Institute; and she serves as a professional corporation owner for Modern Health. Dr. Sullivan has served as an adviser for, and is a shareholder in, Neumora Therapeutics. The other authors report no financial relationships with commercial interests.

Background and Purpose: The best management of acute ischemic stroke patients with a minor stroke and large vessel occlusion is still uncertain. Specific clinical and radiological data may help to select patients who would benefit from endovascular therapy (EVT). We aimed to evaluate the relevance of National Institutes of Health Stroke Scale (NIHSS) subitems for predicting the potential benefit of providing EVT after intravenous thrombolysis (IVT; "bridging treatment") versus IVT alone., Methods: We extracted demographic, clinical, risk factor, radiological, revascularization and outcome data of consecutive patients with M1 or proximal M2 middle cerebral artery occlusion and admission NIHSS scores of 0-5 points, treated with IVT ± EVT between May 2005 and March 2021, from nine prospectively constructed stroke registries at seven French and two Swiss comprehensive stroke centers. Adjusted interaction analyses were performed between admission NIHSS subitems and revascularization modality for two primary outcomes at 3 months: non-excellent functional outcome (modified Rankin Scale score 2-6) and difference in NIHSS score between 3 months and admission., Results: Of the 533 patients included (median age 68.2 years, 46% women, median admission NIHSS score 3), 136 (25.5%) initially received bridging therapy and 397 (74.5%) received IVT alone. Adjusted interaction analysis revealed that only facial palsy on admission was more frequently associated with excellent outcome in patients treated by IVT alone versus bridging therapy (odds ratio 0.47, 95% confidence interval 0.24-0.91; p = 0.013). Regarding NIHSS difference at 3 months, no single NIHSS subitem interacted with type of revascularization., Conclusions: This retrospective multicenter analysis found that NIHSS subitems at admission had little value in predicting patients who might benefit from bridging therapy as opposed to IVT alone. Further research is needed to identify better markers for selecting EVT responders with minor strokes., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Detection of deviant stimuli is crucial to orient and adapt our behavior. Previous work shows that deviant stimuli elicit phasic activation of the locus coeruleus (LC), which releases noradrenaline and controls central arousal. However, it is unclear whether the detection of behaviorally relevant deviant stimuli selectively triggers LC responses or other neuromodulatory systems (dopamine, serotonin, and acetylcholine). We combine human functional MRI (fMRI) recordings optimized for brainstem imaging with pupillometry to perform a mapping of deviant-related responses in subcortical structures. Participants have to detect deviant items in a "local-global" paradigm that distinguishes between deviance based on the stimulus probability and the sequence structure. fMRI responses to deviant stimuli are distributed in many cortical areas. Both types of deviance elicit responses in the pupil, LC, and other neuromodulatory systems. Our results reveal that the detection of task-relevant deviant items recruits the same multiple subcortical systems across computationally different types of deviance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Quantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis?, Methods: This prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) (N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease., Discussion: This transdiagnostic longitudinal case-control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers., Trial Registration: ClinicalTrials.gov Identifier NCT06045897., (© 2023. The Author(s).)

Purpose: The present study aimed to explore the implicit associations between food and bodily stimuli in patients with anorexia nervosa (AN) and control subjects (HC)., Methods: A Go/No-Go Association Task was administrated to 55 participants (28 AN and 27 HC), using food stimuli (low-calorie food vs. high-calorie food) and body stimuli (underweight vs. overweight bodies)., Results: We evidenced an implicit association between food and body stimuli in the AN group, whereas the HC group only showed a tendency. AN and HC groups also exhibited different categorization strategies: the AN group tended to categorize stimuli as low-calorie foods and underweight bodies less than the HC group, and they tended to categorize stimuli as high-calorie foods and overweight bodies more than the HC group., Conclusion: The present study revealed for the first time specificities of the AN population's implicit association between food and body stimuli in terms of association strength and categorization strategy. Furthermore, the results suggest that combining implicit methodologies with other methods could contribute to a better characterization of the physiopathology of AN., Level of Evidence: Level I, experimental study., (© 2023. The Author(s).)

In anorexia nervosa, physical and psychological vulnerability confines the sufferer to the confines of his or her pathology. The physical body is the first victim of undernutrition, but also the first resource for restoring the psychic and emotional body. Reduced food intake has repercussions on cognition and affect, all of which affect relational capacities. Accompanying, understanding and caring for people means reaching out to them and their bodies, to re-establish the link between what has been broken, and to establish a relationship of trust with them., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: Brain-derived neurotrophic factor (BDNF) levels vary in various conditions including alcohol use disorder (AUD). We aimed to identify drivers of these variations., Methods: Twelve patients with AUD were assessed at hospitalisation for alcohol withdrawal and four months later. We looked for associations between the change in serum BDNF levels and (1) length of abstinence, (2) anxiety (Hamilton Anxiety Scale) and depression (Beck-Depression Inventory), (3) one functional BDNF genotype (rs6265) and (4) methylation levels of 12 CpG sites within the BDNF gene (located in exons I, IV and IX)., Results: While abstinence remained, serum BDNF level increased. This increase correlated with the variation of methylation levels of the BDNF gene, and more specifically of exon I. We found no significant effect of length of abstinence, rs6265, depression or anxiety on serum BDNF level., Conclusions: Epigenetic regulation of the BDNF gene may be involved in variations of BDNF blood level associated with alcohol abstinence.

For the past decade, ketamine, an N-methyl-D-aspartate receptor (NMDAr) antagonist, has been considered a promising treatment for major depressive disorder (MDD). Unlike the delayed effect of monoaminergic treatment, ketamine may produce fast-acting antidepressant effects hours after a single administration at subanesthetic dose. Along with these antidepressant effects, it may also induce transient dissociative (disturbing of the sense of self and reality) symptoms during acute administration which resolve within hours. To understand ketamine's rapid-acting antidepressant effect, several biological hypotheses have been explored, but despite these promising avenues, there is a lack of model to understand the timeframe of antidepressant and dissociative effects of ketamine. In this article, we propose a neurocomputational account of ketamine's antidepressant and dissociative effects based on the Predictive Processing (PP) theory, a framework for cognitive and sensory processing. PP theory suggests that the brain produces top-down predictions to process incoming sensory signals, and generates bottom-up prediction errors (PEs) which are then used to update predictions. This iterative dynamic neural process would relies on N-methyl-D-aspartate (NMDAr) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic receptors (AMPAr), two major component of the glutamatergic signaling. Furthermore, it has been suggested that MDD is characterized by over-rigid predictions which cannot be updated by the PEs, leading to miscalibration of hierarchical inference and self-reinforcing negative feedback loops. Based on former empirical studies using behavioral paradigms, neurophysiological recordings, and computational modeling, we suggest that ketamine impairs top-down predictions by blocking NMDA receptors, and enhances presynaptic glutamate release and PEs, producing transient dissociative symptoms and fast-acting antidepressant effect in hours following acute administration. Moreover, we present data showing that ketamine may enhance a delayed neural plasticity pathways through AMPAr potentiation, triggering a prolonged antidepressant effect up to seven days for unique administration. Taken together, the two sides of antidepressant effects with distinct timeframe could constitute the keystone of antidepressant properties of ketamine. These PP disturbances may also participate to a ketamine-induced time window of mental flexibility, which can be used to improve the psychotherapeutic process. Finally, these proposals could be used as a theoretical framework for future research into fast-acting antidepressants, and combination with existing antidepressant and psychotherapy., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)