Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder.

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Default mode network electrophysiological dynamics and causal role in creative thinking.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. The present study employs stereo-electroencephalography in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.

Endoscopic port access resection of left atrial myxoma: Clinical outcomes and a single surgeon's learning curve experience.

Objectives: To evaluate the safety and efficacy of the port access approach for left atrial (LA) myxoma resection and to analyze the learning curve for this procedure. Methods: Thirty-six consecutive patients with LA myxoma who underwent port access surgery between April 2018 and March 2023 were enrolled in this retrospective study. The procedure included (1) unilateral or bilateral femoral artery cannulation; (2) the use of three 5-mm trocars and a 20- to 30-mm port; (3) a transseptal, biatrial, or LA approach depending on the location of the tumor base; and (4) complete or subendocardial tumor resection. CUSUM analysis was used to evaluate the aortic cross-clamp (ACC) time and cardiopulmonary bypass (CPB) time learning curves. Variables among the learning curve phases were compared. Results: The average ACC and CPB times were 49 (range, 45-79) minutes and 127 (range, 120-164) minutes, respectively. There was 1 case of conversion to sternotomy due to aortic root bleeding and 1 case of unilateral pulmonary edema. CUSUMACCtime analysis included 3 phases: phase I, the initial learning period (cases 1-11); phase II, the technical competence period (cases 12-23); and phase III, the challenging period (cases 24-36). Conclusions: The port access approach is safe and feasible for LA myxoma resection. According to the learning curve analysis, 11 cases are required to achieve technical competence, and 23 cases are required to address highly challenging cases.

Clinical outcomes of stereotactic biopsy on children with pontine diffuse midline glioma.

INTRODUCTION: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course. METHODS: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed. We assessed demographic, clinical, radiographic, surgical, and follow-up data. RESULTS: 25 patients were included; 18 (72%) underwent biopsy while 7 (28%) declined. 12 biopsies (67%) were performed with robotic arm and 5 (27%) with frameless stereotaxy. Three biopsied patients (17%) experienced new post-operative neurologic deficits (1 facial palsy, 1 VI nerve palsy and 1 ataxia) that all resolved at 2-week follow-up. All biopsies yielded diagnostic tissue. Fourteen patients (78%) had H3K27M mutation. Median OS for H3K27M patients was 10 months compared to 11 months in the wild-type patients (p = 0.30, log-rank test). Median OS for patients enrolled in clinical trials was 12 months compared to 8 months for non-trial patients (p = 0.076). CONCLUSION: In our series, stereotactic pontine DMG biopsies did not carry any permanent deficit or complication and yielded diagnostic tissue in all patients. Similar post-operative course was observed in both robot-assisted and frameless stereotactic approaches. There was no significant difference in survival based on mutation status or clinical trial enrollment.

Totally Endoscopic Atrial Septal Defect Repair on Beating Heart: Clinical Outcome and Single-Surgeon Learning Curve Experience.

OBJECTIVE: To evaluate the safety and efficacy of the Hanoi ASD procedure, which is totally endoscopic surgery for atrial septal defect (ASD) repair on beating heart. In addition, the present study also aimed to analyze the learning curve for this procedure. METHODS: From May 2016 to February 2023, 198 consecutive ASD patients weighing ≥20 kg were enrolled in the retrospective study. The Hanoi ASD procedure includes (1) unilateral or bilateral femoral arterial cannulation; (2) two or three 5 mm trocars and a 15 mm port; (3) ASD repair on beating heart, preventing air embolism with CO2 insufflation and keeping the left atrium full of blood; and (4) not snaring the inferior vena cava. Cumulative sum (CUSUM) analysis was used to evaluate the cardiopulmonary bypass (CPB) and operation time learning curves. Variables among the learning curve phases were compared. RESULTS: The CPB and operation times were 90 (72 to 115) min and 180 (150 to 220) min, respectively. Total drainage volume was 190 (120 to 290) mL. No endoscopic failure or major complications were complications were excluding factors causing bias, the CUSUMCPBtime analysis for the remaining 131 patients included 3 phases. Phase 1 was the initial learning period (cases 1 to 34), phase 2 represented the technical competence period (cases 35 to 54), and phase 3 was the challenging period (cases 55 to 131). CONCLUSIONS: The Hanoi ASD procedure is safe and feasible for repairing ASD in patients weighing ≥20 kg. According to the learning curve analysis, 34 cases were required to achieve technical efficiency, and 54 cases were required to address highly challenging cases.

Astrocyte Reactivity and Neurodegeneration in the Female Rat Brain Following Alcohol Dependence.

Recent evidence suggests that alcohol use disorder (AUD) may manifest itself differently in women compared to men. Women experience AUDs on an accelerated timeline and may have certain regional vulnerabilities. In male rats, neuronal cell death and astrocyte reactivity are noted following induction of alcohol dependence in an animal model of an AUD. However, the regional and temporal patterns of neurodegeneration and astrocyte reactivity have yet to be fully examined in females using this model. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by different periods of abstinence. Histological markers for FluoroJade B, a label of degenerating neurons, and vimentin, a marker for reactive astrocytes, were utilized. The expression of these markers in cortical and limbic regions was quantified immediately after their last dose (e.g., T0), or 2, 7, and 14 days later. Significant neuronal cell death was noted in the entorhinal cortex and the hippocampus, similar to previous reports in males, but also in several cortical regions not previously observed. Vimentin immunoreactivity was noted in the same regions as previously reported, in addition to three novel regions. Vimentin immunoreactivity also occurred at earlier and later time points in some cortical and hippocampal regions. These data suggest that both neuronal cell death and astrocyte reactivity could be more widespread in females compared to males. Therefore, this study provides a framework for specific regions and time points which should be examined in future studies of alcohol-induced damage that include female rats.

Totally Endoscopic Surgery for Repairing Sinus Venosus Atrial Septal Defect Using Double-Patch Technique on Beating Heart.

OBJECTIVE: Minimally invasive cardiac surgery has not been widely applied in repairing sinus venosus atrial septal defect (SV-ASD). Most were minithoracotomy using the single-patch technique for patients with anomalous pulmonary veins (APVs) connecting to the superior vena cava-right atrium (SVC-RA) junction. It is unclear whether patients with APVs draining high to the SVC can be repaired safely and effectively through port access. METHODS: From May 2019 to October 2022, 11 consecutive SV-ASD patients with APVs connecting high to the SVC were enrolled in this prospective study. One 12 mm port and 2 trocars (5.5 mm and 10 mm) were established. The pleural and pericardial spaces were filled with CO2. The SVC was snared just below the azygos vein. The RA incision was longitudinally extended along the SVC-RA junction to the SVC. The bovine pericardial patches were used to redirect the APV flow to the left atrium through the ASD and to enlarge the SVC and the SVC-RA junction. RESULTS: There were no early or late deaths and no reoperations. The concomitant procedures included 5 patients (45.5%) with patent foramen ovale closure, 2 with ASD extension, and 3 with tricuspid valve repair. No endoscopic failure was recorded. The average cardiopulmonary bypass and operative times were 96 (23) min and 190 (30) min, respectively. No cases of venous stenosis or sinus node dysfunction were noted during follow-up of 16.4 ± 12.2 months. CONCLUSIONS: SV-ASD with the APVs draining high to the SVC could be repaired safely and effectively through port access with a double-patch technique.

Management strategies of unanticipated intracranial stenosis during mechanical thrombectomy for acute stroke: A survey of academic neurointerventionalists.

BACKGROUND: The optimal approach to the management of intracranial atherosclerotic disease (ICAD) at the time of mechanical thrombectomy (MT) for large vessel occlusion (LVO) remains controversial. The goal of this study is to characterize current practices concerning this challenging clinical situation in a survey of practicing neurointerventionalists. METHODS: An electronic questionnaire was sent to a cross-section of North American academic neurointerventionalists using publicly available contact information and departmental websites. Prior to analysis, responses were anonymized and categorized by region. RESULTS: A total of 136/360 responses were recorded from the U.S. and Canada. The mean number of years of practicing as a neurointerventionalist among the respondents was 10.5 (± 6.2 years). ICAD was perceived as a causative factor during MT for LVO in 5-10% of thrombectomy cases. The most common first-line treatment approach for significant ICAD, assuming a TICI 2b or better reperfusion, was medical therapy (77.9% of respondents), followed by angioplasty + stent placement (8.8% of respondents). There were no significant differences in the first line treatment of ICAD in LVO between geographical regions (p = 0.815). CONCLUSION: The approach to underlying ICAD in LVO varies widely; however, the majority of neurointerventionalists prefer medical therapy with DAPT as a first-line treatment approach. The current survey highlights the need for studies that better define the optimal timing and modality of treatment, along with an evidence-based framework for balancing the risks associated with these treatment approaches.

Intermediate-Term Outcomes of Totally Endoscopic Atrial Septal Defect Repair on Beating Heart in Small Children.

Objective: Manipulation in a narrow surgical field and risks of femoral arterial (FA) complications are difficulties when applying totally endoscopic surgery (TES) for congenital heart disease in small children. This study was conducted to investigate the feasibility of TES for atrial septal defect (ASD) repair in children weighing 13 to 20 kg. Methods: From July 2016 to July 2021, 14 patients with a mean age of 5.4 ± 2.2 years and mean weight of 15.57 ± 2.39 kg (range, 13 to 20 kg), underwent TES for ASD repair on the beating heart. FA cannulation was established through a Dacron graft. An additional FA cannula (2 to 4 Fr smaller than the expected size) was placed into the left FA in case of increasing arterial pressure. Three 5 or 5.5 mm trocars and one 12 mm port were used. The surgical field was filled with CO2. No aortic clamp, no aortic root needle, and no snaring of the inferior vena cava were used. The mean follow-up time was 37.9 ± 12.5 months. Results: Cardiopulmonary bypass (CPB) installation time, CPB time, and operation time were 42.6 ± 16.5 min, 113.1 ± 33.1 min, and 209.6 ± 50.6 min, respectively. Total drainage volume was 125.4 ± 89.2 mL. Patients did not need analgesics on day 4 or 5 after surgery. No severe complications, including arterial complications, were recorded during follow-up. Conclusions: By optimizing the surgical field and setting the FA cannula correctly, TES for ASD closure is feasible in small children weighing between 13 and 20 kg.

Prolonged deprivation of arginine or leucine induces PI3K/Akt-dependent reactivation of mTORC1.

The mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase complex that promotes anabolic processes including protein, lipid, and nucleotide synthesis, while suppressing catabolic processes such as macroautophagy. mTORC1 activity is regulated by growth factors and amino acids, which signal through distinct but integrated molecular pathways: growth factors largely signal through the PI3K/Akt-dependent pathway, whereas the availabilities of amino acids leucine and arginine are communicated to mTORC1 by the Rag-GTPase pathway. While it is relatively well described how acute changes in leucine and arginine levels affect mTORC1 signaling, the effects of prolonged amino acid deprivation remain less well understood. Here, we demonstrate that prolonged deprivation of arginine and/or leucine leads to reactivation of mTORC1 activity, which reaches activation levels similar to those observed in nutrient-rich conditions. Surprisingly, we find that this reactivation is independent of the regeneration of amino acids by canonical autophagy or proteasomal degradation but is dependent on PI3K/Akt signaling. Together, our data identify a novel crosstalk between the amino acid and PI3K/Akt signaling pathways upstream of mTORC1. These observations extend our understanding of the role of mTORC1 in growth-related diseases and indicate that dietary intervention by removal of leucine and/or arginine may be an ineffective therapeutic approach.

Totally Endoscopic Resection of Right Atrial Diverticulum: A Case Report.

Right atrial diverticulum is a rare congenital heart defect with only about 30 cases reported. Surgery is the main method of treatment and is indicated when the patients have signs of right heart compression. In this study, we report the case of a 43-year-old male patient who was diagnosed with massive right atrial diverticulum. This patient was the first case who underwent successful repair by totally endoscopic surgery on the beating heart.

Totally endoscopic atrial septal defect repair in a patient with interrupted inferior vena cava with azygos-hemiazygos continuation.

Atrial septal defect combined with interrupted inferior vena cava (IVC), which is a rare condition, makes it impossible to apply totally endoscopic surgery (TES). The most difficulty is how to drain blood from the posthepatic segment of the IVC. In this study, we report a case of a 44-year-old female patient who was diagnosed with secundum atrial septal defect combined with interrupted IVC with azygos-hemiazygos continuation. This patient underwent successful repair by TES with transthoracic cannulation for the posthepatic segment of the IVC.

Congenital coronary vein aneurysm: A case report.

A 61-year-old female patient with chest pain was diagnosed with localized pericardial effusion, resistance to medical therapy. Cardiac magnetic resonance imaging revealed a massive aneurysm originating from coronary veins, which was successfully removed.

Right anterolateral mini-thoracotomy without inferior vena cava cannulation for atrial septal defect repair in small children: A feasible technique.

OBJECTIVE: To evaluate the effectiveness and safety of right anterolateral mini-thoracotomy without inferior vena cava (IVC) cannulation for closing atrial septal defect (ASD) in small children. METHODS: From February 2016 to August 2017, 10 patients (the mean age was 18.5 ±â€¯10.1 months and the mean weight was 8.3 ±â€¯2.1 kg) underwent ASD closure via right anterolateral mini-thoracotomy. The superior vena cava cannula was placed through the right internal jugular vein. A 3-4 cm incision was made on the right chest. The pleural and pericardial cavities were filled with CO2 and the heart was beating during the surgery. Blood returned from IVC was drained by a right heart sucker. All ASDs were closed using artificial patch, continuous suture. Mean follow-up was 18 months (range, 15-22 months). RESULTS: No post-operative complications or deaths occurred. Mean operation time and mean cardiopulmonary bypass time were 140.5 ±â€¯27.8 min and 50.3 ±â€¯16.5 min, respectively. These patients were extubated within the first 6 h. The intensive care unit stay time and the post-operative hospital stay time were 19.6 ±â€¯2.6 h and 7.1 ±â€¯1.2 days, respectively. Follow-up transthoracic echocardiography showed no residual shunts or lung atelectasis. CONCLUSIONS: The right anterolateral mini-thoracotomy without IVC cannulation is feasible for repairing ASD in small children. This technique is effective and safe and can be used as a therapeutic option for ASD.

Totally endoscopic ventricular septal defect repair using bilateral femoral arterial cannulation in an 8-year-old girl.

INTRODUCTION: There are few reports on applying totally endoscopic surgery (TES) for repairing ventricular septal defect (VSD), especially in children. CASE PRESENTATION: We described an 8-year-old girl, weighing 17 kg, who was diagnosed with peri-membranous VSD and patent ductus arteriosus (PDA). The patient had undergone trans-catheter PDA closure first, and 3 weeks later, TES was performed for VSD repair through 4 small trocars (one 12 mm trocar and three 5 mm trocars) without robotic assistance. Arterial line was set up indirectly to the right femoral artery (FA) through a graft with an additional line to the left side for reducing arterial pressure. DISCUSSION: FA cannulation in small children induce some risks, such as: FA trauma, critical lower limb ischaemia, and iliac or femoral arterial stenosis. Our new method of FA cannulation was safe with 13 months of follow-up. The major concerns in this case were repairing VSD through small trocars in a small child. CONCLUSION: Bilateral FA cannulation and the way to set up small trocars may facilitate totally endoscopic VSD repair in small children. However, the safety and efficacy of these approaches needs to be validated by larger studies preferably randomised controlled trials.

Totally Endoscopic Surgical Repair of Partial Atrioventricular Septal Defect in Children: Two Cases.

There have been few reports on the application of totally endoscopic surgery for repairing partial atrioventricular septal defect. In this report, we present two children who were successfully repaired partial atrioventricular septal defect by using totally endoscopic surgery without robotic assistance.

Totally endoscopic atrial septal defect repair using transthoracic aortic cannulation in a 10.5-kg-boy.

INTRODUCTION: Although totally endoscopic surgery (TES) has been widely applied for the treatment of atrial septal defect (ASD), small children receive few benefits from this technique due to risks of the femoral cannulation. CASE PRESENTATION: A 23-month-old boy, weighing 10.5 kg, with the diagnosis of sinus venosus ASD underwent successful repair by TES. We performed this surgery through 4 small trocars (one 12 mm trocar and three 5 mm trocars), without robotic assistance. In this case, we inserted the arterial cannula directly into the ascending aorta instead of the femoral artery (FA). The defects were repaired on the beating heart with CO2 insufflation. DISCUSSION: Femoral cannulation in small children pose some risks, such as increased arterial line pressure, critical lower limb ischaemia, and post-operative iliac or femoral arterial stenosis. Putting the arterial cannula directly into the ascending aorta is a good solution but is difficult to be performed through TES, especially in small children. The major concern of operating on the beating heart is the air embolism, which requires special preventative methods. CONCLUSION: Transthoracic aortic cannulation may facilitate TES in small children. However, the safety and efficacy of this approach needs to be validated by larger studies preferably randomised controlled trials.