Endoscopic third ventriculostomy (ETV) for Chiari 1 malformation: a systematic review and meta-analysis.

Meta-analysis and systematic review. To understand the role of endoscopic third ventriculostomy (ETV) for the treatment of concurrent Chiari Malformation Type I (CMI) and hydrocephalus in adults. A literature search on PubMed and Medline with MeSH terms relating to ETV and CMI identified 155 articles between 1988 and 2024. After excluding pediatric cases and other CNS pathologies with associated CMI, 11 articles met inclusion criteria. The Newcastle-Ottawa Scale was identified to assess heterogeneity and risk of bias among the 11 studies analyzed in this systematic-review and meta-analyses compared pre- and post-operative outcomes to examine the use of ETV as a treatment modality for CMI with hydrocephalus. From the 11 included studies, 35 cases of concurrent CMI and hydrocephalus treated with ETV were identified. ETV provided a pooled rate of symptom resolution or improvement of 66%. Additionally, meta-analysis discovered the following pooled rates: a reduction of tonsillar descent in 94% of patients, decreased ventriculomegaly in 94%, and ETV patency in 99%. Syringomyelia, nausea, papilledema and cerebellar dysfunction did not have sufficient numbers for meaningful statistical analyses. However, in each of these categories, more than 85% of the symptoms or radiographic findings improved. This review summarizes the safety and efficacy of ETV for the concurrent management of acquired CMI with hydrocephalus. Specifically, ETV improves radiological outcomes of both ventriculomegaly and tonsillar descent as well as the most prevalent neurological symptom, headaches.

Pure arterial malformation of the fetal PCA treated with flow diverter stent-case report and literature review.

INTRODUCTION: Thirty-three-year-old female underwent diagnostic work-up for chronic headaches. CASE REPORT: Cerebral DSA on the right side showed fetal posterior cerebral artery (PCA) with unusually shaped arterial malformation on its proximal part. Malformation was formed by multiple convolutions and loops with no arteriovenous shunting. During endovascular procedure, flow diverter stent was placed in the right C6 segment. Patient was put on double antiaggregation therapy. Four weeks after procedure, patient was admitted to ER with signs of dyphasia. No recent ischemic lesions were detected on emergent magnetic resonance. Dyphasia resolved spontaneously. On follow-up magnetic resonance angiography 5 years after the procedure, main portion of malformation has diminished with slightly filling of posterior part supplied by right P1. DISCUSSION: Here, reported finding is consistent with previously described pure arterial malformation (PAM). Main intention of our treatment was to induce malformation remodeling with flow diverter placement. Two main risks arise when using flow diverters on fetal PCA region. Firstly, there is possibility of occluding fetal PCA alongside malformation. On the contrary, high flow through fetal PCA could hinder malformation thrombosis. Some case series reported high rate of fetal PCA occlusion without ischemic sequelae in the PCA teritory. Others consider flow diverters highly ineffective treatment for the fetal PCA aneurysms due to low rate of complete aneurysm occlusion. CONCLUSION: We presented first reported case in which flow diverter was used to treat PAM. Slow malformation thrombosis leaves enough time for collateral circulation to recruit and supply territory of the vessel affected by the malformation.

Waxing and waning consciousness in a patient with a midbrain cavernous malformation: illustrative case.

BACKGROUND: Understanding the intricate relationship between consciousness and the midbrain's structures remains a significant challenge in neuroscience. Transient lesions are perfect examples of the physiological functioning mechanism of these structures. OBSERVATIONS: The authors present the case of a 49-year-old female who experienced a transient disorder of consciousness due to a midbrain hematoma following surgical interventions to remove a cavernous malformation in the midbrain. This case explores the interplay between the ascending reticular activating system (ARAS) and the thalamic centers, highlighting the role of structural disruptions in influencing consciousness levels. Notably, the patient's recovery correlated with the resolution of midbrain edema, reinstating normal ARAS function and consciousness. LESSONS: In patients affected by midbrain lesions, edema can lead to a fluctuating neurological status, which can be difficult to diagnose. This case highlights the midbrain's crucial role in the consciousness network and the need to comprehend the intricate connections between subcortical and cortical structures for a comprehensive understanding of human consciousness. https://thejns.org/doi/10.3171/CASE2411.

Concurrent multiple cerebral cavernous malformations and cauda equina paraganglioma: illustrative case.

BACKGROUND: Cauda equina neuroendocrine tumors (CENETs), previously known as cauda equina paragangliomas, and multiple cerebral cavernous malformations (CCMs) are uncommon conditions affecting the central nervous system. To the authors' knowledge, they have not been reported in the same patient. OBSERVATIONS: The authors present the case of a 45-year-old male with CENET and concurrent incidental MRI findings of multiple CCMs. Familial CCMs are associated with mutations in the KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) genes. Peripheral paragangliomas have been associated with mutations in succinate dehydrogenase (SDHx), RET (multiple endocrine neoplasia 2), VHL (von Hippel-Lindau syndrome), and NF1 (neurofibromatosis type 1) genes. Except for a single case, cauda equina paragangliomas have not been associated with any underlying genetic mutations. LESSONS: It is unclear whether the co-occurrence of these two rare conditions in the same patient is coincidental or suggests a possible shared pathogenesis. https://thejns.org/doi/10.3171/CASE24102.

Injectable chitosan hydrogel effectively controls lesion growth in a venous malformation murine model.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intralesional injection of chitosan hydrogel (CH) combined with sodium tetradecyl sulfate (STS) to sclerose and embolize venous malformations (VMs) by comparison with 3% STS foam and placebo in a mouse model. MATERIALS AND METHODS: Subcutaneous VMs were created by injecting HUVEC_TIE2-L914F cells, mixed with matrigel, into the back of athymic mice (Day [D] 0). After VM-like lesions were established at D10, 70 lesions were randomly assigned to one of six treatment groups (untreated, saline, 3% STS-foam, CH, 1% STS-CH, 3% STS-CH). For 3% STS-foam, the standard Tessari technique was performed. VMs were regularly evaluated every 2-3 days to measure lesion size until the time of collection at D30 (primary endpoint). At D30, VM lesions including the matrigel plugs were culled and evaluated by histological analysis to assess vessel size, chitosan distribution and endothelial expression. One-way analysis of variance (ANOVA) test was performed to compare quantitative variables with normal distribution, otherwise Kruskal-Wallis test followed by pairwise comparisons by a Wilcoxon rank sum test was performed. RESULTS: All VMs were successfully punctured and injected. Six VMs injected with 3% STS-CH showed early skin ulceration with an extrusion of the matrigel plug and were excluded from final analysis. In the remaining 64 VMs, skin ulceration occurred on 26 plugs, resulting in the loss of three 3% STS-foam and one 1% STS-CH plugs. Both chitosan formulations effectively controlled growth of VMs by the end of follow-up compared to untreated or 3% STS-foam groups (P < 0.05). Vessel sizes were smaller with both CH formulations compared to untreated and saline groups (P < 0.05). Additionally, there were smaller vascular channels within the 1% STS-CH group compared to the 3% STS-foam group (P < 0.05). CONCLUSION: Chitosan's ability to control the growth of VMs suggests a promising therapeutic effect that outperforms the gold standard (STS-foam) on several variables.

Clinical and histopathological spectrum of congenital pulmonary airway malformations: A case series.

BACKGROUND: Congenital pulmonary airway malformations (CPAM) are a spectrum of cystic and non-cystic anomalies arising from abnormal airway development in utero, with an incidence of 1 in 25,000 to 35,000 births. CPAM can present prenatally or postnatally with respiratory distress, recurrent infections, or occasionally as an incidental finding. This case series aims to highlight the clinical, radiological, and histopathological characteristics of CPAM through three pediatric cases, which include types 1, 2, and 3 CPAM. CASE PRESENTATION: Case 1: A four-month-old male presented with cough, cold, and respiratory distress. Imaging revealed hypoattenuation and overinflation of the left upper lobe with mediastinal shift. Left upper lobectomy confirmed CPAM type 2. Case 2: A one-month-old female presented with recurrent respiratory distress and infections. Imaging showed a large cystic lesion in the right middle lobe. Right middle lobectomy confirmed CPAM type 3. Case 3: A two-month-old male presented with dyspnea. Imaging showed a large bullae in the right chest with mediastinal shift. Right upper lobectomy confirmed CPAM type 1. CLINICAL DISCUSSION: CPAM is a rare congenital lung malformation characterized by abnormal bronchial development and localized glandular overgrowth. Management involves surgical resection, with the timing of surgery dependent on symptomatology. Early identification and intervention are crucial for preventing complications such as pulmonary hypoplasia and recurrent infections. Histopathological examination post-resection is essential for accurate classification and management of CPAM. CONCLUSION: This case series provides valuable insights into the clinical, radiological, and histopathological features of CPAM, including the types encountered in each case. It underscores the importance of early diagnosis and timely surgical intervention, advocating for routine prenatal and postnatal screenings to effectively identify and manage CPAM.

Bridging the Gap: The Impact of Bowel Management Programs on Daily Life in Pediatric Colorectal Disease.

BACKGROUND: This commentary discusses the social impact of bowel management programs (BMPs) on children with colorectal diseases, including anorectal malformations (ARM), Hirschsprung disease (HD), functional constipation (FC), and spina bifida. Previous studies focused on functional outcomes, but this study bridges the gap to daily life experiences. METHODS: The study examined children's experiences in BMPs, focusing on school participation, vacation ability, and overall patient experience. Cleanliness, defined as fewer than one stool soiling episode per week, was achieved by 70% of participants. RESULTS: Positive patient experiences were linked to achieving stool cleanliness, regardless of the management method. Invasive methods like enemas did not negatively affect experiences if cleanliness was maintained. Validated patient-reported experience measures (PREMs) and patient-reported outcomes measures (PROMs) were used, though the median age of 8.9 years posed limitations. CONCLUSION: The commentary highlights the significance of stool cleanliness in improving patient experiences and supports the effectiveness of various BMP methods. Future research should include longitudinal follow-ups to assess BMP durability and gather data from older children.

Morphological Measurement and Clinical Significance of Abnormal Development of Distal Femur with Hemophilia Knee Arthritis: A Consideration on the Renewal of Total Knee Prosthesis.

OBJECTIVE: The knee joint of hemophiliacs may face the result of local morphological changes due to long-term irritation of synovitis. This study aims to elucidate the morphological characteristics of distal femur in hemophilic arthritis (HA) and compare the compatibility of three types of prostheses with the anteroposterior (AP) and mediolateral (ML) dimensions of the femoral osteotomy surface. METHODS: This study retrospectively and randomly selected 50 patients with HA registered for treatment at our hospital from June 2016 to August 2022 as the study subjects, with an equal number of male osteoarthritis (OA) patients and healthy male individuals set as the control group. This study used medical digitalization software to simulate osteotomies on the distal femur during total knee arthroplasties (TKA) for 50 patients with HA, OA patients, and the healthy population, respectively, and measure the morphological parameters to compare with three commonly used femoral components of TKA in clinical practice. The differences between the femur resection of anteroposterior and mediolateral (FRAP, FRML) osteotomy surface and the prosthesis's BOX-AP/ML were compared in three prostheses. One-way ANOVA and multiple Kruskal-Wallis H test were used for the normal or non-normal distribution data, and pairwise comparisons between groups were conducted using the Bonferroni method, and the linear correlation analysis was utilized to assess the relationship between section femoral morphological data and prosthesis parameters. RESULT: In HA patients, the morphological characteristics of the distal femur were shown as shorter than femur AP (FAP), medial and lateral condyle anterior-posterior dimension (FMCAP, FLCAP), notch width (NW), posterolateral condyle height (PLCH), posteromedial condyle width (PMCW), and posterior condylar axis length (PCAL) dimension. They had comparatively smaller femur section aspect ratios (p < 0.005). They showed longer posterolateral condyle width (PLCW), anterior condyle mediolateral dimension (FRACML), anterolateral condyle height (ALCH), and femur resection anterior condylar mediolateral (FRACML) dimension (p < 0.005). They showed larger distal femur aspect ratio and resection aspect ratio (FAR, FRAR, p < 0.005). All selected prostheses showed ML undercoverage under similar AP dimensions, and ML undersizing of Attune systems was more obvious in three femoral prostheses. CONCLUSION: The distal femur morphological change of HA patient is shown as smaller AP dimension, narrow posterior condyle spacing, lower and shallower trochlear, thinner anterior condyle, wider and lower intercondylar notch and higher posterior-lateral condyle. The selected prostheses showed ML undercoverage under similar AP dimensions. This typical morphological tendency of the distal femur seems to warrant consideration in the process of knee joint prosthesis upgrading.

Cervical intraosseous arteriovenous malformation: report of a rare entity and its management dilemmas.

Intraosseous occurrence of a spinal AVM is anecdotal, with only four such cases reported previously. This is the first report of a spinal intraosseous AVM in the cervical vertebrae. A 44-year-old male patient presented with a 2-month history of progressive quadriparesis and bladder dysfunction. Magnetic resonance imaging showed multiple flow voids within the C4 and C5 vertebral bodies, and an extradural component causing cord compression. CT showed extensive bony destruction at both levels. The diagnosis of an intraosseous AVM was confirmed with spinal angiography. The AVM was noted to be fed by branches from the ascending cervical arteries and the vertebral artery. The nidus was draining into the vertebral venous plexus and thence into the jugular vein through the marginal sinus. The patient underwent partial embolization of the AVM. Surgical resection was attempted but found to be unfeasible due to torrential bleeding. A 360-degree stabilization along with decompressive laminectomies was performed, resulting in clinical improvement and disease stabilization at one year follow-up. The case and its management dilemmas are discussed in light of a brief literature review.

Assessing Health-Related Quality of Life in Children With Spina Bifida in Lithuania.

Introduction In recent years, more emphasis has been placed on improving the health-related quality of life (HRQOL) in children with spina bifida (SB). Chronic disability is understood to impact various aspects of the person's life, family, and social functioning, in addition to the specific needs of the disease. The HRQOL is done to assess the patient's quality of life (QOL) in various domains including physical and mental. Back in the 1900s, few children survived SB, whereas today, they almost have normal life expectancy. By understanding the contributing factors to the quality of life (QOL), more targeted interventions can be put in place in order to maximize the psychological and social well-being of these patients. Aim The aim of this study is to estimate the health-related quality of life (HRQOL) in Lithuanian children with spina bifida (SB) in relation to comorbidities, level of lesions, and mobility. Objectives The objectives of this study are to investigate the HRQOL of Lithuanian children with SB born between 1999 and 2012; to analyze the relation between the HRQOL and its comorbidities, including hydrocephalus, Chiari II malformation, incontinence, and epilepsy; and to determine the relationship of health variables, the level of lesions, and mobility to the HRQOL. Methods This was a quantitative cross-sectional study on children with spina bifida across Lithuania to assess the HRQOL. Subjects were chosen and interviewed from various cities including Kaunas, Vilnius, Marijampole, Gargzdai, Birzai, Panevezys, Palanga, and Alytus. A questionnaire was used as an instrument to measure the HRQOL. The level of lesions, comorbidities, and other health variables were obtained from the medical files and directly from the patient's history. Results Regarding the HRQOL, our study population showed the highest scores in the emotional, medical, intellectual, and social domains. The lowest sub-scores were in recreational, vocational, environmental, and then physical domains. We also found that certain comorbidities including hydrocephalus, epilepsy, and incontinence negatively affected the QOL. In our study group, we also found that the ambulatory group scored significantly higher in the overall QOL. However, when comparing the level of lesions to the HRQOL, we found no statistically significant difference. Conclusion Positive results were obtained regarding the medical, emotional, intellectual, and social aspects of patients with SB in Lithuania as they scored high in this domain. However, the environmental and vocational domains scored low, suggesting that further examination needs to be carried in these domains. We concluded that having various comorbidities including hydrocephalus and incontinence has negative impacts on the QOL. Patients who suffered from epilepsy had a statistically significant lower QOL. No significant difference was found in the association between the level of lesion and the QOL in our study.

Multiple Cavernous Malformation Syndrome in an Infant: A Case Report.

Cerebral cavernomas belong to a group of vascular lesions characterized by varying structural properties and presentations. Clinical manifestations vary among patients and are particularly influenced by age, posing challenges in diagnosis and treatment. Here, we present a pediatric case of a cerebral cavernoma, which is very rare. We further aim to emphasize the importance of a good physical examination.

Familial occurrence of imperforate hymen in premature monozygotic twins and their mother: a case report and literature review.

Background: Imperforate hymen is an uncommon obstructive anomaly of the developing female reproductive tract. There are occasional case reports of imperforate hymen occurring in family clusters, suggesting a plausible familial mode of inheritance. We describe a set of monozygotic premature twins with imperforate hymen noted at birth, whose mother was diagnosed with the same condition as a teenager. We also elucidate the likely underlying mode of inheritance of imperforate hymen. Method: We utilized the CARE (Case Report) guideline in reporting the cases. Case presentation: These are monozygotic twins born prematurely at 30 weeks of gestation, noted at birth to have bulging cyst-like structures protruding from their vaginas. The twins were not dysmorphic and did not have any other congenital malformations. Over the next few weeks, these cyst-like structures (mucoceles) became less prominent. The genital anomaly was diagnosed as imperforate hymen. Their mother was also diagnosed with an imperforate hymen when she was 12 years old and was treated with hymenectomy. Discussion: This unique occurrence of imperforate hymen in a set of premature monozygotic twins and their mother suggests a plausible autosomal or X-linked dominant mode of inheritance. Given the role of genetic inheritance in imperforate hymen development, it is important to screen female relatives of an index case for this genital anomaly.

Lost in transition? Loss of follow-up and quality of life in adults after resection of choledochal malformation in childhood.

Objectives: Choledochal malformation (CM) is a rare disease that can lead to malignancy and potential long-term sequelae despite surgical resection. There is no long-term follow-up data on patients after CM resection in Germany. We aimed to determine the long-term outcome of our patients with a duration of follow-up >10 years and focused on long-term sequelae and health-related quality of life (HRQOL). Methods: All patients who had undergone CM-resection in our department from 01/1978 to 06/2009 were contacted. Patients were interviewed about postoperative complications and their present medical attendance. HRQOL was determined using Pediatric Quality of Life Inventory 4.0 (PedsQL), version for adults. The PedsQL scales the HRQOL from 0 to 100, with higher scores indicating a better HRQOL. Scores were compared to those published for a healthy population. Results: Out of 56 patients who were contacted, 23 (41 %) participated. The median age at time of surgery was 3.1 years (6 days-16.1 years) and at time of the survey 24.3 years (11.1-53.8 years). Eighteen patients (78 %) had ceased their gastroenterologic follow-up at a median time of 4.3 years after surgery. Five (22 %) were still in gastroenterologic follow-up, two of these had an uneventful clinical course, and three (13 %) had ongoing complications attributed to the CM. One of these had undergone hemihepatectomy 34 years postoperatively due to bile duct stenosis, one had undergone removal of bile duct stones 14 years postoperatively, and one suffered from portal vein thrombosis with esophageal and jejunal varices. There was no mortality in our series. Median total HRQOL score was 89. There was no significant difference in the median total health, physical health, and psychosocial health scores of our patients in comparison to the healthy population. Conclusions: We confirmed that the majority of patients after CM resection are lost to follow-up. Those who answered our questionnaire showed a good HRQOL. Given the high rate of severe long-term complications and the life-long risk of malignancy, we recommend a transition program for all patients.

Developmental temperature modulates microplastics impact on amphibian life history without affecting ontogenetic microplastic transfer.

This study examines how temperature influences the response of Japanese tree frogs (Dryophytes japonicus) to microplastic (MP) pollution, assessing whether temperature can regulate the harmful effects of MPs on their life history and the dispersal of MPs across habitats. This analysis aims to understand the ecological and physiological ramifications of MP pollution. Our results demonstrated an ontogenetic transfer of MP particles across amphibian metamorphosis, possibly allowing and facilitating the translocation of MPs across ecosystems. Temperature did not significantly affect the translocation of aquatic MPs to land. However, high temperatures significantly reduced mortality and hindlimb deformities caused by MPs, thereby mitigating their harmful impact on amphibian life histories. Importantly, our study found that MPs cause hindlimb deformities during amphibian metamorphosis, potentially linked to oxidative stress. Additionally, MP exposure and ingestion induced a plastic response in the morphology of the digestive tract and changes in the fecal microbiome, which were evident at high temperatures but not at low temperatures. The effects of MPs persisted even after the frogs transitioned to the terrestrial stage, suggesting that MPs may have complex, long-term impacts on amphibian population sustainability. Our results enhance the understanding of the intricate environmental challenges posed by MPs and underscore the significant role of temperature in ectotherms regarding ontogenetic impacts and pollutant interactions.

Peri-operative Anticoagulation Strategies, Bleeding and Thrombotic Complications in Pediatric Patients Undergoing Intervention for Congenital Portosystemic Shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications. METHODS: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications. RESULTS: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported. CONCLUSIONS: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively. LEVELS OF EVIDENCE: Level II, retrospective study.

Chiari Malformation Type I With Concurrent Bilateral Optic Disc Drusen: Is Follow-up Necessary?

Pseudopapilledema caused by optic disc drusen (ODD) mimics the appearance of papilledema and usually presents as a diagnostic challenge. A young boy with known Chiari malformation type 1 (CM-1) was referred to the pediatric ophthalmology clinic for eye assessment to exclude papilledema due to elevated intracranial pressure (ICP). Despite the ophthalmic examination revealing bilateral optic disc elevation, multimodal imaging techniques such as fundus autofluorescence, optical coherence tomography (OCT), and B-scan ultrasonography are recommended to confirm the distinction between bilateral ODD causing pseudopapilledema and papilledema secondary to elevated ICP. Accidental coexistent papilledema mimickers like ODD need to be considered in patients with CM-1 before making a diagnosis of papilledema to avoid unnecessary invasive procedures. There was no evidence that the presence of ODD excludes the possibility of future optic nerve head changes due to elevated ICP. The multidisciplinary consensus decided on annual ophthalmology follow-ups using multimodal imaging to detect any subtle optic nerve head changes.

Chloride deregulation and GABA depolarization in MTOR related malformations of cortical development.

Focal Cortical Dysplasia, Hemimegalencephaly and Cortical Tuber are pediatric epileptogenic malformations of cortical development (MCDs) frequently pharmaco-resistant and mostly surgically treated by the resection of epileptic cortex. Availability of cortical resection samples allowed significant mechanistic discoveries directly from human material. Causal brain somatic or germline mutations in the AKT/PI3K/DEPDC5/MTOR genes were identified. GABAa mediated paradoxical depolarization, related to altered chloride (Cl-) homeostasis, was shown to participate to ictogenesis in human pediatric MCDs. However, the link between genomic alterations and neuronal hyperexcitability is still unclear. Here we studied the post translational interactions between the mTOR pathway and the regulation of cation-chloride cotransporters (CCC), KCC2 and NKCC1, that are largely responsible for controlling intracellular Cl- and ultimately GABAergic transmission. For this study, 35 children (25 MTORopathies and 10 pseudo controls, diagnosed by histology plus genetic profiling) were operated for drug resistant epilepsy. Postoperative cortical tissues were recorded on multielectrode array (MEA) to map epileptic activities. CCC expression level and phosphorylation status of the WNK1/SPAK-OSR1 pathway was measured during basal conditions and after pharmacological modulation. Direct interactions between mTOR and WNK1 pathway components were investigated by immunoprecipitation. Membranous incorporation of MCD samples in Xenopus laevis oocytes enabled Cl- conductance and equilibrium potential (EGABA) for GABA measurement. Of the 25 clinical cases, half harbored a somatic mutation in the mTOR pathway, while pS6 expression was increased in all MCD samples. Spontaneous interictal discharges were recorded in 65% of the slices. CCC expression was altered in MCDs, with a reduced KCC2/NKCC1 ratio and decreased KCC2 membranous expression. CCC expression was regulated by the WNK1/SPAK-OSR1 kinases through direct phosphorylation of Thr906 on KCC2, that was reversed by WNK1 and SPAK antagonists (NEM and Staurosporine). mSIN1 subunit of MTORC2 was found to interact with SPAK-OSR1 and WNK1. Interactions between these key epileptogenic pathways could be reversed by the mTOR specific antagonist Rapamycin, leading to a dephosphorylation of CCCs and recovery of the KCC2/NKCC1 ratio. The functional effect of such recovery was validated by the restoration of the depolarizing shift in EGABA by rapamycin, measured after incorporation of MCD membranes to X. laevis oocytes, in line with a reestablishment of normal ECl-. Our study deciphers a protein interaction network through a phosphorylation cascade between MTOR and WNK1/SPAK-OSR1 leading to chloride cotransporters deregulation, increased neuronal chloride levels and GABAa dysfunction in malformations of Cortical Development, linking genomic defects and functional effects and paving the way to target epilepsy therapy.

Cardiopulmonary crisis caused by bronchial blocker malposition in a patient with aberrant tracheal anatomy: a case report.

BACKGROUND: Double-lumen tubes (DLTs) and bronchial blockers (BBs) can be used to establish one-lung ventilation (OLV) for thoracic surgery. BBs are a good alternative when DLTs are not suitable or patients have difficult airways. However, BBs are more prone to malposition, leading to adverse events. CASE PRESENTATION: We present a 68-year-old male patient who was scheduled for thoracoscopic left lower lobectomy. The patient was not expected to have airway malformation preoperatively. When the DLT could not be inserted into the bronchus after general anesthesia induction, we used a BB to perform OLV. During surgery, malposition of the BB resulted in the development of an "incomplete balloon valve", leading to a cardiopulmonary crisis. CONCLUSIONS: Previewing chest computed tomography scans to assess the airway anatomy before thoracic surgery is essential. Three-dimensional reconstruction of the airway can provide a more intuitive assessment of airway anatomy. During OLV with BBs, we should pay attention to balloon malposition to prevent cardiopulmonary crises.