Comparing the efficacy and safety of endovascular therapy versus surgical revascularization for critical limb-threatening ischemia: A systematic review and meta-analysis.

INTRODUCTION: Critical limb-threatening ischemia (CLTI) is a severe manifestation of peripheral artery disease (PAD) that can lead to limb amputation and significantly reduce the quality of life. In addition to guideline-directed medical therapy (GDMT), endovascular therapy and surgical revascularization are the two revascularization options for CLTI. In recent years, there has been an ongoing debate about the best approach for CLTI patients. The purpose of this meta-analysis is to examine the current evidence and compare the clinical outcomes of endovascular therapy and surgical revascularization for CLTI. METHODS: We conducted a systematic search of electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) for studies comparing the outcomes of endovascular therapy versus surgery in patients with CLTI. The primary outcomes were major adverse limb events (MALE) and major adverse cardiovascular events (MACE), while secondary outcomes included risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and length of hospital stay. Pooled data was analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Newcastle-Ottawa Scale and Cochrane risk of bias assessment tool were used to assess the bias of included studies. RESULTS: A total of 16 studies (47,609 patients) were included in this meta-analysis. The overall effect favors surgery over endovascular intervention in terms of MALE [odds ratio (OR) 1.13, 95% CI (1.01-1.28), P = 0.04]. Endovascular therapy is associated with lower MACE rates compared to surgery [OR 0.62, 95% CI (0.51-0.76), P < 0.00001]. Furthermore, the risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure as well as the length of hospital stay was lower for endovascular intervention. Finally, there was no statistically significant difference in 30-day mortality between the two groups [OR 0.94, 95% CI 0.79-1.12, P = 0.52; Fig. 3i], and the pooled studies were homogeneous [P = 0.39; I2 = 5%]. CONCLUSION: Surgery may be the preferred treatment option for CLTI patients, as it is associated with a lower risk of MALE than endovascular therapy. However, endovascular therapy may be associated with a lower risk of MACE and lower rates of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and shorter hospital stays. There was no statistically significant difference in 30-day mortality between the two groups. Ultimately, the decision to use endovascular therapy or surgery as the primary treatment strategy should be based on a multi-disciplinary team approach with careful consideration of patient characteristics and anatomy.

Morphometric Analysis of Spina Bifida after Fetal Repair Shows New Subtypes with Associated Outcomes.

Importance: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been correlated to clinical characteristics and outcomes. Objective: To characterize spina bifida lesion types and correlate them with preoperative presentation and postoperative outcomes. Design: Secondary analysis of images and videos obtained during fetoscopic spina bifida repair surgery from 2020-2023. Setting: Fetal surgery was performed at a quaternary care center. Participants: A prospective cohort of patients referred for fetal spina bifida underwent fetoscopic repair under an FDA-approved protocol. Of 60 lesions repaired, 57 had available images and were included in the analysis. Interventions or Exposures: We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. Main Outcomes and Measures: The reproducibility of the lesion classification was assessed via Kappa interrater agreement. Preoperative characteristics analyzed include ventricle size, tonsillar herniation level, lower extremities movement, and lesion dimensions. Outcomes included surgical time, need for patch for skin closure, gestational age at delivery, preterm premature rupture of membranes (PPROM), and neonatal cerebrospinal fluid (CSF) diversion. Results: We distinguished five lesion types that differ across a range of sac sizes, nerve root stretching, and placode exposure, with 93% agreement between examiners (p<0.001). Fetal characteristics at preoperative evaluation differed significantly by lesion type, including lesion volume (p<0.001), largest ventricle size (p=0.008), tonsillar herniation (p=0.005), and head circumference (p=0.03). Lesion level, talipes, and lower extremities movement did not differ by type. Surgical and perinatal outcomes differed by lesion type, including need for patch skin closure (p<0.001), gestational age at delivery (p=0.01), and NICU length of stay (p<0.001). PPROM, CSF leakage at birth, and CSF diversion in the NICU did not differ between lesion groups. Linear regression associated severity of ventriculomegaly with lesion type, but not with tonsillar herniation level. Conclusions and Relevance: There is a distinct phenotypic spectrum in open spina bifida with differential baseline presentation and outcomes. Severity of ventriculomegaly is associated with lesion type, rather than tonsillar herniation level. Our findings expand the classification of spina bifida to reveal a spectrum that warrants further study.

Development of Cholinium-Based API Ionic Liquids with Enhanced Drug Solubility: Biological Evaluation and Interfacial Properties.

We report an efficient sustainable two-step anion exchange synthetic procedure for the preparation of choline API ionic liquids (Cho-API-ILs) that contain active pharmaceutical ingredients (APIs) as anions combined with choline-based cations. We have evaluated the in vitro cytotoxicity for the synthesized compounds using three different cells lines, namely, HEK293 (normal kidney cell line), SW480, and HCT 116 (colon carcinoma cells). The solubility of APIs and Cho-API-ILs was evaluated in water/buffer solutions and was found higher for Cho-API-ILs. Further, we have investigated the antimicrobial potential of the pure APIs, ILs, and Cho-API-ILs against clinically relevant microorganisms, and the results demonstrated the promise of Cho-API-ILs as potent antimicrobial agents to treat bacterial infections. Moreover, the aggregation and adsorption properties of the Cho-API-ILs were observed by using a surface tension technique. The aggregation behavior of these Cho-API-ILs was further supported by conductivity and pyrene probe fluorescence. The thermodynamics of aggregation for Cho-API-ILs has been assessed from the temperature dependence of surface tension. The micellar size and their stability have been studied by dynamic light scattering, transmission electron microscopy, and zeta potential. Therefore, the duality in the nature of Cho-API-ILs has been explored with the upgradation of their physical, chemical, and biopharmaceutical properties, which enhance the opportunities for advances in pharmaceutical sciences.

Symptomatic obstructive hydrocephalus caused by choroid plexus hyperplasia in a pediatric patient: illustrative case.

BACKGROUND: Choroid plexus hyperplasia has been described as a rare cause of communicating hydrocephalus due to cerebrospinal fluid (CSF) overproduction. However, this is the first report of symptomatic obstructive hydrocephalus caused by mechanical obstruction of the aqueduct by a hyperplastic choroid plexus. OBSERVATIONS: A 4-year-old male presented with headaches and intermittent emesis. Magnetic resonance imaging (MRI) of the brain showed abnormal enlargement of the choroid plexus in the lateral ventricles with extension into the third ventricle, resulting in obstruction of the aqueduct of Sylvius, leading to obstructive hydrocephalus. Endoscopic third ventriculostomy (ETV) was chosen as the surgical treatment. During the procedure, high pressure flow of clear CSF was noted. Normal intraventricular anatomy was identified, and no cyst or tumor was found. The postoperative MRI showed a patent third ventriculostomy, without complication, and a significant decrease in supratentorial ventricular size. The patient was discharged 3 days after surgery with a complete resolution of symptoms. LESSONS: Choroid plexus hyperplasia has the potential to cause obstructive hydrocephalus, and it can be effectively treated with ETV. Our hypothesis is that the change in pressure caused by the procedure may have led to an uncorking of the aqueduct by the hyperplastic choroid plexus, contributing to the observed improvement.

Advances in Imaging Modalities for Pediatric Brain and Spinal Cord Tumors.

BACKGROUND: Neuroimaging has evolved from anatomical imaging toward a multi-modality comprehensive anatomical and functional imaging in the past decades, important functional data like perfusion-weighted imaging, permeability imaging, diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI), tractography, metabolic imaging, connectomics, event-related functional imaging, resting state functional imaging, and much more is now being offered. SUMMARY: Precision diagnostics has proven to be essential for precision treatment. Many minimal invasive techniques have been developed, taking advantage of digital subtraction angiography and interventional neuroradiology. Furthermore, intraoperative CT and/or MRI and more recently MR-guided focused ultrasound have complemented the diagnostic and therapeutic armamentarium. KEY MESSAGES: In the current manuscript, we discuss standard imaging sequences including advanced techniques like DWI, DTI, susceptibility-weighted imaging, and 1H magnetic resonance spectroscopy, various perfusion weighted imaging approaches including arterial spin labeling, dynamic contrast enhanced imaging, and dynamic susceptibility contrast imaging. Pre-, intra, and postoperative surgical imaging including visualize imaging will be discussed. The value of connectomics will be presented for its value in neuro-oncology. Minimal invasive therapeutic possibilities of interventional neuroradiology and image-guided laser ablation and MR-guided high-intensity-focused ultrasound will be presented for treatment of pediatric brain and spinal cord tumors. Finally, a comprehensive review of spinal cord tumors and matching neuropathology has been included.

Integrated clinical genomic analysis reveals xenobiotic metabolic genes are downregulated in meningiomas of current smokers.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recently, various genetic classification systems for meningioma have been described. We sought to identify clinical drivers of different molecular changes in meningioma. As such, clinical and genomic consequences of smoking in patients with meningiomas remain unexplored. METHODS: 88 tumor samples were analyzed in this study. Whole exome sequencing (WES) was used to assess somatic mutation burden. RNA sequencing data was used to identify differentially expressed genes (DEG) and genes sets (GSEA). RESULTS: Fifty-seven patients had no history of smoking, twenty-two were past smokers, and nine were current smokers. The clinical data showed no major differences in natural history across smoking status. WES revealed absence of AKT1 mutation rate in current or past smokers compared to non-smokers (p = 0.046). Current smokers had increased mutation rate in NOTCH2 compared to past and never smokers (p < 0.05). Mutational signature from current and past smokers showed disrupted DNA mismatch repair (cosine-similarity = 0.759 and 0.783). DEG analysis revealed the xenobiotic metabolic genes UGT2A1 and UGT2A2 were both significantly downregulated in current smokers compared to past (Log2FC = - 3.97, padj = 0.0347 and Log2FC = - 4.18, padj = 0.0304) and never smokers (Log2FC = - 3.86, padj = 0.0235 and Log2FC = - 4.20, padj = 0.0149). GSEA analysis of current smokers showed downregulation of xenobiotic metabolism and enrichment for G2M checkpoint, E2F targets, and mitotic spindle compared to past and never smokers (FDR < 25% each). CONCLUSION: In this study, we conducted a comparative analysis of meningioma patients based on their smoking history, examining both their clinical trajectories and molecular changes. Meningiomas from current smokers were more likely to harbor NOTCH2 mutations, and AKT1 mutations were absent in current or past smokers. Moreover, both current and past smokers exhibited a mutational signature associated with DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Furthermore, current smokers exhibited downregulation xenobiotic metabolic gene sets, as well as enrichment in gene sets related to mitotic spindle, E2F targets, and G2M checkpoint, which are hallmark pathways involved in cell division and DNA replication control. In aggregate, our results demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens.

Thoracolumbar Scoliosis in Pediatric Patients With Loeys-Dietz Syndrome: A Case Series.

Background Loeys-Dietz syndrome (LDS) is a genetic connective tissue disorder that predominantly affects cardiovascular, skeletal, and craniofacial structures. Associated thoracolumbar scoliosis in LDS can be challenging to manage, though other etiologies of pediatric scoliosis have better-defined management guidelines. We examined our institutional experience regarding the treatment of pediatric patients with LDS and scoliosis. Methodology In this retrospective study, all patients seen at our pediatric tertiary care center from 2004 through 2018 with a diagnosis of LDS were reviewed, and those with radiographic diagnoses of scoliosis (full-length scoliosis X-rays) were included. Demographic, clinical, and radiographic parameters were collected, and management strategies were reported. Results A total of 39 LDS patients whose ages ranged between seven and 13 years were identified. A total of nine patients were radiographically diagnosed with scoliosis, but three patients were excluded due to incomplete medical records, leaving six patients. The median age at scoliosis diagnosis was 11.5 years, with a median follow-up of 51 months. Two patients were successfully managed with observation (average initial Cobb angle (CA): 14°, average final CA: 20.5°). Two were braced, one successfully (initial CA: 15°, final CA: 30°) and one with a progressive disease requiring surgery (initial CA: 40°, final CA: 58°). Of the two who were offered surgical correction, one underwent surgery with a durable correction of spinal deformity (CA: 33° to 19°). One patient underwent a recent correction of aortic root dilatation and was not a candidate for scoliosis surgery. Conclusions Principles of adolescent idiopathic scoliosis management such as bracing for CA of 20-50° and surgery for CA of >50° can be applied to LDS patients with good outcomes. This augments our understanding of the treatment algorithm for pediatric patients with LDS.

The significance of hindbrain herniation reversal following prenatal repair of neural tube defects.

OBJECTIVE: The aim of this study was to determine whether reversal of hindbrain herniation (HBH) on MRI following prenatal repair of neural tube defects (NTDs) is associated with reduced rates of ventriculoperitoneal (VP) shunt placement or endoscopic third ventriculostomy (ETV) within the 1st year of life. METHODS: This is a secondary analysis of prospectively collected data from all patients who had prenatal open repair of a fetal NTD at a single tertiary care center between 2012 and 2020. Patients were offered surgery according to inclusion criteria from the Management of Myelomeningocele Study (MOMS). Patients were excluded if they were lost to follow-up, did not undergo postnatal MRI, or underwent postnatal MRI without a report assessing hindbrain status. Patients with HBH reversal were compared with those without HBH reversal. The primary outcome assessed was surgical CSF diversion (i.e., VP shunt or ETV) within the first 12 months of life. Secondary outcomes included CSF leakage, repair dehiscence, CSF diversion prior to discharge from the neonatal intensive care unit (NICU), and composite neonatal morbidity. Demographic, prenatal sonographic, and operative characteristics as well as outcomes were assessed using standard univariate statistical methods. Multivariate logistic regression models were fit to assess for independent contributions to the primary and secondary outcomes. RESULTS: Following exclusions, 78 patients were available for analysis. Of these patients, 38 (48.7%) had HBH reversal and 40 (51.3%) had persistent HBH on postnatal MRI. Baseline demographic and preoperative ultrasound characteristics were similar between groups. The primary outcome of CSF diversion within the 1st year of life was similar between the two groups (42.1% vs 57.5%, p = 0.17). All secondary outcomes were also similar between groups. Patients who had occurrence of the primary outcome had greater presurgical lateral ventricle width than those who did not (16.1 vs 12.1 mm, p = 0.02) when HBH was reversed, but not when HBH was persistent (12.5 vs 10.7 mm, p = 0.49). In multivariate analysis, presurgical lateral ventricle width was associated with increased rates of CSF diversion before 12 months of life (adjusted OR 1.18, 95% CI 1.03-1.35) and CSF diversion prior to NICU discharge (adjusted OR 1.18, 95% CI 1.02-1.37). CONCLUSIONS: HBH reversal was not associated with decreased rates of CSF diversion in this cohort. Predictive accuracy of the anticipated benefits of prenatal NTD repair may not be augmented by the observation of HBH reversal on MRI.

Cryopreserved human umbilical cord as a meningeal patch during in utero spina bifida repair in a modified ovine model.

OBJECTIVE: Despite in utero spina bifida (SB) repair, more than two-thirds of patients with SB are unable to ambulate independently, and 1 in 4 children need surgery for tethered cord by school age. The objective of this study was to test the cryopreserved human umbilical cord (HUC) as an antiscarring material to reduce tethering and improve function in a modified in utero SB repair model. METHODS: An SB defect (L2-6 levels) without myelotomy was created in fetuses of timed-pregnant ewes at gestational day (GD) 75. On GD 96, the fetal defect was exposed, and the arachnoid layer was removed to disrupt the barrier and expose the spinal cord to simulate human in utero SB repair. The fetuses were randomly assigned to two groups according to the method used to cover the spinal cord: the conventional repair (CR) group, for which myofascial closure was used (n = 7), and the HUC meningeal patch group, for which HUC was used as a meningeal patch (n = 6), followed by primary skin closure. The lambs were delivered at GD 140. Blinded clinical assessment of spinal cord function was performed using the Texas Spinal Cord Injury Scale (TSCIS). Histology of the spine was performed for quantitative assessment of spinal cord tethering, inflammatory markers, and arachnoid layer regeneration. RESULTS: The TSCIS scores were significantly lower in the CR than the HUC meningeal patch group (p = 0.0015) and the controls (p = 0.0018). The loss of spinal cord function in the CR group was mainly due to ataxia and loss of proprioception (p = 0.01 and 0.005 vs control and HUC, respectively). The histology at the repair site showed higher rates of spinal cord tethering in the CR lambs than the HUC lambs at all levels of the repair site (p = 0.01 and 0.02 vs control and HUC, respectively). In the CR with tethering compared with the HUC repair, there was a lower arachnoid layer covering at the repair site (p = 0.001). There was greater astrocyte activation in the posterior column in the CR than in the HUC repair group (p = 0.01). CONCLUSIONS: In a modified ovine SB model, the HUC as a meningeal patch allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero SB repair.

Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper.

A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology.

CXCR4 expression is associated with proneural-to-mesenchymal transition in glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial-mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high-grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single-cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell-autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.

Transcranial magnetic stimulation tractography and the facilitation of gross total resection in a patient with a motor eloquent glioblastoma: illustrative case.

BACKGROUND: In patients with perieloquent tumors, neurosurgeons must use a variety of techniques to maximize survival while minimizing postoperative neurological morbidity. Recent publications have shown that conventional anatomical features may not always predict postoperative deficits. Additionally, scientific conceptualizations of complex brain function have shifted toward more dynamic, neuroplastic theories instead of traditional static, localizationist models. Functional imaging techniques have emerged as potential tools to incorporate these advances into modern neurosurgical care. In this case report, we describe our observations using preoperative transcranial magnetic stimulation data combined with tractography to guide a nontraditional surgical approach in a patient with a motor eloquent glioblastoma. OBSERVATIONS: The authors detail the use of preoperative functional and structural imaging to perform a gross total resection despite tumor infiltration of conventionally eloquent anatomical structures. The authors resected the precentral gyrus, specifically the paracentral lobule, localized using intraoperative mapping techniques. The patient demonstrated mild transient postoperative weakness and made a full neurological recovery by discharge 1 week later. LESSONS: Preoperative functional and structural imaging has potential to not only optimize patient selection and surgical planning, but also facilitate important intraoperative decisions. Innovative preoperative imaging techniques should be optimized and used to identify safely resectable structures.

Repeat laser interstitial thermal therapy for recurrent primary and metastatic intracranial tumors.

Background: Repeat craniotomy in patients with primary and metastatic brain tumors carries significant morbidity and can delay adjuvant treatments. Repeat laser interstitial thermal therapy (LITT) for recurrent disease has been described and could benefit patients with limited cytoreductive options. We aim to describe the indications, safety, and efficacy of repeat LITT for recurrent primary and metastatic intracranial tumors. Methods: Patients undergoing repeat ablations for the same lesion were included in the study. We retrospectively analyzed 13 patients treated with 29 total LITT ablations. Results: Eleven patients were treated for glioblastoma (GBM), while two had brain metastases. Eleven patients had LITT performed only 2 times, while three patients underwent three total iterations of LITT for disease recurrence. Median length of stay after the 1st ablation was 2 days, while the median length of stay after the 2nd ablation was 1 day. The median time to resuming adjuvant treatments after the 1st LITT was 11 days. The median time to resuming adjuvant treatments after the 2nd LITT was 28 days. Four patients after the 1st and 2nd LITT sustained deficits persisting through 30-day follow-up. The median progression-free survival among the GBM patients from the first ablation was 6.0 months, 3.2 months from the 2nd ablation, and 2.1 months from the 3rd ablation. Conclusion: Recurrent tumors, especially GBM, can be safely treated using repeat LITT when surgery cannot be effectively performed. Our results indicate that patients tolerate the procedure well and have a meaningful survival given the salvage nature of the procedure.

Validation of Non-invasive Language Mapping Modalities for Eloquent Tumor Resection: A Pilot Study.

Many studies have established a link between extent of resection and survival in patients with gliomas. Surgeons must optimize the oncofunctional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Preoperative functional imaging modalities are important tools for optimizing the oncofunctional balance. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are non-invasive imaging modalities that can be used for preoperative functional language mapping. Scarce data exist evaluating the accuracy of these preoperative modalities for language mapping compared with gold standard intraoperative data in the same cohort. This study compares the accuracy of fMRI and TMS for language mapping compared with intraoperative direct cortical stimulation (DCS). We also identified significant predictors of preoperative functional imaging accuracy, as well as significant predictors of functional outcomes. Evidence from this study could inform clinical judgment as well as provide neuroscientific insight. We used geometric distances to determine copositivity between preoperative data and intraoperative data. Twenty-eight patients were included who underwent both preoperative fMRI and TMS procedures, as well as an awake craniotomy and intraoperative language mapping. We found that TMS shows significantly superior correlation to intraoperative DCS compared with fMRI. TMS also showed significantly higher sensitivity and negative predictive value than specificity and positive predictive value. Poor cognitive baseline was associated with decreased TMS accuracy as well as increased risk for worsened aphasia postoperatively. TMS has emerged as a promising preoperative language mapping tool. Future work should be done to identify the proper role of each imaging modality in a comprehensive, multimodal approach to optimize the oncofunctional balance.

Assessing Gq-GPCR-induced human astrocyte reactivity using bioengineered neural organoids.

Astrocyte reactivity can directly modulate nervous system function and immune responses during disease and injury. However, the consequence of human astrocyte reactivity in response to specific contexts and within neural networks is obscure. Here, we devised a straightforward bioengineered neural organoid culture approach entailing transcription factor-driven direct differentiation of neurons and astrocytes from human pluripotent stem cells combined with genetically encoded tools for dual cell-selective activation. This strategy revealed that Gq-GPCR activation via chemogenetics in astrocytes promotes a rise in intracellular calcium followed by induction of immediate early genes and thrombospondin 1. However, astrocytes also undergo NF-κB nuclear translocation and secretion of inflammatory proteins, correlating with a decreased evoked firing rate of cocultured optogenetic neurons in suboptimal conditions, without overt neurotoxicity. Altogether, this study clarifies the intrinsic reactivity of human astrocytes in response to targeting GPCRs and delivers a bioengineered approach for organoid-based disease modeling and preclinical drug testing.

Thinning of the Skull Base and Calvarial Thickness in Patients With Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure without secondary causes on neuroimaging. IIH typically occurs in young, obese female patients and, when severe, can cause permanent and irreversible vision loss. The association between skull base thinning in patients with intracranial hypertension and obesity has been previously reported; however, no study has reported these findings in IIH. The goal of our study is to determine whether IIH is independently associated with skull base and calvarial thinning. METHODS: A retrospective, matched case-control study was performed. Each patient diagnosed with IIH (case) was matched with a patient diagnosed with headache (control) by age, gender, and race. Patients were included if they underwent computed tomographic imaging of the head, maxillofacial, or orbits within 3 months of their diagnosis. Exclusion criteria were history of skull base or frontal bone pathology because of surgery or skull trauma, central nervous system infections, or incomplete radiologic data. Patient demographics, medical history, clinical examination, and skull base, calvarial, and zygoma thickness were recorded. Skull base thickness was measured by the height of the auditory canal in the coronal plane. Calvarial thickness was measured just anterior to the foramen rotundum in the coronal plane. Extracranial zygoma thickness was measured and used as an internal imaging control because the zygoma is not subject to intracranial forces. RESULTS: One hundred twenty-six patients were included in the study, 63 cases and 63 controls. Each group comprised 61 female patients (97%), 24 (38%) Caucasian, 23 (37%) black, 1 (2%) Asian, and 15 (24%) others. The average age was 31.5 ± 8.7 years. Patients with IIH were more likely to be obese (n = 60, 95%) compared with the control patients (n = 23, 37%, P < 0.001). All patients with IIH underwent lumbar puncture (LP) with an average opening pressure (OP) of 40.5 ± 15.6 cm H2O, whereas only 13 (20%) controls underwent an LP with a mean OP of 19.5 ± 8.5 cm H2O. There was no statistical difference in mean visual acuity between the IIH and control groups (logMar 0.22 [20/30] ± 0.45 vs logMar 0.09 [20/25] ± 0.30, P = 0.093, respectively). Compared with the controls, patients with IIH were more likely to have headache (97% vs 74%, P = 0.001), pulsatile tinnitus (48% vs 7%, P < 0.001), horizontal binocular diplopia (24% vs 4%, P = 0.006), confrontational visual field deficit (23% vs 2%, P = 0.003), and papilledema (74% vs 0%, P < 0.001). Patients with IIH had thinner skull base and calvarium width compared with the controls (mean skull base thickness 4.17 ± 0.94 mm vs 5.05 ± 1.12 mm, P < 0.001 and mean calvarial width 1.50 ± 0.50 mm vs 1.71 ± 0.61 mm, P = 0.024). Zygoma thickness was similar in both groups (mean zygoma thickness 1.18 ± 0.30 mm in the IIH group vs 1.26 ± 0.35 mm in the control group, P = 0.105). In a subgroup analysis controlling for obesity (body mass index >30 kg/m2), there was no statistically significant difference in skull base, calvarial, or zygoma thickness between obese and nonobese patients. CONCLUSIONS: Patients with IIH have thinner mean skull base and calvarial thickness compared with the controls. There was no difference in the mean extracranial zygoma thickness, which was the internal imaging control. Contrary to previous reports, we did not find an association between obesity and skull base or calvarial thinning. These findings suggest that IIH is associated with skull base and calvarial thinning.

Pearls and Pitfalls of Imaging in Pediatric Brain Tumors.

The central nervous system (CNS) tumors constitute the most common type of solid tumors in the pediatric population. The cerebral and cerebellar parenchyma are the most common site of pediatric CNS neoplasms. Imaging plays an important role in detection, characterization, staging and prognostication of brain tumors. The focus of the current article is pediatric brain tumor imaging with emphasis on pearls and pitfalls of conventional and advanced imaging in various pediatric brain tumor subtypes. The article also elucidates changes in brain tumor terms and entities as applicable to pediatric patients, updated as per World Health Organization (WHO) 2016 classification of primary CNS tumors. This classification introduced the genetic and/or molecular information of primary CNS neoplasms as part of comprehensive tumor pathology report in the routine clinical workflow. The concepts from 2016 classification have been further refined based on current research, by the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) group and published in the form of updates. The updates serve as guidelines in the time interval between WHO updates and expect to be broadly adopted in the subsequent WHO classification. The current review covers most pediatric brain tumors except pituitary tumors, meningeal origin tumors, nerve sheath tumors and CNS lymphoma/leukemia.

TMS Seeded Diffusion Tensor Imaging Tractography Predicts Permanent Neurological Deficits.

Surgeons must optimize the onco-functional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Optimal patient selection and surgical planning requires preoperative identification of nonresectable structures. Transcranial magnetic stimulation is a method of noninvasively mapping the cortical representations of the speech and motor systems. Despite recent promising data, its clinical relevance and appropriate role in a comprehensive mapping approach remains unknown. In this study, we aim to provide direct evidence regarding the clinical utility of transcranial magnetic stimulation by interrogating the eloquence of TMS points. Forty-two glioma patients were included in this retrospective study. We collected motor function outcomes 3 months postoperatively. We overlayed the postoperative MRI onto the preoperative MRI to visualize preoperative TMS points in the context of the surgical cavity. We then generated diffusion tensor imaging tractography to identify meaningful subsets of TMS points. We correlated the resection of preoperative imaging features with clinical outcomes. The resection of TMS-positive points was significantly predictive of permanent deficits (p = 0.05). However, four out of eight patients had TMS-positive points resected without a permanent deficit. DTI tractography at a 75% FA threshold identified which TMS points are essential and which are amenable to surgical resection. TMS combined with DTI tractography shows a significant prediction of postoperative neurological deficits with both a high positive predictive value and negative predictive value.

Laser interstitial thermal therapy for newly diagnosed glioblastoma.

Gliomas are the most frequent primary brain tumor in adults. Patients with glioblastoma (GBM) tumors deemed inoperable with open surgical techniques and treated only with chemo/radiation have a median overall survival of less than 9 months. Laser interstitial thermal therapy (LITT) has emerged as a cytoreductive alternative to surgery for these patients. The present study describes the outcomes of twenty patients with newly diagnosed, IDH wild-type glioblastoma treated with LITT. We retrospectively reviewed patients with newly diagnosed, unresectable GBM who underwent LITT at our institution. Progression-free survival (PFS) was the primary endpoint measured in our study, defined as time from LITT to disease progression. Results Twenty patients were identified with newly diagnosed, inoperable GBM lesions who underwent LITT. The overall median PFS was 4 months (95% CI = 2 - N/A, upper limit not reached). The median progression-free survival (PFS) for patients with less than 1 cm 3 residual tumor (gross total ablation, GTA) was 7 months (95% CI = 6 - N/A, upper limit not reached), compared to 2 months (95% CI = 1 - upper limit not reached) for patients with a lower GTA (p = .0019). The median overall survival was 11 months (95% CI = 6 - upper limit not reached). Preoperative Karnofsky performance score (KPS) less than or equal to 80 and deep-seated tumor location were significantly associated with decreased PFS (HR, .18, p = .03; HR, .08, p = .03, respectively). At the end of 1 month, only 4 patients (20%) experienced persistent motor deficits. LITT is a safe and effective treatment for patients with unresectable, untreated GBM with rates of survival and local recurrence comparable to patients with surgically accessible lesions treated with conventional resection. Careful patient selection is needed to determine if GTA is attainable.